bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the evolutionary rate of positional orthologous genes in prokaryotes using synteny data
Authors: Lemoine Frédéric , Lespinet Olivier , Labedan Bernard 
Published: November 2007

AbstractBackgroundComparison of completely sequenced microbial genomes has revealed how fluid these genomes are. Detecting synteny blocks requires reliable methods to determining the orthologs among the whole set of homologs detected by exhaustive comparisons between each pair of completely sequenced genomes. This is a complex and difficult problem in the field of comparative genomics but will help to better understand the way prokaryotic genomes are evolving.ResultsWe have developed a suite of programs that automate three essential steps to study conservation of gene order, and validated them with a set of 107 bacteria and archaea that cover the majority of the prokaryotic taxonomic space. We identified the whole set of shared homologs between two or more species and computed the evolutionary distance separating each pair of homologs. We applied two strategies to extract from the set of homologs a collection of valid orthologs shared by at least two genomes. The first computes the Reciprocal Smallest Distance (RSD) using the PAM distances separating pairs of homologs. The second method groups homologs in families and reconstructs each family's evolutionary tree, distinguishingbona fideorthologs as well as paralogs created after the last speciation event. Although the phylogenetic tree method often succeeds where RSD fails, the reverse could occasionally be true. Accordingly, we used the data obtained with either methods or their intersection to number the orthologs that are adjacent in for each pair of genomes, the Positional Orthologous Genes (POGs), and to further study their properties. Once all these synteny blocks have been detected, we showed that POGs are subject to more evolutionary constraints than orthologs outside synteny groups, whichever the taxonomic distance separating the compared organisms.ConclusionThe suite of programs described in this paper allows a reliable detection of orthologs and is useful for evaluating gene order conservation in prokaryotes whichever their taxonomic distance. Thus, our approach will make easy the rapid identification of POGS in the next few years as we are expecting to be inundated with thousands of completely sequenced microbial genomes.
Treatment outcome of new pulmonary tuberculosis in Guangzhou, China 1993–2002: a register-based cohort study
Authors: Bao Qing-Song , Du Yu-Hua , Lu Ci-Yong 
Published: November 2007

Abstract

Background
Completion of treatment for tuberculosis (TB) is of utmost priority for TB control programs. The aims of this study were to evaluate the treatment outcome of TB cases registered in Guangzhou during the period 1993–2002, and to identify factors associated with treatment success.

Methods
Two (of eight) districts in Guangzhou were selected randomly as objects of study and their surveillance database was analyzed to assess the treatment outcome and identify factors associated with treatment success for TB cases registered in Guangzhou. Six treatment outcome criteria were assessed based on guidelines set by the World Health Organization (WHO). Logistic regression was used to estimate risk factors for treatment outcome.

Results
A total of 6743 pulmonary tuberculosis cases (4903 males, 1840 females) were included in this study. The treatment success rate (including cured and complete treatment) was 88% (95%CI 87%–89%). One hundred and eight-six (2.8%) patients died and 401 (5.9%) patients defaulted treatment. In multivariate analysis, treatment success was found to be associated with young age, lack of cavitation and compliance with treatment.

Conclusion
The total treatment success rate in the current study was similar to the WHO target for all smear positive cases, while the failure rate and the default rate in 2002 were slightly higher. Good care of elderly patients, early diagnosis of cavitation and compliance with treatment could improve the success rate of TB treatment.
Selecting process quality indicators for the integrated care of vulnerable older adults affected by cognitive impairment or dementia
Authors: Kröger Edeltraut , Tourigny André , Morin Diane , Côté Lise , Kergoat Marie-Jeanne , Lebel Paule , Robichaud Line , Imbeault Shirley , Proulx Solange , Benounissa Zohra 
Published: November 2007

Abstract

Background
This study aimed at evaluating face and content validity, feasibility and reliability of process quality indicators developed previously in the United States or other countries. The indicators can be used to evaluate care and services for vulnerable older adults affected by cognitive impairment or dementia within an integrated service system in Quebec, Canada.

