bluuebunny/crossref_metadata_2025_split huggingface dataset:
AlignMiner: a Web-based tool for detection of divergent regions in multiple sequence alignments of conserved sequences
Authors: Guerrero Darío , Bautista Rocío , Villalobos David P , Cantón Francisco R , Claros M Gonzalo 
Published: June 2010

Abstract

Background
Multiple sequence alignments are used to study gene or protein function, phylogenetic relations, genome evolution hypotheses and even gene polymorphisms. Virtually without exception, all available tools focus on conserved segments or residues. Small divergent regions, however, are biologically important for specific quantitative polymerase chain reaction, genotyping, molecular markers and preparation of specific antibodies, and yet have received little attention. As a consequence, they must be selected empirically by the researcher. AlignMiner has been developed to fill this gap in bioinformatic analyses.

Results
AlignMiner is a Web-based application for detection of conserved and divergent regions in alignments of conserved sequences, focusing particularly on divergence. It accepts alignments (protein or nucleic acid) obtained using any of a variety of algorithms, which does not appear to have a significant impact on the final results. AlignMiner uses different scoring methods for assessing conserved/divergent regions, being the method that provides the highest number of regions with the greatest length, and being the most restrictive. Conserved/divergent regions can be generated either with respect to the consensus sequence or to one master sequence. The resulting data are presented in a graphical interface developed in AJAX, which provides remarkable user interaction capabilities. Users do not need to wait until execution is complete and can.even inspect their results on a different computer. Data can be downloaded onto a user disk, in standard formats. In silico and experimental proof-of-concept cases have shown that AlignMiner can be successfully used to designing specific polymerase chain reaction primers as well as potential epitopes for antibodies. Primer design is assisted by a module that deploys several oligonucleotide parameters for designing primers "on the fly".

Conclusions
AlignMiner can be used to reliably detect divergent regions via several scoring methods that provide different levels of selectivity. Its predictions have been verified by experimental means. Hence, it is expected that its usage will save researchers' time and ensure an objective selection of the best-possible divergent region when closely related sequences are analysed. AlignMiner is freely available at http://www.scbi.uma.es/alignminer.
Natural killer cells control a T-helper 1 response in patients with Behçet's disease
Authors: Yamaguchi Yukie , Takahashi Hayato , Satoh Takashi , Okazaki Yuka , Mizuki Nobuhisa , Takahashi Kazuo , Ikezawa Zenro , Kuwana Masataka 
Published: June 2010

Abstract
Introduction
Behçet's disease (BD) is a multisystem inflammatory disorder, in which a T-helper 1 (Th1)-polarized immune response plays a major role in the pathogenic process. We evaluated the regulatory role of natural killer (NK) cells in Th1-biased immune responses in patients with BD.

Methods
We studied 47 patients with BD, including 10 with active disease (aBD) and 37 with inactive disease (iBD), and 29 healthy controls. The activation status and cytotoxic activity of NK cells were examined by flow cytometry. The levels of mRNAs for immune modulatory and cytotoxic molecules in NK cells were determined by quantitative PCR. The IL-12 signal strength in NK cells was determined by assessing the phosphorylation state of its downstream component, signal transducer and activator of transduction 4, by immunoblotting. Finally, NK cells' ability to modulate the Th1 response was evaluated by co-culturing NK cells and T cells without cell contact.

Results
CD69+-activated NK cells were significantly increased in aBD compared with iBD or control samples, although their cytotoxic activities were similar. The iBD NK cells showed downregulated IL-12 receptor β2 mRNA levels compared with aBD or control NK cells. The increased IL-13 expression was detected in a subset of BD patients: most of them had iBD. The IL-13 expression level in iBD patients was significantly higher than the level in controls, but was not statistically different compared with the level in aBD patients. The gene expression profile in iBD patients was consistent with the NK type 2 phenotype, and the shift to NK type 2 was associated with disease remission. NK cells from iBD patients showed impaired IL-12-induced signal transducer and activator of transduction 4 phosphorylation. Finally, iBD, but not control, NK cells suppressed IFNγ expression by aBD-derived CD4+ T cells in vitro.

