bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of Avian-Pathogenic Escherichia coli Strain O1 Genomic Islands among Extraintestinal and Commensal E. coli Isolates
Authors: Johnson Timothy J. , Wannemuehler Yvonne , Kariyawasam Subhashinie , Johnson James R. , Logue Catherine M. , Nolan Lisa K. 
Published: March 2012

ABSTRACTEscherichia colistrains that cause disease outside the intestine are known as extraintestinal pathogenicE. coli(ExPEC) and include pathogens of humans and animals. Previously, the genome of avian-pathogenicE. coli(APEC) O1:K1:H7 strain O1, from ST95, was sequenced and compared to those of several otherE. colistrains, identifying 43 genomic islands. Here, the genomic islands of APEC O1 were compared to those of other sequencedE. colistrains, and the distribution of 81 genes belonging to 12 APEC O1 genomic islands among 828 human and avian ExPEC and commensalE. coliisolates was determined. Multiple islands were highly prevalent among isolates belonging to the O1 and O18 serogroups within phylogenetic group B2, which are implicated in human neonatal meningitis. Because of the extensive genomic similarities between APEC O1 and other human ExPEC strains belonging to the ST95 phylogenetic lineage, its ability to cause disease in a rat model of sepsis and meningitis was assessed. Unlike other ST95 lineage strains, APEC O1 was unable to cause bacteremia or meningitis in the neonatal rat model and was significantly less virulent than uropathogenicE. coli(UPEC) CFT073 in a mouse sepsis model, despite carrying multiple neonatal meningitisE. coli(NMEC) virulence factors and belonging to the ST95 phylogenetic lineage. These results suggest that host adaptation or genome modifications have occurred either in APEC O1 or in highly virulent ExPEC isolates, resulting in differences in pathogenicity. Overall, the genomic islands examined provide targets for further discrimination of the different ExPEC subpathotypes, serogroups, phylogenetic types, and sequence types.
Important Role for Mycobacterium tuberculosis UvrD1 in Pathogenesis and Persistence apart from Its Function in Nucleotide Excision Repair
Authors: Houghton Joanna , Townsend Carolin , Williams Alan R. , Rodgers Angela , Rand Lucinda , Walker K. Barry , Böttger Erik C. , Springer Burkhard , Davis Elaine O. 
Published: March 2012

ABSTRACTMycobacterium tuberculosissurvives and replicates in macrophages, where it is exposed to reactive oxygen and nitrogen species that damage DNA. In this study, we investigated the roles of UvrA and UvrD1, thought to be parts of the nucleotide excision repair pathway ofM. tuberculosis. Strains in whichuvrD1was inactivated either alone or in conjunction withuvrAwere constructed. Inactivation ofuvrD1resulted in a small colony phenotype, although growth in liquid culture was not significantly affected. The sensitivity of the mutant strains to UV irradiation and to mitomycin C highlighted the importance of the targeted genes for nucleotide excision repair. The mutant strains all exhibited heightened susceptibility to representatives of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI). TheuvrD1and theuvrA uvrD1mutants showed decreased intracellular multiplication following infection of macrophages. Most importantly, theuvrA uvrD1mutant was markedly attenuated following infection of mice by either the aerosol or the intravenous route.
Allele-Dependent Differences in Quorum-Sensing Dynamics Result in Variant Expression of Virulence Genes in Staphylococcus aureus
Authors: Geisinger Edward , Chen John , Novick Richard P. 
Published: March 2012