Methods
A total of 33 clinical experts from three major urban centres in Quebec formed a panel representing two medical specialties (family medicine, geriatrics) and seven health or social services specialties (nursing, occupational therapy, psychology, neuropsychology, pharmacy, nutrition, social work), from primary or secondary levels of care, including long-term care. A modified version of the RAND®/University of California at Los Angeles (UCLA) appropriateness method, a two-round Delphi panel, was used to assess face and content validity of process quality indicators. The appropriateness of indicators was evaluated according to a) agreement of the panel with three criteria, defined as a median rating of 7–9 on a nine-point rating scale, and b) agreement among panellists, judged by the statistical measure of the interpercentile range adjusted for symmetry. Feasibility of quality assessment and reliability of appropriate indicators were then evaluated within a pilot study on 29 patients affected by cognitive impairment or dementia. For measurable indicators the inter-observer reliability was calculated with the Kappa statistic.

Results
Initially, 82 indicators for care of vulnerable older adults with cognitive impairment or dementia were submitted to the panellists. Of those, 72 (88%) were accepted after two rounds. Among 29 patients for whom medical files of the preceding two years were evaluated, 63 (88%) of these indicators were considered applicable at least once, for at least one patient. Only 22 indicators were considered applicable at least once for ten or more out of 29 patients. Four indicators could be measured with the help of a validated questionnaire on patient satisfaction. Inter-observer reliability was moderate (Kappa = 0.57).

Conclusion
A multidisciplinary panel of experts judged a large majority of the initial indicators valid for use in integrated care systems for vulnerable older adults in Quebec, Canada. Most of these indicators can be measured using patient files or patient or caregiver interviews and reliability of assessment from patient-files is moderate.
Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage
Authors: Pelizon Ana Cláudia , Martins Douglas R , Zorzella Sofia FG , Trombone Ana Paula F , Lorenzi Júlio CC , Carvalho Robson F , Brandão Izaíra T , Coelho-Castelo Arlete AM , Silva Célio L , Sartori Alexandrina 
Published: November 2007

AbstractBackgroundVaccination of neonates is generally difficult due to the immaturity of the immune system and consequent higher susceptibility to tolerance induction. Genetic immunization has been described as an alternative to trigger a stronger immune response in neonates, including significant Th1 polarization. In this investigation we analysed the potential use of a genetic vaccine containing the heat shock protein (hsp65) fromMycobacterium leprae(pVAXhsp65) against tuberculosis (TB) in neonate mice. Aspects as antigen production, genomic integration and immunogenicity were evaluated.MethodsHsp65 message and genomic integration were evaluated by RT-PCR and Southern blot, respectively. Immunogenicity of pVAXhsp65 alone or combined with BCG was analysed by specific induction of antibodies and cytokines, both quantified by ELISA.ResultsThis DNA vaccine was transcribed by muscular cells of neonate mice without integration into the cellular genome. Even though this vaccine was not strongly immunogenic when entirely administered (three doses) during early animal's life, it was not tolerogenic. In addition, pVAXhsp65 and BCG were equally able to prime newborn mice for a strong and mixed immune response (Th1 + Th2) to pVAXhsp65 boosters administered later, at the adult life.ConclusionThese results suggest that pVAXhsp65 can be safely used as a priming stimulus in neonate animals in prime-boost similar strategies to control TB. However, priming with BCG or pVAXhsp65, directed the ensuing immune response triggered by an heterologous or homologous booster, to a mixed Th1/Th2 pattern of response. Measures as introduction of IL-12 or GM-CSF genes in the vaccine construct or even IL-4 neutralization, are probably required to increase the priming towards Th1 polarization to ensure control of tuberculosis infection.
Interspecies and intraspecies transmission of triple reassortant H3N2 influenza A viruses
Authors: Yassine Hadi M , Al-Natour Mohammad Q , Lee Chang-Won , Saif Yehia M 
Published: November 2007

