bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of Fluoroquinolone Susceptibility Directly from Whole-Genome Sequence Data by Using Liquid Chromatography-Tandem Mass Spectrometry To Identify Mutant Genotypes
Authors: Wan Nur Ismah Wan Ahmad Kamil , Takebayashi Yuiko , Findlay Jacqueline , Heesom Kate J. , Jiménez-Castellanos Juan-Carlos , Zhang Jay , Graham Lee , Bowker Karen , Williams O. Martin , MacGowan Alasdair P. , Avison Matthew B. 
Published: February 2018

ABSTRACT

Fluoroquinolone resistance in Gram-negative bacteria is multifactorial, involving target site mutations, reductions in fluoroquinolone entry due to reduced porin production, increased fluoroquinolone efflux, enzymes that modify fluoroquinolones, and Qnr, a DNA mimic that protects the drug target from fluoroquinolone binding. Here we report a comprehensive analysis, using transformation and
in vitro
mutant selection, of the relative importance of each of these mechanisms for fluoroquinolone nonsusceptibility using
Klebsiella pneumoniae
as a model system. Our improved biological understanding was then used to generate 47 rules that can predict fluoroquinolone susceptibility in
K. pneumoniae
clinical isolates. Key to the success of this predictive process was the use of liquid chromatography-tandem mass spectrometry to measure the abundance of proteins in extracts of cultured bacteria, identifying which sequence variants seen in the whole-genome sequence data were functionally important in the context of fluoroquinolone susceptibility.
Impact of Homologous Resistance Mutations from Pathogenic Yeast on Saccharomyces cerevisiae Lanosterol 14α-Demethylase
Authors: Sagatova Alia A. , Keniya Mikhail V. , Tyndall Joel D. A. , Monk Brian C. 
Published: February 2018

ABSTRACT

Fungal infections frequently affect immunodeficient individuals and are estimated to kill 1.35 million people per annum. Azole antifungals target the membrane-bound cytochrome P450 monooxygenase lanosterol 14α-demethylase (CYP51; Erg11p). Mutations in CYP51 can render the widely used triazole drugs less effective. The
Candida albicans
CYP51 mutation G464S and the double mutation Y132F G464S (Y140F and G464S by
Saccharomyces cerevisiae
numbering) as well as the CYP51A G54E/R/W mutations of
Aspergillus fumigatus
(G73E/R/W by
S. cerevisiae
numbering) have been reproduced in a recombinant C-terminal hexahistidine-tagged version of
S. cerevisiae
CYP51 (ScErg11p6×His). Phenotypes and X-ray crystal structures were determined for the mutant enzymes. Liquid microdilution assays showed that the G464S mutation in ScErg11p6×His conferred no difference in the susceptibility of yeast to triazole drugs but in combination with the Y140F mutation gave a 4-fold reduction in susceptibility to the short-tailed triazole fluconazole. The ScErg11p6×His Y140F G464S mutant was unstable during purification and was not crystallized. The ScErg11p6×His G73E/R/W mutations conferred increased susceptibly to all triazoles tested in liquid microdilution assays. High-resolution X-ray crystal structures reveal two different conformations of the ligand itraconazole, including a previously unseen conformation, as well as interactions between the tail of this triazole and the E/W73 residue. This study shows that
S. cerevisiae
CYP51 adequately represents some but not all mutations in CYP51s of pathogenic fungi. Insight into the molecular mechanisms of resistance mutations in CYP51 will assist the development of inhibitors that will overcome antifungal resistance.
Assessment of choroidal blood flow using laser speckle flowgraphy
Authors: Calzetti Giacomo , Fondi Klemens , Bata Ahmed M , Luft Nikolaus , Wozniak Piotr A , Witkowska Katarzyna J , Bolz Matthias , Popa-Cherecheanu Alina , Werkmeister René M , Schmidl Doreen , Garhöfer Gerhard , Schmetterer Leopold 
Published: February 2018

