bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of trabecular bone parameters in children from multisequence MRI using texture‐based regression
Authors: Lekadir Karim , Hoogendoorn Corné , Armitage Paul , Whitby Elspeth , King David , Dimitri Paul , Frangi Alejandro F. 
Published: May 2016

Purpose:This paper presents a statistical approach for the prediction of trabecular bone parameters from low‐resolution multisequence magnetic resonance imaging (MRI) in children, thus addressing the limitations of high‐resolution modalities such as HR‐pQCT, including the significant exposure of young patients to radiation and the limited applicability of such modalities to peripheral bones in vivo.Methods:A statistical predictive model is constructed from a database of MRI and HR‐pQCT datasets, to relate the low‐resolution MRI appearance in the cancellous bone to the trabecular parameters extracted from the high‐resolution images. The description of the MRI appearance is achieved between subjects by using a collection of feature descriptors, which describe the texture properties inside the cancellous bone, and which are invariant to the geometry and size of the trabecular areas. The predictive model is built by fitting to the training data a nonlinear partial least square regression between the input MRI features and the output trabecular parameters.Results:Detailed validation based on a sample of 96 datasets shows correlations >0.7 between the trabecular parameters predicted from low‐resolution multisequence MRI based on the proposed statistical model and the values extracted from high‐resolution HRp‐QCT.Conclusions:The obtained results indicate the promise of the proposed predictive technique for the estimation of trabecular parameters in children from multisequence MRI, thus reducing the need for high‐resolution radiation‐based scans for a fragile population that is under development and growth.
Biochemical Characterization of the Active Anti-Hepatitis C Virus Metabolites of 2,6-Diaminopurine Ribonucleoside Prodrug Compared to Sofosbuvir and BMS-986094
Authors: Ehteshami Maryam , Tao Sijia , Ozturk Tugba , Zhou Longhu , Cho Jong Hyun , Zhang Hongwang , Amiralaei Sheida , Shelton Jadd R. , Lu Xiao , Khalil Ahmed , Domaoal Robert A. , Stanton Richard A. , Suesserman Justin E. , Lin Biing , Lee Sam S. , Amblard Franck , Whitaker Tony , Coats Steven J. , Schinazi Raymond F. 
Published: May 2016

ABSTRACT

Ribonucleoside analog inhibitors (rNAI) target the hepatitis C virus (HCV) RNA-dependent RNA polymerase nonstructural protein 5B (NS5B) and cause RNA chain termination. Here, we expand our studies on β-
d
-2′-
C
-methyl-2,6-diaminopurine-ribonucleotide (DAPN) phosphoramidate prodrug 1 (PD1) as a novel investigational inhibitor of HCV. DAPN-PD1 is metabolized intracellularly into two distinct bioactive nucleoside triphosphate (TP) analogs. The first metabolite, 2′-
C
-methyl-GTP, is a well-characterized inhibitor of NS5B polymerase, whereas the second metabolite, 2′-
C
-methyl-DAPN-TP, behaves as an adenosine base analog.
In vitro
assays suggest that both metabolites are inhibitors of NS5B-mediated RNA polymerization. Additional factors, such as rNAI-TP incorporation efficiencies, intracellular rNAI-TP levels, and competition with natural ribonucleotides, were examined in order to further characterize the potential role of each nucleotide metabolite
in vivo
. Finally, we found that although both 2′-
C
-methyl-GTP and 2′-
C
-methyl-DAPN-TP were weak substrates for human mitochondrial RNA (mtRNA) polymerase (POLRMT)
in vitro
, DAPN-PD1 did not cause off-target inhibition of mtRNA transcription in Huh-7 cells. In contrast, administration of BMS-986094, which also generates 2′-
C
-methyl-GTP and previously has been associated with toxicity in humans, caused detectable inhibition of mtRNA transcription. Metabolism of BMS-986094 in Huh-7 cells leads to 87-fold higher levels of intracellular 2′-
C
-methyl-GTP than DAPN-PD1. Collectively, our data characterize DAPN-PD1 as a novel and potent antiviral agent that combines the delivery of two active metabolites.
Individual or Combined Effects of Meropenem, Imipenem, Sulbactam, Colistin, and Tigecycline on Biofilm-Embedded Acinetobacter baumannii and Biofilm Architecture
Authors: Wang Yung-Chih , Kuo Shu-Chen , Yang Ya-Sung , Lee Yi-Tzu , Chiu Chun-Hsiang , Chuang Ming-Fen , Lin Jung-Chung , Chang Feng-Yee , Chen Te-Li 
Published: May 2016