Conclusions
NK cells may control disease flare/remission in BD patients via NK type 2-mediated modulation of the Th1 response.
Phase II Proof-of-Concept Study of Pazopanib Monotherapy in Treatment-Naive Patients With Stage I/II Resectable Non–Small-Cell Lung Cancer
Authors: Altorki Nasser , Lane Maureen E. , Bauer Thomas , Lee Paul C. , Guarino Michael J. , Pass Harvey , Felip Enriqueta , Peylan-Ramu Nili , Gurpide Alfonso , Grannis Frederic W. , Mitchell John D. , Tachdjian Sabrina , Swann R. Suzanne , Huff Anne , Roychowdhury Debasish F. , Reeves Anthony , Ottesen Lone H. , Yankelevitz David F. 
Published: June 2010

Purpose Patients with early-stage, resectable, non–small-cell lung cancer (NSCLC) are at risk for recurrent disease, and 5-year survival rates do not exceed 75%. Angiogenesis inhibitors have shown clinical activity in patients with late-stage NSCLC, raising the possibility that targeting the vascular endothelial growth factor pathway in earlier-stage disease may be beneficial. This proof-of-concept study examined safety and efficacy of short-term, preoperative pazopanib monotherapy in patients with operable stage I/II NSCLC. Patients and Methods Patients scheduled for resection received oral pazopanib 800 mg/d for 2 to 6 weeks preoperatively. Tumor response was measured by high-resolution computed tomography, permitting estimation of change in tumor volume and diameter. Gene-expression profiling was performed on 77 pre- and post-treatment lung samples from 34 patients. Results Of 35 patients enrolled, 33 (94%) had clinical stage I NSCLC and two (6%) had clinical stage II NSCLC. Median treatment duration was 16 days (range, 3 to 29 days). Thirty patients (86%) achieved tumor-volume reduction after pazopanib treatment. Two patients achieved tumor-volume reduction ≥ 50%, and three patients had partial response according to Response Evaluation Criteria in Solid Tumors. Pazopanib was generally well tolerated. The most common adverse events included grade 2 hypertension, diarrhea, and fatigue. One patient developed pulmonary embolism 11 days after surgery. Several pazopanib target genes and other angiogenic factors were dysregulated post-treatment. Conclusion Short-duration pazopanib was generally well tolerated and demonstrated single-agent activity in patients with early-stage NSCLC. Several target genes were dysregulated after pazopanib treatment, validating target-specific response and indicating a persistent pazopanib effect on lung cancer tissue. Further clinical evaluation of pazopanib in NSCLC is planned.
Trabectedin Plus Pegylated Liposomal Doxorubicin in Recurrent Ovarian Cancer
Authors: Monk Bradley J. , Herzog Thomas J. , Kaye Stanley B. , Krasner Carolyn N. , Vermorken Jan B. , Muggia Franco M. , Pujade-Lauraine Eric , Lisyanskaya Alla S. , Makhson Anatoly N. , Rolski Janusz , Gorbounova Vera A. , Ghatage Prafull , Bidzinski Mariusz , Shen Keng , Ngan Hextan Yuen-Sheung , Vergote Ignace B. , Nam Joo-Hyun , Park Youn Choi , Lebedinsky Claudia A. , Poveda Andrés M. 
Published: June 2010

PurposeThe objective of this study was to compare the efficacy and safety of trabectedin plus pegylated liposomal doxorubicin (PLD) with that of PLD alone in women with recurrent ovarian cancer after failure of first-line, platinum-based chemotherapy.Patients and MethodsWomen ≥ 18 years, stratified by performance status (0 to 1 v 2) and platinum sensitivity, were randomly assigned to receive an intravenous infusion of PLD 30 mg/m2followed by a 3-hour infusion of trabectedin 1.1 mg/m2every 3 weeks or PLD 50 mg/m2every 4 weeks. The primary end point was progression-free survival (PFS) by independent radiology assessment.ResultsPatients (N = 672) were randomly assigned to trabectedin/PLD (n = 337) or PLD (n = 335). Median PFS was 7.3 months with trabectedin/PLD v 5.8 months with PLD (hazard ratio, 0.79; 95% CI, 0.65 to 0.96; P = .0190). For platinum-sensitive patients, median PFS was 9.2 months v 7.5 months, respectively (hazard ratio, 0.73; 95% CI, 0.56 to 0.95; P = .0170). Overall response rate (ORR) was 27.6% for trabectedin/PLD v 18.8% for PLD (P = .0080); for platinum-sensitive patients, it was 35.3% v 22.6% (P = .0042), respectively. ORR, PFS, and overall survival among platinum-resistant patients were not statistically different. Neutropenia was more common with trabectedin/PLD. Grade 3 to 4 transaminase elevations were also more common with the combination but were transient and noncumulative. Hand-foot syndrome and mucositis were less frequent with trabectedin/PLD than with PLD alone.ConclusionWhen combined with PLD, trabectedin improves PFS and ORR over PLD alone with acceptable tolerance in the second-line treatment of recurrent ovarian cancer.
Accumulation of Segmental Alterations Determines Progression in Neuroblastoma
Authors: Schleiermacher Gudrun , Janoueix-Lerosey Isabelle , Ribeiro Agnès , Klijanienko Jerzy , Couturier Jérôme , Pierron Gaëlle , Mosseri Véronique , Valent Alexander , Auger Nathalie , Plantaz Dominique , Rubie Hervé , Valteau-Couanet Dominique , Bourdeaut Franck , Combaret Valérie , Bergeron Christophe , Michon Jean , Delattre Olivier 
Published: June 2010