1. Abstract
The triple reassortant H3N2 viruses were isolated for the first time from pigs in 1998 and are known to be endemic in swine and turkey populations in the United States. In 2004, we isolated two H3N2 triple reassortant viruses from two turkey breeder flocks in Ohio and Illinois. Infected hens showed no clinical signs, but experienced a complete cessation of egg production. In this study, we evaluated three triple reassortant H3N2 isolates of turkey origin and one isolate of swine origin for their transmission between swine and turkeys. Although all 4 viruses tested share high genetic similarity in all 8 genes, only the Ohio strain (A/turkey/Ohio/313053/04) was shown to transmit efficiently both ways between swine and turkeys. One isolate, A/turkey/North Carolina/03, was able to transmit from pigs to turkeys but not vice versa. Neither of the other two viruses transmitted either way. Sequence analysis of the HA1 gene of the Ohio strain showed one amino acid change (D to A) at residue 190 of the receptor binding domain upon transmission from turkeys to pigs. The Ohio virus was then tested for intraspecies transmission in three different avian species. The virus was shown to replicate and transmit among turkeys, replicate but does not transmit among chickens, and did not replicate in ducks. Identifying viruses with varying inter- and intra-species transmission potential should be useful for further studies on the molecular basis of interspecies transmission.
Characteristics of Urologists Predict the Use of Androgen Deprivation Therapy for Prostate Cancer
Authors: Shahinian Vahakn B. , Kuo Yong-fang , Freeman Jean L. , Orihuela Eduardo , Goodwin James S. 
Published: November 2007

Purpose We previously have reported wide variations among urologists in the use of androgen deprivation for prostate cancer. Using the Surveillance, Epidemiology, and End Results–Medicare linked database, we examined how individual urologist characteristics influenced the use of androgen deprivation therapy. Methods Participants included 82,375 men with prostate cancer who were diagnosed from January 1, 1992, through December 31, 2002, and the 2,080 urologists who provided care to them. Multilevel analyses were used to estimate the likelihood of androgen deprivation use within 6 months of diagnosis in the overall cohort, in a subgroup in which use would be of uncertain benefit (primary therapy for localized prostate cancer), and in a subgroup in which use would be evidence-based (adjuvant therapy with radiation for locally advanced disease). Results In the overall cohort of patients, a multilevel model adjusted for patient characteristics, tumor characteristics, and urologist characteristics (eg, board certification, academic affiliation, patient panel size, years since medical school graduation) showed that the likelihood of androgen deprivation use was significantly greater for patients who saw urologists without an academic affiliation. This pattern also was noted when the analysis was limited to settings in which androgen deprivation would have been of uncertain benefit. Odds ratios for use in that context were 1.66 (95% CI, 1.27 to 2.16) for urologists with no academic affiliation and 1.45 (95% CI, 1.13 to 1.85) for urologists with minor versus major academic affiliations. Conclusion Use of androgen deprivation for prostate cancer varies by the characteristics of the urologist. Patients of non–academically affiliated urologists were significantly more likely to receive primary androgen deprivation therapy for localized prostate cancer, a setting in which the benefits are uncertain.
Phase II Study of Uracil-Tegafur With Leucovorin in Elderly (≥ 75 years old) Patients With Colorectal Cancer: ECOG 1299
Authors: Hochster Howard S. , Luo Weixiu , Popa Elizabeta C. , Lyman Bruce T. , Mulcahy Mary , Beatty Peter A. , Benson Al Bowen 
Published: November 2007

