bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconstruction of xylose utilization pathway and regulons in Firmicutes
Authors: Gu Yang , Ding Yi , Ren Cong , Sun Zhe , Rodionov Dmitry A , Zhang Weiwen , Yang Sheng , Yang Chen , Jiang Weihong 
Published: April 2010

Abstract

Background
Many Firmicutes bacteria, including solvent-producing clostridia such as Clostridium acetobutylicum, are able to utilize xylose, an abundant carbon source in nature. Nevertheless, homology searches failed to recognize all the genes for the complete xylose and xyloside utilization pathway in most of them. Moreover, the regulatory mechanisms of xylose catabolism in many Firmicutes except Bacillus spp. still remained unclear.

Results
A comparative genomic approach was used to reconstruct the xylose and xyloside utilization pathway and analyze its regulatory mechanisms in 24 genomes of the Firmicutes. A novel xylose isomerase that is not homologous to previously characterized xylose isomerase, was identified in C. acetobutylicum and several other Clostridia species. The candidate genes for the xylulokinase, xylose transporters, and the transcriptional regulator of xylose metabolism (XylR), were unambiguously assigned in all of the analyzed species based on the analysis of conserved chromosomal gene clustering and regulons. The predicted functions of these genes in C. acetobutylicum were experimentally confirmed through a combination of genetic and biochemical techniques. XylR regulons were reconstructed by identification and comparative analysis of XylR-binding sites upstream of xylose and xyloside utilization genes. A novel XylR-binding DNA motif, which is exceptionally distinct from the DNA motif known for Bacillus XylR, was identified in three Clostridiales species and experimentally validated in C. acetobutylicum by an electrophoretic mobility shift assay.

Conclusions
This study provided comprehensive insights to the xylose catabolism and its regulation in diverse Firmicutes bacteria especially Clostridia species, and paved ways for improving xylose utilization capability in C. acetobutylicum by genetic engineering in the future.
Do coder characteristics influence validity of ICD-10 hospital discharge data?
Authors: Hennessy Deirdre A , Quan Hude , Faris Peter D , Beck Cynthia A 
Published: April 2010

Abstract

Background
Administrative data are widely used to study health systems and make important health policy decisions. Yet little is known about the influence of coder characteristics on administrative data validity in these studies. Our goal was to describe the relationship between several measures of validity in coded hospital discharge data and 1) coders' volume of coding (≥13,000 vs. <13,000 records), 2) coders' employment status (full- vs. part-time), and 3) hospital type.

Methods
This descriptive study examined 6 indicators of face validity in ICD-10 coded discharge records from 4 hospitals in Calgary, Canada between April 2002 and March 2007. Specifically, mean number of coded diagnoses, procedures, complications, Z-codes, and codes ending in 8 or 9 were compared by coding volume and employment status, as well as hospital type. The mean number of diagnoses was also compared across coder characteristics for 6 major conditions of varying complexity. Next, kappa statistics were computed to assess agreement between discharge data and linked chart data reabstracted by nursing chart reviewers. Kappas were compared across coder characteristics.

Results
422,618 discharge records were coded by 59 coders during the study period. The mean number of diagnoses per record decreased from 5.2 in 2002/2003 to 3.9 in 2006/2007, while the number of records coded annually increased from 69,613 to 102,842. Coders at the tertiary hospital coded the most diagnoses (5.0 compared with 3.9 and 3.8 at other sites). There was no variation by coder or site characteristics for any other face validity indicator. The mean number of diagnoses increased from 1.5 to 7.9 with increasing complexity of the major diagnosis, but did not vary with coder characteristics. Agreement (kappa) between coded data and chart review did not show any consistent pattern with respect to coder characteristics.

