bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolation and Characterization of FecA- and FeoB-Mediated Iron Acquisition Systems of the SpirocheteLeptospira biflexaby Random Insertional Mutagenesis
Authors: Louvel Hélène , Saint Girons Isabelle , Picardeau Mathieu 
Published: April 2005

ABSTRACTThe specific mechanisms by whichLeptospiraspp. acquire iron from their ecological niches are unknown. A major factor contributing to our ignorance of spirochetal biology is the lack of methods for genetic analysis of these organisms. In this study, we have developed a system for random transposon mutagenesis ofLeptospira biflexausing amarinertransposon,Himar1. To demonstrate the validity ofHimar1in vivo transposon mutagenesis inL. biflexa, a screen of mutants for clones impaired in amino acid biosynthesis was first performed, enabling the identification of tryptophan and glutamate auxotrophs. To investigate iron transporters, 2,000L. biflexatransposon mutants were screened onto media with and without hemin, thus allowing the identification of five hemin-requiring mutants, and the putative genes responsible for this phenotype were identified. Three mutants had distinct insertions in a gene encoding a protein which shares homology with the TonB-dependent receptor FecA, involved in ferric citrate transport. We also identified two mutants with aHimar1insertion into afeoB-like gene, the product of which is required for ferrous iron uptake in many bacterial organisms. Interestingly, the growth inhibition exhibited by thefecAandfeoBmutants was relieved by deferoxamine, suggesting the presence of a ferric hydroxamate transporter. These results confirm the importance of iron for the growth ofLeptospiraand its ability to use multiple iron sources.
Random Insertional Mutagenesis ofLeptospira interrogans, the Agent of Leptospirosis, Using amarinerTransposon
Authors: Bourhy Pascale , Louvel Hélène , Saint Girons Isabelle , Picardeau Mathieu 
Published: April 2005

ABSTRACTThe recent availability of the complete genome sequences ofLeptospira interrogans, the agent of leptospirosis, has allowed the identification of several putative virulence factors. However, to our knowledge, attempts to carry out gene transfer in pathogenicLeptospiraspp. have failed so far. In this study, we show that theHimar1 marinertransposon permits random mutagenesis in the pathogenL. interrogans. We have identified genes that have been interrupted byHimar1insertion in 35L. interrogansmutants. This approach of transposon mutagenesis will be useful for understanding the spirochetal physiology and the pathogenic mechanisms ofLeptospira, which remain largely unknown.
Prospective noise induced changes to hearing among construction industry apprentices
Authors: Seixas N S , Goldman B , Sheppard L , Neitzel R , Norton S , Kujawa S G 
Published: April 2005

Aims:To characterise the development of noise induced damage to hearing.Methods:Hearing and noise exposure were prospectively monitored among a cohort of newly enrolled construction industry apprentices and a comparison group of graduate students, using standard pure tone audiometry and distortion product otoacoustic emissions (DPOAEs). A total of 328 subjects (632 ears) were monitored annually an average of 3.4 times. In parallel to these measures, noise exposure and hearing protection device (HPD) use were extensively monitored during construction work tasks. Recreational/non-occupational exposures also were queried and monitored in subgroups of subjects. Trade specific mean exposure Leqlevels, with and without accounting for the variable use of hearing protection in each trade, were calculated and used to group subjects by trade specific exposure level. Mixed effects models were used to estimate the change in hearing outcomes over time for each exposure group.Results:Small but significant exposure related changes in DPOAEs over time were observed, especially at 4 kHz with stimulus levels (L1) between 50 and 75 dB, with less clear but similar patterns observed at 3 kHz. After controlling for covariates, the high exposure group had annual changes in 4 kHz emissions of about 0.5 dB per year. Pure tone audiometric thresholds displayed only slight trends towards increased threshold levels with increasing exposure groups. Some unexpected results were observed, including an apparent increase in DPOAEs among controls over time, and improvement in behavioural thresholds among controls at 6 kHz only.Conclusions:Results indicate that construction apprentices in their first three years of work, with average noise exposures under 90 dBA, have measurable losses of hearing function. Despite numerous challenges in using DPOAEs for hearing surveillance in an industrial setting, they appear somewhat more sensitive to these early changes than is evident with standard pure tone audiometry.
Epirubicin Increases Long-Term Survival in Adjuvant Chemotherapy of Patients With Poor-Prognosis, Node-Positive, Early Breast Cancer: 10-Year Follow-Up Results of the French Adjuvant Study Group 05 Randomized Trial
Authors: Bonneterre Jacques , Roché Henri , Kerbrat Pierre , Brémond Alain , Fumoleau Pierre , Namer Moïse , Goudier Marie-Josèphe , Schraub Simon , Fargeot Pierre , Chapelle-Marcillac Isabelle 
Published: April 2005

