bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibitory Effects of
d
-Amino Acids on Staphylococcus aureus Biofilm Development
Authors: Hochbaum Allon I. , Kolodkin-Gal Ilana , Foulston Lucy , Kolter Roberto , Aizenberg Joanna , Losick Richard 
Published: August 2011

ABSTRACT

Biofilms are communities of cells held together by a self-produced extracellular matrix typically consisting of protein, exopolysaccharide, and often DNA. A natural signal for biofilm disassembly in
Bacillus subtilis
is certain
d
-amino acids, which are incorporated into the peptidoglycan and trigger the release of the protein component of the matrix.
d
-Amino acids also prevent biofilm formation by the related Gram-positive bacterium
Staphylococcus aureus
. Here we employed fluorescence microscopy and confocal laser scanning microscopy to investigate how
d
-amino acids prevent biofilm formation by
S. aureus
. We report that biofilm formation takes place in two stages, initial attachment to surfaces, resulting in small foci, and the subsequent growth of the foci into large aggregates.
d
-Amino acids did not prevent the initial surface attachment of cells but blocked the subsequent growth of the foci into larger assemblies of cells. Using protein- and polysaccharide-specific stains, we have shown that
d
-amino acids inhibited the accumulation of the protein component of the matrix but had little effect on exopolysaccharide production and localization within the biofilm. We conclude that
d
-amino acids act in an analogous manner to prevent biofilm development in
B. subtilis
and
S. aureus
. Finally, to investigate the potential utility of
d
-amino acids in preventing device-related infections, we have shown that surfaces impregnated with
d
-amino acids were effective in preventing biofilm growth.
The Bacillus subtilis GntR Family Repressor YtrA Responds to Cell Wall Antibiotics
Authors: Salzberg Letal I. , Luo Yun , Hachmann Anna-Barbara , Mascher Thorsten , Helmann John D. 
Published: August 2011

ABSTRACT

The transglycosylation step of cell wall synthesis is a prime antibiotic target because it is essential and specific to bacteria. Two antibiotics, ramoplanin and moenomycin, target this step by binding to the substrate lipid II and the transglycosylase enzyme, respectively. Here, we compare the ramoplanin and moenomycin stimulons in the Gram-positive model organism
Bacillus subtilis
. Ramoplanin strongly induces the LiaRS two-component regulatory system, while moenomycin almost exclusively induces genes that are part of the regulon of the extracytoplasmic function (ECF) σ factor σ
M
. Ramoplanin additionally induces the
ytrABCDEF
and
ywoBCD
operons, which are not part of a previously characterized antibiotic-responsive regulon. Cluster analysis reveals that these two operons are selectively induced by a subset of cell wall antibiotics that inhibit lipid II function or recycling. Repression of both operons requires YtrA, which recognizes an inverted repeat in front of its own operon and in front of
ywoB
. These results suggest that YtrA is an additional regulator of cell envelope stress responses.
Characterization of Invasive and Colonizing Isolates of Streptococcus agalactiae in East African Adults
Authors: Huber Charlotte A. , McOdimba Francis , Pflueger Valentin , Daubenberger Claudia A. , Revathi Gunturu 
Published: August 2011

ABSTRACT

Ninety-five colonizing isolates and 74 invasive isolates of
Streptococcus agalactiae
from Kenyan adults were characterized by using capsular serotyping and multilocus sequence typing. Twenty-two sequence types clustering into five clonal complexes were found. Data support the view that
S. agalactiae
isolates belonging to a limited number of clonal complexes are invasive in adults worldwide.
Host Regulatory Network Response to Infection with Highly Pathogenic H5N1 Avian Influenza Virus
Authors: Li Chengjun , Bankhead Armand , Eisfeld Amie J. , Hatta Yasuko , Jeng Sophia , Chang Jean H. , Aicher Lauri D. , Proll Sean , Ellis Amy L. , Law G. Lynn , Waters Katrina M. , Neumann Gabriele , Katze Michael G. , McWeeney Shannon , Kawaoka Yoshihiro 
Published: August 2011

