bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic multiple sequence alignments: refinement using a genetic algorithm
Authors: Wang Chunlin , Lefkowitz Elliot J 
Published: August 2005

Abstract
Background
Genomic sequence data cannot be fully appreciated in isolation. Comparative genomics – the practice of comparing genomic sequences from different species – plays an increasingly important role in understanding the genotypic differences between species that result in phenotypic differences as well as in revealing patterns of evolutionary relationships. One of the major challenges in comparative genomics is producing a high-quality alignment between two or more related genomic sequences. In recent years, a number of tools have been developed for aligning large genomic sequences. Most utilize heuristic strategies to identify a series of strong sequence similarities, which are then used as anchors to align the regions between the anchor points. The resulting alignment is globally correct, but in many cases is suboptimal locally. We describe a new program, GenAlignRefine, which improves the overall quality of global multiple alignments by using a genetic algorithm to improve local regions of alignment. Regions of low quality are identified, realigned using the program T-Coffee, and then refined using a genetic algorithm. Because a better COFFEE (Consistency based Objective Function For alignmEnt Evaluation) score generally reflects greater alignment quality, the algorithm searches for an alignment that yields a better COFFEE score. To improve the intrinsic slowness of the genetic algorithm, GenAlignRefine was implemented as a parallel, cluster-based program.

Results
We tested the GenAlignRefine algorithm by running it on a Linux cluster to refine sequences from a simulation, as well as refine a multiple alignment of 15 Orthopoxvirus genomic sequences approximately 260,000 nucleotides in length that initially had been aligned by Multi-LAGAN. It took approximately 150 minutes for a 40-processor Linux cluster to optimize some 200 fuzzy (poorly aligned) regions of the orthopoxvirus alignment. Overall sequence identity increased only slightly; but significantly, this occurred at the same time that the overall alignment length decreased – through the removal of gaps – by approximately 200 gapped regions representing roughly 1,300 gaps.

Conclusion
We have implemented a genetic algorithm in parallel mode to optimize multiple genomic sequence alignments initially generated by various alignment tools. Benchmarking experiments showed that the refinement algorithm improved genomic sequence alignments within a reasonable period of time.
The definition of disabling fatigue in children and adolescents
Authors: Fowler Tom , Duthie Pamela , Thapar Anita , Farmer Anne 
Published: August 2005

Abstract

Background
Disabling fatigue is the main illness related reason for prolonged absence from school. Although there are accepted criteria for diagnosing chronic fatigue in adults, it remains uncertain as to how best to define disabling fatigue and Chronic Fatigue Syndrome (CFS) in children and adolescents. In this population-based study, the aim was to identify children who had experienced an episode of disabling fatigue and examine the clinical and demographic differences between those individuals who fulfilled a narrow definition of disabling fatigue and those who fulfilled broader definitions of disabling fatigue.

Methods
Participants (aged 8–17 years) were identified from a population-based twin register. Parent report was used to identify children who had ever experienced a period of disabling fatigue. Standardised telephone interviews were then conducted with the parents of these affected children. Data on clinical and demographic characteristics, including age of onset, gender, days per week affected, hours per day spent resting, absence from school, comorbidity with depression and a global measure of impairment due to the fatigue, were examined. A narrow definition was defined as a minimum of 6 months disabling fatigue plus at least 4 associated symptoms, which is comparable to the operational criteria for CFS in adults. Broader definitions included those with at least 3 months of disabling fatigue and 4 or more of the associated symptoms and those with simply a minimum of 3 months of disabling fatigue. Groups were mutually exclusive.

Results
Questionnaires were returned by 1468 families (65% response rate) and telephone interviews were completed on 99 of the 129 participants (77%) who had experienced fatigue. There were no significant differences in demographic and clinical characteristics or levels of impairment between those who fulfilled the narrower definition and those who fulfilled the broader definitions. The only exception was the reported number of days per week that the child was affected by the fatigue. All groups demonstrated evidence of substantial impairment associated with the fatigue.

