bluuebunny/crossref_metadata_2025_split huggingface dataset:
A first-draft human protein-interaction map
Authors: Lehner Ben , Fraser Andrew G 
Published: August 2004

Abstract
Background
Protein-interaction maps are powerful tools for suggesting the cellular functions of genes. Although large-scale protein-interaction maps have been generated for several invertebrate species, projects of a similar scale have not yet been described for any mammal. Because many physical interactions are conserved between species, it should be possible to infer information about human protein interactions (and hence protein function) using model organism protein-interaction datasets.

Results
Here we describe a network of over 70,000 predicted physical interactions between around 6,200 human proteins generated using the data from lower eukaryotic protein-interaction maps. The physiological relevance of this network is supported by its ability to preferentially connect human proteins that share the same functional annotations, and we show how the network can be used to successfully predict the functions of human proteins. We find that combining interaction datasets from a single organism (but generated using independent assays) and combining interaction datasets from two organisms (but generated using the same assay) are both very effective ways of further improving the accuracy of protein-interaction maps.

Conclusions
The complete network predicts interactions for a third of human genes, including 448 human disease genes and 1,482 genes of unknown function, and so provides a rich framework for biomedical research.
An Ambystoma mexicanumEST sequencing project: analysis of 17,352 expressed sequence tags from embryonic and regenerating blastema cDNA libraries
Authors: Habermann Bianca , Bebin Anne-Gaelle , Herklotz Stephan , Volkmer Michael , Eckelt Kay , Pehlke Kerstin , Epperlein Hans Henning , Schackert Hans Konrad , Wiebe Glenis , Tanaka Elly M 
Published: August 2004

Abstract
Background
The ambystomatid salamander, Ambystoma mexicanum (axolotl), is an important model organism in evolutionary and regeneration research but relatively little sequence information has so far been available. This is a major limitation for molecular studies on caudate development, regeneration and evolution. To address this lack of sequence information we have generated an expressed sequence tag (EST) database for A. mexicanum.

Results
Two cDNA libraries, one made from stage 18-22 embryos and the other from day-6 regenerating tail blastemas, generated 17,352 sequences. From the sequenced ESTs, 6,377 contigs were assembled that probably represent 25% of the expressed genes in this organism. Sequence comparison revealed significant homology to entries in the NCBI non-redundant database. Further examination of this gene set revealed the presence of genes involved in important cell and developmental processes, including cell proliferation, cell differentiation and cell-cell communication. On the basis of these data, we have performed phylogenetic analysis of key cell-cycle regulators. Interestingly, while cell-cycle proteins such as the cyclin B family display expected evolutionary relationships, the cyclin-dependent kinase inhibitor 1 gene family shows an unusual evolutionary behavior among the amphibians.

Conclusions
Our analysis reveals the importance of a comprehensive sequence set from a representative of the Caudata and illustrates that the EST sequence database is a rich source of molecular, developmental and regeneration studies. To aid in data mining, the ESTs have been organized into an easily searchable database that is freely available online.
Phase I Trial of Preoperative Doxorubicin-Based Concurrent Chemoradiation and Surgical Resection for Localized Extremity and Body Wall Soft Tissue Sarcomas
Authors: Pisters Peter W.T. , Patel Shreyaskumar R. , Prieto Victor G. , Thall Peter F. , Lewis Valerae O. , Feig Barry W. , Hunt Kelly K. , Yasko Alan W. , Lin Patrick P. , Jacobson Marc G. , Burgess Michael A. , Pollock Raphael E. , Zagars Gunar K. , Benjamin Robert S. , Ballo Matthew T. 
Published: August 2004