ABSTRACT

Acinetobacter baumannii
biofilms are difficult to eradicate. We investigated the effects of meropenem (2 mg/liter), imipenem (2 mg/liter), sulbactam (4 mg/liter), colistin (2 mg/liter), and tigecycline (2 mg/liter), alone or in combination, on biofilm-embedded carbapenem-resistant and carbapenem-susceptible
A. baumannii
(CRAb and CSAb, respectively) cells, as well as on the architecture of the biofilms.
A. baumannii
ATCC 15151 (Ab15151) and its OXA-82-overproducing transformant, along with two clinical CSAb and two clinical CRAb isolates of differing clonalities, were used. The minimal bactericidal concentrations for biofilm-embedded cells of the six tested isolates were >50-fold those of their planktonic cells. When used individually, meropenem exhibited a higher killing effect than the other four antimicrobials on biofilm-embedded CSAb cells in the colony biofilm assay. For two clinical CRAb isolates, meropenem plus sulbactam or sulbactam plus tigecycline showed >100-fold the bactericidal effect exhibited by these agents used alone after 48 h of treatment. The effect of antimicrobials on the architecture of Ab15151 biofilm emitting green fluorescence was determined by confocal laser scanning microscopy using COMSTAT software. Significant decreases in the maximum biofilm thickness were observed after exposure to meropenem and imipenem. Meropenem plus sulbactam significantly decreased the biomass and mean thickness and increased the roughness coefficient of biofilms, but sulbactam plus tigecycline only decreased the maximum and mean biofilm thickness compared to any of these agents used alone. Meropenem was active against biofilm-embedded CSAb, whereas meropenem plus sulbactam exhibited synergism against biofilm-embedded CRAb and caused significantly more damage to the biofilm architecture than did any of the agents used alone.
A Transposon Screen Identifies Genetic Determinants of Vibrio cholerae Resistance to High-Molecular-Weight Antibiotics
Authors: Dörr Tobias , Delgado Fernanda , Umans Benjamin D. , Gerding Matthew A. , Davis Brigid M. , Waldor Matthew K. 
Published: May 2016

ABSTRACT

Gram-negative bacteria are notoriously resistant to a variety of high-molecular-weight antibiotics due to the limited permeability of their outer membrane (OM). The basis of OM barrier function and the genetic factors required for its maintenance remain incompletely understood. Here, we employed transposon insertion sequencing to identify genes required for
Vibrio cholerae
resistance to vancomycin and bacitracin, antibiotics that are thought to be too large to efficiently penetrate the OM. The screen yielded several genes whose protein products are predicted to participate in processes important for OM barrier functions and for biofilm formation. In addition, we identified a novel factor, designated
vigA
(for vancomycin inhibits growth), that has not previously been characterized or linked to outer membrane function. The
vigA
open reading frame (ORF) codes for an inner membrane protein, and in its absence, cells became highly sensitive to glycopeptide antibiotics (vancomycin and ramoplanin) and bacitracin but not to other large antibiotics or detergents. In contrast to wild-type (WT) cells, the
vigA
mutant was stained with fluorescent vancomycin. These observations suggest that VigA specifically prevents the periplasmic accumulation of certain large antibiotics without exerting a general role in the maintenance of OM integrity. We also observed marked interspecies variability in the susceptibilities of Gram-negative pathogens to glycopeptides and bacitracin. Collectively, our findings suggest that the OM barrier is not absolute but rather depends on specific OM-antibiotic interactions.
Thioridazine as Chemotherapy for Mycobacterium avium Complex Diseases
Authors: Deshpande Devyani , Srivastava Shashikant , Musuka Sandirai , Gumbo Tawanda 
Published: May 2016