Conclusion
Children and adolescents who do not fulfil the current narrow definition of CFS but do suffer from disabling fatigue show comparable and substantial impairment. In primary care settings, a broader definition of disabling fatigue would improve the identification of impaired children and adolescents who require support.
High frequency of the IVS2-2A>G DNA sequence variation in SLC26A5, encoding the cochlear motor protein prestin, precludes its involvement in hereditary hearing loss
Authors: Tang Hsiao-Yuan , Xia Anping , Oghalai John S , Pereira Fred A , Alford Raye L 
Published: August 2005

AbstractBackgroundCochlear outer hair cells change their length in response to variations in membrane potential. This capability, called electromotility, is believed to enable the sensitivity and frequency selectivity of the mammalian cochlea. Prestin is a transmembrane protein required for electromotility. Homozygous prestin knockout mice are profoundly hearing impaired. In humans, a single nucleotide change inSLC26A5, encoding prestin, has been reported in association with hearing loss. This DNA sequence variation, IVS2-2A>G, occurs in the exon 3 splice acceptor site and is expected to abolish splicing of exon 3.MethodsTo further explore the relationship between hearing loss and the IVS2-2A>G transition, and assess allele frequency, genomic DNA from hearing impaired and control subjects was analyzed by DNA sequencing.SLC26A5genomic DNA sequences from human, chimp, rat, mouse, zebrafish and fruit fly were aligned and compared for evolutionary conservation of the exon 3 splice acceptor site. Alternative splice acceptor sites within intron 2 of humanSLC26A5were sought using a splice site prediction program from the Berkeley Drosophila Genome Project.ResultsThe IVS2-2A>G variant was found in a heterozygous state in 4 of 74 hearing impaired subjects of Hispanic, Caucasian or uncertain ethnicity and 4 of 150 Hispanic or Caucasian controls (p = 0.45). The IVS2-2A>G variant was not found in 106 subjects of Asian or African American descent. No homozygous subjects were identified (n = 330). Sequence alignment ofSLC26A5orthologs demonstrated that the A nucleotide at position IVS2-2 is invariant among several eukaryotic species. Sequence analysis also revealed five potential alternative splice acceptor sites in intron 2 of humanSLC26A5.ConclusionThese data suggest that the IVS2-2A>G variant may not occur more frequently in hearing impaired subjects than in controls. The identification of five potential alternative splice acceptor sites in intron 2 of humanSLC26A5suggests a potential mechanism by which expression of prestin might be maintained in cells carrying theSLC26A5IVS2-2A>G DNA sequence variation. Additional studies are needed to evaluate the effect of the IVS2-2A>G transition on splicing ofSLC26A5transcripts and characterize the hearing status of individuals homozygous for the IVS2-2A>G variant.
Expression of transforming growth factor-beta-1 and p27Kip1 in pancreatic adenocarcinomas: relation with cell-cycle-associated proteins and clinicopathologic characteristics
Authors: Culhaci Nil , Sagol Ozgul , Karademir Sedat , Astarcioglu Huseyin , Astarcioglu Ibrahim , Soyturk Mujde , Oztop Ilhan , Obuz Funda 
Published: August 2005

Abstract
Background
The purpose of our study was to investigate the immunohistochemical expression of TGF-β1 and p27 in pancreatic adenocarcinomas and to compare the findings with the clinicopathological features and survival. We also aimed to evaluate the expression of TGF-β1 and p27 in the context of other cell cycle and proliferation markers such as cyclin D1 and Ki-67.

Methods
We examined TGF-β1 and p27 expression immunohistochemically in 63 cases of invasive ductal adenocarcinoma of the pancreas. Standard streptavidin-biotin immunperoxidase method was used for immunostaining and the stained slides were examined microscopically using semiquantitative criteria.

Results
TGF-β1 stained the cytoplasms of the tumor cells in 43 cases [68.3%]. There was a statistically significant difference among TGF-β1 staining scores in terms of clinicopathologic factors such as blood vessel invasion, stage and distant metastasis [p < 0.05]. Of the 63 tumors evaluated 23 [36.5%] were positive for p27 within the nucleus. An inverse correlation was found between p27 immunoreactivity and grade [p < 0.05]. But no significant correlation was found between p27 and other parameters. Among the patients with survival data 27 patients had RO resections and these cases were considered in survival analysis. In the univariate analysis, neither TGF-β1 nor p27 expression was related with patient survival.

