bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recordkeeping in an outsourcing public agency
Authors: Klareld Ann-Sofie 
Published: January 2018

Purpose
The purpose of this paper is to discuss the implications of an outsourcing policy for public recordkeeping. The research question addressed is as follows: What are the current impediments to create, capture, organize and pluralize records produced by contractors to whom work has been outsourced?

Design/methodology/approach
The paper uses four dimensions of the records continuum model (RCM) as a structure for understanding what important aspects of recordkeeping that can be affected by an outsourcing policy and discuss the consequences for the creation of public archives. An investment project at a Swedish public agency with a far-reaching outsourcing policy in the form of a client–contractor model is used as a case to exemplify the problem.

Findings
The findings indicate that the legal framework for recordkeeping needs further development, or clarification as to how it should be interpreted in the outsourcing context. More case studies are needed to provide richer data about recordkeeping challenges arising from outsourcing and further opportunities for theoretical analysis using the RCM.

Originality/value
The RCM has been used in a first attempt to understand various aspects of records management practices and what principles need to be taken into account when making such significant organizational structural and cultural changes.
Gangs, music and the mediatisation of crime: expressions, violations and validations
Authors: Pinkney Craig , Robinson-Edwards Shona 
Published: January 2018

Purpose
The way in which criminologists understand, contextualise and theorise around the mediatised world has raised some critical new questions. The purpose of this paper is to report on qualitative research which looks at the ways in which some forms of social media are utilised by gang members. Gang research in the main is predicated on the notion that gangs are deviant products of social disorganisation; however, there is little written on the “specific” forms of expression used by those associated with gangs.

Design/methodology/approach
The lyrical content of three music videos has been analysed using narrative analysis.

Findings
Music videos have been used as a form of expression for decades. More recently in some cases they have been used as a tool to send threats, promote gang culture and flaunt illegal substances, which is fairly a new concept, in the UK at least. Social media and music videos are not the sole reason why there has been a rise in violence amongst young people; however, this paper aims to further explore some of these notions.

Originality/value
The authors suggest that this form of expression presents challenges in the understanding of gang activity in a mediatised world. The intention is not to further criminalise young people, but to seek understanding and explore the phenomenon of music videos and its position their gang research.
Antimicrobial Activity of Ibuprofen against Cystic Fibrosis-Associated Gram-Negative Pathogens
Authors: Shah Parth N. , Marshall-Batty Kimberly R. , Smolen Justin A. , Tagaev Jasur A. , Chen Qingquan , Rodesney Christopher A. , Le Henry H. , Gordon Vernita D. , Greenberg David E. , Cannon Carolyn L. 
Published: January 2018

ABSTRACTClinical trials have demonstrated the benefits of ibuprofen therapy in cystic fibrosis (CF) patients, an effect that is currently attributed to ibuprofen's anti-inflammatory properties. Yet, a few previous reports demonstrated an antimicrobial activity of ibuprofen as well, although none investigated its direct effects on the pathogens found in the CF lung, which is the focus of this work. Determination of ibuprofen'sin vitroantimicrobial activity againstPseudomonas aeruginosaandBurkholderiaspecies strains through measurements of the endpoint number of CFU and growth kinetics showed that ibuprofen reduced the growth rate and bacterial burden of the tested strains in a dose-dependent fashion. In anin vitroPseudomonasbiofilm model, a reduction in the rate of biomass accumulation over 8 h of growth with ibuprofen treatment was observed. Next, an acutePseudomonaspneumonia model was used to test this antimicrobial activity after the oral delivery of ibuprofen. Following intranasal inoculation, ibuprofen-treated mice exhibited lower CFU counts and improved survival compared with the control animals. Preliminary biodistribution studies performed after the delivery of ibuprofen to mice by aerosol demonstrated a rapid accumulation of ibuprofen in serum and minimum retention in lung tissue and bronchoalveolar lavage fluid. Therefore, ibuprofen-encapsulated polymeric nanoparticles (Ibu-NPs) were formulated to improve the pharmacokinetic profile. Ibu-NPs formulated for aerosol delivery inhibited the growth ofP. aeruginosa in vitroand may provide a convenient dosing method. These results provide an additional explanation for the previously observed therapeutic effects of ibuprofen in CF patients and further strengthen the argument for its use by these patients.
In Vitro
Susceptibility of Mycobacterium tuberculosis to Amikacin, Kanamycin, and Capreomycin
Authors: Dijkstra J. A. , van der Laan T. , Akkerman O. W. , Bolhuis M. S. , de Lange W. C. M. , Kosterink J. G. W. , van der Werf T. S. , Alffenaar J. W. C. , van Soolingen D. 
Published: January 2018