Conclusions
This large study suggests that coder characteristics do not influence the validity of hospital discharge data. Other jurisdictions might benefit from implementing similar employment programs to ours, e.g.: a requirement for a 2-year college training program, a single management structure across sites, and rotation of coders between sites. Limitations include few coder characteristics available for study due to privacy concerns.
Anopheles culicifacies breeding in brackish waters in Sri Lanka and implications for malaria control
Authors: Jude Pavilupillai J , Dharshini Sangaralingam , Vinobaba Muthuladchumy , Surendran Sinnathamby N , Ramasamy Ranjan 
Published: April 2010

Abstract

Background

Anopheles culicifacies is the major vector of both falciparum and vivax malaria in Sri Lanka, while Anopheles subpictus and certain other species function as secondary vectors. In Sri Lanka, An. culicifacies is present as a species complex consisting of species B and E, while An. subpictus exists as a complex of species A-D. The freshwater breeding habit of An. culicifacies is well established. In order to further characterize the breeding sites of the major malaria vectors in Sri Lanka, a limited larval survey was carried out at a site in the Eastern province that was affected by the 2004 Asian tsunami.

Methods
Anopheline larvae were collected fortnightly for six months from a brackish water body near Batticaloa town using dippers. Collected larvae were reared in the laboratory and the emerged adults were identified using standard keys. Sibling species status was established based on Y-chromosome morphology for An. culicifacies larvae and morphometric characteristics for An. subpictus larvae and adults. Salinity, dissolved oxygen and pH were determined at the larval collection site.

Results
During a six month study covering dry and wet seasons, a total of 935 anopheline larvae were collected from this site that had salinity levels up to 4 parts per thousand at different times. Among the emerged adult mosquitoes, 661 were identified as An. culicifacies s.l. and 58 as An. subpictus s.l. Metaphase karyotyping of male larvae showed the presence of species E of the Culicifacies complex, and adult morphometric analysis the presence of species B of the Subpictus complex. Both species were able to breed in water with salinity levels up to 4 ppt.

Conclusions
The study demonstrates the ability of An. culicifacies species E, the major vector of falciparum and vivax malaria in Sri Lanka, to oviposit and breed in brackish water. The sibling species B in the An. subpictus complex, a well-known salt water breeder and a secondary malaria vector in the country, was also detected at the same site. Since global warming and the rise in sea levels will further increase of inland brackish water bodies, the findings have significant implications for the control of malaria in Sri Lanka and elsewhere.
A retroviral mutagenesis screen identifies Cd74 as a common insertion site in murine B-lymphomas and reveals the existence of a novel IFNγ-inducible Cd74 isoform
Authors: Pyrz Magdalena , Wang Bruce , Wabl Matthias , Pedersen Finn Skou 
Published: April 2010

AbstractBackgroundInsertional mutagenesis screens in the mouse are an acknowledged approach to identify genes involved in the pathogenesis of cancer. The potential of these screens to identify genes causally involved in tumorigenesis is not only limited to the murine host, but many of these genes have also been proven to be involved in the oncogenic process in man.ResultsThrough an insertional mutagenesis screen applying murine leukemia viruses in mouse, we found thatCd74was targeted by proviral insertion in tumors of B-cell origin. This locus encodes a protein playing crucial roles in antigen presentation and B-cell homeostasis, and its deregulation is often associated with cancer in man. The distribution of insertions within theCd74locus prompted the identification of an alternative transcript initiated in intron 1 ofCd74encoding an N-terminally truncated Cd74 isoform in tissues from un-infected mice, and transcriptional activation assays revealed a positive effect on the novel intronic promoter by a formerly described intronic enhancer in theCd74locus. Furthermore, we show that the new Cd74 isoform is IFNγ inducible and that its expression is differentially regulated from the canonical Cd74 isoform at the transcriptional level.ConclusionsWe here identifyCd74as a common insertion site in murine B-lymphomas and describe a novel IFNγ-inducible murine Cd74 isoform differentially regulated from the canonical isoform and expressed under the control of an intronic promoter. The distribution and orientation of proviral insertion sites within theCd74locus underscores the causal involvement of the isoforms in the murine B-lymphomagenic process.
Identification of responsive gene modules by network-based gene clustering and extending: application to inflammation and angiogenesis
Authors: Gu Jin , Chen Yang , Li Shao , Li Yanda 
Published: April 2010