Conclusion
Our findings suggest that in pancreatic carcinoma, TGF-β1 expression is related to tumor growth and metastasis. But it is not associated with cell cycle proteins. p27 expression is reduced in pancreatic adenocarcinomas and decreased protein levels of p27 may play a role in the differentiation of pancreatic cancer.
Complications after cryosurgery with new miniature cryoprobes in long hollow bones: An animal trial
Authors: Popken Frank , Meschede Peter , Erberich Heike , Koy Timmo , Bosse Marfalda , Fischer Jürgen H , Eysel Peer 
Published: August 2005

Abstract
Background
In vitro studies show that new miniature cryoprobes are suitable for cryoablation of bone tissue. The aim of this animal trial on 24 sheep was to examine the perioperative complications, particularly the danger of embolism, of cryoablation when using miniature cryoprobes.

Methods
Cryoablations with 2 freeze-thaw cycles each were carried out in the epiphysis of the right tibia and the metaphysis of the left femur. Pulmonary artery pressure (PAP) and central venous pressure (CVP) were measured. Throughout the intra- and perioperative phase, heart rate and oxygen saturation by pulse oxymetry, blood gas and electrolytes were monitored regularly. Postoperative complications were examined up to 24 weeks postoperativ.

Results
As result, no significant increase of PAP, CVP or heart rate were observed. Blood gases were unremarkable, with pO2 and pCO2 remaining constant throughout the operation. Regarding pH, standard bicarbonate and base excess, only a non-significant shift towards a slight acidosis was seen. There was a mean hemoglobin decrease of 0.5 g/dl. One animal showed postoperative wound infection and wound edge necrosis. No major peri- and postoperative complications associated with cryosurgery of bone were observed, especially regarding clinically relevant pulmonary embolism.

Conclusion
Surgery with new types of miniature cryoprobes appears to be a safe alternative to or a complement to conventional resection of abnormal bone tissue.
Endothelial cell injury by high glucose and heparanase is prevented by insulin, heparin and basic fibroblast growth factor
Authors: Han Juying , Mandal Anil K , Hiebert Linda M 
Published: August 2005

Abstract

Background
Uncontrolled hyperglycemia is the main risk factor in the development of diabetic vascular complications. The endothelial cells are the first cells targeted by hyperglycemia. The mechanism of endothelial injury by high glucose is still poorly understood. Heparanase production, induced by hyperglycemia, and subsequent degradation of heparan sulfate may contribute to endothelial injury. Little is known about endothelial injury by heparanase and possible means of preventing this injury.

Objectives
To determine if high glucose as well as heparanase cause endothelial cell injury and if insulin, heparin and bFGF protect cells from this injury.

Methods
Cultured porcine aortic endothelial cells were treated with high glucose (30 mM) and/or insulin (1 U/ml) and/or heparin (0.5 μ g/ml) and /or basic fibroblast growth factor (bFGF) (1 ng/ml) for seven days. Cells were also treated with heparinase I (0.3 U/ml, the in vitro surrogate heparanase), plus insulin, heparin and bFGF for two days in serum free medium. Endothelial cell injury was evaluated by determining the number of live cells per culture and lactate dehydrogenase (LDH) release into medium expressed as percentage of control.

Results
A significant decrease in live cell number and increase in LDH release was found in endothelial cells treated with high glucose or heparinase I. Insulin and/or heparin and/or bFGF prevented these changes and thus protected cells from injury by high glucose or heparinase I. The protective ability of heparin and bFGF alone or in combination was more evident in cells damaged with heparinase I than high glucose.

Conclusion
Endothelial cells injured by high glucose or heparinase I are protected by a combination of insulin, heparin and bFGF, although protection by heparin and/or bFGF was variable.
Artificial neural networks for diagnosis and survival prediction in colon cancer
Authors: Ahmed Farid E 
Published: August 2005

AbstractANNs are nonlinear regression computational devices that have been used for over 45 years in classification and survival prediction in several biomedical systems, including colon cancer. Described in this article is the theory behind the three-layer free forward artificial neural networks with backpropagation error, which is widely used in biomedical fields, and a methodological approach to its application for cancer research, as exemplified by colon cancer. Review of the literature shows that applications of these networks have improved the accuracy of colon cancer classification and survival prediction when compared to other statistical or clinicopathological methods. Accuracy, however, must be exercised when designing, using and publishing biomedical results employing machine-learning devices such as ANNs in worldwide literature in order to enhance confidence in the quality and reliability of reported data.
Screening and identification of differentially expressed transcripts in circulating cells of prostate cancer patients using suppression subtractive hybridization
Authors: Li Xin , Wong Carson , Mysel Ralph , Slobodov Gennady , Metwalli Adam , Kruska Jarrett , Manatt C Scott , Culkin Daniel J , Kropp Bradley P , Lin Hsueh-Kung 
Published: August 2005