ABSTRACT
During the last decade, more than half of humans infected with highly pathogenic avian influenza (HPAI) H5N1 viruses have died, yet virus-induced host signaling has yet to be clearly elucidated. Airway epithelia are known to produce inflammatory mediators that contribute to HPAI H5N1-mediated pathogenicity, but a comprehensive analysis of the host response in this cell type is lacking. Here, we leveraged a system approach to identify and statistically validate signaling subnetworks that define the dynamic transcriptional response of human bronchial epithelial cells after infection with influenza A/Vietnam/1203/2004 (H5N1, VN1203). Importantly, we validated a subset of transcripts from one subnetwork in both Calu-3 cells and mice. A more detailed examination of two subnetworks involved in the immune response and keratinization processes revealed potential novel mediators of HPAI H5N1 pathogenesis and host response signaling. Finally, we show how these results compare to those for a less virulent strain of influenza virus. Using emergent network properties, we provide fresh insight into the host response to HPAI H5N1 virus infection and identify novel avenues for perturbation studies and potential therapeutic interventions for fatal HPAI H5N1 disease.
Hospital cancer deaths: late diagnosis and missed opportunity: Table 1
Authors: Blaney JM , Crawford G , Elder TR , Johnston G , Gavin AT 
Published: August 2011

ObjectivesTo establish factors that influence and contribute to the death of patients with cancer in acute hospitals in Northern Ireland.DesignRetrospective clinical note review.Setting16 acute hospitals, covering 5 Health and Social Care Trusts across Northern Ireland.Participants793 adult patients with cancer who died in an acute hospital between July and December 2007 identified through the Northern Ireland Cancer Registry. Information was available for 695 (88%).ResultsThee main reasons for acute hospital deaths were uncovered. First, 26.3% of patients were diagnosed with cancer during their last hospital admission. These patients were significantly different from the rest of the sample in being older, not partnered, having more comorbidities and fewer hospital admissions in their last year of life (all p<0.001). Second, patients were very ill with 78.7% admitted as an emergency, requiring medical attention as a result of cancer-related (37.4%) and urgent physical symptoms (33.5%). Third, despite 38.3% of patients specifically requesting discharge to their usual residence, hospice or other hospital, this was not achieved. For 76.3%, this was owing to a deterioration in their medical condition. However for 12.4% there was a lack of a suitable bed, a care package was not in place for 4.9% and 3.0% lacked the required family support. In addition, preferred place of death was only recorded for 41% of patients.ConclusionsLate diagnosis of cancer is a problem which requires further research. Training should be in place to ensure that a patient's preferred place of death is discussed, recorded and made part of routine end of life care. To achieve this, all medical staff should know when a patient is dying. Further research is required to establish what enables patients with cancer to die at home.
Communication with survivors of motor vehicle crashes
Authors: Marco Catherine A , Wetzel Lindsay R 
Published: August 2011

BackgroundCommunication with survivors of severe motor vehicle crashes is challenging for emergency physicians. The appropriate timing of death notification to survivors of severe motor vehicle crashes is unknown.ObjectiveTo determine communication preferences among survivors of motor vehicle crashes.MethodsIn this cross-sectional survey study, eligible participants included adult survivors of motor vehicle crashes in which there was a death, between 2005 and 2009. Participants were interviewed and responses to 30 questions about communication were recorded verbatim. Responses were coded and grouped for statistical analysis.ResultsAmong 26 eligible participants, 21 consented to participate (81% participation rate). Survivors' relationship to the deceased included spouse/significant other (33%), friend (24%), child (5%) and no relationship (38%). Survivors had been notified of the death in the prehospital setting (14%), in the emergency department (43%), or later in the inpatient setting (43%). Survivors were notified of the death by family members (43%), indirect communication (14%), police (10%), prehospital provider (10%), or friend (10%). Most participants (88%) had to ask directly to obtain information about the status of others in the crash. Participants demonstrated variable opinions about the ideal time of death notification: some recommended immediately (24%), in the emergency department (24%), in the inpatient setting (29%), or it depends on the circumstances (24%).ConclusionsSurvivors of motor vehicles crashes are notified of fatalities most commonly by family members, most commonly in the hospital setting. Recommendations from survivors about the appropriate timing and setting for death notification varied significantly.
Distributing personal resuscitation manikins in an untrained population: how well are basic life support skills acquired?
Authors: Nielsen Anne Møller , Isbye Dan Lou , Lippert Freddy , Rasmussen Lars Simon 
Published: August 2011