ABSTRACT

Amikacin, kanamycin, and capreomycin are among the most important second-line drugs for multidrug-resistant tuberculosis. Although amikacin and kanamycin are administered at the same dose and show the same pharmacokinetics, they have different WHO breakpoints, suggesting that the two drugs have different MICs. The aim of this study was to investigate possible differences in MICs between the aminoglycosides and capreomycin. Using the direct concentration method, a range of concentrations of amikacin, kanamycin, and capreomycin (0.25, 0.50, 1.0, 2.0, 4.0, 8.0, 16.0, 32.0, and 64.0 mg/liter) were tested against 57 clinical
Mycobacterium tuberculosis
strains. The 7H10 agar plates were examined for mycobacterial growth after 14 days. At 2 mg/liter, 48 strains (84%) were inhibited by amikacin and only 5 strains (9%) were inhibited by kanamycin (
P
< 0.05, Wilcoxon signed-rank test). The median MICs of amikacin, kanamycin, and capreomycin were 2, 4, and 8 mg/liter, respectively. No difference in amikacin, kanamycin, and capreomycin MIC distributions was observed between multidrug-resistant strains and fully susceptible strains. The results indicate that amikacin is more active than kanamycin and capreomycin against
M. tuberculosis
with the absolute concentration method. Determination of the impact of this difference on clinical outcomes in daily practice requires a prospective study, including pharmacokinetic and pharmacodynamic evaluations.
Mycobacterium abscessus Smooth and Rough Morphotypes Form Antimicrobial-Tolerant Biofilm Phenotypes but Are Killed by Acetic Acid
Authors: Clary Gillian , Sasindran Smitha J. , Nesbitt Nathan , Mason Laurel , Cole Sara , Azad Abul , McCoy Karen , Schlesinger Larry S. , Hall-Stoodley Luanne 
Published: January 2018

ABSTRACTMycobacterium abscessushas emerged as an important pathogen in people with chronic inflammatory lung diseases such as cystic fibrosis, and recent reports suggest that it may be transmissible by fomites.M. abscessusexhibits two major colony morphology variants: a smooth morphotype (MaSm) and a rough morphotype (MaRg). Biofilm formation, prolonged intracellular survival, and colony variant diversity can each contribute to the persistence ofM. abscessusand other bacterial pathogens in chronic pulmonary diseases. A prevailing paradigm of chronicM. abscessusinfection is thatMaSmis a noninvasive, biofilm-forming, persistent phenotype andMaRgan invasive phenotype that is unable to form biofilms. We show thatMaRgis hyperaggregative and forms biofilm-like aggregates, which, likeMaSmbiofilm aggregates, are significantly more tolerant than planktonic variants to acidic pHs, hydrogen peroxide (H2O2), and treatment with amikacin or azithromycin. We further show that both variants are recalcitrant to antibiotic treatment inside human macrophage-like cells and thatMaRgis more refractory thanMaSmto azithromycin. Our results indicate that biofilm-like aggregation and protracted intracellular survival may each contribute to the persistence of this problematic pathogen in the face of antimicrobial agents regardless of morphotype. Biofilms of eachM. abscessusvariant are rapidly killed, however, by acetic acid, which may help to prevent local fomite transmission.
Identification of a Novel Genomic Island Associated with
vanD
-Type Vancomycin Resistance in Six Dutch Vancomycin-Resistant Enterococcus faecium Isolates
Authors: Top Janetta , Sinnige Jan C. , Brouwer Ellen C. , Werner Guido , Corander Jukka , Severin Juliëtte A. , Jansen Rogier , Bathoorn E. , Bonten Marc J. M. , Rossen John W. A. , Willems Rob J. L. 
Published: January 2018