ABSTRACT

Agr is an autoinducing, quorum-sensing system that functions in many Gram-positive species and is best characterized in the pathogen
Staphylococcus aureus
, in which it is a global regulator of virulence gene expression. Allelic variations in the
agr
genes have resulted in the emergence of four quorum-sensing specificity groups in
S. aureus
, which correlate with different strain pathotypes. The basis for these predilections is unclear but is hypothesized to involve the phenomenon of quorum-sensing interference between strains of different
agr
groups, which may drive
S. aureus
strain isolation and divergence. Whether properties intrinsic to each
agr
allele directly influence virulence phenotypes within
S. aureus
is unknown. In this study, we examined group-specific differences in
agr
autoinduction and virulence gene regulation by utilizing congenic strains, each harboring a unique
S. aureus
agr
allele, enabling a dissection of
agr
locus-dependent versus genotype-dependent effects on quorum-sensing dynamics and virulence factor production. Employing a reporter fusion to the principal
agr
promoter, P3, we observed allele-dependent differences in the timing and magnitude of
agr
activation. These differences were mediated by polymorphisms within the
agrBDCA
genes and translated to significant variations in the expression of a key transcriptional regulator, Rot, and of several important exoproteins and surface factors involved in pathogenesis. This work uncovers the contribution of divergent quorum-sensing alleles to variant expression of virulence determinants within a bacterial species.
The PhoP/PhoQ System and Its Role in Serratia marcescens Pathogenesis
Authors: Barchiesi Julieta , Castelli María Eugenia , Di Venanzio Gisela , Colombo María Isabel , García Véscovi Eleonora 
Published: March 2012

ABSTRACT

Serratia marcescens
is able to invade, persist, and multiply inside nonphagocytic cells, residing in nonacidic, nondegradative, autophagosome-like vacuoles. In this work, we have examined the physiological role of the PhoP/PhoQ system and its function in the control of critical virulence phenotypes in
S. marcescens
. We have demonstrated the involvement of the PhoP/PhoQ system in the adaptation of this bacterium to growth on scarce environmental Mg
2+
, at acidic pH, and in the presence of polymyxin B. We have also shown that these environmental conditions constitute signals that activate the PhoP/PhoQ system. We have found that the two
S. marcescens
mgtE
orthologs present a conserved PhoP-binding motif and demonstrated that
mgtE1
expression is PhoP dependent, reinforcing the importance of PhoP control in magnesium homeostasis. Finally, we have demonstrated that
phoP
expression is activated intracellularly and that a
phoP
mutant strain is defective in survival inside epithelial cells. We have shown that the
Serratia
PhoP/PhoQ system is involved in prevention of the delivery to degradative/acidic compartments.
Multimodal observational assessment of quality and productivity benefits from the implementation of wireless technology for out of hours working
Authors: Blakey John D , Guy Debbie , Simpson Carl , Fearn Andrew , Cannaby Sharon , Wilson Petra , Shaw Dominick 
Published: March 2012

ObjectivesThe authors investigated if a wireless system of call handling and task management for out of hours care could replace a standard pager-based system and improve markers of efficiency, patient safety and staff satisfaction.DesignProspective assessment using both quantitative and qualitative methods, including interviews with staff, a standard satisfaction questionnaire, independent observation, data extraction from work logs and incident reporting systems and analysis of hospital committee reports.SettingA large teaching hospital in the UK.ParticipantsHospital at night co-ordinators, clinical support workers and junior doctors handling approximately 10 000 tasks requested out of hours per month.Outcome measuresLength of hospital stay, incidents reported, co-ordinator call logging activity, user satisfaction questionnaire, staff interviews.ResultsUsers were more satisfied with the new system (satisfaction score 62/90 vs 82/90, p=0.0080). With the new system over 70 h/week of co-ordinator time was released, and there were fewer untoward incidents related to handover and medical response (OR=0.30, p=0.02). Broad clinical measures (cardiac arrest calls for peri-arrest situations and length of hospital stay) improved significantly in the areas covered by the new system.ConclusionsThe introduction of call handling software and mobile technology over a medical-grade wireless network improved staff satisfaction with the Hospital at Night system. Improvements in efficiency and information flow have been accompanied by a reduction in untoward incidents, length of stay and peri-arrest calls.
How does capacity building of health managers work? A realist evaluation study protocol
Authors: Prashanth N S , Marchal Bruno , Hoeree Tom , Devadasan Narayanan , Macq Jean , Kegels Guy , Criel Bart 
Published: March 2012

