bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Risk Factors for Outcomes After Unrelated Cord Blood Transplantation in Adults With Lymphoid Malignancies: A Study by the Eurocord-Netcord and Lymphoma Working Party of the European Group for Blood and Marrow Transplantation
Authors: Rodrigues Celso A. , Sanz Guillermo , Brunstein Claudio G. , Sanz Jaime , Wagner John E. , Renaud Marc , de Lima Marcos , Cairo Mitchell S. , Fürst Sabine , Rio Bernard , Dalley Christopher , Carreras Enric , Harousseau Jean-Luc , Mohty Mohamad , Taveira Denis , Dreger Peter , Sureda Anna , Gluckman Eliane , Rocha Vanderson 
Published: December 2008

Purpose To determine risk factors of umbilical cord blood transplantation (UCBT) for patients with lymphoid malignancies. Patients and Methods We evaluated 104 adult patients (median age, 41 years) who underwent unrelated donor UCBT for lymphoid malignancies. UCB grafts were two-antigen human leukocyte antigen–mismatched in 68%, and were composed of one (n = 78) or two (n = 26) units. Diagnoses were non-Hodgkin's lymphoma (NHL, n = 61), Hodgkin's lymphoma (HL, n = 29), and chronic lymphocytic leukemia (CLL, n = 14), with 87% having advanced disease and 60% having experienced failure with a prior autologous transplant. Sixty-four percent of patients received a reduced-intensity conditioning regimen and 46% low-dose total-body irradiation (TBI). Median follow-up was 18 months. Results Cumulative incidence of neutrophil engraftment was 84% by day 60, with greater engraftment in recipients of higher CD34+ kg/cell dose (P = .0004). CI of non–relapse-related mortality (NRM) was 28% at 1 year, with a lower risk in patients treated with low-dose total-body irradiation (TBI; P = .03). Cumulative incidence of relapse or progression was 31% at 1 year, with a lower risk in recipients of double-unit UCBT (P = .03). The probability of progression-free survival (PFS) was 40% at 1 year, with improved survival in those with chemosensitive disease (49% v 34%; P = .03), who received conditioning regimens containing low-dose TBI (60% v 23%; P = .001), and higher nucleated cell dose (49% v 21%; P = .009). Conclusion UCBT is a viable treatment for adults with advanced lymphoid malignancies. Chemosensitive disease, use of low-dose TBI, and higher cell dose were factors associated with significantly better outcome.
Phase II Study of an Outpatient Palliative Care Intervention in Patients With Metastatic Cancer
Authors: Follwell Matthew , Burman Debika , Le Lisa W. , Wakimoto Kristina , Seccareccia Dori , Bryson John , Rodin Gary , Zimmermann Camilla 
Published: December 2008

Purpose Although there is increasing advocacy for timely symptom control in patients with cancer, few studies have assessed outpatient palliative care clinics. This study assessed prospectively the efficacy of an Oncology Palliative Care Clinic (OPCC) in improving patient symptom distress and satisfaction. Patients and Methods Eligible patients were new referrals to an OPCC, had metastatic cancer, were at least 18 years old, and were well enough and able to speak and read English sufficiently to provide informed consent and complete questionnaires. Patients received a consultation by a palliative care team. The primary end points of symptom control and patient satisfaction were assessed using the Edmonton Symptom Assessment Scale (ESAS) and patient-adapted Family Satisfaction with Advanced Cancer Care (FAMCARE) scale at baseline, 1 week, and 1 month. Initial and follow-up scores were compared using paired t tests. Results Of 150 patients enrolled, 123 completed 1-week assessments, and 88 completed 4-week assessments. At baseline, the mean ESAS Distress Score (EDS) was 39.5. The mean improvement in EDS was 8.8 points (P < .0001) at 1 week and 7.0 points (P < .0001) at 1 month. Statistically significant improvements were observed for pain, fatigue, nausea, depression, anxiety, drowsiness, appetite, dyspnea, insomnia, and constipation at 1 week (all P ≤ .005) and 1 month (all P ≤ .05). The mean improvement in FAMCARE score was 6.1 points (P < .0001) at 1 week and 5.0 points (P < .0001) at 1 month. Conclusion This phase II study demonstrates efficacy of an OPCC for improvement of symptom control and patient satisfaction with care. Randomized controlled trials are indicated to further evaluate the effectiveness of specialized outpatient palliative care.
Randomized Phase II Trial of Concurrent Cisplatin-Radiotherapy With or Without Neoadjuvant Docetaxel and Cisplatin in Advanced Nasopharyngeal Carcinoma
Authors: Hui Edwin P. , Ma Brigette B. , Leung Sing F. , King Ann D. , Mo Frankie , Kam Michael K. , Yu Brian K. , Chiu Samuel K. , Kwan Wing H. , Ho Rosalie , Chan Iris , Ahuja Anil T. , Zee Benny C. , Chan Anthony T. 
Published: December 2008