ABSTRACT

Genomic comparison of the first six Dutch
vanD
-type vancomycin-resistant
Enterococcus faecium
(VRE) isolates with four
vanD
gene clusters from other enterococcal species and anaerobic gut commensals revealed that the
vanD
gene cluster was located on a genomic island of variable size. Phylogenetic inferences revealed that the Dutch VRE isolates were genetically not closely related and that genetic variation of the
vanD
-containing genomic island was not species specific, suggesting that this island is transferred horizontally between enterococci and anaerobic gut commensals.
Molecular Epidemiology and Mechanism of Sulbactam Resistance in Acinetobacter baumannii Isolates with Diverse Genetic Backgrounds in China
Authors: Yang Yunxing , Fu Ying , Lan Peng , Xu Qingye , Jiang Yan , Chen Yan , Ruan Zhi , Ji Shujuan , Hua Xiaoting , Yu Yunsong 
Published: January 2018

ABSTRACT

Sulbactam is a plausible option for treating
Acinetobacter
infections because of its intrinsic antibacterial activity against the members of the
Acinetobacter
genus, but the mechanisms of sulbactam resistance have not been fully studied in
Acinetobacter baumannii
. In this study, a total of 2,197 clinical
A. baumannii
isolates were collected from 27 provinces in China. Eighty-eight isolates with various MICs for sulbactam were selected on the basis of their diverse clonality and underwent multilocus sequence typing (MLST), antimicrobial susceptibility testing, and resistance gene screening. The copy number and relative expression of
bla
TEM-1D
and
ampC
were measured via quantitative PCR and quantitative reverse transcription-PCR, respectively. The genetic structure of multicopy
bla
TEM-1D
was determined using the whole-genome sequencing technology. The cefoperazone-sulbactam resistance rate of the 2,197 isolates was 39.7%. The rate of positivity for
bla
TEM-1D
or IS
Aba1-ampC
in the sulbactam-nonsusceptible group (64.91% and 78.95%, respectively) was significantly higher than that in the sulbactam-susceptible group (0% and 0%, respectively;
P
< 0.001). The MIC of sulbactam (
P
< 0.001) varied considerably between the groups expressing
ampC
with or without upstream IS
Aba1
. Notably, the genetic structure of the multicopy
bla
TEM-1D
gene in strain ZS3 revealed that
bla
TEM-1D
was embedded within four tandem copies of the cassette IS
26-bla
TEM-1D
-Tn
3
-IS
26
. Therefore,
bla
TEM-1D
and IS
Aba1-ampC
represent the prevalent mechanism underlying sulbactam resistance in clinical
A. baumannii
isolates in China. The structure of the four tandem copies of
bla
TEM-1D
first identified may increase sulbactam resistance.
Posaconazole Tablets in Real-Life Lung Transplantation: Impact on Exposure, Drug-Drug Interactions, and Drug Management in Lung Transplant Patients, Including Those with Cystic Fibrosis
Authors: Launay Manon , Roux Antoine , Beaumont Laurence , Douvry Benoit , Lecuyer Lucien , Douez Emmanuel , Picard Clément , Grenet Dominique , Jullien Vincent , Boussaud Véronique , Guillemain Romain , Billaud Eliane M. 
Published: January 2018

