bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-Genome Sequencing Allows for Improved Identification of Persistent Listeria monocytogenes in Food-Associated Environments
Authors: Stasiewicz Matthew J. , Oliver Haley F. , Wiedmann Martin , den Bakker Henk C. 
Published: June 2015

ABSTRACT

While the food-borne pathogen
Listeria monocytogenes
can persist in food associated environments, there are no whole-genome sequence (WGS) based methods to differentiate persistent from sporadic strains. Whole-genome sequencing of 188 isolates from a longitudinal study of
L. monocytogenes
in retail delis was used to (i) apply single-nucleotide polymorphism (SNP)-based phylogenetics for subtyping of
L. monocytogenes
, (ii) use SNP counts to differentiate persistent from repeatedly reintroduced strains, and (iii) identify genetic determinants of
L. monocytogenes
persistence. WGS analysis revealed three prophage regions that explained differences between three pairs of phylogenetically similar populations with pulsed-field gel electrophoresis types that differed by ≤3 bands. WGS-SNP-based phylogenetics found that putatively persistent
L. monocytogenes
represent SNP patterns (i) unique to a single retail deli, supporting persistence within the deli (11 clades), (ii) unique to a single state, supporting clonal spread within a state (7 clades), or (iii) spanning multiple states (5 clades). Isolates that formed one of 11 deli-specific clades differed by a median of 10 SNPs or fewer. Isolates from 12 putative persistence events had significantly fewer SNPs (median, 2 to 22 SNPs) than between isolates of the same subtype from other delis (median up to 77 SNPs), supporting persistence of the strain. In 13 events, nearly indistinguishable isolates (0 to 1 SNP) were found across multiple delis. No individual genes were enriched among persistent isolates compared to sporadic isolates. Our data show that WGS analysis improves food-borne pathogen subtyping and identification of persistent bacterial pathogens in food associated environments.
Type III Secretion System Translocon Component EseB Forms Filaments on and Mediates Autoaggregation of and Biofilm Formation by Edwardsiella tarda
Authors: Gao Zhi Peng , Nie Pin , Lu Jin Fang , Liu Lu Yi , Xiao Tiao Yi , Liu Wei , Liu Jia Shou , Xie Hai Xia 
Published: June 2015

ABSTRACT

The type III secretion system (T3SS) of
Edwardsiella tarda
plays an important role in infection by translocating effector proteins into host cells. EseB, a component required for effector translocation, is reported to mediate autoaggregation of
E. tarda
. In this study, we demonstrate that EseB forms filamentous appendages on the surface of
E. tarda
and is required for biofilm formation by
E. tarda
in Dulbecco's modified Eagle's medium (DMEM). Biofilm formation by
E. tarda
in DMEM does not require FlhB, an essential component for assembling flagella. Dynamic analysis of EseB filament formation, autoaggregation, and biofilm formation shows that the formation of EseB filaments occurs prior to autoaggregation and biofilm formation. The addition of an EseB antibody to
E. tarda
cultures before bacterial autoaggregation prevents autoaggregation and biofilm formation in a dose-dependent manner, whereas the addition of the EseB antibody to
E. tarda
cultures in which biofilm is already formed does not destroy the biofilm. Therefore, EseB filament-mediated bacterial cell-cell interaction is a prerequisite for autoaggregation and biofilm formation.
Composition of Bacterial Communities Associated with Aurelia aurita Changes with Compartment, Life Stage, and Population
Authors: Weiland-Bräuer Nancy , Neulinger Sven C. , Pinnow Nicole , Künzel Sven , Baines John F. , Schmitz Ruth A. 
Published: June 2015

