bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening of Escherichia coli Species Biodiversity Reveals New Biofilm-Associated Antiadhesion Polysaccharides
Authors: Rendueles Olaya , Travier Laetitia , Latour-Lambert Patricia , Fontaine Thierry , Magnus Julie , Denamur Erick , Ghigo Jean-Marc 
Published: May 2011

ABSTRACT

Bacterial biofilms often form multispecies communities in which complex but ill-understood competition and cooperation interactions occur. In light of the profound physiological modifications associated with this lifestyle, we hypothesized that the biofilm environment might represent an untapped source of natural bioactive molecules interfering with bacterial adhesion or biofilm formation. We produced cell-free solutions extracted from
in vitro
mature biofilms formed by 122 natural
Escherichia coli
isolates, and we screened these biofilm extracts for antiadhesion molecules active on a panel of Gram-positive and Gram-negative bacteria. Using this approach, we showed that 20% of the tested biofilm extracts contained molecules that antagonize bacterial growth or adhesion. We characterized a compound, produced by a commensal animal
E. coli
strain, for which activity is detected only in biofilm extract. Biochemical and genetic analyses showed that this compound corresponds to a new type of released high-molecular-weight polysaccharide whose biofilm-associated production is regulated by the RfaH protein. We demonstrated that the antiadhesion activity of this polysaccharide was restricted to Gram-positive bacteria and that its production reduced susceptibility to invasion and provided rapid exclusion of
Staphylococcus aureus
from mixed
E. coli
and
S. aureus
biofilms. Our results therefore demonstrate that biofilms contain molecules that contribute to the dynamics of mixed bacterial communities and that are not or only poorly detected in unconcentrated planktonic supernatants. Systematic identification of these compounds could lead to strategies that limit pathogen surface colonization and reduce the burden associated with the development of bacterial biofilms on medical devices.

IMPORTANCE
We sought to demonstrate that bacterial biofilms are reservoirs for unknown molecules that antagonize bacterial adhesion. The use of natural strains representative of
Escherichia coli
species biodiversity showed that nonbiocidal antiadhesion polysaccharides are frequently found in mature biofilm extracts (bacterium-free suspensions which contain soluble molecules produced within the biofilm). Release of an antiadhesion polysaccharide confers a competitive advantage upon the producing strain against clinically relevant pathogens such as
Staphylococcus aureus
. Hence, exploring the biofilm environment provides a better understanding of bacterial interactions within complex communities and could lead to improved control of pathogen colonization.
Difficulties in interpretation of post-mortem microbiology results in unexpected infant death: evidence from a multidisciplinary survey
Authors: Pryce Jeremy W , Weber Martin A , Hartley John C , Ashworth Michael T , Malone Marian , Sebire Neil J 
Published: May 2011

BackgroundPost-mortem (PM) microbiological investigations are recommended in cases of sudden unexpected death in infancy (SUDI), and infection is a recognised cause of such deaths, but no current evidence-based guidelines exist for the appropriate interpretation of results.AimTo assess interpretive difficulties using a targeted cross-specialty questionnaire.Methods109 consultant specialists involved in infant death management were given a questionnaire providing information on five hypothetical standardised SUDI cases, which differed only in their PM microbiology findings. Participants classified each case into categories: definite bacterial infection, probable bacterial infection, bacterial growth of uncertain significance and PM contamination.Results63 (57%) specialists responded. There was no clinical scenario in which complete concordance in interpretation of PM microbiology results was established among participants. In cases with pure growth of Group 2 pathogens such as Group B β-haemolyticStreptococcus, 96% of respondents agreed upon probable or definite bacterial infection. With mixed growth of Group 2 pathogens, 83% reported probable or definite bacterial infection. Growth of organisms such asStaphylococcus aureuscaused the most difficulty, with almost equal numbers of participants interpreting the finding as significant or non-significant. There were no consistent differences in interpretation between different specialist groups.ConclusionsWhile there is general agreement in interpretation of PM microbiology findings in some SUDI scenarios, no consensus was achieved for any clinical setting, and variation in the presumed significance between specialists was apparent. In the absence of appropriate evidence-based guidelines, this has practical implications for the management of such deaths in a multidisciplinary setting.
The immunophenotype of osteoclasts and macrophage polykaryons
Authors: Maggiani F , Forsyth R , Hogendoorn P C W , Krenacs T , Athanasou N A 
Published: May 2011

