bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interstitial lung disease following erlotinib (Tarceva®) in a patient who previously tolerated gefitinib (Iressa®)
Authors: Tammaro Kelly A. , Baldwin Patricia D. , Lundberg Ante S. 
Published: September 2005

Objective. To report a case of who a patient developed clinical and radiographical evidence of interstitial lung disease (ILD) on erlotinib after having tolerated gefitinib therapy. Case Summary. A 58-year-old man with stage IV non-small-cell lung cancer (NSCLC) failed first and second line chemotherapy. He then received gefitinib, a small molecule epidermal growth factor receptor (EGFR) inhibitor, a therapy which was well tolerated, but did cause a grade 1 rash. On gefitinib, the patient’s disease remained stable for seven months. Subsequent disease progression was treated with the newer EGFR inhibitor, erlotinib. After 5 days of erlotinib therapy, the patient presented with a sore throat and dyspnea, followed by a grade 2 rash and significant hemoptysis. Erlotinib was discontinued for three days, during which time his symptoms abated. Erlotinib was restarted and the patient again developed sore throat, dyspnea and severe hemotpysis, with progression of the rash to grade 3. Erlotinib therapy was discontinued and the patient recevied prednisone and supplemental oxygen. A CT scan of the chest demonstrated new areas of patchy ground glass opacity bilaterally and increased interstitial markings consistent with ILD. Discussion. The case demonstrates that clinical ILD can occur following erlotinib therapy, even in patients who previously tolerated gefitinib. ILD has not been reported to occur more frequently with erlotinib than with gefitinib. However, the dose of erlotinib employed clinically is the maximum tolerated dose identified in phase 1 trials, and is associated with an increased incidence of grade 3-4rashand diarrhea, as compared to gefitinib. Thus, the observation of clinical ILD following erlotinib, but not gefitinib, may be the consequence of increased potency of erlotinib 150 mg/day compared to gefitinib 250 mg/day. Conclusion. Clinical ILD can occur following erlotinib even in patients who previously tolerated gefitinib. IT is important to carefully monitor pulmonary symptoms in all patients who are receiving erlotinib, as early diagnosis and timely intervention are critical in managing drug-induced ILD.
Palifermin (Kepivance™) for the treatment of oral mucositis in patients with hematologic malignancies requiring hematopoietic stem cell support
Authors: Radtke Michelle L , Kolesar Jill M 
Published: September 2005

Objective. To provide a comprehensive review of the clinical use of the recombinant biological agent, palifermin, with particular reference to its use in its approved indication, oral mucositis resulting from high dose chemotherapy and radiation in patients with hematologic malignancies requiring hematopoietic stem cell support. Data Sources. A MEDLINE search was conducted using the terms ‘palifermin’ and ‘Kepivance.’ All data available from MEDLINE were reviewed. The reference lists from retrieved articles were reviewed and other relevant papers were identified. Data Summary. Keratinocyte growth factor (KGF) is a growth factor that acts specifically on epithelial cells playing a role in proliferation, migration, and morphogenesis. Palifermin is a recombinant human form of KGF. Because of its ability to cause proliferation of the oral mucosa and to protect against mucosal injury, palifermin is a treatment option for patients who are at high risk for oral mucositis, specifically patients with hematological malignancies receiving stem cell transplantation (SCT). In a phase III study of these patients, the overall incidence of World Health Organization (WHO) grade 3 or 4 oral mucositis was significantly reduced in the palifermin group (palifermin=63% versus placebo=98%, P B0.001). Among the patients who experienced WHO grade 3 or 4 oral mucositis the average duration of this grade of mucositis in the palifermin group was six days compared with nine days in the placebo group (P B0.001). Common adverse effects of palifermin include pruritis, erythema, mouth and tongue disorders, and taste alterations.
Overview of drug therapy for multiple myeloma
Authors: Saunders Geoff 
Published: September 2005