ABSTRACT

Mycobacterium avium-intracellulare
complex (MAC) causes an intractable intracellular infection that presents as chronic pulmonary disease. Currently, therapy consists of ethambutol and macrolides and takes several years to complete. The neuroleptic phenothiazine thioridazine kills mycobacteria by inhibiting the electron transport chain. In several experiments with bacterial populations of up to 10
12
CFU/ml, we failed to isolate any bacteria resistant to 3 times the MIC of thioridazine, suggesting the absence of resistant mutants at bacterial burdens severalfold higher than those encountered in patients. In the hollow-fiber model of intracellular MAC (HFS-MAC), thioridazine achieved an extracellular half-life of 16.8 h and an intracellular half-life of 19.7 h. Thioridazine concentrations were >28,000-fold higher inside infected macrophages than in the HFS-MAC central compartment (equivalent to plasma). Thioridazine maximal kill was 5.20 ± 0.75 log
10
CFU/ml on day 7 (
r
2
= 0.96) and 7.19 ± 0.31 log
10
CFU/ml on day 14 (
r
2
= 0.99), the highest seen with any drug in the system. Dose fractionation studies revealed that thioridazine efficacy and acquired drug resistance were driven by the peak concentation-to-MIC ratio, with a 50% effective concentration (EC
50
) of 2.78 ± 0.44 for microbial killing. Acquired drug resistance was encountered by day 21 with suboptimal doses, demonstrating that fluctuating drug concentrations drive evolution faster than static concentrations in mutation frequency studies. However, the thioridazine EC
50
changed 16.14-fold when the concentration of fetal bovine serum was changed from 0% to 50%, suggesting that intracellular potency could be heavily curtailed by protein binding. Efficacy in patients will depend on the balance between trapping of the drug in the pulmonary system and the massive intracellular concentrations versus very high protein binding of thioridazine.
Change in fasting plasma glucose and incident type 2 diabetes mellitus: results from a prospective cohort study
Authors: Mozaffary Amirhossein , Asgari Samaneh , Tohidi Maryam , Kazempour-Ardebili Sara , Azizi Fereidoun , Hadaegh Farzad 
Published: May 2016

ObjectiveTo investigate the association between changes in fasting plasma glucose (FPG) values and incident type 2 diabetes (T2D) in a cohort of the Iranian population.DesignProspective cohort study.SettingThis study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS) to investigate the association between change in FPG between baseline examination (1999–2001) and the second visit (2002–2005) with incident T2D.ParticipantsA total of 3981 non-diabetic participants aged ≥20 years.Outcome measureT2D was defined if the participant was using antidiabetic drugs or if FPG was ≥7 mmol/L or if the 2 h post-challenge plasma glucose (2-hPCG) was ≥11.1 mmol/L.ResultsDuring a median follow-up of 6.17 years, after the second examination, 288 new cases of T2D were identified. In a multivariate Cox proportional hazard analysis using age as timescale, we presented a simple model including FPG change (HR 1.19, 95% CI 1.07 to 1.33) and baseline waist circumference (WC) (HR 1.004, 95% CI 1.001 to 1.008) with a discriminative power (C-index) of 72%. Furthermore, we showed that the highest quartile of FPG change enhanced the T2D risk to 1.65 (95% CI 1.2 to 2.27) compared with the lowest quartile (p for trend=0.004).The independent risk of FPG change resisted further adjustment with 2-hPCG change. Adding the 2-hPCG change only slightly increased the discriminative power of the model including FPG change and baseline value of WC (0.73% vs 0.72%). After the study population had been limited to those with normal fasting glucose/normal glucose tolerance, FPG change remained an independent predictor (HR 1.57, 95% CI 1.31 to 1.88).ConclusionsTwo measurements of FPG obtained about 3 years apart can help to identify populations at risk of incident T2D independently of important traditional risk factors and their changes, including 2-hPCG change.
Comparison of the force applied on oral structures during intubation attempts by novice physicians between the Macintosh direct laryngoscope, Airway Scope and C-MAC PM: a high-fidelity simulator-based study
Authors: Nakanishi Taizo , Shiga Takashi , Homma Yosuke , Koyama Yasuaki , Goto Tadahiro 
Published: May 2016