ABSTRACT

The scyphozoan
Aurelia aurita
is recognized as a key player in marine ecosystems and a driver of ecosystem change. It is thus intensely studied to address ecological questions, although its associations with microorganisms remain so far undescribed. In the present study, the microbiota associated with
A. aurita
was visualized with fluorescence
in situ
hybridization (FISH) analysis, and community structure was analyzed with respect to different life stages, compartments, and populations of
A. aurita
by 16S rRNA gene amplicon sequencing. We demonstrate that the composition of the
A. aurita
microbiota is generally highly distinct from the composition of communities present in ambient water. Comparison of microbial communities from different developmental stages reveals evidence for life stage-specific community patterns. Significant restructuring of the microbiota during strobilation from benthic polyp to planktonic life stages is present, arguing for a restructuring during the course of metamorphosis. Furthermore, the microbiota present in different compartments of the adult medusa (exumbrella mucus and gastric cavity) display significant differences, indicating body part-specific colonization. A novel
Mycoplasma
strain was identified in both compartment-specific microbiota and is most likely present inside the epithelium as indicated by FISH analysis of polyps, indicating potential endosymbiosis. Finally, comparison of polyps of different populations kept under the same controlled laboratory conditions in the same ambient water showed population-specific community patterns, most likely due the genetic background of the host. In conclusion, the presented data indicate that the associated microbiota of
A. aurita
may play important functional roles, e.g., during the life cycle.
FAST CP:protocol of a randomised controlled trial of the efficacy of a 12-week combined Functional Anaerobic and Strength Training programme on muscle properties and mechanical gait deficiencies in adolescents and young adults with spastic-type cerebral palsy
Authors: Gillett Jarred G , Lichtwark Glen A , Boyd Roslyn N , Barber Lee A 
Published: June 2015

IntroductionIndividuals with cerebral palsy (CP) have muscles that are smaller, weaker and more resistant to stretch compared to typically developing people. Progressive resistance training leads to increases in muscle size and strength. In CP, the benefits of resistance training alone may not transfer to improve other activities such as walking; however, the transfer of strength improvements to improved mobility may be enhanced by performing training that involves specific functional tasks or motor skills. This study aims to determine the efficacy of combined functional anaerobic and strength training in (1) influencing muscle strength, structure and function and (2) to determine if any changes in muscle strength and structure following training impact on walking ability and gross motor functional capacity and performance in the short (following 3 months of training) and medium terms (a further 3 months post-training).Methods and analysis40 adolescents and young adults with CP will be recruited to undertake a 12-week training programme. The training programme will consist of 3×75 min sessions per week, made up of 5 lower limb resistance exercises and 2–3 functional anaerobic exercises per session. The calf muscles will be specifically targeted, as they are the most commonly impacted muscles in CP and are a key muscle group involved in walking. If, as we believe, muscle properties change following combined strength and functional training, there may be long-term benefits of this type of training in slowing the deterioration of muscle function in people with spastic-type CP.Ethics and disseminationEthical approval has been obtained from the ethics committees at The University of Queensland (2014000066) and Children's Health Queensland (HREC/15/QRCH/30). The findings will be disseminated by publications in peer-reviewed journals, conferences and local research organisations’ media.Trial registration numberAustralian and New Zealand Clinical Trials Registry (ACTRN12614001217695).
Fetuin-A is related to infarct size, left ventricular function and remodelling after acute STEMI
Authors: Feistritzer Hans-Josef , Klug Gert , Reinstadler Sebastian J , Gröber Marie-Therese , Mair Johannes , Kirchmair Rudolf , Henninger Benjamin , Franz Wolfgang-Michael , Metzler Bernhard 
Published: June 2015

