bluuebunny/crossref_metadata_2025_split huggingface dataset:
IS
5
Element Integration, a Novel Mechanism for Rapid
In Vivo
Emergence of Tigecycline Nonsusceptibility in Klebsiella pneumoniae
Authors: Nielsen Lindsey E. , Snesrud Erik C. , Onmus-Leone Fatma , Kwak Yoon I. , Avilés Ricardo , Steele Eric D. , Sutter Deena E. , Waterman Paige E. , Lesho Emil P. 
Published: August 2014

ABSTRACT

Tigecycline nonsusceptibility is concerning because tigecycline is increasingly relied upon to treat carbapenem- or colistin-resistant organisms. In
Enterobacteriaceae
, tigecycline nonsusceptibility is mediated by the AcrAB-TolC efflux pump, among others, and pump activity is often a downstream effect of mutations in their transcriptional regulators, cognate repressor genes, or noncoding regions, as demonstrated in
Enterobacteriaceae
and
Acinetobacter
isolates. Here, we report the emergence of tigecycline nonsusceptibility in a longitudinal series of multidrug-resistant (MDR) and extensively drug-resistant (XDR)
Klebsiella pneumoniae
isolates collected during tigecycline therapy and the elucidation of its resistance mechanisms. Clinical isolates were recovered prior to and during tigecycline therapy of a 2.5-month-old Honduran neonate. Antimicrobial susceptibility tests to tigecycline determined that the MIC increased from 1 to 4 μg/ml prior to the completion of tigecycline therapy. Unlike other studies, we did not find increased expression of
ramA
,
ramR
,
oqxA
,
acrB
,
marA
, or
rarA
genes by reverse transcription-quantitative PCR (qRT-PCR). Whole-genome sequencing revealed an IS
5
insertion element in nonsusceptible isolates 85 bp upstream of a putative efflux pump operon, here named
kpgABC
, previously unknown to be involved in resistance. Introduction of the
kpgABC
genes in a non-
kpgABC
background increased the MIC of tigecycline 4-fold and is independent of a functional AcrAB-TolC pump. This is the first report to propose a function for
kpgABC
and identify an insertion element whose presence correlated with the
in vivo
development of tigecycline nonsusceptibility in
K. pneumoniae
.
High Prevalence of Extended-Spectrum β-Lactamase, Plasmid-Mediated AmpC, and Carbapenemase Genes in Pet Food
Authors: Seiffert Salome N. , Carattoli Alessandra , Tinguely Regula , Lupo Agnese , Perreten Vincent , Endimiani Andrea 
Published: August 2014

ABSTRACT

We evaluated the pet food contained in 30 packages as a potential origin of extended-spectrum cephalosporin-resistant Gram-negative organisms and β-lactamase genes (
bla
). Live bacteria were not detected by selective culture. However, PCR investigations on food DNA extracts indicated that samples harbored the
bla
CTX-M-15
(53.3%),
bla
CMY-4
(20%), and
bla
VEB-4-like
(6.7%) genes. Particularly worrisome was the presence of
bla
OXA-48-like
carbapenemases (13.3%). The original pet food ingredients and/or the production processes were highly contaminated with bacteria carrying clinically relevant acquired
bla
genes.
Nutritional indicators for gastrointestinal symptoms in female runners: the ‘Marikenloop study’
Authors: ten Haaf Dominique S M , van der Worp Maarten P , Groenewoud Hans M M , Leij-Halfwerk Susanne , Nijhuis-van der Sanden Maria W G , Verbeek André L M , Staal J Bart 
Published: August 2014

