bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasmid Partition Mechanisms
Authors: Baxter Jamie C. , Funnell Barbara E. 
Published: November 2014

ABSTRACT
The stable maintenance of low-copy-number plasmids in bacteria is actively driven by partition mechanisms that are responsible for the positioning of plasmids inside the cell. Partition systems are ubiquitous in the microbial world and are encoded by many bacterial chromosomes as well as plasmids. These systems, although different in sequence and mechanism, typically consist of two proteins and a DNA partition site, or prokaryotic centromere, on the plasmid or chromosome. One protein binds site-specifically to the centromere to form a partition complex, and the other protein uses the energy of nucleotide binding and hydrolysis to transport the plasmid, via interactions with this partition complex inside the cell. For plasmids, this minimal cassette is sufficient to direct proper segregation in bacterial cells. There has been significant progress in the last several years in our understanding of partition mechanisms. Two general areas that have developed are (i) the structural biology of partition proteins and their interactions with DNA and (ii) the action and dynamics of the partition ATPases that drive the process. In addition, systems that use tubulin-like GTPases to partition plasmids have recently been identified. In this chapter, we concentrate on these recent developments and the molecular details of plasmid partition mechanisms.
Virulence Plasmids of Spore-Forming Bacteria
Authors: Adams Vicki , Li Jihong , Wisniewski Jessica A. , Uzal Francisco A. , Moore Robert J. , McClane Bruce A. , Rood Julian I. 
Published: November 2014

ABSTRACT

Plasmid-encoded virulence factors are important in the pathogenesis of diseases caused by spore-forming bacteria. Unlike many other bacteria, the most common virulence factors encoded by plasmids in
Clostridium
and
Bacillus
species are protein toxins.
Clostridium perfringens
causes several histotoxic and enterotoxin diseases in both humans and animals and produces a broad range of toxins, including many pore-forming toxins such as
C. perfringens
enterotoxin, epsilon-toxin, beta-toxin, and NetB. Genetic studies have led to the determination of the role of these toxins in disease pathogenesis. The genes for these toxins are generally carried on large conjugative plasmids that have common core replication, maintenance, and conjugation regions. There is considerable functional information available about the unique
tcp
conjugation locus carried by these plasmids, but less is known about plasmid maintenance. The latter is intriguing because many
C. perfringens
isolates stably maintain up to four different, but closely related, toxin plasmids. Toxin genes may also be plasmid-encoded in the neurotoxic clostridia. The tetanus toxin gene is located on a plasmid in
Clostridium tetani
, but the botulinum toxin genes may be chromosomal, plasmid-determined, or located on bacteriophages in
Clostridium botulinum
. In
Bacillus anthracis
it is well established that virulence is plasmid determined, with anthrax toxin genes located on pXO1 and capsule genes on a separate plasmid, pXO2. Orthologs of these plasmids are also found in other members of the
Bacillus cereus
group such as
B. cereus
and
Bacillus thuringiensis
. In
B. thuringiensis
these plasmids may carry genes encoding one or more insecticidal toxins.
Current primary care management of children aged 1–36 months with urinary tract infections in Europe: large scale survey of paediatric practice
Authors: Hadjipanayis Adamos , Grossman Zachi , del Torso Stefano , van Esso Diego , Dornbusch Hans Juergen , Mazur Artur , Drabik Anna , Montini Giovanni 
Published: November 2014

ObjectiveTo describe current practice among European paediatricians regarding diagnosis and management of urinary tract infections in children aged 1–36 months and to compare these practices with recently published guidelines.DesignWeb-based large scale survey evaluating knowledge of, attitudes towards and the methods for diagnosing, treating and managing urinary tract infections in children.SettingPrimary and secondary care practices in Europe.Sample1129 paediatricians.ResultsA diagnosis of urinary tract infection is considered by 62% of the respondents in children aged 1–36 months with unexplained fever. The preferred method of urine collection is use of a bag (53% for infants <3 months and 59% for children 4–36 months of age). 60% of paediatricians agree that oral and parenteral antibiotics have equal efficacy. Co-amoxiclav is the antibiotic of choice for 41% of participants, while 9% prescribe amoxicillin. 80% of respondents prescribe ultrasound in all children with a confirmed urinary tract infection. 63% of respondents prescribe a cystography when abnormalities are revealed during ultrasound evaluation. A quarter of respondents recommend antibiotic prophylaxis for all children with any vesicoureteral reflux. The data among European countries are very heterogeneous. The three most recent urinary tract infection guidelines (the National Institute for Health and Care Excellence (NICE), the American Academy of Paediatrics and the Italian Society of Paediatric Nephrology) are not followed properly.ConclusionsManagement of febrile urinary tract infections remains controversial and heterogeneous in Europe. Simple, short, practical and easy-to-remember guidelines and educational strategies to ensure their implementation should be developed.
Case fatality rate and associated factors in patients with 22q11 microdeletion syndrome: a retrospective cohort study
Authors: Repetto Gabriela M , Guzmán M Luisa , Delgado Iris , Loyola Hugo , Palomares Mirta , Lay-Son Guillermo , Vial Cecilia , Benavides Felipe , Espinoza Karena , Alvarez Patricia 
Published: November 2014