Abstract

Background
Tumor metastasis and changes in host immunosurveillance are important components in cancer development. Tumor cell invasion into the bloodstream is an essential step for systemic metastasis. Currently, the detection of tumor cells in the circulation is mainly dependent upon the utilization of known epithelial cell markers. However, expression of these molecules is not limited to cancer patients; healthy people also have a small number of epithelial cells in their circulation. Utilizing these markers to detect circulating tumor cells (CTCs) cannot adequately explain the mechanisms of tumor cell survival or their development of metastatic potential in peripheral blood. The immune system can also evolve along with the cancer, actually promoting or selecting the outgrowth of tumor variants. Unfortunately, both metastasis and immunosurveillance remain mysterious and are debatable because we have yet to define the molecules that participate in these processes. We are interested in identifying the existence of expressed genes, or mRNA species, that are specifically associated with circulating cells of cancer-bearing patients using prostate cancer (PCa) as a model.

Results
We established two comprehensive subtracted cDNA libraries using a molecular technique called suppression subtractive hybridization. This technique selectively amplifies transcripts that are specifically expressed in circulating cells of either PCa patients or healthy men. Following sequencing reaction, we showed that 17 out of 23 (73.9%) sequenced clones did not match any mRNAs in the GenBank database. This result suggests that genes associated with alterations in circulating cells of cancer-bearing patients are largely unknown. Semi-quantitative RT-PCR confirmed that two genes are up-regulated in circulating cells of PCa patients, whereas another two genes are down-regulated in the same patients.

Conclusion
The comprehensive gene expression analysis is capable of identifying differentially expressed genes in circulating cells of healthy men and PCa patients. We did not attempt to enrich specific cell types in this study because phenotypes of CTCs and subsets of leukocytes participating in immunosurveillance remain largely unknown. Continuous studies of these differentially expressed genes will eventually lead us to understand the mechanisms involved in tumor metastasis and immune modulation during cancer development.
A quest for therapeutic antigens in bone and soft tissue sarcoma
Authors: Kawaguchi Satoshi , Wada Takuro , Tsukahara Tomohide , Ida Kazunori , Torigoe Toshihiko , Sato Noriyuki , Yamashita Toshihiko 
Published: August 2005

AbstractOver the past three decades, there have been remarkable advances in the treatment of bone and soft tissue sarcomas. These include the introduction of adjuvant chemotherapy, establishment of guidelines for adequate surgical margins, and the development of post-excision reconstruction. There have also been advances in the field of immunotherapy against bone and soft tissue sarcomas, which, unfortunately, have received less attention. However, lack of progress in chemotherapy-based treatments for bone and soft tissue sarcomas has reignited interest in immunotherapeutic approaches. Here we summarize current progress in the immunotherapy of bone and soft tissue sarcomas including the strategies utilized to identify tumor-associated antigens, and the design of clinical trials.
Differential Gene Expression in Ovarian Tumors Reveals Dusp 4 and Serpina 5 As Key Regulators for Benign Behavior of Serous Borderline Tumors
Authors: Sieben Nathalie L.G. , Oosting Jan , Flanagan Adrienne M. , Prat Jaime , Roemen Guido M.J.M. , Kolkman-Uljee Sandra M. , van Eijk Ronald , Cornelisse Cees J. , Fleuren Gert Jan , van Engeland Manon 
Published: August 2005