Purpose The primary objective of this phase I trial was to define the maximum-tolerated dose of continuous-infusion doxorubicin administered with standard preoperative radiation for patients with localized, potentially resectable soft tissue sarcomas of the extremities or body wall. Patients and Methods Twenty-seven patients with radiographically resectable intermediate- or high-grade soft tissue sarcomas were treated. Preoperative external-beam radiation was administered in 25 2-Gy fractions (total dose, 50 Gy). Concurrent continuous-infusion doxorubicin was administered by an initial bolus (4 mg/m2) and subsequent 4-day continuous infusion (12.5, 15.0, 17.5, or 20.0 mg/m2/wk). Radiographic restaging was performed 4 to 7 weeks after chemoradiation, and patients with localized disease underwent surgical resection. Results Chemoradiation was completed as an outpatient procedure in 25 patients (93%). The maximum-tolerated dose of continuous-infusion doxorubicin combined with standard preoperative radiation was 17.5 mg/m2/wk; at this dose level, seven (30%) of 23 patients had grade 3 dermatologic toxicity. Macroscopically complete resection (R0 or R1) was performed in all 26 patients who underwent surgery. Among 22 patients who were treated with doxorubicin 17.5/mg/m2/wk with concurrent radiation and subsequent surgery, 11 patients (50%) had 90% or greater tumor necrosis, including two patients who had complete pathologic responses. Conclusion Preoperative doxorubicin-based chemoradiation appears safe and feasible. The maximum-tolerated dose of continuous-infusion doxorubicin with standard preoperative radiation was 17.5 mg/m2/wk. Pathologic response rates with this regimen are encouraging.
Population Variations in the Initial Treatment of Non–Small-Cell Lung Cancer
Authors: Potosky Arnold L. , Saxman Scott , Wallace Robert B. , Lynch Charles F. 
Published: August 2004

Purpose Dissemination of recommended therapies for non–small-cell lung cancer (NSCLC) have not been described comprehensively. We report the patterns of initial therapy focusing on the investigation of differences in receipt of recommended therapies according to multiple clinical and nonclinical patient characteristics. Methods A population-based random sample of newly diagnosed NSCLC patients diagnosed in 10 separate geographic areas was collected in 1996 (n = 898). Data were obtained from medical records. Multiple logistic regression was used to assess the use of recommended therapies. Results Overall, 52% of NSCLC patients received recommended therapy. Approximately 69%, 48%, and 41% of patients with stages I and II, III, or IV NSCLC received recommended therapy, respectively. For all stages combined, the use of recommended therapy was significantly inversely associated with age and stage at diagnosis. Recommended therapy also was more common in white versus black patients, and in married versus single patients. Stage-specific analyses revealed a significant decline in the use of recommended surgery with increasing age at diagnosis for early-stage NSCLC only, and a significantly lower use of recommended therapy (primarily chemoradiotherapy) for stage III black and Hispanic patients compared with white patients. Conclusion The overall use of recommended therapies for NSCLC is low. Large variations exist in the use of such therapies according to age, race or ethnicity, and marital status. Research combining medical record reviews with other sources of data is needed to better understand the contributions of both patient preferences and physician judgment to these treatment variations.
Health-Related Quality of Life Parameters As Prognostic Factors in a Nonmetastatic Breast Cancer Population: An International Multicenter Study
Authors: Efficace Fabio , Therasse Patrick , Piccart Martine J. , Coens Corneel , Van Steen Kristel , Welnicka-Jaskiewicz Marzena , Cufer Tanja , Dyczka Jaroslaw , Lichinitser Michail , Shepherd Lois , de Haes Hanneke , Sprangers Mirjam A. , Bottomley Andrew 
Published: August 2004

Purpose The purpose of this research was to evaluate whether baseline health-related quality of life (HRQOL) parameters are prognostic factors for survival in locally advanced breast cancer patients. Although the literature highlights the important role of HRQOL parameters in predicting survival in advanced metastatic disease, little evidence exists for earlier stages. Patients and Methods The overall sample consisted of 448 patients randomly assigned to receive cyclophosphamide, epirubicin, and fluorouracil versus epirubicin, cyclophosphamide, and granulocyte colony-stimulating factor. Patients were enrolled in 12 countries. HRQOL baseline scores were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap resampling technique was used to assess the stability of the outcomes. Bootstrap results were then applied for model averaging purposes as a means to account for the observed model selection uncertainty. Results The final multivariate model retained inflammatory breast cancer (T4d) as the only factor predicting overall survival (OS) with a hazard ratio of 1.375 (95% CI, 1.027 to 1.840; P = .03). The presence of inflammatory breast cancer lowers the median survival time from 6.6 to 4.2 years (36% reduction). None of the preselected HRQOL variables were prognostic for OS or disease-free survival, in either the univariate or multivariate analysis. Conclusion Our findings suggest that baseline HRQOL parameters have no prognostic value in a nonmetastatic breast cancer population.
Expression of Hepatoma-Derived Growth Factor Is a Strong Prognostic Predictor for Patients With Early-Stage Non–Small-Cell Lung Cancer
Authors: Ren Hening , Tang Ximing , Lee J. Jack , Feng Lei , Everett Allen D. , Hong Waun Ki , Khuri Fadlo R. , Mao Li 
Published: August 2004