Purpose To compare the toxicities, tumor control, survival, and quality of life of nasopharyngeal cancer (NPC) patients treated with sequential neoadjuvant chemotherapy followed by concurrent cisplatin-radiotherapy (CRT) or CRT alone. Patients and Methods Previously untreated stage III to IVB NPC were randomly assigned to (1) neoadjuvant docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weeks for two cycles, followed by cisplatin 40 mg/m2/wk concurrent with radiotherapy, or (2) CRT alone. Planned accrual was 30 patients per arm to detect 20% difference of toxicities based on 95% CIs. Results From November 2002 to November 2004, 65 eligible patients were randomly assigned to neoadjuvant chemotherapy followed by CRT (n = 34) or CRT alone (n = 31). There was a high rate of grade 3/4 neutropenia (97%) but not neutropenic fever (12%) during neoadjuvant chemotherapy. No significant differences in rates of acute toxicities were observed between the two arms during CRT. Dose intensities of concurrent cisplatin, late RT toxicities and quality of life scores were comparable in both arms. The 3-year progression-free survival for neoadjuvant versus control arm was 88.2% and 59.5% (hazard ratio = 0.49; 95% CI, 0.20 to 1.19; P = .12). The 3-year overall survival for neoadjuvant versus control arm was 94.1% and 67.7% (hazard ratio = 0.24; 95% CI, 0.078 to 0.73; P = .012). Conclusion Neoadjuvant docetaxel-cisplatin followed by CRT was well tolerated with a manageable toxicity profile that allowed subsequent delivery of full-dose CRT. Preliminary results suggested a positive impact on survival. A phase III study to definitively test this neoadjuvant-concurrent strategy is warranted.
Association Between Estrogen Receptor-β Expression and Epidermal Growth Factor Receptor Mutation in the Postoperative Prognosis of Adenocarcinoma of the Lung
Authors: Nose Naohiro , Sugio Kenji , Oyama Tsunehiro , Nozoe Tadahiro , Uramoto Hidetaka , Iwata Teruo , Onitsuka Takamitsu , Yasumoto Kosei 
Published: December 2008

Purpose Adenocarcinoma of the lung unrelated to a smoking habit occurs more frequently in women than men, thus suggesting an association between female hormones and development of these tumors. The aim of this study was to elucidate the correlation between expression of estrogen receptor (ER) and clinicopathologic factors, including a mutation in the tyrosine kinase domain of epidermal growth factor receptor (EGFR), and prognosis in adenocarcinoma of the lung. Patients and Methods This study evaluated 447 resected primary lung adenocarcinoma specimens. The expression of ERα and ERβ was evaluated with an immunohistochemical method. The EGFR mutation was evaluated with polymerase chain reaction. Results A strong cytoplasmic expression of ERα and nuclear expression of ERβ were detected in 49.4% and 48.5% of all patients, respectively. A strong nuclear expression of ERβ was independently associated with the EGFR mutations (odds ratio = 2.947; 95% CI, 1.97 to 4.57; P < .001) and good differentiation (odds ratio = 1.84; 95% CI, 1.21 to 2.80; P = .004) and was correlated with an increasing disease-free survival in patients with EGFR mutations (hazard ratio = 2.18; 95% CI, 1.18 to 4.06; P = .014). However, no prognostic significance was identified in patients without EGFR mutations. No clinicopathologic and/or prognostic significance of a strong expression of cytoplasmic ERα was found. Conclusion A strong nuclear expression of ERβ correlates with EGFR mutations, and its favorable prognostic significance was influenced by the EGFR mutations in adenocarcinoma of the lung.
BRCA Germline Mutations in Jewish Patients With Pancreatic Adenocarcinoma
Authors: Ferrone Cristina R. , Levine Douglas A. , Tang Laura H. , Allen Peter J. , Jarnagin William , Brennan Murray F. , Offit Kenneth , Robson Mark E. 
Published: December 2008