AbstractBackgroundCell responses to environmental stimuli are usually organized as relatively separate responsive gene modules at the molecular level. Identification of responsive gene modules rather than individual differentially expressed (DE) genes will provide important information about the underlying molecular mechanisms. Most of current methods formulate module identification as an optimization problem: find the active sub-networks in the genome-wide gene network by maximizing the objective function considering the gene differential expression and/or the gene-gene co-expression information. Here we presented a new formulation of this task: a group of closely-connected and co-expressed DE genes in the gene network are regarded as the signatures of the underlying responsive gene modules; the modules can be identified by finding the signatures and then recovering the "missing parts" by adding the intermediate genes that connect the DE genes in the gene network.ResultsClustEx, a two-step method based on the new formulation, was developed and applied to identify the responsive gene modules of human umbilical vein endothelial cells (HUVECs) in inflammation and angiogenesis models by integrating the time-course microarray data and genome-wide PPI data. It shows better performance than several available module identification tools by testing on the reference responsive gene sets. Gene set analysis of KEGG pathways, GO terms and microRNAs (miRNAs) target gene sets further supports the ClustEx predictions.ConclusionTaking the closely-connected and co-expressed DE genes in the condition-specific gene network as the signatures of the underlying responsive gene modules provides a new strategy to solve the module identification problem. The identified responsive gene modules of HUVECs and the corresponding enriched pathways/miRNAs provide useful resources for understanding the inflammatory and angiogenic responses of vascular systems.
Descriptive study of stress and satisfaction at work in the Saragossa university services and administration staff
Authors: Tricas Moreno Jose Miguel , Salavera Bordas Carlos , Lucha Lopez Ma Orosia , Vidal Peracho Concepcion , Lucha Lopez Ana Carmen , Estebanez de Miguel Elena , Bernues Vazquez Luis 
Published: April 2010

Abstract

Background
The notion of stress in connection with the work environment became an important topic during the 1970's, when the first studies on the subject were published and the term of work stress was first coined. In 1974, Freudenberger proposed the term burnout to refer to the condition of physical and emotional exhaustion, as well as the associated negative attitudes, resulting from the intense interaction in working with people. The aim of our study is to examine burnout and job satisfaction in Saragossa University Services and Administration Staff (SAS) and detect the main factors which could contribute to too much stress, because job stress has emerged as a major psychosocial influence on mental health, associated with burnout.

Methods
24 people from the Services and Administration Staff in the University of Saragossa participated in the study. The research was carried out during the implementation of a module on Stress Management organised by the University of Saragossa and commissioned to the Unit for Research in Physical Therapy (University School of Health Sciences) from that University. This research is an exploratory research to improve the stress management program. A personal interview was carried out and additionally, participants were given the Maslach Burnout Inventory and the Scale of Satisfaction at Work of Warr, Cook & Wall.

Results
However using small sample this is worth to state that participants present most of them low burnout levels in the burnout scale. Only in one person high exhaustion level was reflected, even though other seven showed mean levels; in the professional self-esteem section, most of them showed high self-esteem, with two cases of low self-esteem and five with mean level.
With regard to satisfaction people participating in the study show mean levels in intrinsic as much as in extrinsic factors and general satisfaction.

Conclusions
Services and Administration Staff from the University of Saragossa shows low burnout levels linked with high professional self-esteem and low emotional exhaustion and depersonalization.
It has been found also medium levels in work satisfaction probably related with the continuous quality improvement efforts in the academics environment to create protective factors in decreasing levels of job stress.
These results show that not only personality or temperament have an influence on burnout and stress, also the job conditions are related with these diseases. These aspects should be taken into account in the design of stress prevention programme at work.
Rapid and Direct Transport of Cell Surface APP to the Lysosome defines a novel selective pathway
Authors: Lorenzen Angela , Samosh Jonathan , Vandewark Kenneth , Anborgh Pieter H , Seah Claudia , Magalhaes Ana C , Cregan Sean P , Ferguson Stephen SG , Pasternak Stephen H 
Published: April 2010

