bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pseudomonas aeruginosa-Induced Bleb-Niche Formation in Epithelial Cells Is Independent of Actinomyosin Contraction and Enhanced by Loss of Cystic Fibrosis Transmembrane-Conductance Regulator Osmoregulatory Function
Authors: Jolly Amber L. , Takawira Desire , Oke Olufolarin O. , Whiteside Sarah A. , Chang Stephanie W. , Wen Emily R. , Quach Kevin , Evans David J. , Fleiszig Suzanne M. J. 
Published: February 2015

ABSTRACT

The opportunistic pathogen
Pseudomonas aeruginosa
can infect almost any site in the body but most often targets epithelial cell-lined tissues such as the airways, skin, and the cornea of the eye. A common predisposing factor is cystic fibrosis (CF), caused by defects in the cystic fibrosis transmembrane-conductance regulator (CFTR). Previously, we showed that when P. aeruginosa enters epithelial cells it replicates intracellularly and occupies plasma membrane blebs. This phenotype is dependent on the type 3 secretion system (T3SS) effector ExoS, shown by others to induce host cell apoptosis. Here, we examined mechanisms for P. aeruginosa-induced bleb formation, focusing on its relationship to apoptosis and the CFTR. The data showed that P. aeruginosa-induced blebbing in epithelial cells is independent of actin contraction and is inhibited by hyperosmotic media (400 to 600 mOsM), distinguishing bacterially induced blebs from apoptotic blebs. Cells with defective CFTR displayed enhanced bleb formation upon infection, as demonstrated using bronchial epithelial cells from a patient with cystic fibrosis and a CFTR inhibitor, CFTR(Inh)-172. The defect was found to be correctable either by incubation in hyperosmotic media or by complementation with CFTR (pGFP-CFTR), suggesting that the osmoregulatory function of CFTR counters P. aeruginosa-induced bleb-niche formation. Accordingly, and despite their reduced capacity for bacterial internalization, CFTR-deficient cells showed greater bacterial occupation of blebs and enhanced intracellular replication. Together, these data suggest that P. aeruginosa bleb niches are distinct from apoptotic blebs, are driven by osmotic forces countered by CFTR, and could provide a novel mechanism for bacterial persistence in the host.

IMPORTANCE
Pseudomonas aeruginosa
is an opportunistic pathogen problematic in hospitalized patients and those with cystic fibrosis (CF). Previously, we showed that P. aeruginosa can enter epithelial cells and replicate within them and traffics to the membrane blebs that it induces. This “bleb-niche” formation requires ExoS, previously shown to cause apoptosis. Here, we show that the driving force for bleb-niche formation is osmotic pressure, differentiating P. aeruginosa-induced blebs from apoptotic blebs. Either CFTR inhibition or CFTR mutation (as seen in people with CF) causes P. aeruginosa to make more bleb niches and provides an osmotic driving force for blebbing. CFTR inhibition also enhances bacterial occupation of blebs and intracellular replication. Since CFTR is targeted for removal from the plasma membrane when P. aeruginosa invades a healthy cell, these findings could relate to pathogenesis in both CF and healthy patient populations.
Implications of private sector Hib vaccine coverage for the introduction of public sector Hib-containing pentavalent vaccine in India: evidence from retrospective time series data
Authors: Sharma Abhishek , Kaplan Warren A , Chokshi Maulik , Hasan Farooqui Habib , Zodpey Sanjay P 
Published: February 2015

