bluuebunny/crossref_metadata_2025_split huggingface dataset:
2,3-Dihydroxybenzoic Acid-Containing Nanofiber Wound Dressings Inhibit Biofilm Formation by Pseudomonas aeruginosa
Authors: Ahire Jayesh J. , Dicks Leon M. T. 
Published: January 2014

ABSTRACT

Pseudomonas aeruginosa
forms biofilms in wounds, which often leads to chronic infections that are difficult to treat with antibiotics. Free iron enhances biofilm formation, delays wound healing, and may even be responsible for persistent inflammation, increased connective tissue destruction, and lipid peroxidation. Exposure of
P. aeruginosa
Xen 5 to the iron chelator 2,3-dihydroxybenzoic acid (DHBA), electrospun into a nanofiber blend of poly(
d
,
l
-lactide) (PDLLA) and poly(ethylene oxide) (PEO), referred to as DF, for 8 h decreased biofilm formation by approximately 75%. This was shown by a drastic decline in cell numbers, from 7.1 log
10
CFU/ml to 4.8 log
10
CFU/ml when biofilms were exposed to DF in the presence of 2.0 mM FeCl
3
6H
2
O. A similar decline in cell numbers was recorded in the presence of 3.0 mM FeCl
3
6H
2
O and DF. The cells were more mobile in the presence of DHBA, supporting the observation of less biofilm formation at lower iron concentrations. DHBA at MIC levels (1.5 mg/ml) inhibited the growth of strain Xen 5 for at least 24 h. Our findings indicate that DHBA electrospun into nanofibers inhibits cell growth for at least 4 h, which is equivalent to the time required for all DHBA to diffuse from DF. This is the first indication that DF can be developed into a wound dressing to treat topical infections caused by
P. aeruginosa
.
Analysis of the mRNA Targetome of MicroRNAs Expressed by Marek’s Disease Virus
Authors: Parnas Oren , Corcoran David L. , Cullen Bryan R. 
Published: January 2014

ABSTRACT
Marek’s disease virus 1 (MDV-1), an oncogenic α-herpesvirus that induces T-cell lymphomas in chickens, serves as model system to study transformation by lymphotropic herpesviruses. Like the oncogenic human γ-herpesviruses Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), MDV-1 encodes several viral microRNAs (miRNAs). One MDV-1 miRNA, miR-M4, shares the same “seed” targeting sequence with both a KSHV miRNA, miR-K11, and cellular miR-155. Importantly, miR-M4 plays a critical role in T-cell transformation by MDV-1, while miR-K11 and cellular miR-155 are thought to play key roles in B-cell transformation by KSHV and EBV, respectively. Here, we present an analysis of the mRNAs targeted by viral miRNAs expressed in the chicken T-cell line MSB1, which is naturally coinfected with MDV-1 and the related nonpathogenic virus MDV-2. Our analysis identified >1,000 endogenous mRNAs targeted by miRNAs encoded by each virus, many of which are targeted by both MDV-1 and MDV-2 miRNAs. We present a functional analysis of an MDV-1 gene, RLORF8, targeted by four MDV-1 miRNAs and a cellular gene, encoding interleukin-18 (IL-18) and targeted by both MDV-1 and MDV-2 miRNAs, and show that ectopic expression of either protein in a form resistant to miRNA inhibition results in inhibition of cell proliferation. Finally, we present a restricted list of 9 genes targeted by not only MDV-1 miR-M4 but also KSHV miR-K11 and human miR-155. Given the critical role played by miR-155 seed family members in lymphomagenesis in humans and chickens, these mRNA targets may contain genes whose inhibition plays a conserved role in herpesvirus transformation.

IMPORTANCE
Herpesviruses cause lymphomas in both humans and chickens, and in both cases, evidence indicates that virally encoded miRNAs, or virally subverted cellular miRNAs, belonging to the miR-155 seed family, play a critical role in this process. However, because each miRNA regulates numerous cellular mRNAs species, it has been difficult to elucidate which miRNA targets are important. Given the evolutionary distance between chickens and humans and the observation that miR-155 is nevertheless highly conserved in both species, we reasoned that the identification of shared miR-155 targets might shed light on this process. Here, we present an analysis of the mRNAs targeted by miRNAs encoded by the oncogenic avian herpesvirus MDV-1 in transformed chicken T cells, including a short list of mRNAs that are also targeted by miR-155 seed family miRNAs in EBV- or KSHV-transformed human B cells, and present an initial functional analysis of some of these miRNA targets.
White matter integrity and cognition in Parkinson's disease: a cross-sectional study
Authors: Auning Eirik , Kjærvik Veslemøy Krohn , Selnes Per , Aarsland Dag , Haram Astrid , Bjørnerud Atle , Hessen Erik , Esnaashari Abdolreza , Fladby Tormod 
Published: January 2014