ObjectiveChromosome 22q11.2 deletion is the most commonly occurring known microdeletion syndrome. Deaths related to the syndrome have been reported, but the magnitude of death has not been quantified. This study evaluated the deletion's impact on survival and its clinical manifestations in a large cohort of Chilean patients.DesignDemographic and clinical data of individuals with 22q11 deletions diagnosed between 1998 and 2013 were collected from medical records and death certificates. Case fatality rate was calculated and compared with national vital statistics. OR with 95% CI analysis was used to assess the association between clinical manifestations and death.SettingGenetic services in tertiary care centres in Chile, following patients with 22q11.2 deletion.OutcomesFatality rate and associated factors.Results59 of 419 patients (14.1%) died during the study period at a median of 3.4 months (range 0 to 32 years of age). Factors associated with death included congenital heart disease (OR 5.27; 95% CI 2.06 to 13.99; p<0.0001), hypocalcaemia (OR 4.27; 95% CI 1.67 to 11.15; p<0.002) and airway malacia (OR 13.37; 95% CI 1.19 to 110.51; p<0.002). Patients with deletions and defects such as tetralogy of Fallot with or without pulmonary atraesia, truncus arteriosus or ventricular septal defect, had a 2.6-fold to 4.6-fold higher death rate compared with nationwide reports for the same types of defects.ConclusionsIn this cohort, we observed a death rate of 14.1%, implying that one in seven patients with 22q11 deletion died during the study period. Significant associations with cardiac defects, hypocalcaemia and airway malacia were observed. Furthermore, the death risk in patients with 22q11 deletion and cardiac defects exceeded the global figures observed in Chile for infants with structurally similar but apparently isolated anomalies. These observations indicate a need to identify patients who may require specific perioperative management to improve survival.
Objectively-assessed and self-reported sedentary time in relation to multiple socioeconomic status indicators among adults in England: a cross-sectional study
Authors: Stamatakis Emmanuel , Coombs Ngaire , Rowlands Alex , Shelton Nicola , Hillsdon Melvyn 
Published: November 2014

ObjectivesTo examine the associations between socioeconomic position (SEP) and multidomain self-reported and objectively-assessed sedentary time (ST).DesignCross-sectional.SettingGeneral population households in England.Participants2289 adults aged 16–96 years who participated in the 2008 Health Survey for England.OutcomesAccelerometer-measured ST, and self-reported television time, non-television leisure-time sitting and occupational sitting/standing. We examined multivariable associations between household income, social class, education, area deprivation for each SEP indicator (including a 5-point composite SEP score computed by aggregating individual SEP indicators) and each ST indicator using generalised linear models.ResultsAccelerometry-measured total ST and occupational sitting/standing were positively associated with SEP score and most of its constituent SEP indicators, while television time was negatively associated with SEP score and education level. Area-level deprivation was largely unrelated to ST. Those in the lowest composite SEP group spent 64 (95% CIs 52 to 76) and 72 (48 to 98), fewer minutes/day in total ST and occupational sitting/standing compared to those in the top SEP group, and an additional 48 (35–60) min/day watching television (p<0.001 for linear trend). Stratified analyses showed that these associations between composite SEP score and total ST were evident only among participants who were in employment.ConclusionsOccupational sitting seems to drive the positive association between SEP and total ST. Lower SEP is linked to higher TV viewing times.
Antibiotic prescribing in long-term care facilities: a qualitative, multidisciplinary investigation
Authors: Fleming Aoife , Bradley Colin , Cullinan Shane , Byrne Stephen 
Published: November 2014