ObjectiveWe examined whether the use of Airway Scope (AWS) and C-MAC PM (C-MAC) decreased the force applied on oral structures during intubation attempts as compared with the force applied with the use of Macintosh direct laryngoscope (DL).DesignProspective cross-over study.ParticipantsA total of 35 novice physicians participated.InterventionsWe used 6 simulation scenarios based on the difficulty of intubation and intubation devices.Outcome measuresOur primary outcome measures were the maximum force applied on the maxillary incisors and tongue during intubation attempts, measured by a high-fidelity simulator.ResultsThe maximum force applied on maxillary incisors was higher with the use of the C-MAC than with the DL and AWS in the normal airway scenario (DL, 26 Newton (N); AWS, 18 N; C-MAC, 52 N; p<0.01) and the difficult airway scenario (DL, 42 N; AWS, 24 N; C-MAC, 68 N; p<0.01). In contrast, the maximum force applied on the tongue was higher with the use of the DL than with the AWS and C-MAC in both airway scenarios (DL, 16 N; AWS, 1 N; C-MAC, 7 N; p<0.01 in the normal airway scenario; DL, 12 N; AWS, 4 N; C-MAC, 7 N; p<0.01 in the difficult airway scenario).ConclusionsThe use of C-MAC, compared with the DL and AWS, was associated with the higher maximum force applied on maxillary incisors during intubation attempts. In contrast, the use of video laryngoscopes was associated with the lower force applied on the tongue in both airway scenarios, compared with the DL. Our study was a simulation-based study, and further research on living patients would be warranted.
TOPS: Trial Of Prevention Strategies for low back pain in patients recently recovered from low back pain—study rationale and protocol
Authors: Stevens Matthew L , Lin Chung-Wei C , Hancock Mark J , Latimer Jane , Buchbinder Rachelle , Grotle Margreth , van Tulder Maurits , New Charles H , Wisby-Roth Trish , Maher Chris G 
Published: May 2016

IntroductionLow back pain (LBP) is the health condition that carries the greatest disability burden worldwide; however, there is only modest support for interventions to prevent LBP. The aim of this trial is to establish the effectiveness and cost-effectiveness of group-based exercise and educational classes compared with a minimal intervention control in preventing recurrence of LBP in people who have recently recovered from an episode of LBP.Methods and analysisTOPS will be a pragmatic comparative effectiveness randomised clinical trial with a parallel economic evaluation combining three separate cohorts (TOPS Workers, TOPS Primary Care, TOPS Defence) with the same methodology. 1482 participants who have recently recovered from LBP will be randomised to either a comprehensive exercise and education programme or a minimal intervention control. Participants will be followed up for a minimum of 1 year. The primary outcome will be days till recurrence of LBP. Effectiveness will be assessed using survival analysis. Cost-effectiveness will be assessed from the societal perspective.Ethics and disseminationThis trial has been approved by the University of Sydney Human Research Ethics Committee (HREC) (ref: 2015/728) and prospectively registered with the Australian and New Zealand Clinical Trials Registry (ref: 12615000939594). We will also obtain ethics approval from the Australian Defence Force HREC. The results of this study will be submitted for publication in a prominent journal and widely publicised in the general media.Trial registration numberAustralian and New Zealand Clinical Trial Registry (ANZCTR) 12615000939594.
Reasons for non-participation in a primary care-based physical activity trial: a qualitative study
Authors: Attwood S , Morton K L , Mitchell J , Van Emmenis M , Sutton S 
Published: May 2016