Purpose The prognostic significance of germline BRCA1 and BRCA2 mutations in Jewish patients with pancreatic adenocarcinoma (PAC) is unknown. Our objective was to define the prevalence of BRCA1 and BRCA2 in an unselected group of Jewish patients and to compare the clinical characteristics and overall survival (OS) of patients with resected BRCA mutation-associated PAC to PAC patients without mutations. Patients and Methods Jewish patients with PAC resected between January 1986 and January 2004 were identified. DNA was extracted from the archived material, anonymized, and genotyped for founder mutations in BRCA1 (185delAG, 5382insC) and BRCA2 (6174delT). Standard two-sided statistical tests were utilized. Results Of the 187 Jewish patients who underwent resection for PAC, tissue was available for 145 patients. Eight subjects (5.5%) had a BRCA founder mutation (two with BRCA1 [1.3%], six with BRCA2 [4.1%]). The BRCA2 founder mutation was identified in 4.1% of patients with pancreatic adenocarcinoma compared with only 1.1% of cancer-free Washington, DC,–area controls (4.1% v 1.1%; P = .007; odds ratio, 3.85; 95% CI, 2.1 to 10.8). Patients with and without BRCA1 or BRCA2 mutations did not differ in age (mean, 66 v 73 years; P = .6) or other clinicopathologic features. OS was not significantly different (median, 6 v 16 months; P = .35). A previous cancer was reported by 24% (35 of 145) of patients with the most common sites being breast cancer (9 of 35; 74%) and prostate cancer (8 of 35; 23%). Conclusion Founder mutations for BRCA1 and BRCA2 were identified in 5.5% of Ashkenazi patients operated on for PAC. BRCA2 mutations were more prevalent than documented by population studies. Consistent with previous reports, BRCA2 mutations are associated with an increased risk of PAC.
New Utility of an Old Marker: Serial α-Fetoprotein Measurement in Predicting Radiologic Response and Survival of Patients With Hepatocellular Carcinoma Undergoing Systemic Chemotherapy
Authors: Chan Stephen L. , Mo Frankie K.F. , Johnson Philip J. , Hui Edwin P. , Ma Brigette B.Y. , Ho Wing M. , Lam Kwok C. , Chan Anthony T.C. , Mok Tony S.K. , Yeo Winnie 
Published: December 2008

Purpose There are limitations in using radiologic evaluation to assess the treatment outcome of patients with hepatocellular carcinoma (HCC). The use of serial α-fetoprotein (AFP) in monitoring response has not been rigorously evaluated. We aimed to study the clinical value of AFP trend in an attempt to validate AFP as a surrogate serologic end point. Patients and Methods Participants from a phase III randomized trial of systemic chemotherapy in HCC were studied. Serum AFP was prospectively collected in parallel with clinical and radiologic outcome. AFP response was defined as a decrease in AFP of more than 20% after a minimum of two cycles of chemotherapy. We studied the relationship between AFP response and treatment outcome in terms of radiologic response and overall survival. Results Of 188 patients, 117 patients with elevated serum AFP (> 20 μg/L) and documented radiologic evaluation had received at least two cycles of chemotherapy. A total of 47 AFP responders were identified. AFP responders had better survival than nonresponders (13.5 v 5.6 months, respectively; P < .0001), and AFP response was strongly associated with radiologic response (P < .0001). Multivariate analysis suggested that AFP response was significantly associated with survival (hazard ratio, 0.413; 95% CI, 0.273 to 0.626; P < .0001). AFP responses were frequently observed in patients with radiologically stable disease (SD) and tended to identify a subgroup of SD patients with better survival. Conclusion Serial AFP measurement is useful in prognostication and monitoring treatment response in HCC patients undergoing systemic chemotherapy. Incorporation of AFP response into the criteria evaluating treatment outcome should be considered in clinical practice and clinical trials of novel agents in HCC.
Natural gas spark ignition engine efficiency and NOx emission improvement using extreme exhaust gas recirculation enabled by partial reforming
Authors: Hosseini V , Checkel M D , Neill W S 
Published: December 2008

