bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prophage Lysin Ply30 Protects Mice from Streptococcus suis and Streptococcus equi subsp. zooepidemicus Infections
Authors: Tang Fang , Li Dezhi , Wang Haojin , Ma Zhe , Lu Chengping , Dai Jianjun 
Published: August 2015

ABSTRACT

Streptococcus suis
and
Streptococcus equi
subsp.
zooepidemicus
are capable of infecting humans and various animals, causing significant problems for the worldwide swine industry. As antibiotic resistance has increased, lysosomal enzymes encoded by phages have shown potential for use against pathogenic bacteria. In this study, a novel bacteriophage lysin, Ply30, encoded by the
S. suis
prophage phi30c, was recombinantly expressed and purified. Ply30 showed high bacteriolysis activity on
S. suis
and
S. equi
subsp.
zooepidemicus in vitro
. The ratio of the optical density at 600 nm (OD
600
) with treatment versus the OD
600
with no treatment for most tested
S. suis
and
S. equi
subsp.
zooepidemicus
strains decreased from 1 to <0.3 and <0.5, respectively, within 1 h. The results of plate viability assays showed that treated bacteria suffered a 1- to 2-log decrease in CFU within 1 h. The optimal concentration of Ply30 was 50 μg/ml, and the optimal pH was 7. Moreover, Ply30 maintained high activity over a wide pH range (pH 6 to 10). The MICs of Ply30 against
Streptococcus
strains ranged from 16 to 512 μg/ml.
In vivo
, a 2-mg dose of Ply30 protected 90% (9/10 mice) of mice from infection with
S. equi
subsp.
zooepidemicus
and 80% (8/10 mice) of mice from infection with
S. suis
. Seven days after lysin Ply30 treatment, bacterial loads were significantly decreased in all tested organs and blood compared with those at 1 h postinfection without Ply30 treatment. Ply30 showed
in vitro
and
in vivo
antimicrobial efficiency and protected mice against two kinds of bacterial infections, indicating that Ply30 may be an effective therapeutic against streptococci.
Eisosome Ultrastructure and Evolution in Fungi, Microalgae, and Lichens
Authors: Lee Jae-Hyeok , Heuser John E. , Roth Robyn , Goodenough Ursula 
Published: August 2015

ABSTRACT

Eisosomes are among the few remaining eukaryotic cellular differentations that lack a defined function(s). These trough-shaped invaginations of the plasma membrane have largely been studied in
Saccharomyces cerevisiae
, in which their associated proteins, including two BAR domain proteins, have been identified, and homologues have been found throughout the fungal radiation. Using quick-freeze deep-etch electron microscopy to generate high-resolution replicas of membrane fracture faces without the use of chemical fixation, we report that eisosomes are also present in a subset of red and green microalgae as well as in the cysts of the ciliate
Euplotes
. Eisosome assembly is closely correlated with both the presence and the nature of cell walls. Microalgal eisosomes vary extensively in topology and internal organization. Unlike fungi, their convex fracture faces can carry lineage-specific arrays of intramembranous particles, and their concave fracture faces usually display fine striations, also seen in fungi, that are pitched at lineage-specific angles and, in some cases, adopt a broad-banded patterning. The conserved genes that encode fungal eisosome-associated proteins are not found in sequenced algal genomes, but we identified genes encoding two algal lineage-specific families of predicted BAR domain proteins, called Green-BAR and Red-BAR, that are candidate eisosome organizers. We propose a model for eisosome formation wherein (i) positively charged recognition patches first establish contact with target membrane regions and (ii) a (partial) unwinding of the coiled-coil conformation of the BAR domains then allows interactions between the hydrophobic faces of their amphipathic helices and the lipid phase of the inner membrane leaflet, generating the striated patterns.
Raising the topic of weight in general practice: perspectives of GPs and primary care nurses
Authors: Blackburn Maxine , Stathi Afroditi , Keogh Edmund , Eccleston Christopher 
Published: August 2015