Background/aimsThere is considerable interest in novel techniques to quantify choroidal blood flow (CBF) in humans. In the present study, we investigated a novel technique to measure CBF based on laser speckle flowgraphy (LSFG) in healthy subjects.MethodsThis study included 31 eyes of 31 healthy, non-smoking subjects aged between 19 and 74 years. A commercial LSFG instrument was used to measure choroidal vessel diameter (CVD) and relative flow volume (RFV) in choroidal vessels that were identified on fundus photos, an approach that was used previously only for retinal vessels. The reproducibility and the effect of isometric exercise on these parameters were investigated. The latter was compared with measurement of subfoveal CBF using laser Doppler flowmetry (LDF).ResultsIntraclass correlation coefficients for CVD and RFV were higher than 0.8 indicating excellent reproducibility. During isometric exercise, we observed an increase in ocular perfusion pressure of approximately 60% (P<0.001). The increase in RFV and CBF was lower, but also highly significant versus baseline (at minute 6 of isometric exercise: RFV 10.5%±4.2%, CBF 8.3%±3.6%; P<0.001 each) indicating choroidal autoregulation.ConclusionLSFG may be a novel approach to study blood flow in choroidal vessels. Data are reproducible and show good agreement with LDF data.Trial registration numberNCT02102880, Results.
Is smoking a risk factor for tinnitus? A systematic review, meta-analysis and estimation of the population attributable risk in Germany
Authors: Veile Annette , Zimmermann Heiko , Lorenz Eva , Becher Heiko 
Published: February 2018

ObjectiveTo assess the epidemiological association of smoking status and tinnitus with a systematic review and meta-analysis and to estimate the population attributable risk in Germany.Data sourcesA systematic literature search in PubMed and ISI-Web of Science Core Collection resulted in 1026 articles that were indexed until 15 September 2015. Additionally, proceedings of the international tinnitus seminars and reference lists of relevant articles were screened.Study selectionTwo reviewers searched independently for epidemiological studies. Tinnitus as a manifestation of tumours, vascular malformations, specific syndromes or as a consequence of surgical and medical treatment was not considered. Moreover, studies conducted among patients of ear, nose and throat clinics were excluded.Data extractionIf only raw data were provided, effect sizes were calculated. Further unpublished data were received by corresponding authors.Data synthesisData of 20 studies were pooled. Current smoking (OR 1.21, 95% CI 1.09 to 1.35), former smoking (OR 1.13, 95% CI 1.01 to 1.26) and ever smoking (OR 1.20, 95% CI 1.11 to 1.30) were significantly associated with tinnitus. Moreover, sensitivity analyses for severe tinnitus (OR 1.32, 95% CI 1.10 to 1.58) and for studies of superior quality (OR 1.15, 95% CI 1.03 to 1.29) showed increased risks. According to this, the population attributable risk estimate in Germany is 3.5%.ConclusionThere is sufficient evidence that smoking is associated with tinnitus. As the review mainly consists of cross-sectional studies, the observed correlation does not give evidence of a causal relationship. Due to the impact of various confounders, further research is needed to provide more evidence on the strength of association and causal relationships.
Protocol for a longitudinal twin birth cohort study to unravel the complex interplay between early-life environmental and genetic risk factors in health and disease: the Chongqing Longitudinal Twin Study (LoTiS)
Authors: Tong Chao , Wen Li , Xia Yinyin , Leong Pamela , Wang Lan , Fan Xin , Han Ting-li , Craig Jeffrey M , Baker Philip , Saffery Richard , Qi Hongbo 
Published: February 2018

IntroductionNon-communicable diseases (NCD) now represent the major burden of adverse health in most countries. It is clear that much of the risk of such conditions begins very early in life, potentially in utero. Given their complex aetiology, an understanding of the origins of NCD requires an in-depth analysis of the interplay between genetic variation and environment, preferably over time. For decades, twin studies have played a key role in understanding such traits. Their strength lies in the ability to disentangle genetic and environmental factors that contribute to a phenotype. This is done by comparing genetically identical monozygotic (MZ) with dizygotic twins, who share on average 50% of genetic variation, or by comparing MZ twins within a pair. This study aims to determine the relative contributions of genes and environment to early-onset intermediate phenotypes related to later adult onset disease (such as growth and neurodevelopment) and to identify specific biomarkers and time points for emergence of phenotypes from infancy, largely independent of underlying genetic factors.Methods/designThe Chongqing Longitudinal Twin Study (LoTiS) will recruit 300 women pregnant with twins, enriched for MZ pregnancies, with follow-up to 3 years of age. Data collection will be undertaken at key time points in gestation (×3), at delivery and postnatally (×9). Maternal and infant biospecimens including blood, urine, hair, nails and buccal swabs along with measures such as fetal scans and body measurements will be collected. Additional information from questionnaires and medical records includes pregnancy, diet, sociodemographics, maternal stress, and infant growth and neurodevelopment.Ethics and disseminationThis study has been approved by the Ethics Committee of Chongqing Medical University (record no: 201530) and has been registered with the Chinese Clinical Trial Registry (registry no: ChiCTR-OOC-16008203). Results of the recruitment and all subsequent analyses will be submitted for publication in peer-reviewed journals.Trial registration numberChiCTR-OOC-16008203; Results.
Usefulness of positron emission tomography/computed tomography in patients with valve-tube graft infection
Authors: García-Arribas Daniel , Vilacosta Isidre , Ortega Candil Aida , Rodríguez Rey Cristina , Olmos Carmen , Pérez Castejón María Jesús , Vivas David , Pérez-García Carlos Nicolás , Carnero-Alcázar Manuel , Fernández-Pérez Cristina , Maroto Luis , Carreras José Luis 
Published: February 2018