ObjectivesTo explore healthcare professionals’ views of antibiotic prescribing in long-term care facilities (LTCFs). To use the findings to recommend intervention strategies for antimicrobial stewardship in LTCFs.DesignQualitative semistructured interviews were conducted. The data were analysed by thematic content analysis. After the interviews, the emerging findings were mapped to the theoretical domains framework (TDF), and the behaviour change wheel and behaviour change technique (BCT) taxonomy were used to recommend future intervention strategies.ParticipantsInterviews were conducted with 37 healthcare professionals who work in LTCFs (10 general practitioners, 4 consultants, 14 nurses, 9 pharmacists) between December 2012 and March 2013.SettingInterviews were conducted in the greater Cork region.ResultsThe main domains from the TDF which emerged were: ‘Knowledge’, ‘Environmental context and resources’, ‘Social influences’, ‘Beliefs about consequences’, ‘Memory, attention and decision making’, with the findings identifying a need for ‘Behavioural regulation’. Many participants believed that antibiotic prescribing was satisfactory at their LTCF, despite the lack of surveillance activities.ConclusionsThis study, using the TDF and BCT taxonomy, has found that antibiotic prescribing in LTCFs is influenced by many social and contextual factors. The challenges of the setting and patient population, the belief about consequences to the patient, and the lack of implementation of guidelines and knowledge regarding antibiotic prescribing patterns are significant challenges to address. On the basis of the study findings and the application of the TDF and BCT taxonomy, we suggest some practical intervention functions for antimicrobial stewardship in LTCFs.
ERG expression in chondrogenic bone and soft tissue tumours
Authors: Shon Wonwoo , Folpe Andrew L , Fritchie Karen J 
Published: November 2014

AimWe studied ERG expression in a large series of chondrogenic bone and soft tissue tumours to assess the value of ERG as a possible marker of chondroid/cartilaginous differentiation.MethodsFormalin-fixed, paraffin-embedded whole sections from 111 bone and soft tissue tumours with chondroid differentiation or a morphology that may mimic cartilaginous differentiation were retrieved. Immunohistochemistry was performed using anti-ERG monoclonal antibody directed against the N terminus. Nuclear staining was scored as negative (<5%), 1+ (5%–25%), 2+ (26%–50%), 3+ (>51%).ResultsNuclear ERG expression was seen in all cases of soft tissue chondroma (8), chondromyxoid fibroma (7), chondroblastic osteosarcoma (6) and clear cell chondrosarcoma (1). 10/12 conventional chondrosarcomas were also positive for ERG. In cases of dedifferentiated chondrosarcoma, the well-differentiated component was positive in 7/9 cases, while all dedifferentiated foci were negative. In cases of mesenchymal chondrosarcoma, the hyaline cartilage component was positive in 2/4 cases, whereas the primitive component in all cases was negative. Variable positivity was identified in extraskeletal myxoid chondrosarcomas (4/9), chondroblastomas (3/8) and mixed tumours/myoepitheliomas (2/11). Only 1/12 chordoma was positive for ERG (1+). Interestingly, 15/17 enchondromas were negative for ERG.ConclusionsIn this study, we further characterise the expression of ERG in mesenchymal tumours and found relatively constant nuclear ERG expression in selected chondrogenic tumours including conventional chondrosarcoma, chondromyxoid fibroma, chondroblastic osteosarcoma and clear cell chondrosarcoma. We also show that ERG may be a helpful ancillary tool in certain select diagnostic scenarios and that awareness of ERG expression in tumours with cartilaginous differentiation is important.
Blood-based candidate biomarkers of the presence of neuropsychiatric systemic lupus erythematosus in children
Authors: Brunner Hermine I , Klein-Gitelman Marisa S , Zelko Frank , Beebe Dean W , Foell Dirk , Lee Jiha , Zaal Ahmad , Jones Jordan , Roebuck-Spencer Tresa , Ying Jun 
Published: November 2014