AimOsteoclasts are multinucleated cells which are specialised to carry out lacunar bone resorption. Osteoclasts form part of the mononuclear phagocyte system, and immunophenotypic criteria for distinction from macrophage polykaryons include expression of CD51 (vitronectin receptor) and absence of HLA-DR and CD14.MethodsThe expression of CD14, CD163, HLA-DR and CD51 in formalin-fixed paraffin-embedded sections of normal bone and neoplastic and non-neoplastic lesions of bone and soft tissue known to contain osteoclasts and macrophage polykaryons respectively was assessed immunohistochemically; the immunophenotype of osteoclast-like giant cells in a wide range of giant cell-containing bone lesions was similarly assessed.ResultsBoth osteoclasts and macrophage polykaryons were found to express CD51. Macrophage polykaryons, but not osteoclasts, expressed CD14 and HLA-DR. CD51+/CD14−/HLA-DR-/CD163– giant cells were noted in all giant-cell lesions of bone, including giant cell tumour of bone, aneurysmal bone cyst, non-ossifying fibroma, chondroblastoma, telangiectatic osteosarcoma, chondromyxoid fibroma, Langerhans cell histiocytosis and brown tumour.ConclusionOur findings indicate that CD51 expression alone is not sufficient for immunocytochemical identification of osteoclasts, which do not express the macrophage-associated antigens CD14 and HLA-DR. Giant cells in most giant cell-rich lesions of bone have an osteoclast phenotype, suggesting that they are formed from mononuclear phagocyte osteoclast precursors.
PHLDA1 Expression Marks the Putative Epithelial Stem Cells and Contributes to Intestinal Tumorigenesis
Authors: Sakthianandeswaren Anuratha , Christie Michael , D'Andreti Carla , Tsui Cary , Jorissen Robert N. , Li Shan , Fleming Nicholas I. , Gibbs Peter , Lipton Lara , Malaterre Jordane , Ramsay Robert G. , Phesse Toby J. , Ernst Matthias , Jeffery Rosemary E. , Poulsom Richard , Leedham Simon J. , Segditsas Stefania , Tomlinson Ian P. M. , Bernhard Oliver K. , Simpson Richard J. , Walker Francesca , Faux Maree C. , Church Nicole , Catimel Bruno , Flanagan Dustin J. , Vincan Elizabeth , Sieber Oliver M. 
Published: May 2011

Abstract
Studies employing mouse models have identified crypt base and position +4 cells as strong candidates for intestinal epithelial stem cells. Equivalent cell populations are thought to exist in the human intestine; however robust and specific protein markers are lacking. Here, we show that in the human small and large intestine, PHLDA1 is expressed in discrete crypt base and some position +4 cells. In small adenomas, PHLDA1 was expressed in a subset of undifferentiated and predominantly Ki-67–negative neoplastic cells, suggesting that a basic hierarchy of differentiation is retained in early tumorigenesis. In large adenomas, carcinomas, and metastases PHLDA1 expression became widespread, with increased expression and nuclear localization at invasive margins. siRNA-mediated suppression of PHLDA1 in colon cancer cells inhibited migration and anchorage-independent growth in vitro and tumor growth in vivo. The integrins ITGA2 and ITGA6 were downregulated in response to PHLDA1 suppression, and accordingly cell adhesion to laminin and collagen was significantly reduced. We conclude that PHLDA1 is a putative epithelial stem cell marker in the human small and large intestine and contributes to migration and proliferation in colon cancer cells. Cancer Res; 71(10); 3709–19. ©2011 AACR.
Randomized Trial of Autologous Cellular Immunotherapy with Sipuleucel-T in Androgen-Dependent Prostate Cancer
Authors: Beer Tomasz M. , Bernstein Guy T. , Corman John M. , Glode L. Michael , Hall Simon J. , Poll Wayne L. , Schellhammer Paul F. , Jones Lori A. , Xu Yi , Kylstra Jelle W. , Frohlich Mark W. 
Published: May 2011