Background. Multiple myeloma accounts for 10% of all haematologic malignancies worldwide. In Europe, over 10 000 new cases and nearly 8000 deaths were attributed to multiple myeloma in 2000. Unlike other malignancies, in which surgery and radiation are important treatment modalities, myeloma is exclusively treated with stem cell transplantation and drug therapy, requiring pharmacists to stay abreast of new developments. The melphalan-prednisolone and vincristine-doxorubicin-dexamethasone (VAD) regimens, which have been standard treatments for multiple myeloma over the past few decades, have yielded responses without real survival benefits. Transplantation utilizing high-dose chemotherapy has produced the only meaningful survival benefits for patients with multiple myeloma, but many patients are not candidates for this aggressive treatment option. More effective therapies for multiple myeloma are needed. Objective. To address the mechanisms of action, safety, and efficacy of novel approaches to the treatment of myeloma involving bortezomib, thalidomide and its analogues, lenalidomide and CC-4047 (ActimidTM), and arsenic trioxide as single agents or in combination regimens. Data sources. Published preclinical and primary clinical trial results, as well as scientific or clinical meeting abstracts. The author determined the relevance and subsequent inclusion of the data. Conclusions. Bortezomib is approved in the US and Europe as single-agent therapy for the treatment of relapsed or refractory multiple myeloma. Thalidomide, its analogues, and arsenic trioxide have demonstrated activity and are under investigation in this disease. Further clinical trials of the efficacy and toxicity of these novel agents are ongoing and will further define optimal combinations and sequencing with conventional therapies.
High Telomerase RNA Expression Level Is an Adverse Prognostic Factor for Favorable-Histology Wilms' Tumor
Authors: Dome Jeffrey S. , Bockhold Carol A. , Li Sierra M. , Baker Scott D. , Green Daniel M. , Perlman Elizabeth J. , Hill D. Ashley , Breslow Norman E. 
Published: September 2005

Purpose A primary objective of the fifth National Wilms Tumor Study (NWTS-5) was to identify prognostic indicators for patients with favorable-histology Wilms' tumor. The prognostic significance of telomerase expression level in primary tumor samples was assessed. Patients and Methods A case-cohort study was conducted involving 291 NWTS-5 registrants. Telomerase activity was measured using the telomeric repeat amplification protocol (TRAP). Expression levels of TERT mRNA (encoding the telomerase catalytic component) and TERC/hTR (the telomerase RNA template) were measured using quantitative real-time polymerase chain reaction. Results After excluding samples because of lack of viable tumor, RNA degradation, or insufficient clinical information, 244 patients remained for the final analysis (96 with relapse and 148 without relapse). Univariate analysis revealed a positive correlation between relative risk (RR) of relapse and levels of TERT mRNA and TERC expression. For each doubling in TERT mRNA and TERC level, the RR increased by a factor of 1.16 (95% CI, 1.04 to 1.29; P = .01) and 1.35 (95% CI, 1.11 to 1.64; P = .003), respectively. The one third of patients whose tumors had the highest TERC expression level had an RR of 2.06 (95% CI, 1.14 to 3.70; P = .02) compared with patients with the lowest level. TERC expression level remained a significant prognostic indicator in a multivariate analysis adjusting for TERT mRNA, tumor stage, and patient age. TRAP level did not correlate with RR of relapse. Telomerase expression levels were not predictive of overall survival. Conclusion Telomerase RNA expression level may provide a clinically useful adjunct to the current risk classification schema for favorable-histology Wilms' tumor.
Parent and Physician Perspectives on Quality of Care at the End of Life in Children With Cancer
Authors: Mack Jennifer W. , Hilden Joanne M. , Watterson Jan , Moore Caron , Turner Brian , Grier Holcombe E. , Weeks Jane C. , Wolfe Joanne 
Published: September 2005