Natural-gas (NG), spark ignition (SI) engines have widespread application in the power generation and upstream oil and gas industries. The manufacturers of these engines are being challenged to meet increasingly stringent nitrogen oxide (NO x) emission regulations without sacrificing fuel conversion efficiency. SI engines may be operated with air—fuel mixtures lean of stoichiometric to achieve higher thermal efficiency and to reduce NO x emissions. Compared with new combustion strategies such as homogeneous charge compression ignition, however, lean SI combustion suffers from a somewhat limited tolerability to mixture dilution and high cyclic variations. Alternatively, NO x emissions may be reduced by using exhaust gas recirculation (EGR) to dilute a stoichiometric air—fuel mixture. This paper investigates the application of reformer gas (RG) to enable a higher mixture dilution of an NG SI engine using EGR. It was found that RG enrichment allows an increase in the EGR dilution of a stoichiometric NG—air mixture from 12 per cent to more than 35 per cent. The optimal level of RG enrichment directly compensates for the combustion phasing retardation effect of EGR. Increasing the RG fraction in the mixture beyond the optimal value adversely affected the combustion process and fuel conversion efficiency. The experimental data suggest that NO x emissions comparable with the forthcoming 2010 US Environmental Protection Agency heavy-duty diesel engine regulations may be achieved using EGR, RG enrichment, and a three-way catalytic converter (TWC). An energy balance showed that there is the potential to increase the overall system fuel conversion efficiency slightly owing to a more optimized combustion process after taking into account the energy losses associated with fuel reforming. The approach of EGR, fuel reforming, and a TWC is suitable for retrofits because it can be accomplished without modifying the engine geometry.
Flow cytometer with mass spectrometer detection for massively multiplexed single-cell biomarker assay
Authors: Tanner Scott D. , Bandura Dmitry R. , Ornatsky Olga , Baranov Vladimir I. , Nitz Mark , Winnik M. A. 
Published: December 2008

Abstract
This paper describes the development and application of new metal-tagging reagents and a novel mass spectrometer (MS) detector for a flow cytometer that enables highly multiplexed measurement of many biomarkers in individual cells. A new class of tagging reagents, based on an acrylic polymer backbone that incorporates a reproducible number of lanthanide elements, has been developed. When linked to antibodies that specifically recognize target proteins of interest, determination of the tag elements is diagnostic for the presence and quantification of the antigen. The use of enriched stable isotope tags provides the opportunity for multiparametric assay. The new instrument uses inductively coupled plasma (ICP) to vaporize, atomize, and ionize individual cells that have been probed using the metal-labeled antibodies. The elemental composition, specifically of the metal tags, is recorded simultaneously using a time-of-flight (TOF)-MS that has been specifically designed for high-speed analysis during the short transient corresponding to the individual cell event. The detector provides for well-resolved atomic fingerprints of many elemental and isotopic tags, with little overlap of neighboring signals (high abundance sensitivity) and wide dynamic range both for a single antigen and between antigens.
Zinc proteomics and the annotation of the human zinc proteome
Authors: Maret Wolfgang 
Published: December 2008

Abstract
Sequence databases can be searched for homologies of zinc coordination motifs with characteristic ligand signatures. Ensuing predictions that 3-10 % of the human genes encodes zinc proteins are most remarkable. But they seem conservative when considering that database mining cannot discover new signatures or coordination environments that employ nonsequential binding of ligands and sulfur-ligand bridges. Predictions also fall short for zinc/protein interactions at protein interfaces and for inhibitory zinc sites. Zinc ions transiently target proteins that are not known to be zinc proteins, adding a hitherto unrecognized dimension to the human zinc proteome. Predicted zinc sites need to be verified experimentally. The metal can be absent or sites may bind metal ions other than zinc because protein coordination environments do not have absolute specificity for zinc. The metaphor of the "galvanization of biology" continues to gain prominence in terms of the sheer number of approximately 3000 human zinc proteins and their annotation with new functions. Clearly, description of zinc proteomes cannot be pursued solely in silico and requires zinc proteomics, an integrated scientific approach. Progress hinges on a combination of bioinformatics, biology, and significantly, analytical and structural chemistry.
"Platinum on the road": Interactions of antitumoral cisplatin with proteins
Authors: Arnesano Fabio , Natile Giovanni 
Published: December 2008

