bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of a Genetic Diagnosis of a Mitochondrial Disorder 5–17 Years After the Death of an Affected Child
Authors: Sexton A. C. , Sahhar M. , Thorburn D. R. , Metcalfe S. A. 
Published: February 2008

AbstractThis study used in‐depth interviews to explore the experiences of parents who were re‐contacted with new genetic results many years after the death of a child with a mitochondrial disorder. At the time of their child's illness, parents had consented to a tissue sample being taken to help with diagnosis of a suspected mitochondrial disorder, and subsequently further DNA testing identified the genetic cause. Parents did not express negative feelings about being re‐contacted with new information, and hoped that continuing research might help other families. Positive aspects included relief from feelings of guilt over the cause of the child's disorder, and having accurate genetic information available for surviving children. Difficult emotional and psychosocial implications included contradictions to previous beliefs about inheritance, deciding how and when to communicate information to surviving children, and coping with new fears for the mother's health if a gene located in the mitochondrial DNA was identified. In half of the families the new results significantly altered the parents’ understanding of the inheritance pattern. This study highlights the impact of new genetic information offered after a delay of several years, which has the potential to re‐open feelings of grief and uncertainty and can present a new inheritance scenario for which research participants or their families are unprepared. Health professionals involved in conveying genetic research results can help to support families through this process.
Prolonged‐release oxycodone enhances the effects of existing gabapentin therapy in painful diabetic neuropathy patients
Authors: Hanna Magdi , O'Brien Cathy , Wilson Margaret C. 
Published: February 2008

AbstractBackground: Neuropathic pain remains one of the most challenging pain syndromes; under‐diagnosed, poorly managed and associated with significant co‐morbidity. With standard therapeutic treatments, responders rarely exceed 50% pain relief and the majority suffer from residual pain. Titration to optimum dose is often limited by dose‐related adverse events.Aims: This randomized, double‐blind, placebo‐controlled study assessed the potential benefit of adding oxycodone (OxyContin® tablets) to gabapentin. The primary endpoint was to evaluate the analgesic efficacy of co‐administration of gabapentin and prolonged‐release oxycodone, whilst also evaluating the use of escape medication, sleep quality and global assessment of pain.Methods: Three hundred and thirty eight patients with moderate to severe painful diabetic neuropathy despite receiving their maximum tolerated dose of gabapentin, had oral prolonged‐release oxycodone or placebo tablets added to their therapy for up to 12weeks.Results: Oxycodone–gabapentin reduced pain score by 33% from baseline to end of treatment. The overall treatment effect was greater with oxycodone–gabapentin than with placebo–gabapentin (P=0.007). Oxycodone–gabapentin also significantly improved pain relief vs gabapentin alone (P=0.003). Oxycodone–gabapentin co‐administration was associated with less escape medication use (P=0.03) and fewer nights of disturbed sleep (P<0.05). Discontinuations due to lack of therapeutic effect were much lower (14% vs 54%) with oxycodone–gabapentin. The commonly seen opiate‐induced adverse events were not exacerbated by the combination of oxycodone and gabapentin.Conclusions: This study provides the first evidence that co‐administration of prolonged‐release oxycodone and existing gabapentin therapy has a clinically meaningful effect in painful diabetic neuropathy.
Antinociceptive effects of high dose remifentanil in male methadone‐maintained patients
Authors: Hay Justin L. , White Jason M. , Bochner Felix , Somogyi Andrew A. 
Published: February 2008

AbstractThe treatment of acute pain in patients maintained on methadone is difficult due to increased pain sensitivity (hyperalgesia) and cross‐tolerance to other opioids. This study aimed to investigate whether remifentanil elicits antinociception in methadone‐maintained subjects in a dose‐dependent manner. Eight chronic methadone‐maintained subjects attended the testing session approximately 20h after their normal methadone dose (range 50–110mgday−1). Following a 20min saline infusion, subjects were administered intravenous remifentanil in seven increasing doses ranging from 0.5 to 3.5μgkg−1min−1, each for 20min. Testing was performed in the last 10 min of each infusion. The testing measures included nociception, as measured by the cold pressor test, withdrawal using the subjective opiate withdrawal scale (SOWS), and subjective opioid effects using the morphine–benzedrine group scale (MBG). Results showed dose‐dependent increase in cold pressor tolerance time from baseline of 15.6±3.5 (mean±SEM)s up to 77.3±24.7s during this dosing protocol. During the infusion typical μ‐opioid receptor agonist side effects were observed, but with no withdrawal. Methadone‐maintained patients demonstrate significant tolerance to remifentanil and may require opioid doses 20–30 higher than required for the treatment of acute pain in opioid‐naïve patients.
Model-Based Comparative Prediction of Transcription-Factor Binding Motifs in Anabolic Responses in Bone
Authors: Chen Andy B. , Hamamura Kazunori , Wang Guohua , Xing Weirong , Mohan Subburaman , Yokota Hiroki , Liu Yunlong 
Published: February 2008