PurposeNeuroblastoma is characterized by two distinct types of genetic profiles, consisting of either numerical or segmental chromosome alterations. The latter are associated with a higher risk of relapse, even when occurring together with numerical alterations. We explored the role of segmental alterations in tumor progression and the possibility of evolution from indolent to aggressive genomic types.Patients and MethodsArray-based comparative genomic hybridization data of 394 neuroblastoma samples were analyzed and linked to clinical data.ResultsIntegration of ploidy and genomic data indicated that pseudotriploid tumors with mixed numerical and segmental profiles may be derived from pseudotriploid tumors with numerical alterations only. This was confirmed by the analysis of paired samples, at diagnosis and at relapse, as in tumors with a purely numerical profile at diagnosis additional segmental alterations at relapse were frequently observed. New segmental alterations at relapse were also seen in patients with segmental alterations at diagnosis. This was not linked to secondary effects of cytotoxic treatments since it occurred even in patients treated with surgery alone. A higher number of chromosome breakpoints were correlated with advanced age at diagnosis, advanced stage of disease, with a higher risk of relapse, and a poorer outcome.ConclusionThese data provide further evidence of the role of segmental alterations, suggesting that tumor progression is linked to the accumulation of segmental alterations in neuroblastoma. This possibility of genomic evolution should be taken into account in treatment strategies of low- and intermediate-risk neuroblastoma and should warrant biologic reinvestigation at the time of relapse.
Integrated Positron Emission Tomography/Computed Tomography May Render Bone Scintigraphy Unnecessary to Investigate Suspected Metastatic Breast Cancer
Authors: Morris Patrick G. , Lynch Colleen , Feeney John N. , Patil Sujata , Howard Jane , Larson Steven M. , Dickler Maura , Hudis Clifford A. , Jochelson Maxine , McArthur Heather L. 
Published: June 2010

Purpose Although the accurate detection of osseous metastases in the evaluation of patients with suspected metastatic breast cancer (MBC) has significant prognostic and therapeutic implications, the ideal diagnostic approach is uncertain. In this retrospective, single-institution study, we compare the diagnostic performance of integrated positron emission tomography/computed tomography (PET/CT) and bone scintigraphy (BSc) in women with suspected MBC. Patients and Methods Women with suspected MBC evaluated with PET/CT and BSc (within 30 days) between January 1, 2003 and June 30, 2008, were identified through institutional databases. Electronic medical records were reviewed, and radiology reports were classified as positive/negative/equivocal for osseous metastases. A nuclear medicine radiologist (blinded to correlative and clinical end points) reviewed all equivocal PET/CT and BSc images and reclassified some reports. Final PET/CT and BSc classifications were compared. Baseline patient/tumor characteristics and bone pathology were recorded and compared to the final imaging results. Results We identified 163 women who had a median age of 52 years (range, 30 to 90 years); 32% had locally advanced breast cancer, 42% had been diagnosed with breast cancer less than 12 weeks before identification. Twenty studies were originally deemed equivocal (five with PET/CT, and 15 with BSc), and 13 (65%) of these studies were reclassified after radiology review. Overall, PET/CT and BSc were highly concordant for reporting osseous metastases with 132 paired studies (81%); 32 (20%) were positive, and 100 (61%) were negative. Thirty-one occurrences (19%) were discordant. Twelve of these (39%) had pathology confirming osseous metastases: nine (of 18) were PET/CT positive and BSc negative; one (of three) was PET/CT positive and BSc equivocal; and two (of two) were PET/CT equivocal and BSc negative. Conclusion This study supports the use of PET/CT in detecting osseous metastases for suspected MBC. Whether PET/CT may supplant BSc in this setting is unknown.
Preoperative Chemotherapy Plus Surgery Versus Surgery Plus Adjuvant Chemotherapy Versus Surgery Alone in Early-Stage Non–Small-Cell Lung Cancer
Authors: Felip Enriqueta , Rosell Rafael , Maestre José Antonio , Rodríguez-Paniagua José Manuel , Morán Teresa , Astudillo Julio , Alonso Guillermo , Borro José Manuel , González-Larriba José Luis , Torres Antonio , Camps Carlos , Guijarro Ricardo , Isla Dolores , Aguiló Rafael , Alberola Vicente , Padilla José , Sánchez-Palencia Abel , Sánchez José Javier , Hermosilla Eduardo , Massuti Bartomeu 
Published: June 2010