Purpose To ascertain parents' and physicians' assessments of quality of end-of-life care for children with cancer and to determine factors associated with high-quality care as perceived by parents and physicians. Methods A survey was conducted between 1997 and 2001 of 144 parents of children who received treatment at the Dana-Farber Cancer Institute and Children's Hospital (Boston, MA) or Children's Hospitals and Clinics of St Paul and Minneapolis, MN, between 1990 and 1999 (65% of those located and eligible) and 52 pediatric oncologists. Results In multivariable models, higher parent ratings of physician care were associated with physicians giving clear information about what to expect in the end-of-life period (odds ratio [OR] = 19.90, P = .02), communicating with care and sensitivity (OR = 7.67, P < .01), communicating directly with the child when appropriate (OR = 11.18, P < .01), and preparing the parent for circumstances surrounding the child's death (OR = 4.84, P = .03). Parent reports of the child's pain and suffering were not significant correlates of parental ratings of care (P = .93 and .35, respectively). Oncologists' ratings of care were inversely associated with the parent's report of the child's experience of pain (OR = 0.15, P = .01) and more than 10 hospital days in the last month of life (OR = 0.24, P < .01). Parent-rated communication factors were not correlates of oncologist-rated care. No association was found between parent and physician care ratings (P = .88). Conclusion For parents of children who die of cancer, doctor-patient communication is the principal determinant of high-quality physician care. In contrast, physicians' care ratings depend on biomedical rather than relational aspects of care.
Care-Related Distress: A Nationwide Study of Parents Who Lost Their Child to Cancer
Authors: Kreicbergs Ulrika , Valdimarsdóttir Unnur , Onelöv Erik , Björk Olle , Steineck Gunnar , Henter Jan-Inge 
Published: September 2005

Purpose Palliative care is an important part of cancer treatment. However, little is known about how care-related factors affect bereaved intimates in a long-term perspective. We conducted a population-based, nationwide study addressing this issue, focusing on potential care-related stressors in parents losing a child to cancer. Methods In 2001, we attempted to contact all parents in Sweden who had lost a child to cancer in 1992 to 1997. The parents were asked, through an anonymous postal questionnaire, about their experience of the care given and to what extent these experiences still affect them today. Results Information was supplied by 449 (80%) of 561 eligible parents. Among 196 parents of children whose pain could not be relieved, 111 (57%) were still affected by it 4 to 9 years after bereavement. Among 138 parents reporting that the child had a difficult moment of death, 78 (57%) were still affected by it at follow-up. The probability of parents reporting that their child had a difficult moment of death was increased (relative risk = 1.4; 95% CI, 1.0 to 1.8) if staff were not present at the moment of death. Ten percent of the parents (25 of 251 parents) were not satisfied with the care given during the last month at a pediatric hematology/oncology center; the corresponding figure for care at other hospitals was 20% (33 of 168 parents; P = .0163). Conclusion Physical pain and the moment of death are two important issues to address in end-of-life care of children with cancer in trying to reduce long-term distress in bereaved parents.
An Experimental Study of the Emergence of Human Communication Systems
Authors: Galantucci Bruno 
Published: September 2005

AbstractThe emergence of human communication systems is typically investigated via 2 approaches with complementary strengths and weaknesses: naturalistic studies and computer simulations. This study was conducted with a method that combines these approaches. Pairs of participants played video games requiring communication. Members of a pair were physically separated but exchanged graphic signals through a medium that prevented the use of standard symbols (e.g., letters). Communication systems emerged and developed rapidly during the games, integrating the use of explicit signs with information implicitly available to players and silent behavior‐coordinating procedures. The systems that emerged suggest 3 conclusions: (a) signs originate from different mappings; (b) sign systems develop parsimoniously; (c) sign forms are perceptually distinct, easy to produce, and tolerant to variations.
Improvement of Mapping Accuracy by Unifying Linkage and Association Analysis
Authors: Lou Xiang-Yang , Ma Jennie Z , Yang Mark C K , Zhu Jun , Liu Peng-Yuan , Deng Hong-Wen , Elston Robert C , Li Ming D 
Published: September 2005