Abstract
Purpose: Sipuleucel-T, an autologous cellular immunotherapy, was investigated in a randomized, double-blind, controlled trial to determine its biologic activity in androgen-dependent prostate cancer (ADPC).
Experimental Design: Patients with prostate cancer detectable by serum prostate-specific antigen (PSA) following radical prostatectomy received 3 to 4 months of androgen suppression therapy, and were then randomized (2:1) to receive sipuleucel-T (n = 117) or control (n = 59). The primary endpoint was time to biochemical failure (BF) defined as serum PSA ≥ 3.0 ng/mL. PSA doubling time (PSADT), time to distant failure, immune response, and safety were also evaluated.
Results: Median time to BF was 18.0 months for sipuleucel-T and 15.4 months for control (HR = 0.936, P = 0.737). Sipuleucel-T patients had a 48% increase in PSADT following testosterone recovery (155 vs. 105 days, P = 0.038). With only 16% of patients having developed distant failure, the treatment effect favored sipuleucel-T (HR = 0.728, P = 0.421). The most frequent adverse events in sipuleucel-T patients were fatigue, chills, and pyrexia. Immune responses to the immunizing antigen were greater in sipuleucel-T patients at Weeks 4 and 13 (P &lt; 0.001, all) and were sustained prior to boosting as measured in a subset of patients a median of 22.6 months (range: 14.3–67.3 months) following randomization.
Conclusions: No significant difference in time to BF could be shown. The finding of increased PSADT in the sipuleucel-T arm is consistent with its biologic activity in ADPC. Long-term follow-up will be necessary to determine if clinically important events, such as distant failure, are affected by therapy. Treatment was generally well tolerated. Clin Cancer Res; 17(13); 4558–67. ©2011 AACR.
Primary Central Nervous System Lymphomas: A Validation Study of Array-Based Comparative Genomic Hybridization in Formalin-Fixed Paraffin-Embedded Tumor Specimens
Authors: Braggio Esteban , McPhail Ellen Remstein , Macon William , Lopes M. Beatriz , Schiff David , Law Mark , Fink Stephanie , Sprau Debra , Giannini Caterina , Dogan Ahmet , Fonseca Rafael , O'Neill Brian Patrick 
Published: May 2011

Abstract
Purpose: Only a limited number of genetic studies have been conducted in primary central nervous system lymphomas (PCNSL), partly due to the rarity of the tumors and the very limited amount of available tissue. In this report, we present the first molecular characterization of copy number abnormalities (CNA) of newly diagnosed PCNSL by array-based comparative genomic hybridization (aCGH) in formalin-fixed paraffin-embedded (FFPE) specimens and compare the results with matched, frozen tumor specimens.
Experimental Design: We conducted aCGH in FFPE tissues from PCNSL. Results were compared with matched, paired, frozen tumors.
Results: Our analysis confirmed the good to fair quality and reliability of the data generated from limited amounts of tumoral FFPE tissue. Overall, all PCNSL cases were characterized by highly complex karyotypes, with a median of 23 CNAs per patient (range, 17–47). Overall, 20 chromosomal regions were recurrently found in more than 40% of cases. Deletions of 6p21, 6q, and 9p21.3 and gain of 12q12-q24.33 were the commonest CNAs. Other minimal affected regions were defined, and novel recurrent CNAs affecting single genes were identified in 3q26.32 (TBL1XR1) and 8q12.1 (TOX).
Conclusions: The results obtained are encouraging. Larger archival tissue collections can now be analyzed to complement the still fragmented knowledge we have of the genetic basis of the PCNSL. Clin Cancer Res; 17(13); 4245–53. ©2011 AACR.
BORIS Binding to the Promoters of Cancer Testis Antigens, MAGEA2, MAGEA3, and MAGEA4, Is Associated with Their Transcriptional Activation in Lung Cancer
Authors: Bhan Sheetal , Negi Sandeep S. , Shao Chunbo , Glazer Chad A. , Chuang Alice , Gaykalova Daria A. , Sun Wenyue , Sidransky David , Ha Patrick K. , Califano Joseph A. 
Published: May 2011

Abstract
Purpose: Aim of this study was to determine whether BORIS (Brother of the Regulator of Imprinted Sites) is a regulator of MAGEA2, MAGEA3, and MAGEA4 genes in lung cancer.
Experimental Design: Changes in expression of MAGEA genes upon BORIS induction/knockdown were studied. Recruitment of BORIS and changes in histone modifications at their promoters upon BORIS induction were analyzed. Luciferase assays were used to study their activation by BORIS. Changes in methylation at these promoters upon BORIS induction were evaluated.
Results: Alteration of BORIS expression by induction/knockdown directly correlated with expression of MAGEA genes. BORIS was enriched at their promoters in H1299 cells, which show high expression of these cancer testis antigens (CTA), compared with normal human bronchial epithelial (NHBE) cells which show low expression of the target CTAs. BORIS induction in A549 cells resulted in increased amounts of BORIS and activating histone modifications at their promoters along with a corresponding increase in their expression. Similarly, BORIS binding at these promoters in H1299 correlates with enrichment of activating modifications, whereas absence of BORIS binding in NHBE is associated with enrichment of repressive marks. BORIS induction of MAGEA3 was associated with promoter demethylation, but no methylation changes were noted with activation of MAGEA2 and MAGEA4.
Conclusions: These data suggest that BORIS positively regulates these CTAs by binding and inducing a shift to a more open chromatin conformation with promoter demethylation for MAGEA3 or independent of promoter demethylation in case of MAGEA2 and MAGEA4 and may be a key effector involved in their derepression in lung cancer. Clin Cancer Res; 17(13); 4267–76. ©2011 AACR.
Chemopreventive Efficacy and Mechanism of Licofelone in a Mouse Lung Tumor Model via Aspiration
Authors: Sharma Sheela , Lee Jin , Zhou Jianliang , Steele Vernon E. 
Published: May 2011