IntroductionThere has been a lot of attention on the role of human resource management interventions to improve delivery of health services in low- and middle-income countries. However, studies on this subject are few due to limited research on implementation of programmes and methodological difficulties in conducting experimental studies on human resource interventions. The authors present the protocol of an evaluation of a district-level capacity-building intervention to identify the determinants of performance of health workers in managerial positions and to understand how changes (if any) are brought about.Methods and analysisThe aim of this study is to understand how capacity building works. The authors will use realist evaluation to evaluate an intervention in Karnataka, India. The intervention is a capacity-building programme that seeks to improve management capacities of health managers at district and subdistrict levels through periodic classroom-based teaching and mentoring support at the workplace. The authors conducted interviews and reviewed literature on capacity building in health to draw out the programme theory of the intervention. Based on this, the authors formulated hypothetical pathways connecting the expected outcomes of the intervention (planning and supervision) to the inputs (contact classes and mentoring). The authors prepared a questionnaire to assess elements of the programme theory—organisational culture, self-efficacy and supervision. The authors shall conduct a survey among health managers as well as collect qualitative data through interviews with participants and non-participants selected purposively based on their planning and supervision performance. The authors will construct explanations in the form of context–mechanism–outcome configurations from the results. This will be iterative and the authors will use a realist evaluation framework to refine the explanatory theories that are based on the findings to explain and validate an improved theory on ‘what works for whom and under what conditions’.DiscussionThe scope for applying realist evaluation to study human resource management interventions in health are discussed.
Tracking the impact of research on policy and practice: investigating the feasibility of using citations in clinical guidelines for research evaluation
Authors: Kryl David , Allen Liz , Dolby Kevin , Sherbon Beverley , Viney Ian 
Published: March 2012

ObjectivesTo investigate the feasibility of using research papers cited in clinical guidelines as a way to track the impact of particular funding streams or sources.SettingIn recent years, medical research funders have made efforts to enhance the understanding of the impact of their funded research and to provide evidence of the ‘value’ of investments in particular areas of research. One of the most challenging areas of research evaluation is around impact on policy and practice. In the UK, the National Institute of Health and Clinical Excellence (NICE) provide clinical guidelines, which bring together current high-quality evidence on the diagnosis and treatment of clinical problems. Research referenced in these guidelines is an indication of its potential to have real impact on health policy and practice.DesignThis study is based on analysis of the authorship and funding attribution of research cited in two NICE clinical guidelines: dementia and chronic obstructive pulmonary disease.ResultsAnalysis identified that around a third of papers cited in the two NICE guidelines had at least one author based in the UK. In both cases, about half of these UK attributed papers contained acknowledgements which allowed the source of funding for the research to be identified. The research cited in these guidelines was found to have been supported by a diverse set of funders from different sectors. The study also investigated the contribution of research groups based in universities, industry and the public sector.ConclusionsThe study found that there is great potential for guidelines to be used as sources of information on the quality of the research used in their development and that it is possible to track the source of the funding of the research. The challenge is in harnessing the relevant information to track this in an efficient way.
PROSpER: PReferences for the Organisation of acute health Services for oldER people: protocol for a mixed methods study: Figure 1
Authors: Howard Kirsten , Arendts Glenn , Jan Stephen , Beck Matthew 
Published: March 2012

BackgroundOrganisation of acute care services for people living in residential aged care facilities (RACF) is a complex area of health policy. For people living in RACF, the emergency department is often used to provide acute care; needs of RACF residents, however, are not always well met. Alternative models of delivering care must be acceptable to a variety of stakeholders; however, little is known about the values and preferences that people attach to aspects of how and where care is delivered.Methods/designThe PROSpER Study examines people's preferences for the organisation of acute healthcare services for older people in RACF. The authors aim to (1) determine which factors influence preferences of residents, carers and providers for how and where acute care is delivered and (2) determine the relative importance of these factors and the acceptable trade-offs between them. Qualitative and quantitative methods will be used. One-on-one interviews will be conducted with RACF residents, their families, staff of RACF and emergency department staff. A discrete choice study will then be designed to quantitatively assess preferences for alternative models of care delivery. Approximately 600 respondents from three respondent groups will be surveyed: older people living in RACF, family members of aged care residents and staff of RACF. A mixed logit model will be used; results will be expressed as parameter estimates (β) and odds of choosing one option over an alternative. Trade-offs between attributes will also be calculated.Ethics and disseminationThe PROSpER Study has been approved by the University of Sydney, Human Research Ethics Committee (Protocol numbers 10653 and 14382) and Royal Perth Hospital Ethics Committee (reference 2009/045). Results will be published in peer-reviewed scientific journals and via conference presentations; a newsletter will also be provided to study participants. A stakeholder roundtable will also be held to discuss the results.
Do home-visit programs for mothers with infants reduce parenting stress and increase social capital in Japan?
Authors: Fujiwara Takeo , Natsume Keiko , Okuyama Makiko , Sato Takuyo , Kawachi Ichiro 
Published: March 2012