Abstract

Background
A central feature of Alzheimer's disease is the cleavage of the amyloid precursor protein (APP) to form beta-amyloid peptide (Aβ) by the β-secretase and γ-secretase enzymes. Although this has been shown to occur after endocytosis of APP from the cell surface, the exact compartments of APP processing are not well defined. We have previously demonstrated that APP and γ-secretase proteins and activity are highly enriched in purified rat liver lysosomes. In order to examine the lysosomal distribution and trafficking of APP in cultured cells, we generated constructs containing APP fused to a C-terminal fluorescent protein tag and N-terminal HA-epitope tag. These were co-transfected with a panel of fluorescent-protein tagged compartment markers.

Results
Here we demonstrate using laser-scanning confocal microscopy that although APP is present throughout the endosomal/lysosomal system in transfected Cos7 and neuronal SN56 cell lines as well as in immunostained cultured mouse neurons, it is enriched in the lysosome. We also show that the Swedish and London mutations reduce the amount of APP in the lysosome. Surprisingly, in addition to its expected trafficking from the cell surface to the early and then late endosomes, we find that cell-surface labelled APP is transported rapidly and directly from the cell surface to lysosomes in both Cos7 and SN56 cells. This rapid transit to the lysosome is blocked by the presence of either the London or Swedish mutations.

Conclusions
These results demonstrate the presence of a novel, rapid and specific transport pathway from the cell surface to the lysosomes. This suggests that regulation of lysosomal traffic could regulate APP processing and that the lysosome could play a central role in the pathophysiology of Alzheimer's disease.
Increased Incidence of Visceral Metastases in Scottish Patients With BRCA1/2-Defective Ovarian Cancer: An Extension of the Ovarian BRCAness Phenotype
Authors: Gourley Charlie , Michie Caroline O. , Roxburgh Patricia , Yap Timothy A. , Harden Sharon , Paul Jim , Ragupathy Kalpana , Todd Radha , Petty Russell , Reed Nick , Hayward Richard L. , Mitchell Paul , Rye Tzyvia , Schellens Jan H.M. , Lubinski Jan , Carmichael James , Kaye Stan B. , Mackean Melanie , Ferguson Michelle 
Published: April 2010

Purpose To compare the frequency of visceral relapse of BRCA1/2-deficient ovarian cancer to that of nonhereditary controls. Patients and Methods All patients diagnosed in Scotland with epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC) and a germline BRCA1/2 mutation were identified. Those with previous malignancy were excluded. Each remaining patient who experienced relapse was matched with two nonhereditary controls. Results Seventy-nine patients with EOC/PPC and germline BRCA1/2 mutations were identified. Fifteen had inadequate clinical data, two had carcinosarcoma, 27 had previous breast cancer, and 16 were in remission. Of the remaining 19 patients who were BRCA1/2 deficient, 14 patients (74%) developed visceral metastases compared with six (16%) of 38 patients in the control group. The percentages of liver, lung, and splenic metastases were 53%, 32%, and 32%, respectively, in the patients compared with 5%, 3%, and 5%, respectively, in the controls. When events occurring outside the matched follow-up period were omitted, the percentages of visceral, liver, lung, and splenic metastases were 58%, 42%, 16%, and 32% in the patients compared with 5%, 0%, 0%, and 3% in controls (P < .001, P < .001, P = .066, and P = .011, respectively). In an independent validation set, the corresponding percentages of visceral, liver, lung, and splenic metastases were 63%, 46%, 13%, and 17% in the patients compared with 11%, 4%, 2%, and 2% in controls (P < .001, P < .001, P = .153, and P = .052, respectively). Conclusion Although sporadic EOC commonly remains confined to the peritoneum, BRCA1/2-deficient ovarian cancer frequently metastasizes to viscera. These data extend the ovarian BRCAness phenotype, imply BRCA1/2-deficient ovarian cancer is biologically distinct, and suggest that patients with visceral metastases should be considered for BRCA1/2 sequencing.
Granulocyte Colony-Stimulating Factor (G-CSF) Treatment of Childhood Acute Myeloid Leukemias That Overexpress the Differentiation-DefectiveG-CSFReceptor Isoform IV Is Associated With a Higher Incidence of Relapse
Authors: Ehlers Stephanie , Herbst Christin , Zimmermann Martin , Scharn Nicole , Germeshausen Manuela , von Neuhoff Nils , Zwaan Christian Michel , Reinhardt Katarina , Hollink Iris H. , Klusmann Jan-Henning , Lehrnbecher Thomas , Roettgers Silja , Stary Jan , Dworzak Michael , Welte Karl , Creutzig Ursula , Reinhardt Dirk 
Published: April 2010