ObjectiveHaemophilus influenzaetype b (Hib) vaccine has been available in India's private sector market since 1997. It was not until 14 December 2011 that the Government of India initiated the phased public sector introduction of a Hib (and DPT, diphtheria, pertussis, tetanus)-containing pentavalent vaccine. Our objective was to investigate the state-specific coverage and behaviour of Hib vaccine in India when it was available only in the private sector market but not in the public sector. This baseline information can act as a guide to determine how much coverage the public sector rollout of pentavalent vaccine (scheduled April 2015) will need to bear in order to achieve complete coverage.Setting16 of 29 states in India, 2009–2012.DesignRetrospective descriptive secondary data analysis.Data(1) Annual sales of Hib vaccines, by volume, from private sector hospitals and retail pharmacies collected by IMS Health and (2) national household surveys.Outcome measuresState-specific Hib vaccine coverage (%) and its associations with state-specific socioeconomic status.ResultsThe overall private sector Hib vaccine coverage among the 2009–2012 birth cohort was low (4%) and varied widely among the studied Indian states (minimum 0.3%; maximum 4.6%). We found that private sector Hib vaccine coverage depends on urban areas with good access to the private sector, parent's purchasing capacity and private paediatricians’ prescribing practices. Per capita gross domestic product is a key explanatory variable. The annual Hib vaccine uptake and the 2009–2012 coverage levels were several times higher in the capital/metropolitan cities than the rest of the state, suggesting inequity in access to Hib vaccine delivered by the private sector.ConclusionsIf India has to achieve high and equitable Hib vaccine coverage levels, nationwide public sector introduction of the pentavalent vaccine is needed. However, the role of private sector in universal Hib vaccine coverage is undefined as yet but it should not be neglected as a useful complement to public sector services.
Prevalence of nosocomial pathogens in German ambulances: the SEKURE study
Authors: Wepler M , Stahl W , von Baum H , Wildermuth S , Dirks B , Georgieff M , Hafner S 
Published: February 2015

ObjectiveThe increasing prevalence of multidrug resistant bacteria is a problem in the inpatient care setting, and in the emergency care system. The aim of this observational, cross-sectional study was to evaluate the prevalence of pathogens on well-defined surfaces in German ambulances that have been designated as ‘ready for service’.MethodsAfter informed consent was obtained, ambulance surfaces were sampled with agar plates for microbiological examination during an unannounced visit. A standardised questionnaire was used to obtain information regarding the disinfection protocols used at each rescue station.ResultsMethicillin resistant staphylococcus aureus contamination was present in 18 sampling surfaces from 11 out of 150 ambulance vehicles (7%) that were designated as ready for service. Contact surfaces directly surrounding patients or staff were most frequently contaminated with pathogens. However, bacterial contamination was not related to annual missions, methods or frequency of disinfection.ConclusionsIn accordance with previous studies, disinfection and cleaning of areas with direct contact to patients or staff seem to be the most challenging. This should also be reflected in disinfection guidelines and the related continuing education.
Effect of feeding fermented rice punch on oestrous induction in anoestrous bitches
Authors: Choi Eul‐Soo , Yang Byoung‐Chul , Park Pu‐Rum , Chae Jung‐Il , Kim Dong‐Ku , Yoo Jae‐Kyu , Kim Dong‐Hoon , Cho Kyu‐Woan , Kong Il‐Keun 
Published: February 2015

IntroductionAs a consequence of poor productivity caused by a long anoestrous period, considerable research effort has been given to oestrus induction in dogs to enhance the productivity of young dogs and to preserve breeds.Materials and methodsOestrus was induced in 30 anoestrous bitches more than three months after the last oestrus. Bitches orally received fermented rice punch with or without bromocriptine once daily for 21 consecutive days. The bitches were divided into two groups (n=10 per group): Group (1) fed fermented rice punch and Group (2) administered bromocriptine (100 µg/kg/day) and fed fermented rice punch.ResultsThe concentration of dopamine in fermented rice punch was 47.2 mg/kg (parts per million). Six of 10 (60.0 per cent) and seven of 10 (70.0 per cent) bitches showed pro‐oestrual bleeding in Groups 1 and 2, respectively. The mean and median values (min–max) to oestrus induction was not significantly different between Groups 1 and 2 (9.7±7.3, 6.5 (3–22) and 11.3±6.6, 7.9 (5–21) days) after treatment commencement (P>0.05). The pregnancy rate was very similar between Groups 1, 2 (66.0%) and control (66.0, 57.0 and 50.0 per cent). The mean and median values (min–max) of pups per bitch are also not significantly different between Groups 1, 2 and control (7.0±1.8, 7.0 (5–9) and 7.5±2.1, 7.5 (5–10) and 7.0±0, 7.0 (7–7)).ConclusionWe suggest that rice punch effectively induces oestrus in bitches.
Four Years Analysis of Cancer Genetic Clinics Activity in France from 1994 to 1997: A Survey on 801 Patients
Authors: Sobol Hagay , Bignon Yves-Jean , Bonaiti Catherine , Cuisenier Jean , Lasset Christine , Lortholary Alain , Noguès Catherine , Stoppa-Lyonnet Dominique , Eisinger François , The French Cooperative Network/Groupe Génétique et Cancer de  
Published: February 2015