ABSTRACT

Appropriate exposure to posaconazole (PSZ) has been limited until the recent approval of the delayed-release oral tablet formulation. Our goal was to determine the exposure obtained by using the standard dose of 300 mg once a day in lung transplant (LT) patients, including patients with cystic fibrosis (CF). PSZ trough concentrations (
C
0
) were determined using a liquid chromatography-tandem mass spectrometry assay. Indicative thresholds of interest were <0.7 mg/liter for prophylaxis and 1 to 3 mg/liter for cure. The tacrolimus (TRL) and everolimus (ERL)
C
0
measured during PSZ exposure were also collected. The interaction with proton-pump inhibitors (PPI) was evaluated. We recorded the results for 21 CF patients with LT (CFLT patients), 11 non-CF patients with LT (NCFLT patients), and 27 nontransplant (NT) patients in pneumology departments. The weights of the NCFLT, CFLT, and NT patients were 59.2 ± 8.4, 48.8 ± 8.4, and 63.7 ± 16.6 kg, respectively (
P
= 0.001* [asterisk means that statistical test is significant]), and the PSZ
C
0
exposures for these patients were 1.9 ± 1.5, 1.1 ± 0.8, and 2.4 ± 1.8 mg/liter, respectively (
P
< 0.00001*). More than 60% of the concentrations were in the therapeutic range. In CFLT patients, the administration of one 300-mg PSZ tablet quickly achieved an exposure similar to that achieved with the PSZ oral suspension formulation (OSF) administered 3 or 4 times a day for several months. The TRL
C
0
/dose ratio (
C
0
/
D
) was 7.4 ± 4.4 mg/liter with PSZ tablets, whereas it was 4.6 ± 0.8 mg/liter with the PSZ oral solution (
P
= 0.034*). The ERL
C
0
/
D
was similar with both formulations. PPI had no impact on the PSZ concentration (1.49 ± 1.07 mg/liter without PPI versus 1.33 ± 1.17 mg/liter with PPI;
P
= 0.4134*). Despite the high levels of exposure, PSZ remained well tolerated (one case of diarrhea and one case of fatigue were reported). PSZ tablet administration allows satisfactory exposure, even in CFLT patients, with a dosage lower than that of the PSZ OSF. This once-a-day formulation was not impacted by PPI, which are extensively used in CF patients.
Novel Pyrimidines as Antitubercular Agents
Authors: Inoyama Daigo , Paget Steven D. , Russo Riccardo , Kandasamy Srinivasan , Kumar Pradeep , Singleton Eric , Occi James , Tuckman Margareta , Zimmerman Matthew D. , Ho Hsin Pin , Perryman Alexander L. , Dartois Véronique , Connell Nancy , Freundlich Joel S. 
Published: January 2018

ABSTRACT

Mycobacterium tuberculosis
infection is responsible for a global pandemic. New drugs are needed that do not show cross-resistance with the existing front-line therapeutics. A triazine antitubercular hit led to the design of a related pyrimidine family. The synthesis of a focused series of these analogs facilitated exploration of their
in vitro
activity,
in vitro
cytotoxicity, and physiochemical and absorption-distribution-metabolism-excretion properties. Select pyrimidines were then evaluated for their pharmacokinetic profiles in mice. The findings suggest a rationale for the further evolution of this promising series of antitubercular small molecules, which appear to share some similarities with the clinical compound PA-824 in terms of activation, while highlighting more general guidelines for the optimization of small-molecule antitubercular agents.
The C-Terminal Region of Bacillus subtilis SwrA Is Required for Activity and Adaptor-Dependent LonA Proteolysis
Authors: Hughes Anna C. , Subramanian Sundharraman , Dann Charles E. , Kearns Daniel B. 
Published: January 2018

ABSTRACT

SwrA is the master activator of flagellar biosynthesis in
Bacillus subtilis
, and SwrA activity is restricted by regulatory proteolysis in liquid environments. SwrA is proteolyzed by the LonA protease but requires a proteolytic adaptor protein, SmiA. Here, we show that SwrA and SmiA interact directly. To better understand SwrA activity, SwrA was randomly mutagenized and loss-of-function and gain-of-function mutants were localized primarily to the predicted unstructured C-terminal region. The loss-of-function mutations impaired swarming motility and activation from the

P
fla-che

promoter. The gain-of-function mutations increased protein stability but did not abolish SmiA binding, suggesting that SmiA association was a precursor to, but not sufficient for, LonA-dependent proteolysis. Finally, one allele abolished simultaneously SwrA activity and regulatory proteolysis, suggesting that the two functions may be in steric competition.

IMPORTANCE
SwrA is the master activator of flagellar biosynthesis in
Bacillus subtilis
, and its mechanism of activation is poorly understood. Moreover, SwrA levels are restricted by SmiA, the first adaptor protein reported for the Lon family of proteases. Here, we show that the C-terminal region of SwrA is important for both transcriptional activation and regulatory proteolysis. Competition between the two processes at this region may be critical for responding to cell contact with a solid surface and the initiation of swarming motility.
Genotyping Multidrug-Resistant Mycobacterium tuberculosis from Primary Sputum and Decontaminated Sediment with an Integrated Microfluidic Amplification Microarray Test
Authors: Linger Yvonne , Knickerbocker Christopher , Sipes David , Golova Julia , Franke Molly , Calderon Roger , Lecca Leonid , Thakore Nitu , Holmberg Rebecca , Qu Peter , Kukhtin Alexander , Murray Megan B. , Cooney Christopher G. , Chandler Darrell P. 
Published: January 2018