Purpose The French Adjuvant Study Group 05 (FASG-05) showed that fluorouracil 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 100 mg/m2 (FEC 100) was superior to the same regimen with epirubicin 50 mg/m2 (FEC 50) in terms of disease-free survival (DFS) and overall survival (OS) in adjuvant treatment of early breast cancer. We report 10-year data on efficacy, and long-term side effects for FASG-05. Patients and Methods We randomly assigned 565 patients to treatment with FEC 50 or FEC 100 after surgery. Postmenopausal patients also received tamoxifen for 3 years, and almost all patients (96%) also received radiotherapy. Results Median follow-up was 110 months. The 10-year DFS was 45.3% (95% CI, 41.9% to 48.7%) with FEC 50 and 50.7% (95% CI, 47.3% to 54.1%) with FEC 100 (Wilcoxon P = .036; log-rank P = .08). The 10-year OS was 50.0% (95% CI, 46.7% to 53.3%) with FEC 50 and 54.8% (95% CI, 51.3% to 58.3%) with FEC 100 (Wilcoxon P = .038; log-rank P = .05). Delayed cardiac toxicity (before relapse) occurred in four patients (1.5%) in the FEC 50 arm and three patients (1.1%) in the FEC 100 arm. Cardiac toxicity after relapse occurred in six (4.3%) and five (4.1%) patients treated with FEC 50 and FEC 100, respectively. Conclusion Treatment with adjuvant FEC 100 demonstrated superior DFS and OS versus FEC 50 at 10 years of follow-up. This survival advantage was not offset by long-term complications such as cardiac toxicity and second malignancy. Given the risk-benefit ratio, FEC 100 is a more optimal regimen for long-term survival in patients with poor prognosis.
Sentinel Node Biopsy After Neoadjuvant Chemotherapy in Breast Cancer: Results From National Surgical Adjuvant Breast and Bowel Project Protocol B-27
Authors: Mamounas Eleftherios P. , Brown Ann , Anderson Stewart , Smith Roy , Julian Thomas , Miller Barbara , Bear Harry D. , Caldwell Christopher B. , Walker Alonzo P. , Mikkelson Wendy M. , Stauffer Jay S. , Robidoux Andre , Theoret Heather , Sovan Atilla , Fisher Bernard , Wickerham D. Lawrence , Wolmark Norman 
Published: April 2005

Purpose Experience with sentinel node biopsy (SNB) after neoadjuvant chemotherapy is limited. We examined the feasibility and accuracy of this procedure within a randomized trial in patients treated with neoadjuvant chemotherapy. Patients and Methods During the conduct of National Surgical Adjuvant Breast and Bowel Project trial B-27, several participating surgeons attempted SNB before the required axillary dissection in 428 patients. All underwent lymphatic mapping and an attempt to identify and remove a sentinel node. Lymphatic mapping was performed with radioactive colloid (14.7%), with lymphazurin blue dye alone (29.9%), or with both (54.7%). Results Success rate for the identification and removal of a sentinel node was 84.8%. Success rate increased significantly with the use of radioisotope (87.6% to 88.9%) versus with the use of lymphazurin alone (78.1%, P = .03). There were no significant differences in success rate according to clinical tumor size, clinical nodal status, age, or calendar year of random assignment. Of 343 patients who had SNB and axillary dissection, the sentinel nodes were positive in 125 patients and were the only positive nodes in 70 patients (56.0%). Of the 218 patients with negative sentinel nodes, nonsentinel nodes were positive in 15 (false-negative rate, 10.7%; 15 of 140 patients). There were no significant differences in false-negative rate according to clinical patient and tumor characteristics, method of lymphatic mapping, or breast tumor response to chemotherapy. Conclusion These results are comparable to those obtained from multicenter studies evaluating SNB before systemic therapy and suggest that the sentinel node concept is applicable following neoadjuvant chemotherapy.
Prognostic Value of Histologic Subtypes in Renal Cell Carcinoma: A Multicenter Experience
Authors: Patard Jean-Jacques , Leray Emmanuelle , Rioux-Leclercq Nathalie , Cindolo Luca , Ficarra Vincenzo , Zisman Amnon , De La Taille Alexandre , Tostain Jacques , Artibani Walter , Abbou Claude C. , Lobel Bernard , Guillé François , Chopin Dominique K. , Mulders Peter F.A. , Wood Christopher G. , Swanson David A. , Figlin Robert A. , Belldegrun Arie S. , Pantuck Allan J. 
Published: April 2005