ObjectiveTo investigate the relationship between plasma fetuin-A, an anti-inflammatory glycoprotein which might be involved in myocardial healing after acute infarction, and infarct size, left ventricular (LV) function and dimensions as well as the occurrence of adverse remodelling at 4 months after acute ST segment elevation myocardial infarction (STEMI).MethodsIn this single-centre prospective, observational study, 89 patients underwent cardiac MR within the first week and 4 months after mechanical reperfusion for first STEMI. Infarct size, LV function and dimensions were assessed at both time points. Fetuin-A levels were determined from blood samples drawn at a median of 49 h (IQR 30–59 h) after STEMI by an immunofluorescent assay.ResultsFetuin-A levels (median 568 µg/mL, IQR 478–763 µg/mL) were significantly correlated with infarct size and LV ejection fraction at baseline and follow-up (all p<0.05). Moreover, fetuin-A was related to the increase in the end-diastolic volume index (r=−0.383, p<0.001). According to multivariate logistic regression analysis, fetuin-A concentrations (HR=0.17, 95% CI 0.03 to 0.89, p=0.036) besides the presence of late microvascular obstruction (HR=10.03, 95% CI 0.98 to 102.43, p=0.05) were significantly related to the occurrence of adverse LV remodelling at 4 months.ConclusionsCirculating fetuin-A at day 2 after STEMI is related to acute and chronic infarct size, LV function and dimensions. In addition, it might be useful to identify patients at increased risk for adverse LV remodelling.
Novel Cell-Penetrating Peptide-Based Vaccine Induces Robust CD4+ and CD8+ T Cell–Mediated Antitumor Immunity
Authors: Derouazi Madiha , Di Berardino-Besson Wilma , Belnoue Elodie , Hoepner Sabine , Walther Romy , Benkhoucha Mahdia , Teta Patrick , Dufour Yannick , Yacoub Maroun Céline , Salazar Andres M. , Martinvalet Denis , Dietrich Pierre-Yves , Walker Paul R. 
Published: June 2015

AbstractVaccines that can coordinately induce multi-epitope T cell–mediated immunity, T helper functions, and immunologic memory may offer effective tools for cancer immunotherapy. Here, we report the development of a new class of recombinant protein cancer vaccines that deliver different CD8+ and CD4+ T-cell epitopes presented by MHC class I and class II alleles, respectively. In these vaccines, the recombinant protein is fused with Z12, a novel cell-penetrating peptide that promotes efficient protein loading into the antigen-processing machinery of dendritic cells. Z12 elicited an integrated and multi-epitopic immune response with persistent effector T cells. Therapy with Z12-formulated vaccines prolonged survival in three robust tumor models, with the longest survival in an orthotopic model of aggressive brain cancer. Analysis of the tumor sites showed antigen-specific T-cell accumulation with favorable modulation of the balance of the immune infiltrate. Taken together, the results offered a preclinical proof of concept for the use of Z12-formulated vaccines as a versatile platform for the development of effective cancer vaccines. Cancer Res; 75(15); 3020–31. ©2015 AACR.
Heregulin–ErbB3-Driven Tumor Growth Persists in PI3 Kinase Mutant Cancer Cells
Authors: Yarar Defne , Lahdenranta Johanna , Kubasek William , Nielsen Ulrik B. , MacBeath Gavin 
Published: June 2015