ObjectivesAmong runners the reported prevalence of exercise-induced gastrointestinal (GI) symptoms is high (25%–83%). We aimed to investigate the prevalence of GI symptoms in women during a 5–10 km run in general and to explore the association between nutritional intakes and GI symptoms.SettingAs part of the Marikenloop-study (a cohort study to identify predictor variables of running injuries), a cross-sectional questionnaire was distributed in interested runners of the ‘2013 Marikenloop’.Participants433 female runners filled in the questionnaire.Primary and secondary outcome measuresThe primary outcome measure was the frequency of running-related GI symptoms during running in general and during the last (training) run. Furthermore, dietary intake was determined before and during this run. Secondary outcome measures were several demographic and anthropometric variables.ResultsDuring running in general, 40% of the participants suffered from GI symptoms and during their last run, 49%. The GI symptoms side ache, flatulence, urge to defecate and regurgitation and/or belching were most commonly reported. Lower age (OR=0.98, 95% CI 0.96 to 1.00), minor running experience (OR=3.1, 95% CI 1.7 to 5.7), higher body mass index (OR=1.1, 95% CI 1.0 to 1.2), consuming carbohydrate-containing drinks during running (OR=10.5, 95% CI 1.4 to 80.3) and experiencing GI symptoms during running in general OR=5.0, 95% CI 3.2 to 7.8) significantly contributed to GI symptoms during the last run in the logistic regression analysis. In contrast, time of eating and carbohydrate-containing drinks consumed prior to the run were not related to GI symptoms.ConclusionsIn conclusion, the current study confirms the high prevalence of GI symptoms in female runners. Several predictor variables contributed to the GI symptoms but more research is needed to specify the effects of prerunning eating and carbohydrate-containing drinks on GI symptoms during running.Trial registration numberMarikenloop study 2013: 50-50310-98-156 (ZonMw).
IGF1R Inhibition in Mammary Epithelia Promotes Canonical Wnt Signaling and Wnt1-Driven Tumors
Authors: Rota Lauren M. , Albanito Lidia , Shin Marcus E. , Goyeneche Corey L. , Shushanov Sain , Gallagher Emily J. , LeRoith Derek , Lazzarino Deborah A. , Wood Teresa L. 
Published: August 2014

Abstract
Triple-negative breast cancer (TNBC) is an aggressive disease subtype that, unlike other subtypes, lacks an effective targeted therapy. Inhibitors of the insulin-like growth factor receptor (IGF1R) have been considered for use in treating TNBC. Here, we provide genetic evidence that IGF1R inhibition promotes development of Wnt1-mediated murine mammary tumors that offer a model of TNBC. We found that in a double transgenic mouse model carrying activated Wnt1 and mutant Igf1r, a reduction in IGF1R signaling reduced tumor latency and promoted more aggressive phenotypes. These tumors displayed a squamous phenotype with increased expression of keratins 5/6 and β-catenin. Notably, cell lineage analyses revealed an increase in basal (CD29hi/CD24+) and luminal (CD24+/CD61+/CD29lo) progenitor cell populations, along with increased Nanog expression and decreased Elf5 expression. In these doubly transgenic mice, lung metastases developed with characteristics of the primary tumors, unlike MMTV-Wnt1 mice. Mechanistic investigations showed that pharmacologic inhibition of the IGF1R in vitro was sufficient to increase the tumorsphere-forming efficiency ofMMTV-Wnt1 tumor cells. Tumors from doubly transgenic mice also exhibited an increase in the expression ratio of the IGF-II-sensitive, A isoform of the insulin receptor versus the IR-B isoform, which when stimulated in vitro resulted in enhanced expression of β-catenin. Overall, our results revealed that in Wnt-driven tumors, an attenuation of IGF1R signaling accelerates tumorigenesis and promotes more aggressive phenotypes with potential implications for understanding TNBC pathobiology and treatment. Cancer Res; 74(19); 5668–79. ©2014 AACR.
DNA Methylation Map of Human Atherosclerosis
Authors: Zaina Silvio , Heyn Holger , Carmona F. Javier , Varol Nuray , Sayols Sergi , Condom Enric , Ramírez-Ruz José , Gomez Antonio , Gonçalves Isabel , Moran Sebastian , Esteller Manel 
Published: August 2014

Background—
Epigenetic alterations may contribute to the development of atherosclerosis. In particular, DNA methylation, a reversible and highly regulated DNA modification, could influence disease onset and progression because it functions as an effector for environmental influences, including diet and lifestyle, both of which are risk factors for cardiovascular diseases.

Methods and Results—
To address the role of DNA methylation changes in atherosclerosis, we compared a donor-matched healthy and atherosclerotic human aorta sample using whole-genome shotgun bisulfite sequencing. We observed that the atherosclerotic portion of the aorta was hypermethylated across many genomic loci in comparison with the matched healthy counterpart. Furthermore, we defined specific loci of differential DNA methylation using a set of donor-matched aortic samples and a high-density (>450 000 CpG sites) DNA methylation microarray. The functional importance in the disease was corroborated by crossing the DNA methylation signature with the corresponding expression data of the same samples. Among the differentially methylated CpGs associated with atherosclerosis onset, we identified genes participating in endothelial and smooth muscle functions. These findings provide new clues toward a better understanding of the molecular mechanisms of atherosclerosis.