BackgroundDistress during child rearing is known as a risk factor for child maltreatment. In addition, it is known that social capital can be a preventive factor for child maltreatment. The purpose of this study is to evaluate whether the home-visit program reduces parenting stress and increases the social capital in the community.MethodsThe home-visit program was implemented when the infants were 1–2 month of age (by public health nurses or midwives) and/or 4 months of age for those mothers who agreed to a home visit by trained community staff. Self-administered questionnaires on parenting stress scale and social capital were sent to all mothers who delivered a baby between August and November 2009 in two cities in the Aichi prefecture, Japan.ResultsAmong 936 mothers, 347 mothers (follow-up rate: 37%) completed both questionnaires. Scores on parenting stress scale scores at 4 months were lower than those at 1–2 months among the four groups (no home visit, home visit at 1–2 months, home visit at 4 months and both). The social trust scores at 4 months were higher than those at 1–2 months in every group; however, multivariate regression analysis showed that there were no differences in the reduction of the parenting stress scale scores and increase in social trust between the four groups.ConclusionThe home-visit program conducted once or twice by public health nurses or trained community staff for mothers with infants showed no substantial reduction in maternal stress and no increase in social trust.
CT-guided cryoablation for palliation of secondary trigeminal neuralgia from head and neck malignancy
Authors: Dar Suhail A , Love Zachary , Prologo John D , Hsu Daniel Pierce 
Published: March 2012

BackgroundFacial pain is a common presentation secondary to tumoral invasion, rendering an individual unable to perform basic activities such as eating and talking. Cryotherapy may be appropriate in patients seeking immediate pain relief for trigeminal neuralgia (TN) near the end of life with its minimal invasiveness and procedural morbidity. While cryosurgery has been effectively demonstrated in the treatment of primary TN, this study is unique as it is the first documented use of CT guidance and treatment of secondary TN using percutaneous cryoablation.AimTo perform and report experience with CT-guided percutaneous cryoablation, a palliative treatment for TN secondary to recurrent invasive head and neck carcinoma, in patients previously treated with chemotherapy, radiotherapy and/or surgery with the goal of improving functional status and quality of life.MethodsPalliative cryoablation procedures performed under CT guidance on recurrent head and neck malignancy between September 2010 and June 2011 were retrospectively analyzed. The procedure was performed under general anesthesia or conscious sedation. For each patient, 1–2 cryoprobes were placed in the tumor and two or four freeze-thaw cycles were performed. Patients were evaluated for facial pain relief immediately after treatment by telephone follow-up.ResultsThree patients underwent treatment for three masses using CT-guided percutaneous cryoablation. On imaging, technical success was achieved in all cases with hypodense ice formation encompassing symptomatic lesions on the CT scan. No procedural complications were encountered with post-procedure pain relief and reduction in required pain medication noted in all patients. One patient had 1 month of pain relief before the symptoms returned.ConclusionCT-guided percutaneous cryoablation is an efficient minimally invasive method for the palliative treatment of TN secondary to recurrent invasive head and neck carcinoma as a result of direct tumoral invasion of the extracranial divisions of the trigeminal nerve. Patients meeting the therapeutic criteria of individuals treated for musculoskeletal metastatic lesions may benefit from this treatment. The results suggest it may not currently be a curative technique as one patient's symptoms returned, but it could prove useful as an adjunct to current palliative therapies with minimal invasiveness and procedural morbidity, especially in patients seeking pain palliation, improved functional status and improved quality of life near the end of life.
Suppression of Tak1 Promotes Prostate Tumorigenesis
Authors: Wu Min , Shi Lihong , Cimic Adela , Romero Lina , Sui Guangchao , Lees Cynthia J. , Cline J. Mark , Seals Darren F. , Sirintrapun Joseph S. , McCoy Thomas P. , Liu Wennuan , Kim Jin Woo , Hawkins Gregory A. , Peehl Donna M. , Xu Jianfeng , Cramer Scott D. 
Published: March 2012