Abstract
PI3K is frequently mutated in cancer and plays an important role in cell growth and survival. Heregulin (HRG)-mediated autocrine or paracrine signaling through the receptor tyrosine kinase ErbB3 potently activates the PI3K/AKT pathway and has been shown to mediate resistance to a wide variety of anticancer agents. Although PI3K functions downstream of HRG–ErbB3, it is unknown whether activating mutations in PI3K render HRG ineffective. If so, patients with PI3K mutations would not be expected to benefit from ErbB3-directed therapies. Here, we find that a subset of cell lines harboring activating PI3K mutations can be further growth-stimulated by HRG, and this effect is blocked by incubation with seribantumab (MM-121), a monoclonal anti-ErbB3 antibody. Although expression of mutant PI3K in wild-type PI3K cells frequently results in loss of HRG-stimulated growth, some cell lines continue to respond to HRG. In cell lines where HRG-stimulated growth is lost, this loss is invariably accompanied by a reduction in ErbB3 levels, a corresponding increase in basal phosphorylation levels of FOXO-family transcription factors, and a reduction in HRG-induced downstream signaling. Importantly, HRG-stimulated growth is partially rescued by re-expressing ErbB3. This response is blocked by seribantumab, indicating that ErbB3 levels rather than downstream signaling proteins limit HRG-stimulated growth in PI3K mutant cells. Overall, these results suggest that activating mutations in PI3K do not preclude potential benefit from ErbB3-directed therapy, but that it may be important to measure ErbB3 levels in patients with PI3K mutant cancers to determine if they would benefit. Mol Cancer Ther; 14(9); 2072–80. ©2015 AACR.
AKT Antagonist AZD5363 Influences Estrogen Receptor Function in Endocrine-Resistant Breast Cancer and Synergizes with Fulvestrant (ICI182780) In Vivo
Authors: Ribas Ricardo , Pancholi Sunil , Guest Stephanie K. , Marangoni Elisabetta , Gao Qiong , Thuleau Aurélie , Simigdala Nikiana , Polanska Urszula M. , Campbell Hayley , Rani Aradhana , Liccardi Gianmaria , Johnston Stephen , Davies Barry R. , Dowsett Mitch , Martin Lesley-Ann 
Published: June 2015

Abstract
PI3K/AKT/mTOR signaling plays an important role in breast cancer. Its interaction with estrogen receptor (ER) signaling becomes more complex and interdependent with acquired endocrine resistance. Targeting mTOR combined with endocrine therapy has shown clinical utility; however, a negative feedback loop exists downstream of PI3K/AKT/mTOR. Direct blockade of AKT together with endocrine therapy may improve breast cancer treatment. AZD5363, a novel pan-AKT kinase catalytic inhibitor, was examined in a panel of ER+ breast cancer cell lines (MCF7, HCC1428, T47D, ZR75.1) adapted to long-term estrogen deprivation (LTED) or tamoxifen (TamR). AZD5363 caused a dose-dependent decrease in proliferation in all cell lines tested (GI50 &lt; 500 nmol/L) except HCC1428 and HCC1428-LTED. T47D-LTED and ZR75-LTED were the most sensitive of the lines (GI50 ∼100 nmol/L). AZD5363 resensitized TamR cells to tamoxifen and acted synergistically with fulvestrant. AZD5363 decreased p-AKT/mTOR targets leading to a reduction in ERα-mediated transcription in a context-specific manner and concomitant decrease in recruitment of ER and CREB-binding protein (CBP) to estrogen response elements located on the TFF1, PGR, and GREB1 promoters. Furthermore, AZD5363 reduced expression of cell-cycle–regulatory proteins. Global gene expression highlighted ERBB2-ERBB3, ERK5, and IGFI signaling pathways driven by MYC as potential feedback-loops. Combined treatment with AZD5363 and fulvestrant showed synergy in an ER+ patient-derived xenograft and delayed tumor progression after cessation of therapy. These data support the combination of AZD5363 with fulvestrant as a potential therapy for breast cancer that is sensitive or resistant to E-deprivation or tamoxifen and that activated AKT is a determinant of response, supporting the need for clinical evaluation. Mol Cancer Ther; 14(9); 2035–48. ©2015 AACR.
Integration of Downstream Signals of Insulin-like Growth Factor-1 Receptor by Endoplasmic Reticulum Stress for Estrogen-Induced Growth or Apoptosis in Breast Cancer Cells
Authors: Fan Ping , Cunliffe Heather E. , Maximov Philipp Y. , Agboke Fadeke A. , McDaniel Russell E. , Zou Xiaojun , Ramos Pilar , Russell Megan L. , Jordan V. Craig 
Published: June 2015