Conclusions—
Our data identify an atherosclerosis-specific DNA methylation profile that highlights the contribution of different genes and pathways to the disorder. Interestingly, the observed gain of DNA methylation in the atherosclerotic lesions justifies efforts to develop DNA demethylating agents for therapeutic benefit.
Visual Information Processing From Multiple Displays
Authors: Johnston James C. , Ruthruff Eric , Lien Mei-Ching 
Published: August 2014

Objective: In this study, we examined how effectively people can monitor new stimuli on a peripheral display while carrying out judgments on an adjacent central display. Background: Improved situation awareness is critical for improved operator performance in aviation and many other domains. Given the limited extent of foveal processing, acquiring additional information from peripheral vision offers high potential gains. Method: Participants carried out a sequence of central perceptual judgments while simultaneously monitoring the periphery for new stimuli. Peripheral detection was measured as a function of central-judgment difficulty, the relative timing of the two tasks, and peripheral event rate. Results: Participants accurately detected and located peripheral targets, even at the highest eccentricity explored here (~30°). Peripheral detection was not reduced by increased central-task difficulty but was reduced when peripheral targets arrived later in the processing of central stimuli and when peripheral events were relatively rare. Conclusion: Under favorable conditions—high-contrast stimuli and high event rate—people can successfully monitor peripheral displays for new events while carrying out an unrelated continuous task on an adjacent display. Application: In many fields, such as aviation, existing displays were designed with low-contrast stimuli that provide little opportunity for peripheral vision. With appropriate redesign, operators might successfully monitor multiple displays over a large visual field. Designers need to be aware of nonvisual factors, such as low event rate and relative event timing, that can lead to failures to detect peripheral stimuli.
Important Methodological Issues in Evaluating Community-Based Interventions
Authors: Parker Richard , Bush Jack , Harris Daryl 
Published: August 2014

Background: Evaluation of offending behavior programs has become reasonably controversial in recent times as some researchers have advocated that evaluations should use a treatment as received (TR) model, which ignores dropouts and refusers, despite criticism that this removes the ability to make inferences about the effectiveness of the program. Some of those arguing in favor of a TR methodology suggest that the large number of noncompleters in community-based evaluations will make it impossible to detect treatment effects. A further issue with evaluation of community-based offender behavior programs is the fact that many programs are reasonably long. Evaluation methodologies inherited from custodial programs count recidivism from day one—which is before any benefits from the program are hypothesized to occur. Objectives: This article explores these issues to find solutions that are scientifically robust but also sensitive to actual program effects. Conclusion: The current authors argue that evaluations should use an intention-to-treat (ITT) model which includes noncompleters and that, using this methodology, an effective program, delivered with high integrity, should be able to demonstrate an impact on offending. However, the time period selected for evaluation should relate to the hypothesized effects of the program, not just begin from the start of supervision or commencement of the program. In doing so, the evaluators should ensure that both treatment and control groups are treated equally.
Language ability of young English language learners: Definition, configuration, and implications
Authors: Gu Lin 
Published: August 2014

In this study I examined the dimensionality of the latent ability underlying language use that is needed to fulfill the demands young learners face in English-medium instructional environments, where English is used as the means of instruction for teaching subject matters. Previous research on English language use by school-age children provided evidence that language proficiency for academic studies relates to, yet differs from, the language ability needed for social communications. Focusing on learners of English as a foreign language (EFL), I investigated the nature of language proficiency of school-age EFL learners in light of their learning experience. Analyses were based on test performance from the TOEFL Junior® Comprehensive test a proficiency assessment of English as a foreign language for young learners between the ages of 11 and 15, developed by the Educational Testing Service. The results showed that the two ability constructs (i.e., academic and social language), although theoretically distinct and educationally relevant, were statistically indistinguishable based on EFL learners’ test performance. It was also found that the test performance could be explained best by a higher-order model, indicating that the language ability of these young EFL learners was structurally similar to that usually found with adult learners in a foreign language environment. The outcomes highlight the interrelatedness of learning environment, age and language proficiency. On the one hand, the nature of the ability construct can vary across groups of learners due to differences in learning environments. On the other hand, learners of different ages who share similar learning environments could be similar in terms of the latent representation of their language proficiency. The study concludes that the interpretation of young EFL learners’ language proficiency needs to take into consideration how language components are developmentally related to each other as a function of learning experience in a foreign language environment.
Ceftriaxone Potentiates Warfarin Activity Greater Than Other Antibiotics in the Treatment of Urinary Tract Infections
Authors: Saum Lindsay M. , Balmat Ryan P. 
Published: August 2014