ObjectiveTo examine select brain-reactive proteins for their usefulness to serve as blood-based biomarkers in the screening for neurocognitive deficits in childhood-onset systemic lupus erythematosus (cSLE-NCD).MethodsPatients withcSLE (n=40) were studied longitudinally (month 1; month 18): working memory, psychomotor speed and visuoconstructional ability were assessed using formal neurocognitive testing to determine the presence of cSLE-NCD. Patients also completed the computerised Paediatric Automated Neuropsychological Assessment Metrics. The following brain-reactive proteins were measured in the blood: neutrophil gelatinase associated lipocalin (NGAL), S100B, S100A8/9, antibodies to NR2 glutamate receptor (aNR2-AB), ribosomal-P (aP-AB), glycoprotein-1 (aGP1-AB), and lupus anticoagulant.ResultscSLE-NCD was present in 6 of 40 patients at baseline and 4 of 27 patients with 18-month information. aP-AB positivity was more commonly present with cSLE-NCD than without (p=0.05). aP-ABs were negatively associated with performance on tests assessing working memory, psychomotor speed and visuoconstructional ability in using formal neurocognitive testing. There were also significant negative associations between aP-AB, S100A8/9, aNR2-AB, aGP1-AB, and lupus anticoagulant and accuracy rates on select Paediatric Automated Neuropsychological Assessment Metrics subtests (p<0.05). Over time, decline in cognitive performance was more pronounced among patients with higher NGAL and aNR2-AB levels. Combinations of serum levels of S100A8/9, S100B, NGAL, aNR2-AB and aP-AB were able to identify cSLE-NCD (sensitivity: 100%; specificity 76%) in exploratory analysis.ConclusionsSelect brain-reactive proteins in the blood are associated with cognitive performance and the presence of cSLE-NCD, cross-sectionally and over time. This raises the possibility that testing of these proteins may assist with the screening of cSLE-NCD.
The Lazarus Funnel: a blinded prospective randomized in vitro trial of a novel CE-marked thrombectomy assist device
Authors: Fargen Kyle M , Mocco J , Gobin Y Pierre 
Published: November 2014

IntroductionThe use of retrievable stents for acute ischemic stroke (AIS) may result in the release of distal emboli in 12–22% of cases. The Lazarus Funnel is a novel CE-marked thrombectomy assist device designed to capture the stentriever and thrombus to minimize the likelihood of distal embolization. To study this technology, we performed a randomized blinded in vitro evaluation of this device.MethodsA cerebral flow model was used as an in vitro simulator for cerebral arterial thrombectomy procedures. Stratified block randomization was performed following embolus injection into one of three cohorts: Solitaire stentriever plus guide catheter (control); control plus proximal Funnel placement; or control plus distal Funnel placement. Time to embolectomy, recanalization, and incidence of distal emboli were determined by a blinded observer.ResultsForty-five thrombectomy trials were performed (15 in each group). The average time required for thrombectomy in each group was 8 min 26 s, 11 min 0 s and 9 min 24 s, respectively (p=NS). Use of the Funnel was associated with significantly improved recanalization compared with stentriever alone (p<0.01). Use of the proximal Funnel resulted in a 25% increase in successful recanalization and a 20% reduction in distal emboli. Use of the distal Funnel resulted in a 200% increase in successful recanalization and a 60% reduction in emboli.ConclusionsIn this AIS embolism flow model with Solitaire thrombectomy, the Lazarus Funnel resulted in a significant increase in recanalization and significant reduction in distal emboli without increase in time to recanalization.
Endovascular management of intracranial blister aneurysms: spectrum and limitations of contemporary techniques
Authors: Ashour Ramsey , Dodson Stephen , Aziz-Sultan M Ali 
Published: November 2014

BackgroundIntracranial blister aneurysms are rare lesions that are notoriously more difficult to treat than typical saccular aneurysms. High complication rates associated with surgery have sparked considerable interest in endovascular techniques, though not well-studied, to treat blister aneurysms.ObjectiveTo evaluate our experience using various endovascular approaches to treat blister aneurysms.MethodsAll consecutive blister aneurysms treated using an endovascular approach by the study authors over a 3-year period were retrospectively analyzed. A literature review was also performed.ResultsNine patients with blister aneurysms underwent 11 endovascular interventions. In various combinations, stents were used in 8/11, coils in 5/11, and Onyx in 3/11 procedures. At mean angiographic follow-up of 200 days, 8/9 aneurysms were completely occluded by endovascular means alone requiring no further treatment and 1/9 aneurysms required surgical bypass/trapping after one failed surgical and two failed endovascular treatments. At mean clinical follow-up of 416 days, modified Rankin Scale scores were improved in six patients, stable in two, and worsened in one patient. One complication occurred in 11 procedures (9%), resulting in a permanent neurologic deficit. No unintended endovascular parent vessel sacrifice, intraprocedural aneurysmal ruptures, antiplatelet-related complications, post-treatment aneurysmal re-ruptures, or deaths occurred.ConclusionThis series highlights both the spectrum and limitations of endovascular techniques currently used to treat blister aneurysms, including a novel application of stent-assisted Onyx embolization. Long-term follow-up and experience in larger studies are required to better define the role of endovascular therapy in the management of these difficult lesions.
Endothelin A Receptor/β-Arrestin Signaling to the Wnt Pathway Renders Ovarian Cancer Cells Resistant to Chemotherapy
Authors: Rosanò Laura , Cianfrocca Roberta , Tocci Piera , Spinella Francesca , Di Castro Valeriana , Caprara Valentina , Semprucci Elisa , Ferrandina Gabriella , Natali Pier Giorgio , Bagnato Anna 
Published: November 2014