Purpose To analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience. Patients and Methods Four thousand sixty-three patients from eight international centers were included in this retrospective study. Histologic subtype (1997 International Union Against Cancer [UICC] criteria of tumor response), age, sex, TNM stage, Fuhrman grade, tumor size, Eastern Cooperative Oncology Goup performance status (ECOG PS), and overall survival were determined in all cases. The prognostic values of clear cell, papillary, and chromophobe histologic features were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively. Results Clear cell, papillary, and chromophobe carcinomas accounted for 3,564 (87.7%), 396 (9.7%) and 103 (2.5%) cases, respectively. In univariate analysis, a trend toward a better survival was observed when clear cell, papillary, and chromophobe histologies were considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, Fuhrman grade and ECOG PS, but not histology, were retained as independent prognostic variables (P < .001). Conclusion The stratification in three main renal cell carcinoma histologic subtypes as defined by the 1997 UICC–American Joint Committee on Cancer consensus should not be considered a major prognostic variable comparable to TNM stage, Fuhrman grade and ECOG PS.
Chemokine ReceptorCXCR4Expression in Colorectal Cancer Patients Increases the Risk for Recurrence and for Poor Survival
Authors: Kim Joseph , Takeuchi Hiroya , Lam Stella T. , Turner Roderick R. , Wang He-Jing , Kuo Christine , Foshag Leland , Bilchik Anton J. , Hoon Dave S.B. 
Published: April 2005

PurposeLiver metastasis is the predominant cause of colorectal cancer (CRC) related mortality. Chemokines, soluble factors that orchestrate hematopoetic cell movement, have been implicated in directing cancer metastasis, although their clinical relevance in CRC has not been defined. Our hypothesis was that the chemokine receptor CXCR4 expressed by CRC is a prognostic factor for poor disease outcome.MethodsCRC cell lines (n = 6) and tumor specimens (n = 139) from patients with different American Joint Committee on Cancer (AJCC) stages of CRC were assessed. Microarray screening of select specimens and cell lines identified CXCR4 as a prominent chemokine receptor. CXCR4 expression in tumor and benign specimens was assessed by quantitative real-time reverse transcription polymerase chain reaction and correlated with disease recurrence and overall survival.ResultsHigh CXCR4 expression in tumor specimens (n = 57) from AJCC stage I/II patients was associated with increased risk for local recurrence and/or distant metastasis (risk ratio, 1.35; 95% CI, 1.09 to 1.68; P = .0065). High CXCR4 expression in primary tumor specimens (n = 35) from AJCC stage IV patients correlated with worse overall median survival (9 months v 23 months; RR, 2.53; 95% CI, 1.19 to 5.40; P = .016). CXCR4 expression was significantly higher in liver metastases (n = 39) compared with primary CRC tumors (n = 100; P < .0001).ConclusionCXCR4, a well-characterized chemokine receptor for T-cells, is differentially expressed in CRC. CXCR4 gene expression in primary CRC demonstrated significant associations with recurrence, survival, and liver metastasis. The CXCR4-CXCL12 signaling mechanism may be clinically relevant for patients with CRC and represents a potential novel target for disease-directed therapy.
Phase II Clinical Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, in Metastatic and Locally Advanced Breast Cancer
Authors: Low Jennifer A. , Wedam Suparna B. , Lee James J. , Berman Arlene W. , Brufsky Adam , Yang Sherry X. , Poruchynsky Marianne S. , Steinberg Seth M. , Mannan Nitin , Fojo Tito , Swain Sandra M. 
Published: April 2005