Abstract
Understanding the regulatory mechanism that controls the alteration of global gene expression patterns continues to be a challenging task in computational biology. We previously developed an ant algorithm, a biologically-inspired computational technique for microarray data, and predicted putative transcription-factor binding motifs (TFBMs) through mimicking interactive behaviors of natural ants. Here we extended the algorithm into a set of web-based software, Ant Modeler, and applied it to investigate the transcriptional mechanism underlying bone formation. Mechanical loading and administration of bone morphogenic proteins (BMPs) are two known treatments to strengthen bone. We addressed a question: Is there any TFBM that stimulates both “anabolic responses of mechanical loading” and “BMP-mediated osteogenic signaling”? Although there is no significant overlap among genes in the two responses, a comparative model-based analysis suggests that the two independent osteogenic processes employ common TFBMs, such as a stress responsive element and a motif for peroxisome proliferator-activated receptor (PPAR). The post-modeling in vitro analysis using mouse osteoblast cells supported involvements of the predicted TFBMs such as PPAR, Ikaros 3, and LMO2 in response to mechanical loading. Taken together, the results would be useful to derive a set of testable hypotheses and examine the role of specific regulators in complex transcriptional control of bone formation.
Reconstruction of Pathways Associated with Amino Acid Metabolism in Human Mitochondria
Authors: Guda Purnima , Guda Chittibabu , Subramaniam Shankar 
Published: February 2008

Abstract
We have used a bioinformatics approach for the identification and reconstruction of metabolic pathways associated with amino acid metabolism in human mitochondria. Human mitochondrial proteins determined by experimental and computational methods have been superposed on the reference pathways from the KEGG database to identify mitochondrial pathways. Enzymes at the entry and exit points for each reconstructed pathway were identified, and mitochondrial solute carrier proteins were determined where applicable. Intermediate enzymes in the mitochondrial pathways were identified based on the annotations available from public databases, evidence in current literature, or our MITOPRED program, which predicts the mitochondrial localization of proteins. Through integration of the data derived from experimental, bibliographical, and computational sources, we reconstructed the amino acid metabolic pathways in human mitochondria, which could help better understand the mitochondrial metabolism and its role in human health.
Prediction of Protein-Protein Interactions Using Protein Signature Profiling
Authors: Mahdavi Mahmood A. , Lin Yen-Han 
Published: February 2008

Abstract
Protein domains are conserved and functionally independent structures that play an important role in interactions among related proteins. Domain-domain interactions have been recently used to predict protein-protein interactions (PPI). In general, the interaction probability of a pair of domains is scored using a trained scoring function. Satisfying a threshold, the protein pairs carrying those domains are regarded as “interacting”. In this study, the signature contents of proteins were utilized to predict PPI pairs in Saccharomyces cerevisiae, Caenorhabditis elegans, and Homo sapiens. Similarity between protein signature patterns was scored and PPI predictions were drawn based on the binary similarity scoring function. Results show that the true positive rate of prediction by the proposed approach is approximately 32% higher than that using the maximum likelihood estimation method when compared with a test set, resulting in 22% increase in the area under the receiver operating characteristic (ROC) curve. When proteins containing one or two signatures were removed, the sensitivity of the predicted PPI pairs increased significantly. The predicted PPI pairs are on average 11 times more likely to interact than the random selection at a confidence level of 0.95, and on average 4 times better than those predicted by either phylogenetic profiling or gene expression profiling.
Computational Prediction of Rice (Oryza Sativa) miRNA Targets
Authors: Archak Sunil , Nagaraju J. 
Published: February 2008