Purpose Hepatoma-derived growth factor (HDGF), which is unrelated to hepatocyte growth factor, can stimulate DNA synthesis and cell proliferation on entering the nucleus. We hypothesize that HDGF plays an important role in biologic behavior of early-stage non–small-cell lung cancer (NSCLC). Patients and Methods Ninety-eight patients with pathologic stage I NSCLC who underwent curative surgery were studied. Immunohistochemistry was used to determine the expression level of HDGF in the tumor specimens. The intensity of the protein staining and percentage of stained tumor cells were used to determine a labeling index. Statistical analyses, all two-sided, were performed to determine the prognostic effect of HDGF expression levels on clinical parameters and outcomes. Results The mean ± standard deviation HDGF labeling index in the 98 tumors was 185 ± 41. Patients whose tumors had higher HDGF indexes (≥ 185) had a significantly poorer probability of overall survival at 5 years after surgery than did those with lower HDGF indexes (0.26 v 0.82; P < .0001). Similarly, the 5-year disease-specific and disease-free survival probabilities were lower in those with higher HDGF indexes (0.42 v 0.92, and 0.34 v 0.71; P < .0001 and P = .0008; respectively). Multivariate analysis indicated that HDGF level was an independent predictor of overall, disease-specific, and disease-free survivals. Conclusion Overexpression of HDGF is common in early-stage NSCLC. The expression level in tumor cells is strongly correlated with poor overall, disease-specific, and disease-free survivals, suggesting HDGF may be a powerful prognostic marker for patients with early-stage NSCLC.
Randomized Trial of a Shared Decision-Making Intervention Consisting of Trade-Offs and Individualized Treatment Information for BRCA1/2 Mutation Carriers
Authors: van Roosmalen M.S. , Stalmeier P.F.M. , Verhoef L.C.G. , Hoekstra-Weebers J.E.H.M. , Oosterwijk J.C. , Hoogerbrugge N. , Moog U. , van Daal W.A.J. 
Published: August 2004

Purpose To evaluate a shared decision-making intervention (SDMI) for BRCA1/2 mutation carriers who have to make a choice between screening and prophylactic surgery for breasts and/or ovaries. Patients and Methods The SDMI consisted of two value assessment sessions, using the time trade-off method, followed by individualized treatment information based on (quality-adjusted) life expectancy. After the baseline assessment (2 weeks after a positive DNA test result), women were randomly assigned to the SDMI group (n = 44), receiving the SDMI 2 months after the test result, or to the control group (n = 44). The short- and long-term effects, 3 and 9 months after the test result, were assessed using questionnaires. Data were collected on well-being, treatment choice, and decision-related outcomes. Results In the short term, the SDMI had no effect. In the long term, with respect to well-being, patients in the SDMI group had less intrusive thoughts (P = .05) and better general health (P = .01) and tended to be less depressed (P = .07). With respect to decision-related outcomes for the breasts, the SDMI group held stronger preferences (P = .02) and agreed more strongly to having weighed the pros and cons (P = .01). No effect was found on treatment choice. In the long term, interaction effects between the SDMI and cancer history were found. The SDMI showed an overall beneficial effect for unaffected women, whereas affected women tended to experience detrimental effects. Conclusion We conclude that the SDMI improved decision making in unaffected BRCA1/2 mutation carriers. Supporting decision making in a systematic way using trade-offs is beneficial for these women.
Breast Cancer With Synchronous Metastases: Trends in Survival During a 14-Year Period
Authors: Andre Fabrice , Slimane Khemaies , Bachelot Thomas , Dunant Arianne , Namer Moise , Barrelier Alain , Kabbaj Omar , Spano Jean Philippe , Marsiglia Hugo , Rouzier Roman , Delaloge Suzette , Spielmann Marc 
Published: August 2004