BackgroundSelf-instruction with a DVD and a simple personal manikin is an effective alternative to traditional basic life support (BLS) courses.ObjectiveTo evaluate the effect of distributing DVD training kits to untrained laypersons. BLS skills were compared according to 2005 guidelines for resuscitation after 3.5 months with those obtained in untrained laypersons who completed the same course with instructor facilitation.MethodsBLS skills of 55 untrained laypersons were assessed using the Laerdal ResusciAnne and PC Skill Reporting System in a 3 min test and a total score (12–48 points) was calculated. The participants received a DVD training kit without instructions. The test was repeated after 3.5 months. Data were compared with data from a previous published study where participants completed the same course in groups with instructor facilitation.ResultsThere was no statistically significant difference in the total score after 3.5 months. The ‘DVD—self-instructor’ group obtained 33 (29–37) points and the ‘DVD—with instructor’ group obtained 34 (32–37) points, p=0.16. The ‘DVD—with instructor’ group performed significantly better in checking responsiveness and had a significantly shorter ‘total hands-off time’ (s) (85 (76–94) vs 96 (82–120), p=0.002) and delay until first compression or ventilation group (29 s (17–40) vs 33 s (22–48), p=0.04).ConclusionsSince no significant difference in total BLS score was found after 3.5 months between untrained laypersons who either completed a DVD-based BLS course in groups with instructor facilitation or received the same DVD training kit without instruction, the latter seems more efficient.
A simple three-step dispatch rule may reduce lights and sirens responses to motor vehicle crashes
Authors: Isenberg Derek , Cone David C , Stiell Ian G 
Published: August 2011

IntroductionMost patients involved in motor vehicle crashes (MVCs) are not seriously injured. However, dispatch protocols require an ambulance be sent with lights and sirens (L&S) to the vast majority of MVCs. L&S have been shown to reduce response times minimally. The rate of injuries among prehospital workers is nearly 15 times higher among ambulances operating with L&S than those without.ObjectiveTo derive a dispatch rule to reduce the need for L&S response by using MVC characteristics that could easily be described by a 9-1-1 caller. The US Centers for Disease Control Field Triage Guidelines were used as the standard for requiring L&S response; it was assumed that if a patient did not require transport to a trauma centre, he/she did not need an L&S response.MethodsData were extracted from prehospital patient care reports (PCRs) of patients transported by ambulance to a level I trauma centre between July 2007 and June 2008 with injuries sustained in MVCs. Patients with completed prehospital PCRs and hospital charts were included in the study. Five MVC characteristics were extracted that could easily be identified by a 9-1-1 caller. Using various permutations of these MVC characteristics, a dispatch rule was developed to determine when an ambulance should respond to an MVC without L&S. The sensitivity and specificity of this dispatch rule were calculated for both patients who met trauma centre triage criteria, and those who used trauma centre resources.Results509 patients were included in the analysis. The following dispatch rule was developed for an ambulance response without L&S to a MVC: (1) the MVC does not occur on an interstate/highway, (2) and the MVC involves more than one car. AND (3) all patients are ambulatory. This dispatch rule was 95.9% sensitive and 33.5% specific for patients who met trauma centre criteria, and 97.7% sensitive and 32.5% specific for patients who required trauma centre resources. The study was limited by the large number of patients for whom prehospital PCRs were not available.ConclusionsA simple three-step dispatch rule for MVCs can safely reduce L&S responses by one-third, as judged by need for transport to a trauma centre or use of trauma centre resources. Prospective validation is needed.
Pattern of growth of very low birth weight preterm infants, assessed using the WHO Growth Standards, is associated with neurodevelopment
Authors: Nash Andrea , Dunn Michael , Asztalos Elizabeth , Corey Mary , Mulvihill-Jory Bridget , O’Connor Deborah L. 
Published: August 2011