ObjectiveWe used diffusion tensor imaging (DTI) to test the following hypotheses: (1) there is decreased white matter (WM) integrity in non-demented Parkinson’s disease (PD), (2) WM integrity is differentially reduced in PD and early Alzheimer’s disease (AD) and (3) DTI changes in non-demented PD are specifically associated with cognitive performance.MethodsThis study included 18 non-demented patients with PD, 18 patients with mild cognitive impairment due to incipient AD and 19 healthy elderly normal control (NC) participants in a cross-sectional design. The participants underwent DTI, and tract-based spatial statistics was used to analyse and extract radial diffusivity and fractional anisotropy. Correlations between scores from a battery of neuropsychological tests and DTI were performed in the PD group.ResultsPatients with PD had significant differences in DTI in WM underlying the temporal, parietal and occipital cortex as compared with NC. There were no significant differences between the PD and AD groups in the primary region of interest analyses, but compared with NC there was a tendency for more anterior changes in AD in contrast to more posterior changes in PD. In a secondary whole-brain analysis there were frontoparietal areas with significant differences between AD and PD. In patients with PD, there were significant correlations between DTI parameters in WM underlying the prefrontal cortex and executive and visuospatial abilities.ConclusionsIn early, non-demented PD we found reduced WM integrity underlying the temporal, parietal and occipital cortices. In addition, WM integrity changes in prefrontal areas were associated with executive and visuospatial ability. These findings support that DTI may be an important biomarker in early PD, and that WM changes are related to cognitive impairment in PD.
Developing a complex intervention to improve prescribing safety in primary care: mixed methods feasibility and optimisation pilot study
Authors: Grant Aileen M , Guthrie Bruce , Dreischulte Tobias 
Published: January 2014

Objectives(A) To measure the extent to which different candidate outcome measures identified high-risk prescribing that is potentially changeable by the data-driven quality improvement in primary care (DQIP) intervention.(B) To explore the value of reviewing identified high-risk prescribing to clinicians.(C) To optimise the components of the DQIP intervention.DesignMixed method study.SettingGeneral practices in two Scottish Health boards.Participants4 purposively sampled general practices of varying size and socioeconomic deprivation.Outcome measuresPrescribing measures targeting (1) high-risk use of the non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelets; (2) ‘Asthma control’ and (3) ‘Antithrombotics in atrial fibrillation (AF)’.InterventionThe prescribing measures were used to identify patients for review by general practices. The ability of the measures to identify potentially changeable high-risk prescribing was measured as the proportion of patients reviewed where practices identified a need for action. Field notes were recorded from meetings between researchers and staff and key staff participated in semistructured interviews exploring their experience of the piloted intervention processes.ResultsPractices identified a need for action in 68%, 25% and 18% of patients reviewed for prescribing measures (1), (2) and (3), respectively. General practitioners valued being prompted to review patients, and perceived that (1) ‘NSAID and antiplatelet’ and (2) ‘antithrombotics in AF’ were the most important to act on. Barriers to initial and ongoing engagement and to sustaining improvements in prescribing were identified.Conclusions‘NSAIDs and antiplatelets’ measures were selected as the most suitable outcome measures for the DQIP trial, based on evidence of this prescribing being more easily changeable. In response to the barriers identified, the intervention was designed to include a financial incentive, additional ongoing feedback on progress and reprompting review of patients, whose high-risk prescribing was restarted after a decision to stop.Trial registration numberClinicaltrials.govNCT01425502.
Cardiac output response and peripheral oxygen extraction during exercise among symptomatic hypertrophic cardiomyopathy patients with and without left ventricular outflow tract obstruction
Authors: Critoph Christopher H , Patel Vimal , Mist Bryan , Elliott Perry M 
Published: January 2014