Background: The cephalosporin class has been associated with an increased risk of bleeding among elderly patients receiving warfarin. Urinary tract infections (UTI) are the most prevalent infection in elderly patients. Objective: To determine the extent of interaction between antibiotics used in the treatment of UTI, particularly specific cephalosporins and warfarin. Methods: A retrospective chart review was conducted on chronic warfarin patients with a diagnosis of UTI treated with ceftriaxone, a first-generation cephalosporin, penicillin, or ciprofloxacin. The primary outcome was the comparison of the extent of international normalized ratio (INR) change from baseline between each antibiotic group. Results: The ceftriaxone group was found to have a statistically significant higher peak INR value compared to all other studied antibiotics (ceftriaxone: 3.56, first-generation cephalosporins: 2.66, penicillins: 2.98, ciprofloxacin: 2.3; P = .004), a statistically significant greater extent of change in INR value (+1.19, +0.66, +0.8, +0.275; P = .006), and a statistically significant greater percentage change in INR value when compared to ciprofloxacin (54.4% vs 12.7%; P = .037). Conclusion: Ceftriaxone interacts with warfarin to increase a patient’s INR value more than other commonly administered antibiotics for UTI treatment. Other antibiotics should be preferred for UTI treatment in patients on warfarin.
What Influences Banks Lending in Sub-Saharan Africa?
Authors: Amidu Mohammed 
Published: August 2014

This article analyses the broad determinants of bank lending in Sub-Saharan Africa (SSA) using both micro-bank and macro-country level data of 264 banks across 24 SSA countries. The core finding is that the structure of banking markets influences credit delivery in SSA in an environment where the financial sector is reformed and banks are allowed to operate freely. Also, there is an evidence to suggest a link between bank credit and the financial strength of the banks. The overall results suggest that regulatory initiative, which restricts banking activities, imposes severe entry requirements and requires high regulatory capital, influences banks’ decisions to supply loans. JEL Classification: E52, G21, G28, N27
Reforms, Ownership and Determinants of Efficiency: An Empirical Study of Commercial Banks in India
Authors: Arora Padmasai 
Published: August 2014

Major steps were taken in Indian banking sector in the early 1990s to liberalise commercial bank functioning in order to improve their efficiency. The measurement of bank efficiency provides the foundation for consequent inquiry into reasons producing efficiency differences. This article measures technical efficiency of balanced panel of 54 commercial banks operating in India during 1991–92 to 2006–07 using Data Envelopment Analysis (DEA) with an aim to study effects of reforms and ownership on bank efficiency. Since existing literature lacks uniformity in methodology used for identifying determinants of efficiency in banking, this study employs a blend of tests including profitability analysis (suggested by Spong et al., 1995 ) and found evidence that financial reform, ownership and listing of bank shares have influenced bank efficiency in India. However, no conclusive evidence was found regarding a relationship between size and efficiency. In addition, ‘most’ efficient banks were found to be characterised by higher Net Profit as percentage of Total Assets (NPTA) and higher Profits per Employee (PPE) while ‘least’ efficient banks reported higher levels of Non-Performing Assets (NPAs). JEL Classification: G21, G32
Rediscovering GF Becker’s early axiomatic deduction of a multiaxial nonlinear stress–strain relation based on logarithmic strain
Authors: Neff Patrizio , Münch Ingo , Martin Robert 
Published: August 2014