Purpose To evaluate the tolerability and effectiveness of uracil-tegafur (UFT) with leucovorin (LV) in the treatment of elderly patients with advanced colorectal cancer. Patients and Methods Patients ≥ 75 years of age with previously untreated colorectal cancer were eligible for this phase II, single-arm, open-label, multicenter cooperative group clinical trial. UFT 100 mg/m2 plus LV 30 mg orally every 8 hours for 28 days every 35 days was administered until progression. Results Fifty-eight patients were enrolled between June 2000 and July 2001, and 55 were treated. The median age of treated patients was 81 years (range, 75 to 90 years), 26 patients were (47%) women, and 80% had good performance status (0 to 1). The observed overall response rate was 22% (95% CI, 11.8% to 35.0%). The estimated median overall survival time was 13.0 months (95% CI, 9.6 to 17.4 months), and median progression-free survival time was 4.6 months (95% CI, 2.6 to 6.7 months). Among the 56 treated patients (including one ineligible patient), 31 (55%) experienced grade 3 to 4 toxicities, most commonly diarrhea (25%) and GI toxicity (36%), with patients older than 85 years of age at highest risk. Conclusion The results of this trial support the efficacy of oral UFT/LV in elderly patients with colorectal cancer. The regimen is tolerated moderately well overall, particularly as compared with other fluoropyrimidine regimens, although there is increased GI toxicity in the most elderly. These results suggest that studies using newer oral fluoropyrimidine analogs should be investigated in this patient population.
Long-Term Toxicity Monitoring via Electronic Patient-Reported Outcomes in Patients Receiving Chemotherapy
Authors: Basch Ethan , Iasonos Alexia , Barz Allison , Culkin Ann , Kris Mark G. , Artz David , Fearn Paul , Speakman John , Farquhar Rena , Scher Howard I. , McCabe Mary , Schrag Deborah 
Published: November 2007

Purpose In cancer treatment trials, clinicians traditionally report patient toxicity symptoms. Alternatively, patients could provide this information directly. Patients and Methods The Common Terminology Criteria for Adverse Events (CTCAE) is the mandated instrument for tracking patient toxicity symptoms in National Cancer Institute (NCI)-sponsored cancer treatment trials. We adapted CTCAE symptom items into patient language and uploaded these to an online platform. Lung cancer outpatients receiving chemotherapy were invited to self-report selected symptoms at visits via waiting area computers or optional home access. Symptom reports were printed for nurses at visits, but no instructions were given with regard to use of this information. Results From June 2005 through March 2006, 125 patients were invited to participate, and 107 chose to enroll. Mean length of participation was 42 weeks (range, 1 to 71 weeks), by which time 35% died. The average number of clinic visits was 12 (range, 1 to 40 visits). At each consecutive visit, most patients (mean, 78%) logged in without significant attrition. Reasons for failure to log in included having no reminder and having inadequate time. Although 76% of enrollees had home computers, only 15% self-reported from home. Satisfaction with the system was high (90%), but only 51% felt communication was improved. All participating nurses understood the reports and felt this information was useful for clinical decisions, documentation, and discussions. However, only one of seven nurses discussed reports with patients frequently, with insufficient time being the most common barrier to discussions. Conclusion Online patient self-reporting is a feasible long-term strategy for toxicity symptom monitoring during chemotherapy, even among patients with advanced cancer and high symptom burdens. However, without explicit reminders and clinician feedback, patients demonstrated limited voluntary interest in self-reporting between visits.
Prospective Study of Long-Term Impact of Adjuvant High-Dose and Conventional-Dose Chemotherapy on Health-Related Quality of Life
Authors: Buijs Ciska , Rodenhuis Sjoerd , Seynaeve Caroline M. , van Hoesel Quirinus G.C.M. , van der Wall Elsken , Smit Wim J.M. , Nooij Marianne A. , Voest Emile , Hupperets Pierre , TenVergert Els M. , van Tinteren Harm , Willemse Pax H.B. , Mourits Marian J.E. , Aaronson Neil K. , Post Wendy J. , de Vries Elisabeth G.E. 
Published: November 2007