ObjectiveReduction of left ventricular outflow tract obstruction (LVOTO) often improves symptoms in hypertrophic cardiomyopathy (HCM), but the correlation between exercise performance and measured LVOT gradients is weak. We investigated the relationship between LVOTO and cardiorespiratory responses during exercise.MethodsThe study cohort included 70 patients with HCM (32 with LVOTO, 55 male, age 47±13) attending a dedicated cardiomyopathy clinic and 28 normal volunteers. All underwent cardiopulmonary exercise testing with simultaneous non-invasive haemodynamic assessment using finger plethysmography. Main outcome measures were peak oxygen consumption, cardiac index and arteriovenous oxygen difference.ResultsWhen compared with controls, patients had reduced peak exercise oxygen consumption (22.4±6.1 vs 34.7±7.7 mL/kg/min, p<0.0001) and cardiac index (5.5±1.9 vs 9.4±2.9 L/min/m2, p<0.0001). At all workloads, stroke volume index (SVI) was lower and arteriovenous oxygen difference greater in patients. During all stages of exercise, LVOTO in patients was associated with failure to augment SVI and higher oxygen consumption; cardiac reserve (4.4±2.7 vs 6.3±3.6 L/min, p=0.025) and peak mean arterial pressure (104±16 vs 112±16 mm Hg, p=0.033) were lower. Multivariable predictors of cardiac output response were age (β: −0.11; CI −0.162 to −0.057; p<0.0001), peak LVOT gradient (β: −0.018; CI −0.034 to −0.002; p=0.031) and gender (β: −2.286; CI −0.162 to −0.577; p=0.01). Within the obstructive cohort, different patterns of SV response were elicited in patients with similar clinical features.ConclusionsCardiac reserve is reduced in HCM because of failure of SV augmentation. LVOTO exacerbates this abnormal response, but haemodynamic responses vary significantly. Non-invasive exercise haemodynamic assessment may improve understanding of symptoms and help tailor therapy.
Military surgery in the new curriculum: whither general surgery training in uniform?
Authors: Shastri-Hurst Neil , Naumann D N , Bowley D M , Whitbread T 
Published: January 2014

BackgroundThe nature of general surgical training within the UK has undergone significant changes recently, including the evolution of theIntercollegiate Surgical Curriculum Programme(ISCP).In 2013, new task-specific goals tailored towards military surgery were incorporated into the general surgery curriculum. In order to meet the demands of training the next generation of military general surgeons, a new compendium of workplace-based assessments (WBAs) is now required.Addressing the needIn 2013, the ISCP general surgery curriculum was revised to include new, military-specific WBAs to allow formative assessment of a trainees’ experience and preparedness for their future deployed role. Index procedures considered mandatory for a deployed military general surgeon to be effectivein the fieldare now included in the general surgery curriculum. These will permit formative assessment of trainees and also permit revalidation of deployed skills among the consultant cadre.ConclusionsGeneral surgical training in the UK is in a transitional period, and the move towards increased sub-specialisation appears inexorable as evidenced by the split of Vascular Surgery into a separate specialty, along with its own training pathway and curriculum. With the ‘generalist’ demands on deployed surgeons in the Defence Medical Services, the task of training towards broader surgical competencies may appear daunting. Inclusion of defined military WBAs into the curriculum should help focus trainees and their trainers to identify the deployed general surgicalskill set,identify the appropriate learning opportunities/placements required to enable the acquisition of relevant competencies and document their attainment and later retention.
MATHEMATICAL TREATMENTS THAT SOLVE SINGLE MOLECULES
Authors: FLOMENBOM OPHIR 
Published: January 2014

In this article, we talk about the ways that scientists can solve single molecule trajectories. Solving single molecules, that is, finding the model from the data, is complicated at least as much as measuring single molecules. We must filter the noise and take care of every step in the analysis when constructing the most accurate model from the data. Here, we present valuable solutions. Ways that solve clean discrete data are first presented. We review here our reduced dimensions forms (RDFs): unique models that are canonical forms of discrete data, and the statistical and numerical toolbox that builds a RDF from finite, clean, two-state data. We then review our most recent filter that "tackles" the noise when measuring two state noisy photon trajectories. The filter is a numerical algorithm with various special statistical treatments that is based on a general likelihood function that we have developed recently. We show the strengths of the filter (also over other approaches) and talk about its various new variants. This filter (with minor adjustments) can solve the noise in any discrete state trajectories, yet, extensions are needed in "tackling" the noise from other data, e.g. continuous data. Only the combined procedures enable creating the most accurate model from noisy discrete trajectories from single molecules. These concepts and methods (with adjustments) are valuable also when solving continuous trajectories and fluorescence resonance energy transfer trajectories. We also present a set of simple methods that can help any scientist with treating the trajectory perhaps encouraging applying the involved methods. The involved methods will appear in software that we are developing now, helping therefore the experimentalists utilizing these methods on real data. Comparisons with other known methods in this field are made. [Formula: see text]Special Issue Comment: This article about mathematical treatments when solving single molecules is related to the reviews in this Special Issue about measuring enzymes67 and about FRET experiments2 and about the software QUB.6
SOLVING SINGLE BIOMOLECULES BY ADVANCED FRET-BASED SINGLE-MOLECULE FLUORESCENCE TECHNIQUES
Authors: RUEDAS-RAMA M. J. , ALVAREZ-PEZ J. M. , ORTE A. 
Published: January 2014