Purpose Ovarian serous borderline tumors (SBT) are characterized by arborizing papillae lined by stratified epithelial cells, varying atypia, and absence of stromal invasion. Originally, these tumors have been classified as borderline because they behaved in a remarkably indolent manner, even with widespread tumor deposits called implants and the presence of lymph node involvement. The molecular biology of these lesions has just begun to be explored. High prevalence of B-RAF/K-RAS mutations in SBTs in contrast to serous carcinomas (SCAs) indicates that the mitogenic RAS-RAF-MEK-ERK-MAP kinase pathway is crucial for the pathogenesis of SBTs. The purpose of this study was to further unravel the genetic pathways through which SBTs develop, with a special focus on explaining the generally benign SBT behavior. Materials and Methods We generated RNA expression profiles of 38 ovarian serous neoplasms. Global Test pathway analysis and significance analysis of microarrays (SAM) of the expression profiles was performed. Results SAM and Global Testing showed that although the mitogenic pathway is activated in SBTs, activation of downstream genes involved in extracellular matrix (ECM) degradation is absent, suggesting an uncoupling of both events. In addition, we show that two genes involved in regulating this uncoupling, ERK-inhibitor Dusp 4 and uPA-inhibitor Serpina 5, are downregulated in SCAs in contrast to SBTs. In SCAs, this was associated with downstream MMP-9 activation at both mRNA and protein level. Conclusion We propose that the putative tumor suppressor genes Dusp 4 and Serpina 5 provide a major clue to the indolent behavior of SBTs.
Chemoendocrine Therapy for Premenopausal Women With Axillary Lymph Node–Positive, Steroid Hormone Receptor–Positive Breast Cancer: Results From INT 0101 (E5188)
Authors: Davidson Nancy E. , O'Neill Anne M. , Vukov Allen M. , Osborne C. Kent , Martino Silvana , White Douglas R. , Abeloff Martin D. 
Published: August 2005

Purpose Chemotherapy, tamoxifen, and ovarian ablation/suppression (OA/OS) are effective adjuvant approaches for premenopausal, steroid hormone receptor–positive breast cancer. The value of combined therapy has not been clearly established. Patients and Methods Premenopausal women with axillary lymph node–positive, steroid hormone receptor–positive breast cancer (1,503 eligible patients) were randomly assigned to six cycles of cyclophosphamide, doxorubicin, and fluorouracil (CAF), CAF followed by 5 years of monthly goserelin (CAF-Z), or CAF followed by 5 years of monthly goserelin and daily tamoxifen (CAF-ZT). The primary end points were time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS) for CAF-Z versus CAF, and CAF-ZT versus CAF-Z. Results With a median follow-up of 9.6 years, the addition of tamoxifen to CAF-Z improved TTR and DFS but not OS. There was no overall advantage for addition of goserelin to CAF. Conclusion Addition of tamoxifen to CAF-Z improves outcome for premenopausal node-positive, receptor-positive breast cancer. The role of OA/OS alone or with other endocrine agents should be studied more intensely.
Role of Depression As a Predictor of Mortality Among Cancer Patients After Stem-Cell Transplantation
Authors: Prieto Jesús M. , Atala Jorge , Blanch Jordi , Carreras Enric , Rovira Montserrat , Cirera Esteve , Espinal Anna , Gasto Cristóbal 
Published: August 2005

Purpose To determine the association between depression and survival among cancer patients at 1, 3, and 5 years after stem-cell transplantation (SCT). Patients and Methods This was a prospective cohort study of 199 hematologic cancer patients who survived longer than 90 days after SCT and who were recruited in a University-based hospital between July 1994 and August 1997. Patients received a psychiatric assessment at four consecutive time points during hospitalization for SCT, yielding a total of 781 interviews. Depression diagnoses were determined on the basis of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Results Eighteen (9.0%) and 17 patients (8.5%) met criteria for major and minor depression, respectively. Multivariate Cox regression models found major depression to be predictive of higher 1-year (hazard ratio [HR], 2.59; 95% CI, 1.21 to 5.53; P = .014) and 3-year mortality (HR, 2.04; 95% CI, 1.03 to 4.02; P = .041) but not 5-year mortality (HR, 1.48; 95% CI, 0.76 to 2.87; P = .249). Minor depression had no effect on any mortality outcome. Other multivariate significant predictors of higher mortality were higher regimen toxicity in the 1-, 3-, and 5-year models; older age and acute lymphoblastic leukemia in the 3- and 5-year models; chronic myelogenous leukemia in the 3-year model; and lower functional status and intermediate/higher risk status in the 5-year model. Use of peripheral-blood stem cells predicted lower mortality in the 5-year model. Conclusion After adjusting for multiple factors, major depression predicted higher 1- and 3-year mortality among cancer patients after SCT, underscoring the importance of adequate diagnosis and treatment of major depression.