Abstract
Our previous study comparing inhalation and aspiration to administer agents directly to lung indicated that aspiration route is as effective as inhalation while reducing costs for equipment and chemopreventive agent. This study evaluated the chemopreventive efficacy and mechanism of licofelone, a dual inhibitor of COX-2 and 5-lipoxygenase (5-Lox), via oropharyngeal aspiration against mouse lung adenoma. Eight-week-old female A/J mice were given three doses of benzo[a]pyrene (B[a]P; 2 mg/dose, gavage) to induce lung adenomas. After dysplasia developed, the mice were given licofelone (0, 0.03, 0.1, or 0.3 mg/kg) for 16 weeks, and tumor incidence and multiplicity in lung were measured. In addition, the expression of a series of biomarkers in lung cancer progression was evaluated at 2 and 16 weeks. Licofelone showed dose-related inhibition of B[a]P-induced tumor incidence and multiplicity at 0.03 and 0.1 mg/kg following 16-week treatment. Licofelone also showed dose-dependent inhibition of COX-2 (25%–41%) and 5-Lox (35%–61%) at 2 and 16 weeks and proliferating cell nuclear antigen (PCNA; 41%–61%) at 16 weeks. A dose-dependent increase in apoptosis (1.5- to 2.4-fold) was also observed in licofelone groups. A marginal inhibition of survivin was observed at one dose. In conclusion, this study showed that licofelone via aspiration showed chemopreventive efficacy against mouse lung adenoma with good correlation to early and late biomarkers of lung cancer progression. This is the first study to show that the aspiration route can be an excellent inexpensive alternative to inhalation for direct delivery of drugs to rodent lungs for efficacy testing of potential chemopreventive agents. Cancer Prev Res; 4(8); 1233–42. ©2011 AACR.
ECG Identification of Scar-Related Ventricular Tachycardia With a Left Bundle-Branch Block Configuration
Authors: Wijnmaalen Adrianus P. , Stevenson William G. , Schalij Martin J. , Field Michael E. , Stephenson Kent , Tedrow Usha B. , Koplan Bruce A. , Putter Hein , Epstein Lawrence M. , Zeppenfeld Katja 
Published: May 2011

Background—

A left bundle-branch block (LBBB)-like pattern with a dominant S-wave in V
1
is common in idiopathic ventricular arrhythmias (VA). Discrimination between idiopathic and scar-related LBBB pattern VA has important clinical implications. We hypothesized that the VA QRS morphology is influenced by the presence of ventricular scar, allowing ECG discrimination of VA arising from structurally normal versus scarred myocardium.

Methods and Results—

Twelve-lead ECGs of 297 LBBB pattern monomorphic VA were recorded during catheter ablation procedures. QRS morphology characteristics associated with scar-related VA were identified in retrospective analysis of 118 LBBB pattern VA (95 scar-related, 23 idiopathic) to develop a stepwise algorithm that was prospectively tested in 179 LBBB pattern VA (120 scar-related, 59 idiopathic). The diagnosis of scar was based on sinus rhythm surface ECG, cardiovascular imaging, and electroanatomic catheter mapping. A precordial transition beyond V
4
, notching of the S-wave downstroke in lead V
1
or V
2
, and a duration from the onset of QRS to the S-nadir in V
1
>90 ms were independent predictors for scar-related VA. The proposed algorithm classified a VA as scar-related if any of these criteria was met. If none of the criteria was present, a VA was classified as idiopathic. In prospective validation, the algorithm was highly sensitive (96%) and specific (83%) for the identification of scar-related LBBB pattern VA.