Purpose Although new drugs were approved during the 1990s for the treatment of metastatic breast cancer, it is not clear whether their use has changed the outcome of patients in daily practice. This study sought to determine whether survival has improved over time for breast cancer patients who had metastases at diagnosis. Patients and Methods A total of 724 patients have been treated in three French cancer centers for an initially metastatic breast cancer between 1987 and 2000; 343 were diagnosed between 1987 and 1993, and 381 were diagnosed between 1994 and 2000. Tumor characteristics, treatments, and outcomes of these patients were compared by χ2 test, log-rank test, and Cox regression analysis. Results Characteristics were not different between the patients diagnosed from 1987 to 1993 and those diagnosed from 1994 to 2000. Ten percent of patients treated from 1987 to 1994 and 58% of patients treated from 1994 to 2000 have received either a taxane or a new aromatase inhibitor. The 3-year overall survival rates were 27% for patients treated from 1987 to 1993 and 44% for patients treated from 1994 to 2000 (P < .001). The treatment period (1994 to 2000 v 1987 to 1993) was a prognostic factor in multivariate analysis (relative risk, 0.6; P < .001). Conclusion The survival of breast cancer patients presenting with metastases at diagnosis has improved over time. This study strongly suggests that this improvement is related to treatment.
Use of the University of California Los Angeles Integrated Staging System to Predict Survival in Renal Cell Carcinoma: An International Multicenter Study
Authors: Patard Jean-Jacques , Kim Hyung L. , Lam John S. , Dorey Frederick J. , Pantuck Allan J. , Zisman Amnon , Ficarra Vincenzo , Han Ken-Ryu , Cindolo Luca , De La Taille Alexandre , Tostain Jacques , Artibani Walter , Dinney Colin P. , Wood Christopher G. , Swanson David A. , Abbou Claude C. , Lobel Bernard , Mulders Peter F.A. , Chopin Dominique K. , Figlin Robert A. , Belldegrun Arie S. 
Published: August 2004

Purpose To evaluate ability of the University of California Los Angeles Integrated Staging System (UISS) to stratify patients with localized and metastatic renal cell carcinoma (RCC) into risk groups in an international multicenter study. Patients and Methods 4,202 patients from eight international academic centers were classified according to the UISS, which combines TNM stage, Fuhrman grade, and Eastern Cooperative Oncology Group performance status. Distribution of the UISS categories was assessed in the overall population and in each center. Results The UISS stratified both localized and metastatic RCC into three different risk groups (P < .001). For localized RCC, the 5-year survival rates were 92%, 67%, and 44% for low-, intermediate-, and high-risk groups, respectively. A trend toward a higher risk of death was observed in all centers for increasing UISS risk category. For metastatic RCC, the 3-year survival rates were 37%, 23%, and 12% for low-, intermediate-, and high-risk groups, respectively; in 6 of 8 centers, a trend toward a higher risk of death was observed for increasing UISS risk category. A greater variability in survival rates among centers was observed for high-risk patients. Conclusion This study defines the general applicability of the UISS for predicting survival in patients with RCC. The UISS is an accurate predictor of survival for patients with localized RCC applicable to external databases. Although the UISS may be useful for patients with metastatic RCC, it may be less accurate in this subset of patients due to the heterogeneity of patients and treatments.
Prophylactic Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor Decrease Febrile Neutropenia After Chemotherapy in Children With Cancer: A Meta-Analysis of Randomized Controlled Trials
Authors: Sung Lillian , Nathan Paul C. , Lange Beverly , Beyene Joseph , Buchanan George R. 
Published: August 2004

Purpose To determine whether prophylactic hematopoietic colony-stimulating factors (CSFs) used in children with cancer reduce the rate of febrile neutropenia, hospitalization duration, documented infection rate, parenteral antibiotic duration, amphotericin B use, or infection-related mortality. Methods We included studies in this meta-analysis if their populations consisted of children, if there was randomization between CSFs and placebo or no therapy, if CSFs were administered prophylactically (before neutropenia or febrile neutropenia), and if chemotherapy treatments preceding CSFs and placebo or no therapy were identical. From 971 reviewed study articles, 16 were included. Results The mean rate of febrile neutropenia in the control arms was 57% (range, 39% to 100%). Using a random effects model, CSFs were associated with a reduction in febrile neutropenia, with a rate ratio of 0.80 (95% CI, 0.67 to 0.95; P = .01), and a decrease in hospitalization length, with a weighted mean difference of −1.9 days (95% CI, −2.7 to −1.1 days; P < .00001). CSF use was also associated with reduction in documented infections (rate ratio, 0.78; 95% CI, 0.62 to 0.97; P = .02) and reduction in amphotericin B use (rate ratio, 0.50; 95% CI, 0.28 to 0.87; P = .02). There was no difference in duration of parenteral antibiotic therapy (weighted mean difference, −4.3; 95% CI, −10.6 to 2.0 days; P = .2) or infection-related mortality (rate ratio, 1.02; 95% CI, 0.34 to 3.06; P = .97). Conclusion CSFs were associated with a 20% reduction in febrile neutropenia and shorter duration of hospitalization; however, CSFs did not reduce infection-related mortality.
Acetaminophen (Paracetamol) Improves Pain and Well-Being in People With Advanced Cancer Already Receiving a Strong Opioid Regimen: A Randomized, Double-Blind, Placebo-Controlled Cross-Over Trial
Authors: Stockler Martin , Vardy Janette , Pillai Avinesh , Warr David 
Published: August 2004