Purpose Ixabepilone (BMS-247550) is an epothilone B analog that stabilizes microtubules and has antitumor activity in taxane-refractory patients in phase I studies. In a phase II trial, we evaluated the efficacy and safety of ixabepilone in women with metastatic and locally advanced breast cancer. Patients and Methods Breast cancer patients with measurable disease who had paclitaxel and/or docetaxel as prior neoadjuvant, adjuvant, or metastatic therapy were treated with ixabepilone at 6 mg/m2/d intravenously on days 1 through 5 every 3 weeks. Levels of glutamate (glu) -terminated and acetylated α-tubulin, markers of microtubule stabilization, were detected by Western blot and by immunohistochemistry in a subset of matched pre- and post-treatment tumor biopsies. Results Thirty-seven patients received 153 cycles of ixabepilone. The best responses were a complete response in one patient (3%), partial responses in seven patients (19%), and stable disease in 13 patients (35%). Grade 3 and 4 toxicities included neutropenia (35%), febrile neutropenia (14%), fatigue (14%), diarrhea (11%), nausea/vomiting (5%), myalgia/arthralgia (3%), and sensory neuropathy (3%). Two patients were removed from study because of prolonged grade 2 or 3 neurotoxicity, and three patients were removed from study for other grade 3 and 4 nonhematologic toxicities. Compared with baseline levels, levels of both glu-terminated and acetylated α-tubulin were increased in tumor biopsies performed after ixabepilone therapy. Conclusion An objective response was seen in 22% of the patients in a population who had been previously treated with a taxane. Sensory neuropathy was mild with grade 3 neurotoxicity rarely seen. Microtubule stabilization occurred in tumor biopsies after treatment with ixabepilone.
Risk Factors and Individual Probabilities of Melanoma for Whites
Authors: Cho Eunyoung , Rosner Bernard A. , Feskanich Diane , Colditz Graham A. 
Published: April 2005

Purpose Incidence and mortality of cutaneous melanoma is rising rapidly in the United States; therefore, identifying risk factors for melanoma and integrating them into a clinical and population risk estimation tool may help guide prevention efforts and identify participants for preventive interventions. Methods We examined risk factors for melanoma in three large prospective studies of women and men. We observed 152,949 women and 25,206 men free of cancer at baseline for up to 14 years. Results A total of 535 incident cases of invasive melanoma (444 women and 91 men) were included in the analysis. We combined the three studies to examine risk factors and to build a risk model to calculate melanoma risk score. Older age, male sex, family history of melanoma, higher number of nevi, history of severe sunburn, and light hair color were each associated with significantly elevated risk of melanoma and were included in the final risk prediction. Participants at the highest decile of risk had a more than three-fold increase in risk of melanoma compared with those in the lowest decile (observed relative risk, 3.61; expected relative risk, 4.20). The measure of discriminatory accuracy as summarized by an age-and sex-adjusted concordance statistic of 0.62 (95% CI, 0.58 to 0.65) indicated that the model had reasonable ability to differentiate those who will develop melanoma and those who will remain free from the disease. Conclusion We identified several risk factors for melanoma and developed statistical models with adequate performance and discriminatory accuracy.
Influence of Structure on the Unusual Spectral Behavior of 4-Dialkylamino-1,8-naphthalimide
Authors: Banthia Sandip , Samanta Anunay 
Published: April 2005

Abstract
Spectral behavior of 4-amino-1,8-naphthalimide derivatives differing in their amino functionality has been studied in different solvents with varying polarity. The results reveal that despite the +I effect of the methyl group, the charge-transfer absorption band maximum of N-ethyl-4-dimethylamino-1,8-naphthalimide (3) is blue-shifted with respect to that of the un-substituted and monoethyl-substituted derivatives, 1 and 2, respectively. AM1 calculations indicate a lower ground state dipole moment of 3 compared to 1 or 2. The single crystal structure of 3 suggests that low dipole moment and blue-shift of its CT maximum are due to twisting of the dimethylamino moiety relative to the 1,8-naphthalimide ring.
Interspecific competition and rarity in mudsnails: feeding interactions between and withinHydrobia acuta neglectaand sympatricHydrobiaspecies
Authors: Barnes R.S.K. 
Published: April 2005