Abstract
Estrogen (E2) exerts a dual function on E2-deprived breast cancer cells, with both initial proliferation and subsequent induction of stress responses to cause apoptosis. However, the mechanism by which E2 integrally regulates cell growth or apoptosis-associated pathways remains to be elucidated. Here, E2 deprivation results in many alterations in stress-responsive pathways. For instance, E2-deprived breast cancer cells had higher basal levels of stress-activated protein kinase, c-Jun N-terminal kinase (JNK), compared with wild-type MCF-7 cells. E2 treatment further constitutively activated JNK after 24 hours. However, inhibition of JNK (SP600125) was unable to abolish E2- induced apoptosis, whereas SP600125 alone arrested cells at the G2 phase of the cell cycle and increased apoptosis. Further examination showed that inhibition of JNK increased gene expression of TNFα and did not effectively attenuate expression of apoptosis-related genes induced by E2. A notable finding was that E2 regulated both JNK and Akt as the downstream signals of insulin-like growth factor-1 receptor (IGFIR)/PI3K, but with distinctive modulation patterns: JNK was constitutively activated, whereas Akt and Akt-associated proteins, such as PTEN and mTOR, were selectively degraded. Endoplasmic reticulum–associated degradation (ERAD) was involved in the selective protein degradation. These findings highlight a novel IGFIR/PI3K/JNK axis that plays a proliferative role during the prelude to E2-induced apoptosis and that the endoplasmic reticulum is a key regulatory site to decide cell fate after E2 treatment.
Implications: This study provides a new rationale for further exploration of E2-induced apoptosis to improve clinical benefit. Mol Cancer Res; 13(10); 1367–76. ©2015 AACR.
Chemopreventive Effects of Korean Angelica versus Its Major Pyranocoumarins on Two Lineages of Transgenic Adenocarcinoma of Mouse Prostate Carcinogenesis
Authors: Tang Su-Ni , Zhang Jinhui , Wu Wei , Jiang Peixin , Puppala Manohar , Zhang Yong , Xing Chengguo , Kim Sung-Hoon , Jiang Cheng , Lü Junxuan 
Published: June 2015

AbstractWe showed previously that daily gavage of Angelica gigas Nakai (AGN) root ethanolic extract starting 8 weeks of age inhibited growth of prostate epithelium and neuroendocrine carcinomas (NE-Ca) in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Because decursin (D) and its isomer decursinol angelate (DA) are major pyranocoumarins in AGN extract, we tested the hypothesis that D/DA represented active/prodrug compounds against TRAMP carcinogenesis. Three groups of male C57BL/6 TRAMP mice were gavage treated daily with excipient vehicle, AGN (5 mg per mouse), or equimolar D/DA (3 mg per mouse) from 8 weeks to 16 or 28 weeks of age. Measurement of plasma and NE-Ca D, DA, and their common metabolite decursinol indicated similar retention from AGN versus D/DA dosing. The growth of TRAMP dorsolateral prostate (DLP) in AGN- and D/DA-treated mice was inhibited by 66% and 61% at 16 weeks and by 67% and 72% at 28 weeks, respectively. Survival of mice bearing NE-Ca to 28 weeks was improved by AGN, but not by D/DA. Nevertheless, AGN- and D/DA-treated mice had lower NE-Ca burden. Immunohistochemical and mRNA analyses of DLP showed that AGN and D/DA exerted similar inhibition of TRAMP epithelial lesion progression and key cell-cycle genes. Profiling of NE-Ca mRNA showed a greater scope of modulating angiogenesis, epithelial–mesenchymal transition, invasion–metastasis, and inflammation genes by AGN than D/DA. The data therefore support D/DA as probable active/prodrug compounds against TRAMP epithelial lesions, and they cooperate with non-pyranocoumarin compounds to fully express AGN efficacy against NE-Ca. Cancer Prev Res; 8(9); 835–44. ©2015 AACR.
A Clinical Study of Pharyngolaryngectomy with Total Esophagectomy
Authors: Kamiyama Ryosuke , Mitani Hiroki , Yonekawa Hiroyuki , Fukushima Hirofumi , Sasaki Toru , Shimbashi Wataru , Seto Akira , Koizumi Yuh , Ebina Aya , Kawabata Kazuyoshi 
Published: June 2015