AIM: In order to evaluate the characteristics and the evolution of cancer genetics activity in France, a survey was conducted at the national level during a period of 4 years from 1994 to 1997 through the French Cooperative Network, a multidisciplinary group formed to investigate inherited tumors.METHOD: A questionnaire was sent to all the 29 French non‐specialized cancer genetic clinics to evaluate activity during a period of 4 consecutive weeks each year from 1994 to 1997. Items concerning the cancer genetic clinics, the consultees and the types of consultation were explored.RESULTS: A total number of 801 consultees were seen during the period of analysis. Some prominent characteristics of patients attending cancer genetic clinics were found. The majority of these are women (88%), and the mean age of consultees is 48 years. Fifty five percent of consultees are affected with cancer, and breast (personal and/or family history) is the most frequent site involved (63%). A genetic predisposition is certain or likely in about 53% of cases and unlikely in only 13% of consultations. The majority of consultations are devoted to new families (71%). The mean duration of consultations is 50 minutes, but 40% have a duration of at least 1 hour. Variations of several parameters during the 4 years period were observed and analyzed. Finally, since duration of consultations (more or equal to 1 hour) and personal or family history of breast/ovarian cancer appeared as pivotal elements in our study and consequently may affect the organization of clinics and the structuring as well as the evolution of cancer genetic activity in France, we analyzed more precisely the factors significantly associated with these 2 elements.CONCLUSION: Study compliance was fair (60% of centers) and these results give a good measure of cancer genetic activity in France. The variation of parameters from one year to another may reflect modifications in medical practice (medical orientation rather than research focus and content of cancer genetic clinics) and/or scientific breakthroughs in cancer genetics such as identification of genes predisposing to cancer.
FOXP3–miR-146–NF-κB Axis and Therapy for Precancerous Lesions in Prostate
Authors: Liu Runhua , Yi Bin , Wei Shi , Yang Wei-Hsiung , Hart Karen M. , Chauhan Priyanka , Zhang Wei , Mao Xicheng , Liu Xiuping , Liu Chang-Gong , Wang Lizhong 
Published: February 2015

Abstract
The tumor-suppressive activity of FOXP3 has been observed in tumor initiation, but the underlying mechanism still remains largely unknown. Here, we identified a FOXP3–microRNA-146 (miR-146)–NF-κB axis in vitro and in vivo in prostate cancer cells. We observed that FOXP3 dramatically induced the expression of miR-146a/b, which contributed to transcriptional inhibition of IRAK1 and TRAF6, in prostate cancer cell lines. Tissue-specific deletion of Foxp3 in mouse prostate caused a significant reduction of miR-146a and upregulation of NF-κB activation. In addition, prostatic intraepithelial neoplasia lesions were observed in miR-146a–mutant mice as well as in Foxp3-mutant mice. Notably, the NF-κB inhibitor bortezomib inhibited cell proliferation and induced apoptosis in prostate epithelial cells, attenuating prostatic intraepithelial neoplasia formation in Foxp3-mutant mice. Our data suggest that the FOXP3–miR-146–NF-κB axis has a functional role during tumor initiation in prostate cancer. Targeting the miR-146–NF-κB axis may provide a new therapeutic approach for prostate cancers with FOXP3 defects. Cancer Res; 75(8); 1714–24. ©2015 AACR.
TWIST1-Induced miR-424 Reversibly Drives Mesenchymal Programming while Inhibiting Tumor Initiation
Authors: Drasin David J. , Guarnieri Anna L. , Neelakantan Deepika , Kim Jihye , Cabrera Joshua H. , Wang Chu-An , Zaberezhnyy Vadym , Gasparini Pierluigi , Cascione Luciano , Huebner Kay , Tan Aik-Choon , Ford Heide L. 
Published: February 2015