ObjectiveTo explore general practitioners’ (GPs) and primary care nurses’ perceived barriers to raising the topic of weight in general practice.DesignA qualitative study using the Theoretical Domains Framework (TDF). 34 semistructured interviews were conducted to explore views, opinions and experiences of initiating a discussion about weight. Content and thematic analyses were used to analyse the interview transcripts.SettingGeneral practices located in one primary care trust in the South West of England.Participants17 GPs and 17 nurses aged between 32 and 66 years. The modal age range for GPs was 30–39 years and for nurses, 40–49 years.ResultsBarriers were synthesised into three main themes: (1) limited understanding about obesity care, (2) concern about negative consequences, and (3) having time and resources to raise a sensitive topic. Most barriers were related to raising the topic in more routine settings, rather than when dealing with an associated medical condition. GPs were particularly worried about damaging their relationship with patients and emphasised the need to follow their patient's agenda.ConclusionsUncertainty about obesity, concerns about alienating patients and feeling unable to raise the topic within the constraints of a 10 min consultation, is adding to the reluctance of GPs and nurses to broach the topic of weight. Addressing these concerns through training or by providing evidence of effective interventions that are feasible to deliver within consultations may lead to greater practitioner engagement and willingness to raise the topic.
Physician and other healthcare personnel responses to hospital stroke quality of care performance feedback: a qualitative study
Authors: Ross Joseph S , Williams Linda , Damush Teresa M , Matthias Marianne 
Published: August 2015

BackgroundUnderstanding how physicians and other healthcare personnel respond to hospital performance feedback initiatives may have important implications for quality improvement efforts. Our objective was to explore responses to the inaugural feedback of hospital performance on stroke quality of care measures among relevant physicians and personnel at the US Department of Veterans Health Administration (VHA) hospitals.MethodsQualitative interviews with hospital administrators, physicians, nurses and quality managers at 12 VHA hospitals in the USA after the inaugural national release of the report on quality of acute stroke care processes. Interview transcripts were analysed using an immersion/crystallisation approach to identify recurrent themes.ResultsInterviews were completed with 41 individuals at 12 VHA hospitals from diverse regions of the USA; the majority were clinicians, either physicians or nurses, and nearly all had 20 years of experience or more. Interviewees described general perceptions of internal performance feedback that were both positive and negative, such as the notion that performance feedback could provide value to clinicians and hospitals, but at the same time voiced concerns about being inundated with such data. Interviewees also expressed scepticism about public reporting of performance data, citing numerous concerns and limitations. However, when interviewees described specific experiences with performance feedback, nearly all reactions were positive, including excitement, interest and feeling validated about a job well done.DiscussionPhysicians and other healthcare personnel described hospital performance feedback on stroke quality of care measures to be broadly valuable but identified areas of concern related to the measurement process and public reporting.
Prognostic significance of TRAIL signalling molecules in cervical squamous cell carcinoma
Authors: Yao Qian , Du Juan , Lin Jie , Luo Yiming , Wang Yuxiang , Liu Yan , Zhang Bo , Ren Caixia , Liu Congrong 
Published: August 2015

AimTumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that preferentially induces apoptosis in cancer cells while exhibiting little or no toxicity in normal cells. In this study, we evaluated the clinicopathological significance of TRAIL signalling members’ expression profiles in cervical squamous cell carcinoma (CSCC).MethodsTRAIL, DR5, caspase-8 and cellular FLICE-inhibitory protein (c-FLIP) protein expression was investigated in 72 stage IA2-IIIA CSCC patients using immunohistochemistry. Correlation between protein expression and clinicopathological features, radiotherapy response and survival was statistically analysed.ResultsPositive c-FLIP expression was an independent negative indicator for disease-free survival (DFS) (p=0.015) in multivariate Cox regression analysis. The DR5 nuclear positive group (p=0.069 by log rank test) showed some advantage of radiotherapy for overall survival (OS) compared with the DR5 nuclear negative cohort (p=0.568 by log rank test). In addition, loss of TRAIL expression was associated with worse differentiation (p=0.004), while absence of caspase-8 staining was more frequently observed in cases with lymphovascular invasion (p=0.035).ConclusionsHigh c-FLIP expression is shown to be an independent prognostic variable, DR5 nuclear expression may serve as a predictive biomarker for radiotherapy, and TRAIL as well as caspase-8 loss may be associated with malignant progression.
Residents’ knowledge of quality improvement: the impact of using a group project curriculum
Authors: Duello Katherine , Louh Irene , Greig Hope , Dawson Nancy 
Published: August 2015