ObjectiveInfection of valved aortic grafts is a rare entity whose diagnosis remains challenging. Positron emission tomography (PET)/CT has become a criterion for the diagnosis of infective endocarditis (IE) in prosthetic valves, but its role on ascending aortic graft infections remains unclear. This study aims to assess the diagnostic value of PET/CT in patients with valved aortic graft infection.Methods12 episodes with a valved aortic graft who had undergone a PET/CT due to suspicion of IE were prospectively included (group I) and compared with five controls free of infection who underwent PET/CT for other reasons (group II). Pathological uptake of 18F-fluorodeoxyglucose (FDG) and its pattern at the prosthetic valve and aortic graft were studied.ResultsDiagnosis of IE was confirmed in 9 out of 12 episodes of group I. 18F-FDG uptake was detectable in eight out of nine cases with a final diagnosis of IE. The most repeated pattern of uptake was homogeneous around the valve and heterogeneous around the tube. There was one false-negative study. Of the three patients in which IE was ruled out, there were two false positives and one true negative. In group II, there were three patients with a positive PET/CT study, two of them had active aortitis and the third was considered false positive.Conclusions18F-FDG PET/CT shows high sensitivity in the detection of infected aortic grafts. Thus, this technique should be considered in the diagnostic work-up of patients with suspicion of aortic graft infection. However, further validation of this approach is needed.
Physician global assessments for disease activity in rheumatoid arthritis are all over the map!
Authors: Turk Matthew , Pope Janet E 
Published: February 2018

IntroductionPhysician global assessments of disease activity (medical doctor (MD) globals) are important outcomes. MD globals may vary based on their age, gender, practice setting and experience (number of patients seen per year and years in practice).MethodsWe determined the variability of MD globals, surveying rheumatologists from the Canadian Rheumatology Association using rheumatoid arthiritis (RA) cases rated by MD for disease activity from 0 to 10. Cases were developed to span the spectrum of disease activity. Kappa, intraclass correlation (ICC) coefficients and linear mixed models were used.Results109 responded to the survey (approximately 30% response). The range of MD globals for the same scenario was as high as 7.6 out of 10, indicating vast discrepancies between physicians. Some scenarios outlined changes in individual patients; however, physicians surveyed were often in disagreement as to how much the patient recovered or worsened but the direction was the same (ie, if better all agreed). When physician-related factors were analysed separately, MD global scores were significantly influenced by age and experience (ranked by a physician, number of patients seen per year and years in clinical practice) in linear mixed models. Multivariate analysis revealed borderline significance for two age categories (56–65 years, P=0.049; over 65 years, P=0.058) and those who have seen 600–800 patients per year (P=0.056).ConclusionsThis emphasises the need to establish evaluation criteria in RA for disease. Perhaps, a catalogue of patient scenarios that range from 0 to 10 could be developed, standardised and agreed on to decrease the wide variability of ranking by rheumatologists.
On Plesionika persica (Kemp, 1925) and P. reflexa Chace, 1985 (Crustacea: Decapoda: Pandalidae) from India
Authors: CHAN TIN-YAM , CHAKRABORTY REKHA DEVI , PURUSHOTHAMAN P. , KUBERAN G. , YANG CHIEN-HUI 
Published: February 2018