ObjectivesTo explore reasons for non-participation in a primary care-based physical activity trial and understand how these may contribute to recruitment of non-representative research samples. We also aimed to elicit non-participants’ own recommendations for enhancing trial uptake in primary care.DesignSemistructured telephone interviews with non-participants to a randomised controlled trial of a very brief intervention for promoting physical activity conducted in primary care (the Very Brief Interventions trial), with thematic analysis of interview transcripts.Setting5 general practice (GP) surgeries in the East of England, UK.ParticipantsInterviews were completed with 10 female and 6 male non-participants of white ethnicity and aged between 40 and 71 years. 13 of the 16 interviewees were either active or moderately active according to the GP Physical Activity Questionnaire (GPPAQ).ResultsInterviewees discussed a range of reasons for non-participation. These included beliefs surrounding the personal relevance of the trial based on preconceptions of intervention content. Many interviewees considered themselves either sufficiently active or too functionally limited to increase activity levels further, so rendering participation pointless in their view. Other identified barriers included a lack of free time, for trial participation and for increasing physical activity, and dissatisfaction with appointment scheduling systems in place at GP surgeries. Interviewees questioned the appropriateness of primary care as a context for delivering interventions to promote physical activity. In general, interviewees were positively disposed towards the idea of trial participation, especially if personal benefits are made salient, but suggested that interventions could be delivered in a different setting such as the internet.ConclusionsTo increase participation in physical activity promotion trials conducted in primary care, the content of invitation materials and procedures for contacting potential participants require reconsideration. Specific recommendations include streamlining intervention materials and enhancing their relevance to the health concerns of invitees.Trial registration numberISRCTN72691150; Pre-results.
Geological structure of the northern part of the Eastern Black Sea from regional seismic reflection data including the DOBRE-2 CDP profile
Authors: Sydorenko G. , Stephenson R. , Yegorova T. , Starostenko V. , Tolkunov A. , Janik T. , Majdanski M. , Voitsitskiy Z. , Rusakov O. , Omelchenko V. 
Published: May 2016

Abstract
The margin of the northeastern Black Sea is formed by the Crimea and Kerch peninsulas, which separate it from the Azov Sea to the north. The age and architecture of the sedimentary successions in this area are described from exploration reflection seismic profiling acquired in the area, in addition to the regional DOBRE-2 CDP profile acquired in 2007. The sediments range in age from Mesozoic to Quaternary and can be divided into five seismo-stratigraphic complexes linked to the tectono-sedimentological evolution of the area. The present regional basin architecture consists of a series of basement structural highs separating a series of sedimentary depocentres and is mainly a consequence of the compressional tectonic regime affecting the area since the Eocene. This has focused shortening deformation and uplift along the axis of the Crimea–Caucasus Inversion Zone on the Kerch Peninsula and Kerch Shelf of the Black Sea. Two major sedimentary basins that mainly formed during this time – the Sorokin Trough in the Black Sea and the Indolo-Kuban Trough to the north of the Kerch Peninsula in the Azov Sea – formed as marginal troughs to the main inversion zone.
The value of fieldwork in making connections between onshore outcrops and offshore models: an example from India
Authors: Racey Andy , Fisher John , Bailey Haydon , Roy Sandip Kumar 
Published: May 2016

Abstract
Fieldwork provides an efficient and economical way of obtaining genuine geological data that can be used to constrain, test and develop exploration models in frontier areas. This study of the Cretaceous outcrops of NW India has been used to characterize models for petroleum systems postulated to have developed beneath the Deccan volcanic sequence, offshore western India, where well data are not available. To date, exploration of ‘sub-Deccan plays’ has mainly been limited to the NW, where the presence of a working Cretaceous petroleum system has been proven in the offshore Kutch Basin.
A revised chronostratigraphic framework has been defined for the Cretaceous section as a result of new biostratigraphic data collected during this study and a thorough revision of existing palaeontological data. The revised framework, together with lithofacies observations from the field, has provided a basis for regional sequence stratigraphic correlation, which has been used to link data from onshore outcrops to models of offshore petroleum systems.
A Lower Cretaceous clastic package that, in part, corresponds to the Lower Goru and Bhuj Formation reservoirs of the Indus Basin of Pakistan and the Kutch Basin in India has been correlated across the region. Towards the top of this package, a transition from fluvial to shallow-marine sedimentation marks the onset of a marine transgression that reaches its peak in the Turonian. Marly limestones and claystones associated with this regionally mapped event are a potential topseal to the Lower Cretaceous clastic package. Geochemical evaluation of several outcrop locations has identified potential source-prone facies that, if present downdip in the offshore, may provide a mechanism for charging a pre-Deccan play.
The solution to AI, what real researchers do, and expectations for CS classrooms
Authors: Langford John , Meyer Bertrand , Guzdial Mark 
Published: May 2016

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