Abstract
Epithelial-to-mesenchymal transition (EMT) is a dynamic process that relies on cellular plasticity. Recently, the process of an oncogenic EMT, followed by a reverse mesenchymal-to-epithelial transition (MET), has been implicated as critical in the metastatic colonization of carcinomas. Unlike governance of epithelial programming, regulation of mesenchymal programming is not well understood in EMT. Here, we describe and characterize the first microRNA that enhances exclusively mesenchymal programming. We demonstrate that miR-424 is upregulated early during a TWIST1 or SNAI1-induced EMT, and that it causes cells to express mesenchymal genes without affecting epithelial genes, resulting in a mixed/intermediate EMT. Furthermore, miR-424 increases motility, decreases adhesion, and induces a growth arrest, changes associated with a complete EMT that can be reversed when miR-424 expression is lowered, concomitant with an MET-like process. Breast cancer patient miR-424 levels positively associate with TWIST1/2 and EMT-like gene signatures, and miR-424 is increased in primary tumors versus matched normal breast. However, miR-424 is downregulated in patient metastases versus matched primary tumors. Correspondingly, miR-424 decreases tumor initiation and is posttranscriptionally downregulated in macrometastases in mice, suggesting the need for biphasic expression of miR-424 to transit the EMT–MET axis. Next-generation RNA sequencing revealed miR-424 regulates numerous EMT and cancer stemness-associated genes, including TGFBR3, whose downregulation promotes mesenchymal phenotypes, but not tumor-initiating phenotypes. Instead, we demonstrate that increased MAPK–ERK signaling is critical for miR-424–mediated decreases in tumor-initiating phenotypes. These findings suggest miR-424 plays distinct roles in tumor progression, potentially facilitating earlier, but repressing later, stages of metastasis by regulating an EMT–MET axis. Cancer Res; 75(9); 1908–21. ©2015 AACR.
Development and Validation of a Melanoma Risk Score Based on Pooled Data from 16 Case–Control Studies
Authors: Davies John R. , Chang Yu-mei , Bishop D. Timothy , Armstrong Bruce K. , Bataille Veronique , Bergman Wilma , Berwick Marianne , Bracci Paige M. , Elwood J. Mark , Ernstoff Marc S. , Green Adele , Gruis Nelleke A. , Holly Elizabeth A. , Ingvar Christian , Kanetsky Peter A. , Karagas Margaret R. , Lee Tim K. , Le Marchand Loïc , Mackie Rona M. , Olsson Håkan , Østerlind Anne , Rebbeck Timothy R. , Reich Kristian , Sasieni Peter , Siskind Victor , Swerdlow Anthony J. , Titus Linda , Zens Michael S. , Ziegler Andreas , Gallagher Richard P. , Barrett Jennifer H. , Newton-Bishop Julia 
Published: February 2015