AbstractUsing production of faecal pellets as a proxy for feeding rate, possible reciprocal effects of the widespread and abundant mudsnailsHydrobia ulvaeandHydrobia ventrosaon the rareHydrobia acuta neglectawere investigated under the sea‐water salinity conditions in which all three species occur naturally in East Anglia, UK.Over a density range equivalent to 1000–34 000 m−2,H. acutaandH. ventrosa(though notH. ulvae) at some point displayed an intraspecific reduction in egestion with increase in density. ForH. acuta, every 5000 extra snails above a threshold of 16 000 m−2reduced egestion by up to 8%; and forH. ventrosa, every 5000 extra snails above a threshold of 8000 m−2reduced egestion by an average 7%.Keeping the density of one test species constant at 4000 m−2whilst varying that of a sympatric one from 0 up to 30 000 m−2indicates thatH. ulvaehas a marked effect onH. acutaat all densities, decreasing its egestion by 10% for every 5000 m−2H. ulvaealso present, but thatH. acutahas no such reciprocal effect onH. ulvae.H. ventrosahad no effect on egestion inH. acuta, althoughH. acutadid have some minor effect onH. ventrosa, on average decreasing its egestion by 3% for every 5000 m−2H. acutapresent.The intensity of intraspecific competition withinH. acuta, therefore, exceeds that exerted onH. acutabyH. ventrosa, and likewise intraspecific effects withinH. ventrosagenerally outweigh any interspecific effect fromH. acuta. The effect ofH. ulvaeonH. acuta, however, exceeds that intraspecifically withinH. acuta.These results are discussed in relation to the rarity ofH. acuta neglecta.Copyright © 2005 John Wiley & Sons, Ltd.
The relationship of records in multiple databases to their usage or citedness
Authors: Hood William Wellesley , Wilson Concepción Shimizu 
Published: April 2005

AbstractPapers in journals are indexed in bibliographic databases in varying degrees of overlap. The question has been raised as to whether papers that appear in multiple databases (highly overlapping) are in any way more significant (such as being more highly cited) than papers that are indexed in few databases. This paper uses a dataset from fuzzy set theory to compare low overlap papers with high overlap ones, and finds that more highly overlapping papers are in fact more highly cited.
Somatic transgenesis in the avian model system
Authors: Ishii Yasuo , Mikawa Takashi 
Published: April 2005

AbstractThe chick embryo is a versatile model system, in which classical embryology can be combined with modern molecular approaches. In the last two decades, several efficient methods have been developed to introduce exogenous genes into the chick embryo. These techniques allow alteration of gene expression levels in a spatially and temporally restricted manner, thereby circumventing embryonic lethality and/or eliminating secondary effects in other tissues. Here, we present the current status of avian somatic transgenic techniques, focusing on electroporation and retrovirus‐mediated gene transfer. Electroporation allows quick and efficient gain‐of‐function studies based on transient misexpression of genes. Retroviral vectors, which are capable of integrating exogenous genes into the host chromosome, permit analysis of long‐term effects of gene misexpression. The variety of methods available for somatic transgenesis, along with the recent completion of the chicken genome, are transforming the chick embryo into one of the most attractive model systems to examine function of genes that are important for embryonic development. Birth Defects Research (Part C) 75:19–27, 2005. © 2005 Wiley‐Liss, Inc.
Epigenetic reprogramming throughout preimplantation development and consequences for assisted reproductive technologies
Authors: Wrenzycki Christine , Herrmann Doris , Lucas‐Hahn Andrea , Gebert Claudia , Korsawe Karin , Lemme Erika , Carnwath Joseph W. , Niemann Heiner 
Published: April 2005

AbstractKnowledge about preimplantation development is important both for basic reproductive biology and for practical applications, including livestock breeding and regenerative medicine. During preimplantation development, epigenetic modifications such as DNA methylation and histone modifications are involved in the regulation of imprinted and nonimprinted genes, in the initiation of X chromosome inactivation, and the adjustment of telomere length. The underlying events are particularly vulnerable to external factors. Characterization of expression profiles in in vivo–derived embryos of different developmental stages and understanding the mechanisms and dynamics underlying the reprogramming process are the first steps towards the analysis of the complex gene regulatory networks. They provide a baseline for the analysis of manipulated embryos of all mammalian species, including humans, to improve embryo technologies and related therapeutic applications. Birth Defects Research (Part C) 75:1–9, 2005. © 2005 Wiley‐Liss, Inc.