AbstractIt is well known that pedigree/family data record information on the coexistence in founder haplotypes of alleles at nearby loci and the cotransmission from parent to offspring that reveal different, but complementary, profiles of the genetic architecture. Either conventional linkage analysis that assumes linkage equilibrium or family-based association tests (FBATs) capture only partial information, leading to inefficiency. For example, FBATs will fail to detect even very tight linkage in the case where no allelic association exists, while a violation of the assumption of linkage equilibrium will result in biased estimation and reduced efficiency in linkage mapping. In this article, by using a data augmentation technique and the EM algorithm, we propose a likelihood-based approach that embeds both linkage and association analyses into a unified framework for general pedigree data. Relative to either linkage or association analysis, the proposed approach is expected to have greater estimation accuracy and power. Monte Carlo simulations support our theoretical expectations and demonstrate that our new methodology: (1) is more powerful than either FBATs or classic linkage analysis; (2) can unbiasedly estimate genetic parameters regardless of whether association exists, thus remedying the bias and less precision of traditional linkage analysis in the presence of association; and (3) is capable of identifying tight linkage alone. The new approach also holds the theoretical advantage that it can extract statistical information to the maximum extent and thereby improve mapping accuracy and power because it integrates multilocus population-based association study and pedigree-based linkage analysis into a coherent framework. Furthermore, our method is numerically stable and computationally efficient, as compared to existing parametric methods that use the simplex algorithm or Newton-type methods to maximize high-order multidimensional likelihood functions, and also offers the computation of Fisher's information matrix. Finally, we apply our methodology to a genetic study on bone mineral density (BMD) for the vitamin D receptor (VDR) gene and find that VDR is significantly linked to BMD at the one-third region of the wrist.
Fine Mapping and Physical Characterization of Two Linked Quantitative Trait Loci Affecting Milk Fat Yield in Dairy Cattle on BTA26
Authors: Gautier Mathieu , Barcelona Rosa Roy , Fritz Sébastien , Grohs Cécile , Druet Tom , Boichard Didier , Eggen André , Meuwissen Theo H E 
Published: September 2005

Abstract
Previously, a highly significant QTL affecting fat yield and protein yield and mapped to the bovine BTA26 chromosome has been reported to segregate in the French Holstein cattle population. To confirm and refine the location of this QTL, the original detection experiment was extended by adding 12 new families and genotyping 25 additional microsatellite markers (including 11 newly developed markers). Data were then analyzed by an approach combining both linkage and linkage disequilibrium information, making it possible to identify two linked QTL separated by 20 cM corresponding to ∼29 Mb. The presence of a QTL affecting protein yield was confirmed but its position was found to be more telomeric than the two QTLunderlying fat yield. Each identified QTL affecting milk fat yield was physically mapped within a segment estimated to be &lt;500 kb. Two strong functional candidate genes involved, respectively, in fatty acid metabolism and membrane permeability were found to be localized within this segment while other functional candidate genes were discarded. A haplotype comprising the favorable allele at each QTL position appears to be overrepresented in the artificial insemination bull population.
High-Resolution Association Mapping of Quantitative Trait Loci: A Population-Based Approach
Authors: Fan Ruzong , Jung Jeesun , Jin Lei 
Published: September 2005

AbstractIn this article, population-based regression models are proposed for high-resolution linkage disequilibrium mapping of quantitative trait loci (QTL). Two regression models, the “genotype effect model” and the “additive effect model,” are proposed to model the association between the markers and the trait locus. The marker can be either diallelic or multiallelic. If only one marker is used, the method is similar to a classical setting by Nielsen and Weir, and the additive effect model is equivalent to the haplotype trend regression (HTR) method by Zaykin et al. If two/multiple marker data with phase ambiguity are used in the analysis, the proposed models can be used to analyze the data directly. By analytical formulas, we show that the genotype effect model can be used to model the additive and dominance effects simultaneously; the additive effect model takes care of the additive effect only. On the basis of the two models, F-test statistics are proposed to test association between the QTL and markers. By a simulation study, we show that the two models have reasonable type I error rates for a data set of moderate sample size. The noncentrality parameter approximations of F-test statistics are derived to make power calculation and comparison. By a simulation study, it is found that the noncentrality parameter approximations of F-test statistics work very well. Using the noncentrality parameter approximations, we compare the power of the two models with that of the HTR. In addition, a simulation study is performed to make a comparison on the basis of the haplotype frequencies of 10 SNPs of angiotensin-1 converting enzyme (ACE) genes.
The Genetic Architecture of Sucrose Responsiveness in the Honeybee (Apis mellifera L.)
Authors: Rueppell Olav , Chandra Sathees B C , Pankiw Tanya , Fondrk M Kim , Beye Martin , Hunt Greg , Page Robert E 
Published: September 2005