Purpose To determine whether adding regular acetaminophen (paracetamol) could improve pain and well-being in people with advanced cancer and pain despite strong opioids. Patients and Methods Participants took acetaminophen for 48 hours and placebo for 48 hours. The order (acetaminophen or placebo first) was randomly allocated. Pain was the primary outcome. Preferences, number of opioid breakthrough doses, overall well-being, nausea and vomiting, drowsiness, constipation, and cold sweats were secondary outcomes. Patients rated themselves daily with visual analog scales (VAS) and a verbal numeric scale (VNS) for pain, all scaled from 0 to 10. Results Thirty patients completed the trial. The oral opioid was morphine in 23 patients and hydromorphone in seven patients. The median daily opioid dose in oral morphine equivalents was 200 mg (range, 20 to 2,100 mg). Nonsteroidal anti-inflammatory drugs, corticosteroids, or both were used by 16 patients. Pain and overall well-being were better for patients receiving acetaminophen than for those receiving placebo. The mean difference was 0.4 (95% CI, 0.1 to 0.8; P = .03) in VNS for pain, 0.6 (95% CI, −0.1 to 1.3; P = .09) in VAS for pain, and 0.7 (95% CI, 0.0 to 1.4; P = .05) in VAS for overall well-being. More patients preferred the period they took acetaminophen (n = 14) than the period they took placebo (n = 8), but many had no preference (n = 8). There were no differences in the other outcomes. Conclusion Acetaminophen improved pain and well-being without major side effects in patients with cancer and persistent pain despite a strong opioid regimen. Its addition is worth considering in all such patients.
Platelet-Derived Growth Factor Receptor Inhibitor Imatinib Mesylate and Docetaxel: A Modular Phase I Trial in Androgen-Independent Prostate Cancer
Authors: Mathew Paul , Thall Peter F. , Jones Donnah , Perez Cherie , Bucana Corazon , Troncoso Patricia , Kim Sun-Jin , Fidler Isaiah J. , Logothetis Christopher 
Published: August 2004

Purpose To study the platelet-derived growth factor receptor (PDGFR) inhibitor imatinib mesylate in androgen-independent prostate cancer (AIPC), alone and in combination with docetaxel, we designed a modular phase I trial. Our goals were to (1) evaluate the toxicity and maximum-tolerated dose of docetaxel with imatinib, and (2) evaluate the decline of prostate-specific antigen (PSA) induced by imatinib alone, and imatinib and docetaxel. Patients and Methods Twenty-eight men with AIPC and bone metastases were enrolled to receive imatinib 600 mg daily lead-in for 30 days, then imatinib 600 mg daily and one of six possible doses of docetaxel weekly for 4 weeks every 6 weeks. Results During the imatinib lead-in module, one dose-limiting toxicity (DLT) event was observed, while two (7%) of 28 had PSA decline (both < 50%). With imatinib and docetaxel, cycle 1 DLT was found in three of 12 patients at docetaxel 30 mg/m2, in three of four patients at docetaxel 45 mg/m2, and in five of six patients at docetaxel 35 mg/m2. DLTs (n = 40 total events) were principally fatigue (35%) and nausea (20%). Eight (38%) of 21 had PSA decline greater than 50%, and six (29%) of 21 had PSA decline less than 50%. Serial PSA declines beyond 18 months were observed. PDGFR-expressing tumor declined on serial bone marrow biopsies with combination therapy alone. Conclusion With imatinib 600 mg daily, the maximum-tolerated dose of docetaxel was determined to be 30 mg/m2 weekly for 4 weeks every 6 weeks. Long-term responses were observed. The role of imatinib in modulating outcomes to docetaxel in AIPC is being tested in a randomized phase II trial.