Conclusions—
The QRS morphology of VA is different between scar-related and idiopathic VA. A simple ECG algorithm is sensitive for identifying scar-related LBBB VA, which could be helpful in guiding further evaluation of these patients.
New Predictive Models of Heart Failure Mortality Using Time-Series Measurements and Ensemble Models
Authors: Subramanian Devika , Subramanian Venkataraman , Deswal Anita , Mann Douglas L. 
Published: May 2011

Background—
Morbidity and mortality rates associated with heart failure remain high. A wide variety of demographic and clinical factors as well as biomarkers are associated with increased mortality rates. Despite this, most multivariate predictive models for heart failure mortality have predictive accuracies characterized by a C-statistic (area under the receiver operating curve) of ≈0.74.

Methods and Results—

We analyzed data on 963 patients enrolled in the Vesnarinone Evaluation of Survival Trial (VEST), including circulating levels of 2 cytokines (tumor necrosis factor and interleukin-6) and their receptors sampled at baseline and at 8, 16, and 24 weeks. We built multivariate logistic regression models by using standard clinical variables and time-series of cytokine and cytokine receptor levels, using independent components analysis to handle collinearity among cytokine measurements, and L2-penalized stepwise regression for variable selection. We also built ensemble models with these data, using gentle boosting. Our multivariate logistic regression model using time-series cytokine measurements predicts 1-year mortality rates significantly better (
P
=0.001) than the baseline model, with a C-statistic of 0.81±0.03. Without the cytokines, the baseline model has a C-statistic of 0.73±0.03, and, with only baseline cytokine and cytokine receptor levels added, the model has a C-statistic of 0.74±0.04. An ensemble model of 100 decision stumps with serial cytokine measurements has a significantly better (
P
=0.04) C-statistic of 0.84±0.02. An ensemble model with baseline cytokine data and without the serial measurements has a C-statistic of 0.74±0.04.

Conclusions—
Significant gains in accuracy of one year mortality prediction in chronic heart failure can be obtained by using logistic regression models that incorporate serial measurements of biomarkers such as cytokine and cytokine receptor levels. Ensemble models capture inherent variability in large patient populations, and boost predictive accuracy through the use of time-series measurements.
Changing Characteristics and Mode of Death Associated With Chronic Heart Failure Caused by Left Ventricular Systolic Dysfunction
Authors: Cubbon Richard M. , Gale Christopher P. , Kearney Lorraine C. , Schechter Clyde B. , Brooksby W. Paul , Nolan Jim , Fox Keith A.A. , Rajwani Adil , Baig Wazir , Groves David , Barlow Pauline , Fisher Anthony C. , Batin Phillip D. , Kahn Matthew B. , Zaman Azfar G. , Shah Ajay M. , Byrne Jon A. , Lindsay Steven J. , Sapsford Robert J. , Wheatcroft Stephen B. , Witte Klaus K. , Kearney Mark T. 
Published: May 2011

Background—
Therapies for patients with chronic heart failure caused by left ventricular systolic dysfunction have advanced substantially over recent decades. The cumulative effect of these therapies on mortality, mode of death, symptoms, and clinical characteristics has yet to be defined.

Methods and Results—

This study was a comparison of 2 prospective cohort studies of outpatients with chronic heart failure caused by left ventricular systolic dysfunction performed between 1993 and 1995 (historic cohort: n=281) and 2006 and 2009 (contemporary cohort: n=357). In the historic cohort, 83% were prescribed angiotensin-converting enzyme inhibitors and 8.5% were prescribed β-adrenoceptor antagonists, compared with 89% and 80%, respectively, in the contemporary cohort. Mortality rates over the first year of follow-up declined from 12.5% to 7.8% between eras (
P
=0.04), and sudden death contributed less to contemporary mortality (33.6% versus 12.7%;
P
<0.001). New York Heart Association class declined between eras (
P
<0.001). QTc dispersion across the chest leads declined from 85 ms (SD, 2) to 34 ms (SD, 1) and left ventricular end-diastolic dimensions declined from 65 mm (SD, 0.6) to 59 mm (SD, 0.5) (both
P
<0.001).

Conclusions—
Survival has significantly improved in patients with chronic heart failure caused by left ventricular systolic dysfunction over the past 15 years; furthermore, sudden death makes a much smaller contribution to mortality, and noncardiac mortality is a correspondingly greater contribution. This has been accompanied by an improvement in symptoms and some markers of adverse electric and structural left ventricular remodeling.