Purpose To evaluate and compare health-related quality of life (HRQOL) after conventional- and high-dose adjuvant chemotherapy in patients with high-risk breast cancer. Patients and Methods Patients were randomly assigned to either a conventional or high-dose chemotherapy regimen; both regimens were followed by radiotherapy and tamoxifen. HRQOL was evaluated until disease progression using the Short Form-36 (SF-36), Visual Analog Scale, and Rotterdam Symptom Checklist and assessed every 6 months for 5 years after random assignment. For the SF-36, data from healthy Dutch women with the same age distribution served as reference values. Results Eight hundred four patients (conventional-dose chemotherapy, n = 405; high-dose chemotherapy, n = 399) were included. Median follow-up time was 57 months. Directly after high-dose chemotherapy, HRQOL decreased more compared with conventional chemotherapy for all SF-36 subscales. After 1 year, the reference value of healthy women was reached in both groups. Small differences were observed between the two groups in the role-physical and role-emotional subscales, but 1 year after treatment, these differences were minor and not clinically relevant. During follow-up, patients with a lower educational level and many complaints before chemotherapy experienced a worse HRQOL. Conclusion Shortly after high-dose chemotherapy, HRQOL was more affected than after conventional-dose chemotherapy. One year after random assignment, differences were negligible. Identifying patients who have a higher chance of persistent impaired quality of life after treatment (which, in the present study, included patients with a lower educational level and many complaints before chemotherapy) is important and may open the way for better patient-tailored prevention strategies.
Quantitative Justification of the Change From 10% to 30% for Human Epidermal Growth Factor Receptor 2 Scoring in the American Society of Clinical Oncology/College of American Pathologists Guidelines: Tumor Heterogeneity in Breast Cancer and Its Implications for Tissue Microarray–Based Assessment of Outcome
Authors: Moeder Christopher B. , Giltnane Jennifer M. , Harigopal Malini , Molinaro Annette , Robinson Andrew , Gelmon Karen , Huntsman David , Camp Robert L. , Rimm David L. 
Published: November 2007

Purpose The variability in scoring of immunohistochemistry, whether a result of true heterogeneity or artifacts in preparation, has led to decreased reliability in companion diagnostics and the recommendation for new standards (eg, the American Society of Clinical Oncology/College of American Pathologists [ASCO-CAP] guidelines). The basis of this problem is the amount of tissue required to be representative of an entire tumor. Because protein expression on tissue microarrays (TMAs) can be rigorously measured and one 0.6-mm spot is equivalent to two to three high-power fields, we used TMAs to assess levels of heterogeneity and to determine optimal representation as a function of outcome. Patients and Methods We analyzed estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER-2) expression in two cohorts (n = 676 and n = 152) on a series of four to five separate TMA cores and assessed heterogeneity by linear regression analysis. Minimum, average, and maximum scores were generated for each set, which were then assessed for prognostic and predictive value. Results Each marker shows some heterogeneity, but average r values between 0.7 and 0.8 are seen between TMA spots. Analysis for prognostic value shows that the highest maximum score (of five spots) is the most prognostic for ER, whereas a high HER-2 minimum score is most prognostic for poor outcome and most predictive of response to trastuzumab. Conclusion These results suggest that the representivity required for each biomarker may be a function of its role in tumorigenesis. Furthermore, these results provide scientific basis for the ASCO-CAP guidelines for assessment of HER-2 expression but perhaps suggest that the 30% figure is still too conservative.
Meeting the Quality Assurance Challenges of the 1980s: Team Auditing by Toxicologists and QA Professionals
Authors: Hoover B. Kristin , Baldwin Judith K. 
Published: November 2007

The major challenge of the 1980s is to continue to provide a productive contribution to the conduct of scientific research. Major factors that may be expected to affect the ability of quality assurance to meet this challenge are economics, ever changing and expanding regulatory requirements, increasing test complexity, computerization, and continuing product liability needs. Team auditing is an effective way to utilize resources to meet the requirements imposed by these factors. This approach results in a highly cost-efficient use of personnel in order to accomplish large and difficult tasks in a short period of time. In addition, it can decrease the need for large-scale training programs and be used as a method for upgrading present staff expertise. Individual perspectives are broadened as team members learn from each other. Morale is improved as the professional isolation of working alone or in small units is overcome. If team auditing is to be successful, it must be properly planned and executed. The team must be selected, objectives established, methods defined, and time constraints determined. These factors and ways to build a cohesive audit team capable of accomplishing specific goals will be discussed in detail. In addition, useful applications of this approach will be suggested.