ABSTRACT

There is a growing awareness that molecular diagnostics for detect-to-treat applications will soon need a highly multiplexed mutation detection and identification capability. In this study, we converted an open-amplicon microarray hybridization test for multidrug-resistant (MDR)
Mycobacterium tuberculosis
into an entirely closed-amplicon consumable (an amplification microarray) and evaluated its performance with matched sputum and sediment extracts. Reproducible genotyping (the limit of detection) was achieved with ∼25
M. tuberculosis
genomes (100 fg of
M. tuberculosis
DNA) per reaction; the estimated shelf life of the test was at least 18 months when it was stored at 4°C. The test detected
M. tuberculosis
in 99.1% of sputum extracts and 100% of sediment extracts and showed 100% concordance with the results of real-time PCR. The levels of concordance between
M. tuberculosis
and resistance-associated gene detection were 99.1% and 98.4% for sputum and sediment extracts, respectively. Genotyping results were 100% concordant between sputum and sediment extracts. Relative to the results of culture-based drug susceptibility testing, the test was 97.1% specific and 75.0% sensitive for the detection of rifampin resistance in both sputum and sediment extracts. The specificity for the detection of isoniazid (INH) resistance was 98.4% and 96.8% for sputum and sediment extracts, respectively, and the sensitivity for the detection of INH resistance was 63.6%. The amplification microarray reported the correct genotype for all discordant phenotype/genotype results. On the basis of these data, primary sputum may be considered a preferred specimen for the test. The amplification microarray design, shelf life, and analytical performance metrics are well aligned with consensus product profiles for next-generation drug-resistant
M. tuberculosis
diagnostics and represent a significant ease-of-use advantage over other hybridization-based tests for diagnosing MDR tuberculosis.
Peptide Uptake Is Essential for
Borrelia burgdorferi
Viability and Involves Structural and Regulatory Complexity of its Oligopeptide Transporter
Authors: Groshong Ashley M. , Dey Abhishek , Bezsonova Irina , Caimano Melissa J. , Radolf Justin D. 
Published: January 2018

ABSTRACT

Borrelia burgdorferi
is an extreme amino acid (AA) auxotroph whose genome encodes few free AA transporters and an elaborate oligopeptide transport system (
B. burgdorferi
Opp [
Bb
Opp]).
Bb
Opp consists of five oligopeptide-binding proteins (OBPs), two heterodimeric permeases, and a heterodimeric nucleotide-binding domain (NBD). Homology modeling based on the crystal structure of liganded
Bb
OppA4 revealed that each OBP likely binds a distinct range of peptides. Transcriptional analyses demonstrated that the OBPs are differentially and independently regulated whereas the permeases and NBDs are constitutively expressed. A conditional NBD mutant failed to divide in the absence of inducer and replicated in an IPTG (isopropyl-β-
d
-thiogalactopyranoside) concentration-dependent manner. NBD mutants grown without IPTG exhibited an elongated morphotype lacking division septa, often with flattening at the cell center due to the absence of flagellar filaments. Following cultivation in dialysis membrane chambers, NBD mutants recovered from rats not receiving IPTG also displayed an elongated morphotype. The NBD mutant was avirulent by needle inoculation, but infectivity was partially restored by oral administration of IPTG to infected mice. We conclude that peptides are a major source of AAs for
B. burgdorferi
both
in vitro
and
in vivo
and that peptide uptake is essential for regulation of morphogenesis, cell division, and virulence.

IMPORTANCE
Borrelia burgdorferi
, the causative agent of Lyme disease, is an extreme amino acid (AA) auxotroph with a limited repertoire of annotated single-AA transporters. A major issue is how the spirochete meets its AA requirements as it transits between its arthropod vector and mammalian reservoir. While previous studies have confirmed that the
B. burgdorferi
oligopeptide transport (
opp
) system is capable of importing peptides, the importance of the system for viability and pathogenesis has not been established. Here, we evaluated the
opp
system structurally and transcriptionally to elucidate its ability to import a wide range of peptides during the spirochete’s enzootic cycle. Additionally, using a novel mutagenesis strategy to abrogate
opp
transporter function, we demonstrated that peptide uptake is essential for bacterial viability, morphogenesis, and infectivity. Our studies revealed a novel link between borrelial physiology and virulence and suggest that peptide uptake serves an intracellular signaling function regulating morphogenesis and division.