The use of Förster resonance energy transfer (FRET) has undergone a renaissance in the last two decades, especially in the study of structure of biomolecules, biomolecular interactions, and dynamics. Thanks to powerful advances in single-molecule fluorescence (SMF) techniques, seeing molecules at work is a reality, which has helped to build up the mindset of molecular machines. In the last few years, many technical developments have broadened the applications of SMF-FRET, expanding the amount of information that can be recovered from individual molecules. Here, we focus on the non-standard SMF-FRET techniques, such as two-color coincidence detection (TCCD), alternating laser excitation (ALEX), multiparameter fluorescence detection (MFD); the addition of fluorescence lifetime as an orthogonal dimension in single-molecule experiments; or the development of novel and improved methods of analysis constituting to a set of advanced methodologies that may become routine tools in a close future.[Formula: see text]Special Issue Comment: This review about advanced single-molecule FRET techniques is specially related to the review by Jørgensen and Hatzakis,6who detail experimetal strategies to solve the activity of single enzymes. The advanced techniques described in our paper may serve as interesting alternatives when applied to enzyme studies. Our manuscript is also related to the reviews in this Special Issue that deal with model solving.22,130
CORE-SIZE DEPENDENT PHOTOLUMINESCENCE BLINKING OF ISOLATED QUANTUM DOT-FULLERENE HYBRIDS
Authors: ZANG HUIDONG , XU ZHIHUA , COTLET MIRCEA 
Published: January 2014

We demonstrate the possibility to bias the photoluminescence blinking of isolated colloidal quantum dots coupled to fullerenes by varying the quantum dot core size. Changing the core size affects the energy offset between the donor and acceptor and directly affects the driving force for electron transfer between the two moieties. Single particle photoluminescence measurements reveal dramatic reduction in the on-time associated with the photoluminescence blinking in quantum dot-fullerene hybrids when the quantum dot core size decreases, a manifestation associated with enhanced electron transfer. [Formula: see text]Special Issue Comment: This project is about the blink properties of QDs in the presence of electron acceptor moieties and it connects with two articles from this Special Issue involving treatments when solving single molecules.1,2
HDAC2 Provides a Critical Support to Malignant Progression of Hepatocellular Carcinoma through Feedback Control of mTORC1 and AKT
Authors: Noh Ji Heon , Bae Hyun Jin , Eun Jung Woo , Shen Qingyu , Park Se Jin , Kim Hyung Seok , Nam Boas , Shin Woo Chan , Lee Eun Kyung , Lee Kyungbun , Jang Ja-Jun , Park Won Sang , Lee Jung Young , Nam Suk Woo 
Published: January 2014

AbstractAberrant regulation of histone deacetylase 2 (HDAC2) contributes to malignant progression in various cancers, but the underlying mechanism leading to the activation of oncogenic HDAC2 remains unknown. In this study, we show that HDAC2 expression is upregulated in a large cohort of patients with human hepatocellular carcinoma, and that high expression of HDAC2 was significantly associated with poor prognosis of patients with hepatocellular carcinoma. We found that mTORC1/NF-κBp50 signaling is necessary for the growth factor–induced HDAC2 and is sustained in hepatocellular carcinoma, but not in normal hepatic cells. Growth factor–induced mTORC1 activates the nuclear translocation of NF-κBp50, where it binds to the intragenic sequences of the HDAC2 gene and promotes its transcription. Hepatocellular carcinoma tissues derived from chemical-induced mouse and rat liver cancer models validated that mTORC1 activation and NF-κBp50 nuclear translocation are essential for the transcriptional activation of oncogenic HDAC2 in hepatocellular carcinoma. In addition, we demonstrate that HDAC2 is required to maintain mTORC1 activity by stabilizing the mTOR/RAPTOR complex. Elevated expression of HDAC2 triggers a positive feedback loop that activates AKT phosphorylation via the transcriptional modulation of phosphoinositide signaling molecules. Bioinformatics analysis of HDAC2 signature and immunoblot analysis of mesenchymal genes also evidenced that HDAC2 plays a role in the malignant behavior of tumor cells by Snail induction and simultaneously E-cadherin suppression in hepatocellular carcinoma cells. These findings establish a molecular mechanism responsible for the activation of oncogenic HDAC2, which explains how growth factor–induced HDAC2 maintains mitogenic signaling and function during hepatocellular malignant progression and provide a novel strategy for therapeutic intervention in liver cancer. Cancer Res; 74(6); 1728–38. ©2014 AACR.
MET Signaling in Colon Cancer Stem-like Cells Blunts the Therapeutic Response to EGFR Inhibitors
Authors: Luraghi Paolo , Reato Gigliola , Cipriano Elia , Sassi Francesco , Orzan Francesca , Bigatto Viola , De Bacco Francesca , Menietti Elena , Han May , Rideout William M. , Perera Timothy , Bertotti Andrea , Trusolino Livio , Comoglio Paolo M. , Boccaccio Carla 
Published: January 2014