Abstract
Bioinformatic approaches have complemented experimental efforts to inventorize plant miRNA targets. We carried out global computational analysis of rice (Oryza sativa) transcriptome to generate a comprehensive list of putative miRNA targets. Our predictions (684 unique transcripts) showed that rice miRNAs mediate regulation of diverse functions including transcription (41%), catalysis (28%), binding (18%), and transporter activity (11%). Among the predicted targets, 61.7% hits were in coding regions and nearly 72% targets had a solitary miRNA hit. The study predicted more than 70 novel targets of 34 miRNAs putatively regulating functions like stress-response, catalysis, and binding. It was observed that more than half (55%) of the targets were conserved between O. sativa indica and O. sativa japonica. Members of 31 miRNA families were found to possess conserved targets between rice and at least one of other grass family members. About 44% of the unique targets were common between two dissimilar miRNA prediction algorithms. Such an extent of cross-species conservation and algorithmic consensus confers confidence in the list of rice miRNA targets predicted in this study.
Construction, Characterization, and Chromosomal Mapping of a Fosmid Library of the White-Cheeked Gibbon (Nomascus Leucogenys)
Authors: Chen Liping , Ye Jianping , Liu Yan , Wang Jinghuan , Su Weiting , Yang Fengtang , Nie Wenhui 
Published: February 2008

Abstract
Gibbons have experienced extensive karyotype rearrangements during evolution and represent an ideal model for studying the underlying molecular mechanism of evolutionary chromosomal rearrangements. It is anticipated that the cloning and sequence characterization of evolutionary chromosomal breakpoints will provide vital insights into the molecular force that has driven such a radical karyotype reshuffle in gibbons. We constructed and characterized a high-quality fosmid library of the white-cheeked gibbon (Nomascus leucogenys) containing 192,000 non-redundant clones with an average insert size of 38 kb and 2.5-fold genome coverage. By end sequencing of 100 randomly selected fosmid clones, we generated 196 sequence tags for the library. These end-sequenced fosmid clones were then mapped onto the chromosomes of the white-cheeked gibbon by fluorescence in situ hybridization, and no spurious chimeric clone was detected. BLAST search against the human genome showed a good correlation between the number of hit clones and the number of chromosomes, an indication of unbiased chromosomal distribution of the fosmid library. The chromosomal distribution of the mapped clones is also consistent with the BLAST search result against human and white-cheeked gibbon genomes. The fosmid library and the mapped clones will serve as a valuable resource for further studying gibbons’ chromosomal rearrangements and the underlying molecular mechanism as well as for comparative genomic study in the lesser apes.
Transcriptome and Proteome Expressions Involved in Insulin Resistance in Muscle and Activated T-Lymphocytes of Patients with Type 2 Diabetes
Authors: Stentz Frankie B. , Kitabchi Abbas E. 
Published: February 2008

Abstract
We analyzed the genes expressed (transcriptomes) and the proteins translated (proteomes) in muscle tissues and activated CD4+ and CD8+ T-lymphocytes (T-cells) of five Type 2 diabetes (T2DM) subjects using Affymetrix microarrays and mass spectrometry, and compared them with matched non-diabetic controls. Gene expressions of insulin receptor (INSR), vitamin D receptor, insulin degrading enzyme, Akt, insulin receptor substrate-1 (IRS-1), IRS-2, glucose transporter 4 (GLUT4), and enzymes of the glycolytic pathway were decreased at least 50% in T2DM than in controls. However, there was greater than two-fold gene upregulation of plasma cell glycoprotein-1, tumor necrosis factor α (TNFα), and gluconeogenic enzymes in T2DM than in controls. The gene silencing for INSR or TNFα resulted in the inhibition or stimulation of GLUT4, respectively. Proteome profiles corresponding to molecular weights of the above translated transcriptomes showed different patterns of changes between T2DM and controls. Meanwhile, changes in transcriptomes and proteomes between muscle and activated T-cells of T2DM were comparable. Activated T-cells, analogous to muscle cells, expressed insulin signaling and glucose metabolism genes and gene products. In conclusion, T-cells and muscle in T2DM exhibited differences in expression of certain genes and gene products relative to non-diabetic controls. These alterations in transcriptomes and proteomes in T2DM may be involved in insulin resistance.
Mycobacterial PE_PGRS Proteins Contain Calcium-Binding Motifs with Parallel β-Roll Folds
Authors: Bachhawat Nandita , Singh Balvinder 
Published: February 2008