Purpose To address whether preoperative chemotherapy plus surgery or surgery plus adjuvant chemotherapy prolongs disease-free survival compared with surgery alone among patients with resectable non–small-cell lung cancer. Patients and Methods In this phase III trial, 624 patients with stage IA (tumor size > 2 cm), IB, II, or T3N1 were randomly assigned to surgery alone (212 patients), three cycles of preoperative paclitaxel-carboplatin followed by surgery (201 patients), or surgery followed by three cycles of adjuvant paclitaxel-carboplatin (211 patients). The primary end point was disease-free survival. Results In the preoperative arm, 97% of patients started the planned chemotherapy, and radiologic response rate was 53.3%. In the adjuvant arm, 66.2% started the planned chemotherapy. Ninety-four percent of patients underwent surgery; surgical procedures and postoperative mortality were similar across the three arms. Patients in the preoperative arm had a nonsignificant trend toward longer disease-free survival than those assigned to surgery alone (5-year disease-free survival 38.3% v 34.1%; hazard ratio [HR] for progression or death, 0.92; P = .176). Five-year disease-free survival rates were 36.6% in the adjuvant arm versus 34.1% in the surgery arm (HR 0.96; P = .74). Conclusion In early-stage patients, no statistically significant differences in disease-free survival were found with the addition of preoperative or adjuvant chemotherapy to surgery. In this trial, in which the treatment decision was made before surgery, more patients were able to receive preoperative than adjuvant treatment.
The Role of Ondansetron in the Treatment of Schizophrenia
Authors: Bennett Allison C , Vila Tania M 
Published: June 2010

Objective: To evaluate the efficacy of ondansetron for the treatment of schizophrenia. Data Sources: Searches of MEDLINE (1950–March 2010) and Google Scholar were performed. Key search terms included ondansetron, Zofran, serotonin antagonists, 5-HT, serotonin receptor, and schizophrenia. Study Selection and Data Extraction: All articles published in English identified from the data sources were evaluated. All studies and case reports evaluating ondansetron for the treatment of schizophrenia were reviewed. Data Synthesis: Six clinical trials, including 3 double-blind, randomized trials, and 2 case reports pertinent to ondansetron use in schizophrenia, were identified. Ondansetron daily doses ranged from 4 to 16 mg, with doses administered once or twice daily. Ondansetron was used as monotherapy in 3 trials and as an adjunct to therapy with clozapine, haloperidol, or risperidone, respectively, in 3 trials. Studies were of varying durations, ranging from a single-dose study with a 3-hour follow-up to three 12-week studies. Most studies evaluated ondansetron's efficacy in treating schizophrenia as measured with changes in Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale, and Clinical Global Impression scale scores. In the 2 largest trials, with a combined patient population of 151, treatment with adjunctive ondansetron resulted in statistically significant improvement in negative symptoms as assessed with PANSS. In all studies, ondansetron was well tolerated, with no severe adverse reactions reported. Conclusions: Ondansetron may be effective as an adjunct to antipsychotics for the treatment of schizophrenia, specifically negative symptoms, as assessed with PANSS. Due to the variation in concurrent therapies and dosing regimens, it is difficult to establish an optimal dose from the reviewed trials. Further large, randomized, double-blind, active-controlled studies would be helpful in determining the role of ondansetron in the treatment of schizophrenia.
Amoxicillin-Induced Hemolytic Anemia in a Child with Glucose 6-Phosphate Isomerase Deficiency
Authors: Rossi Francesca , Ruggiero Simona , Gallo Mariapina , Simeone Gelsomina , Maria Sofia , Matarese Rosaria , Nobili Bruno 
Published: June 2010