The availability of Indian specimens of Plesionika persica (Kemp, 1925) and P. reflexa Chace, 1985 provided more information on the taxonomy around these two species. Moreover, it is the first record of P. persica to India. Although P. taiwanica Chan and Yu, 2000 is superficially rather similar to P. persica, there are many differences between them and probably it is inappropriate to establish a species group for these two species. It is likely that all previous records of P. ensis (A. Milne-Edwards, 1881) from India actually represent P. reflexa Chace, 1985. Nevertheless, the present Indian specimens of P. reflexa have more than 10% COI sequence divergence from the topotypic materials of both P. ensis and P. reflexa, and the epipods at the pereiopods III and IV reduced or absent. This data further highlights the confusing taxonomy in the “P. ensis” group.
Synoptic–Dynamic Climatology of the Aleutian High
Authors: Colucci Stephen J. , Ehrmann Thomas S. 
Published: February 2018

Abstract
A climatology of the anticyclone that commonly appears over the Aleutian Islands in the wintertime Northern Hemisphere stratosphere is presented. Applying a geometric moments technique to a reanalysis dataset and updating a previously published definition, 68 Aleutian high (AH) events have been identified during 35 winter (October–March) seasons (1979/80–2013/14), or about 2 events per season. The events lasted an average of approximately 33 days. Thirteen of the 68 AH events each temporally and spatially coincided with tropospheric blocking identified with a wave-breaking definition, while 41 of the AH onsets each coincided with a persistently positive geopotential height anomaly in the troposphere. Also, 41 of the 68 AH events each coincided with or were followed by an objectively defined disturbance (split or displacement) to the stratospheric polar vortex. Finally, 47 of these disturbance events were each preceded by an AH onset, such that in almost all winters (33 out of 35), an early season AH was followed by a later-season polar vortex disturbance (PVD).
Potential vorticity (PV) inversion revealed that the geopotential height rises associated with composite AH onset were forced primarily by anticyclonic PV increases in the stratosphere, with the troposphere providing a lesser contribution. Poleward eddy heat fluxes in the stratosphere preceded and especially followed composite AH onset, consistent with the findings that composite AH onset was forced primarily by anticyclonic PV increases in the stratosphere and that many AH onsets were each followed by a PVD onset.
The Response of the Ozone Layer to Quadrupled CO2 Concentrations
Authors: Chiodo G. , Polvani L. M. , Marsh D. R. , Stenke A. , Ball W. , Rozanov E. , Muthers S. , Tsigaridis K. 
Published: February 2018

Abstract
An accurate quantification of the stratospheric ozone feedback in climate change simulations requires knowledge of the ozone response to increased greenhouse gases. Here, an analysis is presented of the ozone layer response to an abrupt quadrupling of CO2 concentrations in four chemistry–climate models. The authors show that increased CO2 levels lead to a decrease in ozone concentrations in the tropical lower stratosphere, and an increase over the high latitudes and throughout the upper stratosphere. This pattern is robust across all models examined here, although important intermodel differences in the magnitude of the response are found. As a result of the cancellation between the upper- and lower-stratospheric ozone, the total column ozone response in the tropics is small, and appears to be model dependent. A substantial portion of the spread in the tropical column ozone is tied to intermodel spread in upwelling. The high-latitude ozone response is strongly seasonally dependent, and shows increases peaking in late winter and spring of each hemisphere, with prominent longitudinal asymmetries. The range of ozone responses to CO2 reported in this paper has the potential to induce significant radiative and dynamical effects on the simulated climate. Hence, these results highlight the need of using an ozone dataset consistent with CO2 forcing in models involved in climate sensitivity studies.
Impact of a Standardized Beta-Lactam Allergy Questionnaire on Aztreonam Use
Authors: Clark Kacie E. , Briand Mary E. , Kapoor Om , Pirasteh Ameen 
Published: February 2018