Several Canadian professional organizations recently recommended that the growth of preterm infants be monitored using the World Health Organization Growth Standards (WHO-GS) after hospital discharge. The WHO-GS are a prescriptive set of growth charts that describe how term infants should grow under ideal environmental conditions. Whether preterm infants following this pattern of growth have better outcomes than infants that do not has yet to be evaluated. Our aim was to determine whether the pattern of growth of very low birth weight (VLBW) infants during the first 2 years, assessed using the WHO-GS or the traditional Centers for Disease Control and Prevention reference growth charts (CDC-RGC), is associated with neurodevelopment. Pattern of weight, length, and head circumference gain of appropriate-for-gestation VLBW preterm infants (n = 289) from birth to 18–24 months corrected age was classified, using the WHO-GS and CDC-RGC, as sustained (change in Z-score ≤1 SD), decelerated (decline >1 SD), or accelerated (incline >1 SD). Development was assessed using the Bayley Scales of Infant and Toddler Development (BSID)-III at 18–24 months corrected age. Using the WHO-GS, children with a decelerated pattern of weight gain had lower cognitive (10 points), language (6 points), and motor (4 points) scores than infants with sustained weight gain (p < 0.05), even after adjustment for morbidities. No association was found using the CDC-RGC. In conclusion, a decelerated pattern of weight gain, determined with the WHO-GS, but not the CDC-GRC, is associated with poorer neurodevelopment scores on the BSID-III than a pattern of sustained growth.
Effects of Photoacoustic Imaging and Photothermal Ablation Therapy Mediated by Targeted Hollow Gold Nanospheres in an Orthotopic Mouse Xenograft Model of Glioma
Authors: Lu Wei , Melancon Marites P. , Xiong Chiyi , Huang Qian , Elliott Andrew , Song Shaoli , Zhang Rui , Flores Leo G. , Gelovani Juri G. , Wang Lihong V. , Ku Geng , Stafford R. Jason , Li Chun 
Published: August 2011

Abstract
Advancements in nanotechnology have made it possible to create multifunctional nanostructures that can be used simultaneously to image and treat cancers. For example, hollow gold nanospheres (HAuNS) have been shown to generate intense photoacoustic signals and induce efficient photothermal ablation (PTA) therapy. In this study, we used photoacoustic tomography, a hybrid imaging modality, to assess the intravenous delivery of HAuNS targeted to integrins that are overexpressed in both glioma and angiogenic blood vessels in a mouse model of glioma. Mice were then treated with near-infrared laser, which elevated tumor temperature by 20.7°C. We found that PTA treatment significantly prolonged the survival of tumor-bearing mice. Taken together, these results show the feasibility of using a single nanostructure for image-guided local tumor PTA therapy with photoacoustic molecular imaging. Cancer Res; 71(19); 6116–21. ©2011 AACR.
miR-375 Is Activated by ASH1 and Inhibits YAP1 in a Lineage-Dependent Manner in Lung Cancer
Authors: Nishikawa Eri , Osada Hirotaka , Okazaki Yasumasa , Arima Chinatsu , Tomida Shuta , Tatematsu Yoshio , Taguchi Ayumu , Shimada Yukako , Yanagisawa Kiyoshi , Yatabe Yasushi , Toyokuni Shinya , Sekido Yoshitaka , Takahashi Takashi 
Published: August 2011

Abstract
Lung cancers with neuroendocrine (NE) features are often very aggressive but the underlying molecular mechanisms remain elusive. The transcription factor ASH1/ASCL1 is a master regulator of pulmonary NE cell development that is involved in the pathogenesis of lung cancers with NE features (NE-lung cancers). Here we report the definition of the microRNA miR-375 as a key downstream effector of ASH1 function in NE-lung cancer cells. miR-375 was markedly induced by ASH1 in lung cancer cells where it was sufficient to induce NE differentiation. miR-375 upregulation was a prerequisite for ASH1-mediated induction of NE features. The transcriptional coactivator YAP1 was determined to be a direct target of miR-375. YAP1 showed a negative correlation with miR-375 in a panel of lung cancer cell lines and growth inhibitory activities in NE-lung cancer cells. Our results elucidate an ASH1 effector axis in NE-lung cancers that is functionally pivotal in controlling NE features and the alleviation from YAP1-mediated growth inhibition. Cancer Res; 71(19); 6165–73. ©2011 AACR.
Recombinant Human Erythropoietin in Combination with Chemotherapy Increases Breast Cancer Metastasis in Preclinical Mouse Models
Authors: Hedley Benjamin D. , Chu Jenny E. , Ormond D. George , Beausoleil Michel S. , Boasie Alexandra , Allan Alison L. , Xenocostas Anargyros 
Published: August 2011