Abstract
The PE_PGRS family of proteins unique to mycobacteria is demonstrated to contain multiple calcium-binding and glycine-rich sequence motifs GGXGXD/NXUX. This sequence repeat constitutes a calcium-binding parallel β-roll or parallel β-helix structure and is found in RTX toxins secreted by many Gram-negative bacteria. It is predicted that the highly homologous PE_PGRS proteins containing multiple copies of the nona-peptide motif could fold into similar calcium-binding structures. The implication of the predicted calcium-binding property of PE_PGRS proteins in the light of macrophage-pathogen interaction and pathogenesis is presented.
FASMA: A Service to Format and Analyze Sequences in Multiple Alignments
Authors: Costantini Susan , Colonna Giovanni , Facchiano Angelo M. 
Published: February 2008

Abstract
Multiple sequence alignments are successfully applied in many studies for understanding the structural and functional relations among single nucleic acids and protein sequences as well as whole families. Because of the rapid growth of sequence databases, multiple sequence alignments can often be very large and difficult to visualize and analyze. We offer a new service aimed to visualize and analyze the multiple alignments obtained with different external algorithms, with new features useful for the comparison of the aligned sequences as well as for the creation of a final image of the alignment. The service is named FASMA and is available at http://bioinformatica.isa.cnr.it/FASMA/.
Homotopy theory of well-generated algebraic triangulated categories
Authors: Tabuada Gonçalo 
Published: February 2008

AbstractFor every regular cardinal α, we construct a cofibrantly generated Quillen model structure on a category whose objects are essentially dg categories which are stable under suspensions, cosuspensions, cones and α-small sums.Using results of Porta, we show that the category of well-generated (algebraic) triangulated categories in the sense of Neeman is naturally enhanced by our Quillen model category.
Relative pairing in cyclic cohomology and divisor flows
Authors: Lesch Matthias , Moscovici Henri , Pflaum Markus J. 
Published: February 2008

AbstractWe construct invariants of relative K-theory classes of multiparameter dependent pseudodifferential operators, which recover and generalize Melrose's divisor flow and its higher odd-dimensional versions of Lesch and Pflaum. These higher divisor flows are obtained by means of pairing the relative K-theory modulo the symbols with the cyclic cohomological characters of relative cycles constructed out of the regularized operator trace together with its symbolic boundary. Besides giving a clear and conceptual explanation to the essential features of the divisor flows, namely homotopy invariance, additivity and integrality, this construction allows to uncover the previously unknown even-dimensional counterparts. Furthermore, it confers to the totality of these invariants a purely topological interpretation, that of implementing the classical Bott periodicity isomorphisms in a manner compatible with the suspension isomorphisms in both K-theory and in cyclic cohomology. We also give a precise formulation, in terms of a natural Clifford algebraic suspension, for the relationship between the higher divisor flows and the spectral flow.
Tolosa–Hunt syndrome misdiagnosed as sinusitis complication
Authors: Lachanas V A , Karatzias G T , Tsitiridis I , Panaras I , Sandris V G 
Published: February 2008

AbstractObjective:Tolosa–Hunt syndrome is a rare condition of painful ophthalmoplegia combined with ipsilateral ocular motor nerve palsies, caused by non-specific granulomatous inflammation in the cavernous sinus, superior orbital fissure or orbit. A case of Tolosa–Hunt syndrome misdiagnosed as sinusitis orbital complication is reported.Case report:A patient suffering from left periorbital pain, upper eyelid oedema and ptosis, and horizontal diplopia, diagnosed as sinusitis orbital complication, was referred to our department. Clinical evaluation revealed only a left VIth nerve paresis. Haematological studies, cerebrospinal fluid tests and computed tomography scanning were negative. A magnetic resonance imaging (MRI) scan showed enhancement of the left cavernous sinus. Corticosteroid therapy was commenced, and within three days all symptoms disappeared. A diagnosis of Tolosa–Hunt syndrome was made. Follow-up MRI studies were normal.Conclusion:Tolosa–Hunt syndrome, although rare, is a nosological entity that otolaryngologists must bear in mind. Magnetic resonance imaging studies are essential in the diagnosis and follow up of these patients, in order to avoid a mistaken Tolosa–Hunt syndrome diagnosis.
Change in hearing during ‘wait and scan’ management of patients with vestibular schwannoma
Authors: Stangerup S-E , Caye-Thomasen P , Tos M , Thomsen J 
Published: February 2008