Abstract
When the antitumor activity of cisplatin was discovered, no one would have thought of the existence of specific proteins able to transport Pt across the cell membrane or to specifically recognize DNA modified by this drug. However, such proteins do exist and, furthermore, are specific for the Pt substrate considered. It follows that proteins are deeply involved in managing the biological activity of cisplatin. It is expected that, after the first 20 years in which most of the efforts were devoted to understanding its mode of interaction with DNA and consequent structural and functional alterations, the role of proteins will be more deeply scavenged. How cisplatin can survive the attack of the many platinophiles present in the extracellular and intracellular media is the issue addressed in this article. Significantly, differences are observed between cisplatin, carboplatin, and oxaliplatin.
HPL-2/HP1 Prevents Inappropriate Vulval Induction in Caenorhabditis elegans by Acting in Both HYP7 and Vulval Precursor Cells
Authors: Schott Sonia , Ramos Fabien , Coustham Vincent , Palladino Francesca 
Published: December 2008

Abstract
A current model for Caenorhabditis elegans vulval cell fate specification is that SynMuv genes act redundantly in the hyp7 hypodermal syncytium to repress the LIN-3/EGF inducer and prevent ectopic vulval induction of vulva precursor cells (VPCs). Here we show that the SynMuv gene hpl-2/HP1 has an additional function in VPCs, where it may act through target genes including LIN-39/Hox.
Detailed Recombination Studies Along Chromosome 3B Provide New Insights on Crossover Distribution in Wheat (Triticum aestivum L.)
Authors: Saintenac Cyrille , Falque Matthieu , Martin Olivier C , Paux Etienne , Feuillet Catherine , Sourdille Pierre 
Published: December 2008

Abstract
In wheat (Triticum aestivum L.), the crossover (CO) frequency increases gradually from the centromeres to the telomeres. However, little is known about the factors affecting both the distribution and the intensity of recombination along this gradient. To investigate this, we studied in detail the pattern of CO along chromosome 3B of bread wheat. A dense reference genetic map comprising 102 markers homogeneously distributed along the chromosome was compared to a physical deletion map. Most of the COs (90%) occurred in the distal subtelomeric regions that represent 40% of the chromosome. About 27% of the proximal regions surrounding the centromere showed a very weak CO frequency with only three COs found in the 752 gametes studied. Moreover, we observed a clear decrease of CO frequency on the distal region of the short arm. Finally, the intensity of interference was assessed for the first time in wheat using a Gamma model. The results showed m values of 1.2 for male recombination and 3.5 for female recombination, suggesting positive interference along wheat chromosome 3B.
Cis-regulatory Variation Is Typically Polyallelic in Drosophila
Authors: Gruber Jonathan D , Long Anthony D 
Published: December 2008

AbstractGene expression levels vary heritably, with ∼25–35% of the loci affecting expression acting in cis. We characterized standing cis-regulatory variation among 16 wild-derived strains of Drosophila melanogaster. Our experiment's robust biological and technical replication enabled precise estimates of variation in allelic expression on a high-throughput SNP genotyping platform. We observed concordant, significant differential allelic expression (DAE) in 7/10 genes queried with multiple SNPs, and every member of a set of eight additional, one-assay genes suggest significant DAE. Four of the high-confidence, multiple-assay genes harbor three or more statistically distinguishable allelic classes, often at intermediate frequency. Numerous intermediate-frequency, detectable regulatory polymorphisms cast doubt on a model in which cis-acting variation is a product of deleterious mutations of large effect. Comparing our data to predictions of population genetics theory using coalescent simulations, we estimate that a typical gene harbors 7–15 cis-regulatory sites (nucleotides) at which a selectively neutral mutation would elicit an observable expression phenotype. If standing cis-regulatory variation is actually slightly deleterious, the true mutational target size is larger.
Mcm10 Mediates the Interaction Between DNA Replication and Silencing Machineries
Authors: Liachko Ivan , Tye Bik K 
Published: December 2008

Abstract
The connection between DNA replication and heterochromatic silencing in yeast has been a topic of investigation for &gt;20 years. While early studies showed that silencing requires passage through S phase and implicated several DNA replication factors in silencing, later works showed that silent chromatin could form without DNA replication. In this study we show that members of the replicative helicase (Mcm3 and Mcm7) play a role in silencing and physically interact with the essential silencing factor, Sir2, even in the absence of DNA replication. Another replication factor, Mcm10, mediates the interaction between these replication and silencing proteins via a short C-terminal domain. Mutations in this region of Mcm10 disrupt the interaction between Sir2 and several of the Mcm2–7 proteins. While such mutations caused silencing defects, they did not cause DNA replication defects or affect the association of Sir2 with chromatin. Our findings suggest that Mcm10 is required for the coupling of the replication and silencing machineries to silence chromatin in a context outside of DNA replication beyond the recruitment and spreading of Sir2 on chromatin.