Abstract
Purpose: Erythropoiesis-stimulating agents (ESA) are used clinically for treating cancer-related anemia. Recent clinical trials have reported increased adverse events and reduced survival in ESA-treated breast cancer patients receiving chemotherapy, potentially related to erythropoietin (EPO)-induced cancer progression. However, minimal preclinical data are available about the impact of EPO on metastatic cell behavior and/or the metastatic process, and this was the goal of our study.
Experimental Design: Breast cancer cell lines were treated with recombinant human EPO (rHuEPO) and screened for expression of EPO receptors (EPOR). MDA-MB-231 and MDA-MB-435 cell lines were used for functional assays in vitro (two-dimensional/three-dimensional growth and survival) and in vivo (tumorigenicity and metastasis), in the presence or absence of EPO and/or cytotoxic agents.
Results: A large variation in EPOR expression across cell lines was observed. In vitro, rHuEPO had a protective effect on radiation-treated MDA-MB-435 cells (P &lt; 0.05); however, rHuEPO treatment alone or combined with chemotherapy or hypoxia did not influence cell survival. In vivo, rHuEPO increased lung metastases in immunocompromised mice injected with MDA-MB-231 or MDA-MB-435 cells and treated with chemotherapy relative to mice treated with chemotherapy alone (P &lt; 0.05).
Conclusions: The lack of an in vitro effect of rHuEPO highlights the importance of in vivo studies to delineate the effects of EPO on the metastatic process. These studies may begin to uncover the underlying functional explanation for the observed EPO-related adverse events and decreased survival in ESA-treated metastatic breast cancer patients undergoing chemotherapy. Clin Cancer Res; 17(19); 6151–62. ©2011 AACR.
A Gene Expression–Based Predictor for Myeloma Patients at High Risk of Developing Bone Disease on Bisphosphonate Treatment
Authors: Wu Ping , Walker Brian A. , Brewer Daniel , Gregory Walter M. , Ashcroft John , Ross Fiona M. , Jackson Graham H. , Child Anthony J. , Davies Faith E. , Morgan Gareth J. 
Published: August 2011

AbstractPurpose: Myeloma bone disease impairs quality of life and is associated with impaired survival. Even with effective bisphosphonate treatment, a significant proportion of patients still develop skeletal-related events (SRE). Identifying such patients at presentation would allow treatment modification.Experimental Design: To investigate the molecular basis of bone disease at presentation and to develop a predictive signature for patients at high risk of developing SREs on bisphosphonates, 261 presenting myeloma samples were analyzed by global gene expression profiling. The derived “SRE gene signature” was complemented by the integration of associated clinical parameters to generate an optimal predictor.Results: Fifty genes were significantly associated with presenting bone disease, including the WNT signaling antagonist DKK1 and genes involved in growth factor signaling and apoptosis. Higher serum calcium level and the presence of bone disease and hyperdiploidy at presentation were associated with high risk of SRE development. A gene signature derived from the fourteen genes overexpressed in the SRE group was able to identify patients at high risk of developing an SRE on treatment. These genes either belonged to the IFN-induced family or were involved in cell signaling and mitosis. Multivariate logistic model selection yielded an optimal SRE predictor comprising seven genes and calcium level, which was validated as an effective predictor in a further set of patients.Conclusions: The simple expression-based SRE predictor can effectively identify individuals at high risk of developing bone disease while being on bisphosphonates. This predictor could assist with developing future trials on novel therapies aimed at reducing myeloma bone disease. Clin Cancer Res; 17(19); 6347–55. ©2011 AACR.