ABSTRACT

Background
The Accreditation Council for Graduate Medical Education requires residents to learn and demonstrate proficiency in practice improvement. Quality improvement (QI) projects are a way to improve patient care as well as facilitate education on this core competency. There are inherent barriers to completing these goals in the structure of residency training including rigorous resident schedules and a limited number of projects and resources.

Objectives
We developed a QI programme using an experiential class project and incorporated it into our Internal Medicine Resident Core Curriculum to improve the residents’ knowledge of QI methods. We assessed the residents’ experience, knowledge and interest in practice and QI subject matter with a survey preimplementation and postimplementation.

Methods
In 2009, 24 residents in the Internal Medicine resident programme completed a survey measuring their experience, knowledge and interest in QI initiatives. They then completed a QI 1-year programme, with monthly, 1-hour sessions combining didactics and a resident-designed project. At the conclusion of the year, the residents completed the same survey, and the results were compared and analysed.

Results
Postcurriculum questionnaires revealed residents were more knowledgeable about QI methods, showing improvement in knowledge about institutional-wide QI projects, better preparation for implementing a QI project, and more likely to participate in QI in the future. The project completed was one which improved patients’ knowledge of their anticipated date of discharge from the hospital.

Conclusions
A class quality project can teach QI to residents incorporating both didactic and practical methods to maximise the experience and minimise the barriers. We found that this method improved residents experience, knowledge and interest in quality initiatives.
Development of the Biostatistics and Clinical Epidemiology Skills (BACES) assessment for medical residents
Authors: Barlow Patrick B , Skolits Gary , Heidel Robert Eric , Metheny William , Smith Tiffany Lee 
Published: August 2015

ABSTRACT

Background
Although biostatistics and clinical epidemiology are essential for comprehending medical evidence, research has shown consistently low and variable knowledge among postgraduate medical trainees. Simultaneously, there has been an increase in the complexity of statistical methods among top-tier medical journals.

Aims
To develop the Biostatics and Clinical Epidemiology Skills (BACES) assessment by (1) establishing content validity evidence of the BACES; (2) examining the model fit of the BACES items to an Item Response Theory (IRT) model; and (3) comparing IRT item estimates with those of traditional Classical Test Theory (CTT) indices.

Methods
Thirty multiple choice questions were written to focus on interpreting clinical epidemiological and statistical methods. Content validity was assessed through a four-person expert review. The instrument was administered to 150 residents across three academic medical centres in southern USA during the autumn of 2013. Data were fit to a two-parameter logistic IRT model and the item difficulty, discrimination and examinee ability values were compared with traditional CTT item statistics.

Results
147 assessments were used for analysis (mean (SD) score 14.38 (3.38)). Twenty-six items, 13 devoted to statistics and 13 to clinical epidemiology, successfully fit a two-parameter logistic IRT model. These estimates also significantly correlated with their comparable CTT values.

Conclusions
The strength of the BACES instrument was supported by (1) establishing content validity evidence; (2) fitting a sample of 147 residents’ responses to an IRT model; and (3) correlating the IRT estimates with their CTT values, which makes it a flexible yet rigorous instrument for measuring biostatistical and clinical epidemiological knowledge.
Barriers to healthcare seeking among medical students: a cross sectional study from South India
Authors: Menon Vikas , Sarkar Siddharth , Kumar Santosh 
Published: August 2015

ABSTRACT

Objective
To determine the barriers to seeking help from healthcare services reported by medical students at an Indian medical school, and to compare the barriers for using physical health services with those for using mental health services.