Abstract
Background: We report the development of a cutaneous melanoma risk algorithm based upon seven factors; hair color, skin type, family history, freckling, nevus count, number of large nevi, and history of sunburn, intended to form the basis of a self-assessment Web tool for the general public.
Methods: Predicted odds of melanoma were estimated by analyzing a pooled dataset from 16 case–control studies using logistic random coefficients models. Risk categories were defined based on the distribution of the predicted odds in the controls from these studies. Imputation was used to estimate missing data in the pooled datasets. The 30th, 60th, and 90th centiles were used to distribute individuals into four risk groups for their age, sex, and geographic location. Cross-validation was used to test the robustness of the thresholds for each group by leaving out each study one by one. Performance of the model was assessed in an independent UK case–control study dataset.
Results: Cross-validation confirmed the robustness of the threshold estimates. Cases and controls were well discriminated in the independent dataset [area under the curve, 0.75; 95% confidence interval (CI), 0.73–0.78]. Twenty-nine percent of cases were in the highest risk group compared with 7% of controls, and 43% of controls were in the lowest risk group compared with 13% of cases.
Conclusion: We have identified a composite score representing an estimate of relative risk and successfully validated this score in an independent dataset.
Impact: This score may be a useful tool to inform members of the public about their melanoma risk. Cancer Epidemiol Biomarkers Prev; 24(5); 817–24. ©2015 AACR.
Dense and Nondense Mammographic Area and Risk of Breast Cancer by Age and Tumor Characteristics
Authors: Bertrand Kimberly A. , Scott Christopher G. , Tamimi Rulla M. , Jensen Matthew R. , Pankratz V. Shane , Norman Aaron D. , Visscher Daniel W. , Couch Fergus J. , Shepherd John , Chen Yunn-Yi , Fan Bo , Wu Fang-Fang , Ma Lin , Beck Andrew H. , Cummings Steven R. , Kerlikowske Karla , Vachon Celine M. 
Published: February 2015

AbstractBackground: Mammographic density (MD) is a strong breast cancer risk factor. We previously reported associations of percent mammographic density (PMD) with larger and node-positive tumors across all ages, and estrogen receptor (ER)–negative status among women ages &lt;55 years. To provide insight into these associations, we examined the components of PMD [dense area (DA) and nondense area (NDA)] with breast cancer subtypes.Methods: Data were pooled from six studies including 4,095 breast cancers and 8,558 controls. DA and NDA were assessed from digitized film-screen mammograms and standardized across studies. Breast cancer odds by density phenotypes and age according to histopathologic characteristics and receptor status were calculated using polytomous logistic regression.Results: DA was associated with increased breast cancer risk [OR for quartiles: 0.65, 1.00 (Ref), 1.22, 1.55; Ptrend &lt;0.001] and NDA was associated with decreased risk [ORs for quartiles: 1.39, 1.00 (Ref), 0.88, 0.72; Ptrend &lt;0.001] across all ages and invasive tumor characteristics. There were significant trends in the magnitude of associations of both DA and NDA with breast cancer by increasing tumor size (Ptrend &lt; 0.001) but no differences by nodal status. Among women &lt;55 years, DA was more strongly associated with increased risk of ER+ versus ER− tumors (Phet = 0.02), while NDA was more strongly associated with decreased risk of ER− versus ER+ tumors (Phet = 0.03).Conclusions: DA and NDA have differential associations with ER+ versus ER− tumors that vary by age.Impact: DA and NDA are important to consider when developing age- and subtype-specific risk models. Cancer Epidemiol Biomarkers Prev; 24(5); 798–809. ©2015 AACR.
Association between Regular Aspirin Use and Circulating Markers of Inflammation: A Study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: Lang Kuhs Krystle A. , Hildesheim Allan , Trabert Britton , Kemp Troy J. , Purdue Mark P. , Wentzensen Nicolas , Katki Hormuzd A. , Pinto Ligia A. , Loftfield Erikka , Safaeian Mahboobeh , Chaturvedi Anil K. , Shiels Meredith S. 
Published: February 2015