Abstract
More than 30% of primary prostate cancers contain a consensus deletion of an approximately 800 kb locus on chromosome 6q15.1. The MAP3K7 gene, which encodes TGF-β activated kinase-1 (Tak1), is a putative prostate tumor suppressor gene within this region whose precise function remains obscure. In this study, we investigated the role of Tak1 in human and murine prostate cancers. In 50 well-characterized human cancer specimens, we found that Tak1 expression was progressively lost with increasing Gleason grade, both within each cancer and across all cancers. In murine prostate stem cells and Tak1-deficient prostatic epithelial cells, Tak1 loss increased proliferation, migration, and invasion. When prostate stem cells attenuated for Tak1 were engrafted with fetal urogenital mesenchyme, the histopathology of the grafts reflected the natural history of prostate cancer leading from prostatic intraepithelial neoplasia to invasive carcinoma. In the grafts containing Tak1-suppressed prostate stem cells, p38 and c-jun-NH2-kinase activity was attenuated and proliferation was increased. Together, our findings functionally validate the proposed tumor suppressor role of Tak1 in prostate cancer. Cancer Res; 72(11); 2833–43. ©2012 AACR.
Loss of the Ceramide Transfer Protein Augments EGF Receptor Signaling in Breast Cancer
Authors: Heering Johanna , Weis Nicole , Holeiter Monika , Neugart Felix , Staebler Annette , Fehm Tanja N. , Bischoff Annabell , Schiller Jürgen , Duss Stephan , Schmid Simone , Korte Thomas , Herrmann Andreas , Olayioye Monilola A. 
Published: April 2012

Abstract
Triple-negative breast cancers (TNBC) are especially refractory to treatment due to their negative hormone receptor and ErbB2/HER2 status. Therefore, the identification of cancer-associated deregulated signaling pathways is necessary to develop improved targeted therapies. Here, we show that expression of the ceramide transfer protein CERT is reduced in TNBCs. CERT transfers ceramide from the endoplasmic reticulum to the Golgi complex for conversion into sphingomyelin (SM). We provide evidence that by regulating cellular SM levels, CERT determines the signaling output of the EGF receptor (EGFR/ErbB1), which is upregulated in approximately 70% of TNBCs. CERT downregulation in breast cancer cells enhanced ErbB1 lateral mobility, ligand-induced autophosphorylation, internalization, and chemotaxis. Together, our findings provide a link between lipid metabolism at the Golgi with signaling at the plasma membrane, thereby implicating CERT loss in the progression of TNBCs. Cancer Res; 72(11); 2855–66. ©2012 AACR.
Estrogen Promotes ER-Negative Tumor Growth and Angiogenesis through Mobilization of Bone Marrow–Derived Monocytes
Authors: Iyer Vandana , Klebba Ina , McCready Jessica , Arendt Lisa M. , Betancur-Boissel Monica , Wu Meng-Fen , Zhang Xiaomei , Lewis Michael T. , Kuperwasser Charlotte 
Published: March 2012

Abstract
Estrogen has a central role in the genesis and progression of breast cancers whether they are positive or negative for the estrogen receptor (ER). While therapies that disrupt estrogen biosynthesis or ER activity can treat these diseases in postmenopausal women, in younger women where ovarian function remains intact, these anti-estrogen therapies are not as effective. Moreover, emerging clinical evidence suggests that estrogen may promote other cancers. Thus, circulating estrogens may participate in cancer pathogenesis in ways that are not yet understood. In this study, we show that estrogen can promote the outgrowth of murine xenograft tumors established from patient-derived ER-negative breast cancer cells by influencing the mobilization and recruitment of a proangiogenic population of bone marrow–derived myeloid cells. ERα expression was necessary and sufficient in the bone marrow–derived cells themselves to promote tumor formation in response to estrogen. Our findings reveal a novel way in which estrogen promotes tumor formation, with implications for the development and application of anti-estrogen therapies to treat cancer in premenopausal women. Cancer Res; 72(11); 2705–13. ©2012 AACR.