Methods
In 2014, we invited all medical students across the nine semesters of training at a government medical college in Puducherry, India, to complete a 28 item questionnaire about perceived barriers to seeking healthcare services. The questionnaire enquired about barriers to using physical and mental healthcare services separately.

Results
Completed responses were available from 461 of 509 students (response rate 90.6%). Stigma, confidentiality issues, lack of awareness about where to seek help and fear of unwanted intervention were more commonly reported for mental healthcare seeking (OR 4.21, 4.01, 3.19 and 2.43, respectively), while issues relating to cost, lack of time and fear of side effects were observed less frequently (OR 0.45, 0.46 and 0.57, respectively) compared with physical healthcare seeking. In comparison with physical health, students were more indifferent to their mental health issues and preferred self-diagnosis and informal consultations over formal documented care.

Conclusions
Barriers to seeking healthcare services differ for mental and physical health issues. Many system based barriers such as stigma, confidentiality issues and poor awareness of service location were reported by students. Institutional programmes should use this information for improving the usage, satisfaction and effectiveness of healthcare delivery systems for medical students.
An Exploration with Novel Shape Signature of GMSC Distance Function to Track the Object
Authors: Sidram M. H. , Bhajantri Nagappa U. 
Published: August 2015

The process explicitly dedicated to estimate the path of the object as it moves along the region of scene in the image plane is the principle of tracking. In other words, it is a strategy to detect and track moving object through a sequence of frames. In this work, optical flow based on Horn–Schunk with Barren, Fleet and Beuchemin (BFB) kernel has been employed to estimate the motion vectors. The peripheries of moving objects are extracted for different shape signatures such as boundary, edge, area, curvature and centroid distance functions. Fourier descriptors (FD) of particular shape signature for each of the candidate templates and model template are computed. Similarity between the model template and candidate templates is confirmed by corresponding minimum Minkowski distance (MD). Subsequently, best match candidate template will be updated by model template in view of tracking process. However, centroid distance function has remarked some potentials and hence it has further motivated to mine it to throw in the proposed novel criteria such as the geometric mean of segmented centroid (GMSC) distance function to track the object. The proposed method of GMSC distance function has shown significant change in the tracking outcome.
The Rate at Which the Energy of Solutions for a Class ofp-Laplacian Wave Equation Decays
Authors: Mokeddem Soufiane , Mansour Khaled Ben Walid 
Published: August 2015

We will investigate the decay estimate of the energy of the global solutions to thep-Laplacian wave equation with dissipation of the formutt-div (∇xup-2∇xu)+σ(t)(ut-div (∇xutm-2∇xut))=0under suitable assumptions on the positive functionσ. For this end we use the multiplier method combined with nonlinear integral inequalities given by Martinez; the proof is based on the construction of a special weight function that depends on the behavior ofσ.
Sensitivity of Small Cell Lung Cancer to BET Inhibition Is Mediated by Regulation of ASCL1 Gene Expression
Authors: Lenhart Ryan , Kirov Stefan , Desilva Heshani , Cao Jian , Lei Ming , Johnston Kathy , Peterson Russell , Schweizer Liang , Purandare Ashok , Ross-Macdonald Petra , Fairchild Craig , Wong Tai , Wee Susan 
Published: August 2015

Abstract
The BET (bromodomain and extra-terminal) proteins bind acetylated histones and recruit protein complexes to promote transcription elongation. In hematologic cancers, BET proteins have been shown to regulate expression of MYC and other genes that are important to disease pathology. Pharmacologic inhibition of BET protein binding has been shown to inhibit tumor growth in MYC-dependent cancers, such as multiple myeloma. In this study, we demonstrate that small cell lung cancer (SCLC) cells are exquisitely sensitive to growth inhibition by the BET inhibitor JQ1. JQ1 treatment has no impact on MYC protein expression, but results in downregulation of the lineage-specific transcription factor ASCL1. SCLC cells that are sensitive to JQ1 are also sensitive to ASCL1 depletion by RNAi. Chromatin immunoprecipitation studies confirmed the binding of the BET protein BRD4 to the ASCL1 enhancer, and the ability of JQ1 to disrupt the interaction. The importance of ASCL1 as a potential driver oncogene in SCLC is further underscored by the observation that ASCL1 is overexpressed in &gt;50% of SCLC specimens, an extent greater than that observed for other putative oncogenes (MYC, MYCN, and SOX2) previously implicated in SCLC. Our studies have provided a mechanistic basis for the sensitivity of SCLC to BET inhibition and a rationale for the clinical development of BET inhibitors in this disease with high unmet medical need. Mol Cancer Ther; 14(10); 2167–74. ©2015 AACR.
Durability of Kinase-Directed Therapies—A Network Perspective on Response and Resistance
Authors: Murray Brion W. , Miller Nichol 
Published: August 2015