ObjectivePatients with advanced hypopharyngeal or cervical esophageal cancer have a comparatively high risk of also developing thoracic esophageal cancer. Pharyngolaryngectomy with total esophagectomy is highly invasive, and few reports about it exist. We examined the postoperative complications and respective countermeasures and prognoses of patients who underwent pharyngolaryngectomy with total esophagectomy.Study DesignCase series with chart review.SettingDepartment of Head and Neck Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Japan.Subjects and MethodsWe examined the postoperative complications and respective countermeasures and prognoses of 40 patients who underwent pharyngolaryngectomy with total esophagectomy in our hospital.ResultsPostoperative complications were observed in 23 patients (57.5%) and consisted of 8 groups: tracheal region necrosis in 5 patients; neck abscess formation/wound infection in 5; fistula in 4; tracheostomy suture leakage in 2; ileus in 2; lymphorrhea in 2; pulmonary complications in 2; and other complications, including hemothorax, tracheoinnominate artery fistula, temporary cardiac arrest due to intraoperative mediastinum operation, methicillin‐resistant Staphylococcus aureus enteritis, and sepsis, in 1 patient each. A lethal complication—brachiocephalic vein hemorrhage due to tracheostomy suture leakage and hemorrhagic shock due to tracheoinnominate artery fistula—occurred in 2 (5%) patients. The crude 5‐year survival rate was 48.6%.ConclusionsSerious postoperative complications were related to tracheostomaplasty. Although pharyngolaryngectomy with total esophagectomy is highly invasive, we believe that our outlined treatment method is the most appropriate for cases of advanced hypopharyngeal or cervical esophageal cancer that also requires concurrent surgery for esophageal cancer.
Immobilization in External Rotation Versus Internal Rotation After Primary Anterior Shoulder Dislocation
Authors: Whelan Daniel B. , Kletke Stephanie N. , Schemitsch Geoffrey , Chahal Jaskarndip 
Published: June 2015

Background: The recurrence rate after primary anterior shoulder dislocation is high, especially in young, active individuals. Recent studies have suggested external rotation immobilization as a method to reduce the rate of recurrent shoulder dislocation in comparison to traditional sling immobilization. Purpose: To assess and summarize evidence from randomized controlled trials on the effect of internal rotation versus external rotation immobilization on the rate of recurrence after primary anterior shoulder dislocation. Study Design: Meta-analysis. Methods: PubMed, MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and abstracts from recent proceedings were searched for eligible studies. Two reviewers selected studies for inclusion, assessed methodological quality, and extracted data. Results: Six randomized controlled trials (632 patients) were included in this review. Demographic and prognostic variables measured at baseline were similar in the pooled groups. The average age was 30.1 years in the pooled external rotation group and 30.3 years in the pooled internal rotation group. Two studies found that external rotation immobilization reduced the rate of recurrence after initial anterior shoulder dislocation compared with conventional internal rotation immobilization, whereas 4 studies failed to find a significant difference between the 2 groups. This meta-analysis suggested no overall significant difference in the rate of recurrence among patients treated with internal rotation versus external rotation immobilization (risk ratio, 0.69; 95% CI, 0.42-1.14; P = .15). There was no significant difference in the rate of compliance between internal and external rotation immobilization ( P = .43). The Western Ontario Shoulder Instability Index scores were pooled across 3 studies, and there was no significant difference between the 2 groups ( P = .54). Conclusion: Immobilization in external rotation is not significantly more effective in reducing the recurrence rate after primary anterior shoulder dislocation than immobilization in internal rotation. Additionally, this review suggests that there is minimal difference in patients’ perceptions of their health-related quality of life after immobilization in internal versus external rotation.