Methods: This quasi-experimental study compared the aztreonam utilization in patients with self-reported beta-lactam allergies admitted to an inpatient service between two study periods (pre- and post-implementation). Post-implementation followed the initiation of a standardized beta-lactam allergy questionnaire, a student pharmacist–driven performance improvement project for beta-lactam allergy documentation. Interviews clarified the allergy, reaction history, and any previous tolerance of beta-lactams. If receiving aztreonam at the time of the questionnaire, recommendations were made for changes in therapy if deemed appropriate by the pharmacist. Results: A total of 95 patients were included in the pre-implementation group versus 65 patients in the post-implementation group. Baseline characteristics were similar. The average number of aztreonam doses per 1000 patient-days in the post-implementation group was decreased (21.23 vs 9.05, P = .003). The average number of days of therapy per 1000 patient-days in the post-implementation group was decreased (8.79-4.24, P = .016). An increase in the number of aztreonam de-escalations was observed post-implementation ( P = .003). A total of 122 questionnaires were completed with 114 allergy documentation updates. There were no reported instances of adverse events. Conclusion: Utilization of a standardized beta-lactam allergy questionnaire as a pharmacy education tool resulted in a statistically significant decrease in aztreonam utilization, based on doses, days of therapy, and de-escalations.
Probation officers’ judgements: A study using personal construct theory
Authors: Mullineux Judith C , Taylor Brian J , Giles Melanie L 
Published: February 2018

• Summary Social workers and probation officers are frequently called upon to make judgements about the likelihood of re-offending. However, whilst the use of risk assessment instruments is now commonplace, the cognitive processes through which these judgements are made are rarely explicit. • Findings This study used the repertory grid method to elicit the constructs of judgements about re-offending of 15 experienced probation officers. Primary factors in their judgements were related to: (1) responsibility and risk taking behaviour; (2) criminal history; (3) self-awareness; and (4) stability. Personality characteristics, substance misuse and family dysfunction were also important. The findings are discussed in relation to two theoretical frameworks for understanding decision making: heuristics and biases and image theory, which focuses on values. • Application It is suggested that the design and implementation of assessment tools should be undertaken in the light of the constructs used in making professional judgements which inform the relevant decision making.
Relationship between measured plastic limit and plastic limit estimated from undrained shear strength, water content ratio and liquidity index
Authors: Spagnoli Giovanni , Feinendegen Martin 
Published: February 2018

AbstractThe detection of the plastic limit of clays is subject to human error. Several attempts have been made to correlate across studies the geotechnical properties of fine-grained soils (water content, liquidity index, shear strength, etc.). Based on the premise that the liquidity index and water content ratio can be correlated directly, an alternative method to obtain indirectly the plastic limit is suggested here. The present study investigated 40 natural clayey samples of various mineralogies and origins and other publicly available data, where Atterberg limits and undrained shear strength values obtained with the vane shear tests were given. The liquidity index and water-content ratio correlate very well for defined undrained shear strength values of the clays. Solving the liquidity index equation for the plastic limit, estimated plastic limit values obtained by the liquidity index/water-content ratio relationship were compared with laboratory plastic-limit values. Preliminary results based on 62 values show an exponential trend with a multiple regression coefficient of 0.79. The data need to be confirmed on a larger database, however.
Hematopoiesis by iPSC-derived hematopoietic stem cells of aplastic anemia that escape cytotoxic T-cell attack
Authors: Espinoza J. Luis , Elbadry Mahmoud I. , Chonabayashi Kazuhisa , Yoshida Yoshinori , Katagiri Takamasa , Harada Kenichi , Nakagawa Noriharu , Zaimoku Yoshitaka , Imi Tatsuya , Takamatsu Hiroyuki , Ozawa Tatsuhiko , Maruyama Hiroyuki , Hassanein Hassan A. , Khalifa A. Noreldin Amal , Takenaka Katsuto , Akashi Koichi , Hamana Hiroshi , Kishi Hiroyuki , Akatsuka Yoshiki , Nakao Shinji 
Published: February 2018

Key Points
HLA-lacking iPSC-derived HSCs from aplastic anemia patients show a hematopoietic ability similar to wild-type iPSC-HSCs. iPSC-HSCs that lack HLA-B4002 escape specific T-cell attack.
Combination of the low anticoagulant heparin CX-01 with chemotherapy for the treatment of acute myeloid leukemia
Authors: Kovacsovics Tibor J. , Mims Alice , Salama Mohamed E. , Pantin Jeremy , Rao Narayanam , Kosak Ken M. , Ahorukomeye Peter , Glenn Martha J. , Deininger Michael W. N. , Boucher Kenneth M. , Bavisotto Linda M. , Gutierrez-Sanchez Gerardo , Kennedy Thomas P. , Marcus Stephen G. , Shami Paul J. 
Published: February 2018

Key Points
In a pilot study, the nonanticoagulant heparin derivative CX-01 was well tolerated when combined with chemotherapy for the treatment of AML. Preliminary results show encouraging complete remission rates and rapid platelet recovery.