PurposeThis prospective, multicenter Acute Myeloid Leukemia Berlin-Frankfurt-Muenster (AML-BFM) 98 study randomly tested the ability of granulocyte colony-stimulating factor (G-CSF) to reduce infectious complications and to improve outcomes in children and adolescents with acute myeloid leukemia (AML). However, a trend toward an increased incidence of relapses in the standard-risk (SR) group after G-CSF treatment was observed.Patients and MethodsOf 154 SR patients in the AML-BFM 98 cohort, 50 patients were tested for G-CSF receptor (G-CSFR) RNA isoform I and IV expression, G-CSFR cell surface expression, and acquired mutations in the G-CSFR gene.ResultsIn patients randomly assigned to receive G-CSF after induction, 16 patients overexpressing the G-CSFR isoform IV showed an increased 5-year cumulative incidence of relapse (50% ± 13%) compared with 14 patients with low-level isoform IV expression (14% ± 10%; log-rank P = .04). The level of G-CSFR isoform IV had no significant effect in patients not receiving G-CSF (P = .19). Multivariate analyses of the G-CSF–treated subgroup, including the parameters G-CSFR isoform IV overexpression, sex, and favorable cytogenetics as covariables, revealed the prognostic relevance of G-CSFR isoform IV overexpression for 5-year event-free survival (P = .031) and the 5-year cumulative incidence of relapse (P = .049).ConclusionOur results demonstrate that children and adolescents with AMLs that overexpress the differentiation-defective G-CSFR isoform IV respond to G-CSF administration after induction, but with a significantly higher incidence of relapse.
Urologist Density and County-Level Urologic Cancer Mortality
Authors: Odisho Anobel Y. , Cooperberg Matthew R. , Fradet Vincent , Ahmad Ardalan E. , Carroll Peter R. 
Published: April 2010

Purpose The surgical work force distribution at the county level varies widely across the United States, and the impact of differential access on cancer outcomes is unclear. We used urologists as a test case because they are the first care providers for urologic cancers, can easily be identified from available data sources, and are unevenly distributed throughout the country. The goal of this study was to determine the effect of increasing urologist density on local prostate, bladder, and kidney cancer mortality. Patients and Methods Using county-level data from the Area Resource File, US Census, National Cancer Institute, and Centers for Disease Control, regression models were built for prostate, bladder, and kidney cancer mortality, controlling for categorized urologist density, county demographics, socioeconomic factors, and preexisting health care infrastructure. Results For each of the three cancers, there was a statistically significant cancer-specific mortality reduction associated with counties that had more than zero urologists (16% to 22% reduction for prostate cancer, 17% to 20% reduction for bladder cancer, and 8% to 14% reduction for kidney cancer with increasing urologist density) relative to zero urologists. However, increasing density greater than two urologists per 100,000 people had no statistically significant impact on mortality for any of the tumors studied. Conclusion The presence of a urologist is associated with lower mortality for urologic cancers in that county, but increasing urologist density does not yield further improvements. Therefore, a nuanced and geographically aware policy toward the size and distribution of the future work force is most likely to provide the greatest population-level improvement in cancer mortality outcomes.