Abstract
Metastatic colorectal cancer remains largely incurable, although in a subset of patients, survival is prolonged by new targeting agents such as anti-EGF receptor (anti-EGFR) antibodies. This disease is believed to be supported by a subpopulation of stem-like cells termed colon cancer–initiating cell (CCIC), which may also confer therapeutic resistance. However, how CCICs respond to EGFR inhibition has not been fully characterized. To explore this question, we systematically generated CCICs through spheroid cultures of patient-derived xenografts of metastatic colorectal cancer. These cultures, termed “xenospheres,” were capable of long-term self-propagation in vitro and phenocopied the original patient tumors in vivo, thus operationally defining CCICs. Xenosphere CCICs retained the genetic determinants for EGFR therapeutic response in vitro and in xenografts; like the original tumors, xenospheres harboring a mutated KRAS gene were resistant to EGFR therapy, whereas those harboring wild-type RAS pathway genes (RASwt) were sensitive. Notably, the effects of EGFR inhibition in sensitive CCICs could be counteracted by cytokines secreted by cancer-associated fibroblasts. In particular, we found that the MET receptor ligand hepatocyte growth factor (HGF) was especially active in supporting in vitro CCIC proliferation and resistance to EGFR inhibition. Ectopic production of human HGF in CCIC xenografts rendered the xenografts susceptible to MET inhibition, which sensitized the response to EGFR therapy. By showing that RASwt CCICs rely on both EGFR and MET signaling, our results offer a strong preclinical proof-of-concept for concurrent targeting of these two pathways in the clinical setting. Cancer Res; 74(6); 1857–69. ©2014 AACR.
TGF-β–Induced Upregulation of malat1 Promotes Bladder Cancer Metastasis by Associating with suz12
Authors: Fan Yu , Shen Bing , Tan Mingyue , Mu Xinyu , Qin Yan , Zhang Fang , Liu Yong 
Published: January 2014

Abstract
Purpose: TGF-β promotes tumor invasion and metastasis by inducing an epithelial–mesenchymal transition (EMT). However, the underlying mechanisms causing this are not entirely clear. Long noncoding RNAs (lncRNA) have been shown to play important regulatory roles in cancer progression. The lncRNA malat1 (metastasis associated lung adenocarcinoma transcript 1) is a critical regulator of the metastasis phenotype of lung cancer cells.
Experimental Design: We, therefore, investigated whether TGF-β regulates malat1 expression to promote tumor metastasis of bladder cancer. The expression levels of malat1 and EMT markers were assayed in specimens of bladder cancer. The role of malat1 in regulating bladder cancer metastasis was evaluated in cell and animal models.
Results: TGF-β induces malat1 expression and EMT in bladder cancer cells. malat1 overexpression is significantly correlated with poor survival in patients with bladder cancer. malat1 and E-cadherin expression is negatively correlated in vitro and in vivo. malat1 knockdown inhibits TGF-β–induced EMT. malat1 is associated with suppressor of zeste 12 (suz12), and this association results in decrease of E-cadherin expression and increase of N-cadherin and fibronectin expression. Furthermore, targeted inhibition of malat1 or suz12 suppresses the migratory and invasive properties induced by TGF-β. Finally, we demonstrated that malat1 or suz12 knockdown inhibits tumor metastasis in animal models.
Conclusion: These data suggest that malat1 is an important mediator of TGF-β–induced EMT, and suggest that malat1 inhibition may represent a promising therapeutic option for suppressing bladder cancer progression. Clin Cancer Res; 20(6); 1531–41. ©2014 AACR.