Abstract
One of the best examples of a natural behavioral syndrome is the pollen-hoarding syndrome in honeybees that ties together multiple behavioral phenotypes, ranging from foraging behavior to behavioral ontogeny and learning performance. A central behavioral factor is the bees' responsiveness to sucrose, measured as their proboscis extension reflex. This study examines the genetics of this trait in diploid worker and haploid male honeybees (drones) to learn more about the genetic architecture of the overall behavioral syndrome, using original strains selected for pollen-hoarding behavior. We show that a significant proportion of the phenotypic variability is determined by genotype in males and workers. Second, our data present overwhelming evidence for pleiotropic effects of previously identified quantitative trait loci for foraging behavior (pln-QTL) and epistatic interactions among them. Furthermore, we report on three genomic QTL scans (two reciprocal worker backcrosses and one drone hybrid population) derived from our selection strains. We present at least one significant and two putative new QTL directly affecting the sucrose response of honeybees. Thus, this study demonstrates the modular genetic architecture of behavioral syndromes in general, and elucidates the genetic architecture of the pollen-hoarding behavioral syndrome in particular. Understanding this behavioral syndrome is important for understanding the division of labor in social insects and social evolution itself.
Genomewide Nonadditive Gene Regulation in Arabidopsis Allotetraploids
Authors: Wang Jianlin , Tian Lu , Lee Hyeon-Se , Wei Ning E , Jiang Hongmei , Watson Brian , Madlung Andreas , Osborn Thomas C , Doerge R W , Comai Luca , Chen Z Jeffrey 
Published: September 2005

AbstractPolyploidy has occurred throughout the evolutionary history of all eukaryotes and is extremely common in plants. Reunification of the evolutionarily divergent genomes in allopolyploids creates regulatory incompatibilities that must be reconciled. Here we report genomewide gene expression analysis of Arabidopsis synthetic allotetraploids, using spotted 70-mer oligo-gene microarrays. We detected &gt;15% transcriptome divergence between the progenitors, and 2105 and 1818 genes were highly expressed in Arabidopsis thaliana and A. arenosa, respectively. Approximately 5.2% (1362) and 5.6% (1469) genes displayed expression divergence from the midparent value (MPV) in two independently derived synthetic allotetraploids, suggesting nonadditive gene regulation following interspecific hybridization. Remarkably, the majority of nonadditively expressed genes in the allotetraploids also display expression changes between the parents, indicating that transcriptome divergence is reconciled during allopolyploid formation. Moreover, &gt;65% of the nonadditively expressed genes in the allotetraploids are repressed, and &gt;94% of the repressed genes in the allotetraploids match the genes that are expressed at higher levels in A. thaliana than in A. arenosa, consistent with the silencing of A. thaliana rRNA genes subjected to nucleolar dominance and with overall suppression of the A. thaliana phenotype in the synthetic allotetraploids and natural A. suecica. The nonadditive gene regulation is involved in various biological pathways, and the changes in gene expression are developmentally regulated. In contrast to the small effects of genome doubling on gene regulation in autotetraploids, the combination of two divergent genomes in allotetraploids by interspecific hybridization induces genomewide nonadditive gene regulation, providing a molecular basis for de novo variation and allopolyploid evolution.