Abstract
The high mortality of epithelial ovarian cancer (EOC) is mainly caused by resistance to the available therapies. In EOC, the endothelin-1 (ET-1, EDN1)–endothelin A receptor (ETAR, EDNRA) signaling axis regulates the epithelial–mesenchymal transition (EMT) and a chemoresistant phenotype. However, there is a paucity of knowledge about how ET-1 mediates drug resistance. Here, we define a novel bypass mechanism through which ETAR/β-arrestin-1 (β-arr1, ARRB1) links Wnt signaling to acquire chemoresistant and EMT phenotype. We found that ETAR/β-arr1 activity promoted nuclear complex with β-catenin and p300, resulting in histone acetylation, chromatin reorganization, and enhanced transcription of genes, such as ET-1, enhancing the network that sustains chemoresistance. Silencing of β-arr1 or pharmacologic treatment with the dual ETAR/ETBR antagonist macitentan prevented core complex formation and restored drug sensitivity, impairing the signaling pathways involved in cell survival, EMT, and invasion. In vivo macitentan treatment reduced tumor growth, vascularization, intravasation, and metastatic progression. The combination of macitentan and cisplatinum resulted in the potentiation of the cytotoxic effect, indicating that macitentan can enhance sensitivity to chemotherapy. Investigations in clinical specimens of chemoresistant EOC tissues confirmed increased recruitment of β-arr1 and β-catenin to ET-1 gene promoter. In these tissues, high expression of ETAR significantly associated with poor clinical outcome and chemoresistance. Collectively, our findings reveal the existence of a novel mechanism by which ETAR/β-arr1 signaling is integrated with the Wnt/β-catenin pathway to sustain chemoresistance in EOC, and they offer a solid rationale for clinical evaluation of macitentan in combination with chemotherapy to overcome chemoresistance in this setting. Cancer Res; 74(24); 7453–64. ©2014 AACR.
Personal Navigation Increases Colorectal Cancer Screening Uptake
Authors: Ritvo Paul G. , Myers Ronald E. , Paszat Lawrence F. , Tinmouth Jill M. , McColeman Joshua , Mitchell Brian , Serenity Mardie , Rabeneck Linda 
Published: November 2014

Abstract
Background: Prior randomized, controlled trials (RCTs) indicate that patient navigation can boost colorectal cancer screening rates in primary care. The sparse literature on pragmatic trials of interventions designed to increase colorectal cancer screening adherence motivated this trial on the impact of a patient navigation intervention that included support for performance of the participants' preferred screening test (colonoscopy or stool blood testing).
Materials and Methods: Primary care patients (n = 5,240), 50 to 74 years of age, with no prior diagnosis of bowel cancer and no record of a recent colorectal cancer screening test, were identified at the Group Health Centre in northern Ontario. These patients were randomly assigned to an intervention group (n = 2,629) or a usual care control group (n = 2,611). Intervention group participants were contacted by a trained nurse navigator by telephone to discuss colorectal cancer screening. Interested patients met with the navigator, who helped them identify and arrange for performance of the preferred screening test. Control group participants received usual care. Multivariate analyses were conducted using medical records data to assess intervention impact on screening adherence within 12 months after randomization.
Results: Mean patient age was 59 years, and 50% of participants were women. Colorectal cancer screening adherence was higher in the intervention group (35%) than in the control group (20%), a difference that was statistically significant (OR, 2.11; confidence interval, 1.87–2.39).
Conclusion: Preference-based patient navigation increased screening uptake in a pragmatic RCT.
Impact: Patient navigation increased colorectal cancer screening rates in a pragmatic RCT in proportions similar to those observed in explanatory RCTs. Cancer Epidemiol Biomarkers Prev; 24(3); 506–11. ©2014 AACR.