AbstractAim:To evaluate hearing changes during ‘wait and scan’ management of patients with vestibular schwannoma.Subjects:Over a 10-year period, 636 patients have prospectively been allocated to ‘wait and scan’ management, with annual magnetic resonance scanning and audiological examination.Results:At the time of diagnosis, 334 patients (53 per cent) had good hearing and speech discrimination of better than 70 per cent; at the end of the 10-year observation period, this latter percentage was 31 per cent. In 17 per cent of the patients, speech discrimination at diagnosis was 100 per cent; of these, 88 per cent still had good hearing at the end of the observation period. However, in patients with even a small initial speech discrimination loss, only 55 per cent maintained good hearing at the end of the observation period.Conclusion:After comparing the hearing results of hearing preservation surgery and of radiation therapy with those of ‘wait and scan’ management, it appears that, in vestibular schwannoma patients with a small tumour and normal speech discrimination, the main indication for active treatment should be established tumour growth.
Re-operation for secondary hyperparathyroidism
Authors: Debruyne F , Geuens G , Vander Poorten V , Delaere P 
Published: February 2008

AbstractObjective:In cases of re-operation for secondary hyperparathyroidism, to evaluate the extent to which the location of recurrent hyperplasia was predicted by (1) operative data from the first intervention, and (2) pre-operative imaging (before the re-operation).Methods:The files of 18 patients undergoing surgery for recurrent secondary hyperparathyroidism were reviewed. The surgical findings were compared both with the report of the initial operation and with the results of pre-operative imaging (i.e. ultrasonography, Mibi scintigraphy or computed tomography).Results:The location of the recurrent hyperplasia corresponded with the data for the primary intervention in about one-third of patients. There was a partial correlation in one-third of patients, and no correlation at all in one-third. Pre-operative imaging enabled better prediction of the location of recurrent disease.Conclusion:Surgeons should have both sources of information at their disposal when planning a re-intervention for secondary hyperparathyroidism. However, in our series, the predictive value of imaging was superior to that of information deduced from the previous surgical record.
Induction chemotherapy with S-1 plus cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck
Authors: Choi Y J , Chung J S , Shin H-J , Cho G J , Wang S G , Lee B J , Cho B M , Joo Y D , Sohn C H 
Published: February 2008

AbstractObjective:This study was performed to assess the efficacy and safety profile of combination treatment with S-1 and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck.Design:Eligibility criteria comprised: histologically confirmed squamous cell carcinoma of the head and neck; stage three or four disease with no evidence of distant metastasis; evaluable lesions; adequate organ function; age 20–80 years; and a performance status of two or less. Cisplatin was infused over one hour on day one (75 mg/m2) and S-1 was administered orally for 14 consecutive days (days two to 15). The dosages of S-1 were calculated according to the patients' body surface area: 50 mg twice a day (body surface area <1.5 m2) or 60 mg twice a day (body surface area >1.5 m2). Each course was repeated every three weeks. After two courses, tumour response was evaluated by computed tomography and laryngoscopy. If a response was evident (either complete or partial), the patient received one more course of chemotherapy, before undergoing radical treatment such as radiotherapy or surgery.Results:All 30 patients were assessable for toxicity, and 29 patients for treatment response. The overall response was 89.7 per cent (complete response: nine; partial response: 17). The two-year estimated overall survival rate was 79.2 per cent. Adverse reactions occurred 128 times during 81 courses in the 30 cases. The most common grade three to four adverse event was neutropenia, which occurred in eight patients. Cases of non-haematological grade three or four toxicity included nausea and vomiting in four patients, stomatitis in two and diarrhoea in one.Conclusion:S-1 plus cisplatin combination chemotherapy is effective against locally advanced squamous cell carcinoma of the head and neck, with only mild toxicity.