Abstract
Background: Regular aspirin use may decrease cancer risk by reducing chronic inflammation. However, associations between aspirin use and circulating markers of inflammation have not been well studied.
Methods: Serum levels of 78 inflammatory markers were measured in 1,819 55- to 74-year-old men and women in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Data were combined from three completed case–control studies and reweighted to the PLCO screening arm. Self-reported aspirin and ibuprofen use (number of tablets taken per day/week/month) over the previous 12 months was collected at baseline. Associations between (i) nonregular (&lt;4 tablets/month), (ii) low (1–4 tablets/week), (iii) moderate (1 tablet/day), or (iv) high (2+ tablets/day) regular aspirin or ibuprofen use and marker levels were assessed with weighted logistic regression.
Results: Aspirin use was nominally associated with (Ptrend across categories ≤ 0.05) decreased levels of chemokine C-C motif ligand 15 [CCL15; OR, 0.5; 95% confidence intervals (CI), 0.3–0.8; moderate versus nonregular use]; soluble vascular endothelial growth factor receptor 2 (sVEGFR2; OR, 0.7; 95% CI, 0.4–1.0); soluble tumor necrosis factor receptor 1 (sTNFR1; OR, 0.6; 95% CI, 0.4–0.9) and increased levels of CCL13 (OR, 1.3; 95% CI, 0.8–2.1); CCL17 (OR, 1.1; 95% CI, 0.7–1.9) and interleukin 4 (IL4; OR, 1.6; 95% CI, 0.9–2.8). Trends were not statistically significant following correction for multiple comparisons. Likewise, no statistically significant associations were observed between ibuprofen use and marker levels.
Conclusions: No significant associations were observed between regular aspirin use and the inflammatory markers assessed.
Impact: Additional studies are needed to better understand the relationship between aspirin use, chronic inflammation, and cancer risk. Cancer Epidemiol Biomarkers Prev; 24(5); 825–32. ©2015 AACR.
Androgen Receptor Gene Aberrations in Circulating Cell-Free DNA: Biomarkers of Therapeutic Resistance in Castration-Resistant Prostate Cancer
Authors: Azad Arun A. , Volik Stanislav V. , Wyatt Alexander W. , Haegert Anne , Le Bihan Stephane , Bell Robert H. , Anderson Shawn A. , McConeghy Brian , Shukin Robert , Bazov Jenny , Youngren Jack , Paris Pamela , Thomas George , Small Eric J. , Wang Yuzhuo , Gleave Martin E. , Collins Colin C. , Chi Kim N. 
Published: February 2015

Abstract
Purpose: Although novel agents targeting the androgen–androgen receptor (AR) axis have altered the treatment paradigm of metastatic castration-resistant prostate cancer (mCRPC), development of therapeutic resistance is inevitable. In this study, we examined whether AR gene aberrations detectable in circulating cell-free DNA (cfDNA) are associated with resistance to abiraterone acetate and enzalutamide in mCRPC patients.
Experimental Design: Plasma was collected from 62 mCRPC patients ceasing abiraterone acetate (n = 29), enzalutamide (n = 19), or other agents (n = 14) due to disease progression. DNA was extracted and subjected to array comparative genomic hybridization (aCGH) for chromosome copy number analysis, and Roche 454 targeted next-generation sequencing of exon 8 in the AR.
Results: On aCGH, AR amplification was significantly more common in patients progressing on enzalutamide than on abiraterone or other agents (53% vs. 17% vs. 21%, P = 0.02, χ2). Missense AR exon 8 mutations were detected in 11 of 62 patients (18%), including the first reported case of an F876L mutation in an enzalutamide-resistant patient and H874Y and T877A mutations in 7 abiraterone-resistant patients. In patients switched onto enzalutamide after cfDNA collection (n = 39), an AR gene aberration (copy number increase and/or an exon 8 mutation) in pretreatment cfDNA was associated with adverse outcomes, including lower rates of PSA decline ≥ 30% (P = 0.013, χ2) and shorter time to radiographic/clinical progression (P = 0.010, Cox proportional hazards regression).
Conclusions: AR gene aberrations in cfDNA are associated with resistance to enzalutamide and abiraterone in mCRPC. Our data illustrate that genomic analysis of cfDNA is a minimally invasive method for interrogating mechanisms of therapeutic resistance in mCRPC. Clin Cancer Res; 21(10); 2315–24. ©2015 AACR.