Abstract
Protein kinase–directed cancer therapies yield impressive initial clinical responses, but the benefits are typically transient. Enhancing the durability of clinical response is dependent upon patient selection, using drugs with more effective pharmacology, anticipating mechanisms of drug resistance, and applying concerted drug combinations. Achieving these tenets requires an understanding of the targeted kinase's role in signaling networks, how the network responds to drug perturbation, and patient-to-patient network variations. Protein kinases create sophisticated, malleable signaling networks with fidelity coded into the processes that regulate their presence and function. Robust and reliable signaling is facilitated through network processes (e.g., feedback regulation, and compensatory signaling). The routine use of kinase-directed therapies and advancements in both genomic analysis and tumor cell biology are illuminating the complexity of tumor network biology and its capacity to respond to perturbations. Drug efficacy is attenuated by alterations of the drug target (e.g., steric interference, compensatory activity, and conformational changes), compensatory signaling (bypass mechanisms and phenotype switching), and engagement of other oncogenic capabilities (polygenic disease). Factors influencing anticancer drug response and resistance are examined to define the behavior of kinases in network signaling, mechanisms of drug resistance, drug combinations necessary for durable clinical responses, and strategies to identify mechanisms of drug resistance. Mol Cancer Ther; 14(9); 1975–84. ©2015 AACR.
Progression of Lung Cancer Is Associated with Increased Dysfunction of T Cells Defined by Coexpression of Multiple Inhibitory Receptors
Authors: Thommen Daniela S. , Schreiner Jens , Müller Philipp , Herzig Petra , Roller Andreas , Belousov Anton , Umana Pablo , Pisa Pavel , Klein Christian , Bacac Marina , Fischer Ozana S. , Moersig Wolfgang , Savic Prince Spasenija , Levitsky Victor , Karanikas Vaios , Lardinois Didier , Zippelius Alfred 
Published: August 2015

Abstract
Dysfunctional T cells present in malignant lesions are characterized by a sustained and highly diverse expression of inhibitory receptors, also referred to as immune checkpoints. Yet, their relative functional significance in different cancer types remains incompletely understood. In this study, we provide a comprehensive characterization of the diversity and expression patterns of inhibitory receptors on tumor-infiltrating T cells from patients with non–small cell lung cancer. In spite of the large heterogeneity observed in the amount of PD-1, Tim-3, CTLA-4, LAG-3, and BTLA expressed on intratumoral CD8+ T cells from 32 patients, a clear correlation was established between increased expression of these inhibitory coreceptors and progression of the disease. Notably, the latter was accompanied by a progressively impaired capacity of T cells to respond to polyclonal activation. Coexpression of several inhibitory receptors was gradually acquired, with early PD-1 and late LAG-3/BTLA expression. PD-1 blockade was able to restore T-cell function only in a subset of patients. A high percentage of PD-1hi T cells was correlated with poor restoration of T-cell function upon PD-1 blockade. Of note, PD-1hi expression marked a particularly dysfunctional T-cell subset characterized by coexpression of multiple inhibitory receptors and thus may assist in identifying patients likely to respond to inhibitory receptor–specific antibodies. Overall, these data may provide a framework for future personalized T-cell–based therapies aiming at restoration of tumor-infiltrating lymphocyte effector functions. Cancer Immunol Res; 3(12); 1344–55. ©2015 AACR.