Objective:To describe the first case of amoxicillin-induced nonimmune hemolytic anemia in a child with glucose-6-phosphate isomerase (GPI) deficiency.Case Summary:A 3-year-old boy with GPI deficiency was admitted for upper respiratory tract infection and fever. The patient was treated with a standard dose of amoxicillin (50 mg/kg/day). On hospital admission, the child had a chronic moderately low hemoglobin level (8.6 g/dL), but within 24 hours of the first amoxicillin dose, the hemoglobin level markedly decreased (5.8 g/dL), the reticulocyte level increased (58%), and the urine darkened. Results of the direct and indirect Coomb's tests were negative and the acute hemolytic phase ended spontaneously 8 days after amoxicillin withdrawal (hemoglobin 9.5 g/dL, reticulocytes 22%).Discussion:All previous cases of amoxicillin-induced hemolytic anemia have been attributed to an immune mechanism. Given the absence of anti-reticulocyte antibodies (Coomb's test), we suggest that the amoxicillin-induced hemolytic anemia in our patient occurred via a nonimmune mechanism favored by the child's GPI deficiency. Based on a MEDLINE search, we believe this to be the first report of amoxicillin-induced nonimmune hemolytic anemia in a child with GPI deficiency. GPI deficiency has been associated with well-compensated chronic hemolytic anemia that can become clinically relevant consequent to the administration of drugs. GPI deficiency can lead to impairment of the system that removes free radicals generated by amoxicillin, thereby resulting in oxidation of hemoglobin and destabilization of red cell membranes, with acute hemolysis and severe hemoglobinuria. The Naranjo probability score was consistent with a probable relationship between the hemolytic anemia and amoxicillin therapy.Conclusions:This report reinforces the hypothesis that a drug-sensitivity reaction is closely related to a genetically transmitted enzyme deficiency.
Psychiatric Symptoms in Adults With Down Syndrome and Alzheimer's Disease
Authors: Urv Tiina K. , Zigman Warren B. , Silverman Wayne 
Published: June 2010

AbstractChanges in psychiatric symptoms related to specific stages of dementia were investigated in 224 adults 45 years of age or older with Down syndrome. Findings indicate that psychiatric symptoms are a prevalent feature of dementia in the population with Down syndrome and that clinical presentation is qualitatively similar to that seen in Alzheimer's disease within the general population. Psychiatric symptoms related to Alzheimer's disease vary by the type of behavior and stage of dementia, but do not seem to be influenced by sex or level of premorbid intellectual impairment. Some psychiatric symptoms may be early indicators of Alzheimer's disease and may appear prior to substantial changes in daily functioning. Improvements in understanding the progression of dementia in individuals with Down syndrome may lead to improved diagnosis and treatment.
Comparisons Between Individuals With Autism Spectrum Disorders and Individuals With Down Syndrome in Adulthood
Authors: Esbensen Anna J. , Bishop Somer , Seltzer Marsha Mailick , Greenberg Jan S. , Taylor Julie Lounds 
Published: June 2010

Abstract
Differences between 70 adults with autism spectrum disorders and intellectual disability and 70 age-matched adults with Down syndrome were examined on variables indicative of independence in adult life. Adults with autism spectrum disorder had less residential independence and social contact with friends, had more limited functional abilities and literacy, exhibited more behavior problems, had more unmet service needs, and received fewer services as compared to adults with Down syndrome. Reflecting these differences, adults with autism spectrum disorder were less likely to be classified as having high or moderate levels of independence in adult life as compared to adults with Down syndrome. Predictors of independence in adult life differed for adults with autism spectrum disorder as compared with adults who have Down syndrome. Implications for service delivery are discussed.
Parenting With Mild Intellectual Deficits: Parental Expectations and the Educational Attainment of Their Children
Authors: Taylor Julie Lounds , Hurd Heather Doescher , Seltzer Marsha Mailick , Greenberg Jan S. , Floyd Frank J. 
Published: June 2010

Abstract
We examined how the educational expectations that parents with mild intellectual deficits had for their children shaped their children's attainment, and how parents' own intellectual limitations affected this process. We identified 612 parents with mild intellectual deficits and 2,712 comparison parents from the Wisconsin Longitudinal Study, a prospective longitudinal study in which participants were followed from ages 18 to 64. Compared to the norm, parents with mild intellectual deficits expected their children to complete less education, even after controlling for sociodemographic background variables, and children of parents with mild intellectual deficits did, in fact, complete fewer years of education. For both groups, parental expectations were the strongest predictor of attainment. Results suggest that disparities in education are shaped in part by parents' beliefs about educational opportunities.