We discuss a completely forgotten work of the geologist GF Becker on the ideal isotropic nonlinear stress–strain function ( Am J Sci 1893; 46: 337–356). Due to the fact that the mathematical modelling of elastic deformations has evolved greatly since the original publication we give a modern reinterpretation of Becker’s work, combining his approach with the current framework of the theory of nonlinear elasticity. Interestingly, Becker introduces a multiaxial constitutive law incorporating the logarithmic strain tensor, more than 35 years before the quadratic Hencky strain energy was introduced by Heinrich Hencky in 1929. Becker’s deduction is purely axiomatic in nature. He considers the finite strain response to applied shear stresses and spherical stresses, formulated in terms of the principal strains and stresses, and postulates a principle of superposition for principal forces which leads, in a straightforward way, to a unique invertible constitutive relation, which in today’s notation can be written as [Formula: see text] where TBiot is the Biot stress tensor, log( U) is the principal matrix logarithm of the right Biot stretch tensor [Formula: see text], [Formula: see text] denotes the trace and dev3 X =  X − (1/3) tr ( X) · 11 denotes the deviatoric part of a matrix [Formula: see text]. Here, G is the shear modulus and K is the bulk modulus. For Poisson’s number ν = 0 the formulation is hyperelastic and the corresponding strain energy [Formula: see text] has the form of the maximum entropy function.
Histones to the cytosol: exportin 7 is essential for normal terminal erythroid nuclear maturation
Authors: Hattangadi Shilpa M. , Martinez-Morilla Sandra , Patterson Heide Christine , Shi Jiahai , Burke Karly , Avila-Figueroa Amalia , Venkatesan Srividhya , Wang Junxia , Paulsen Katharina , Görlich Dirk , Murata-Hori Maki , Lodish Harvey F. 
Published: August 2014

Key PointsHistones migrate into the cytoplasm of normal erythroblasts during maturation, leading to extruded nuclei largely depleted of protein. Loss of nuclear exportin Xpo7 inhibits normal erythroid nuclear condensation and enucleation; histones remain in Xpo7-knockdown nuclei.
Molecular Mechanisms Underlying Fasting Modulated Liver Insulin Sensitivity and Metabolism in Male Lipodystrophic Bscl2/Seipin-Deficient Mice
Authors: Chen Weiqin , Zhou Hongyi , Saha Pradip , Li Luge , Chan Lawrence 
Published: August 2014

AbstractBscl2 −/− mice recapitulate many of the major metabolic manifestations in Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) individuals, including lipodystrophy, hepatomegly, hepatic steatosis, and insulin resistance. The mechanisms that underlie hepatic steatosis and insulin resistance in Bscl2−/− mice are poorly understood. To address this issue, we performed hyperinsulinemic-euglycemic clamp on Bscl2−/− and wild-type mice after an overnight (16-h) fast, and found that Bscl2−/− actually displayed increased hepatic insulin sensitivity. Interestingly, liver in Bscl2−/− mice after a short term (4-h) fast had impaired acute insulin signaling, a defect that disappeared after a 16-hour fast. Notably, fasting-dependent hepatic insulin signaling in Bscl2−/− mice was not associated with liver diacylglyceride and ceramide contents, but could be attributable in part to the expression of hepatic insulin signaling receptor and substrates. Meanwhile, increased de novo lipogenesis and decreased β-oxidation led to severe hepatic steatosis in fed or short-fasted Bscl2−/− mice whereas liver lipid accumulation and metabolism in Bscl2−/− mice was markedly affected by prolonged fasting. Furthermore, mice with liver-specific inactivation of Bscl2 manifested no hepatic steatosis even under high-fat diet, suggesting Bscl2 does not play a cell autonomous role in regulating liver lipid homeostasis. Overall, our results offered new insights into the metabolic adaptations of liver in response to fasting and uncovered a novel fasting-dependent regulation of hepatic insulin signaling in a mouse model of human BSCL2.
Actinic keratosis on the rise in Australia
Authors: Perera Eshini , McGuigan Sean , Sinclair Rodney 
Published: August 2014

Objectives:To report the burden and cost of actinic keratosis (AK) treatment in Australia and to forecast the number of AK treatments and the associated costs to 2020.Design and setting:A retrospective study of data obtained from medicare Australia for AK treated by cryotherapy between 1 January 1994 and 31 December 2012, by year and by state or territory.Results:The total number of AK cryotherapy treatments increased from 247,515 in 1994 to 643,622 in 2012, and we estimate that the number of treatments will increase to 831,952 (95% CI 676,919 to 986,987) by 202. The total Medicare Benefits Schedule (MBS) benefits paid out for AK in 2012 was $19.6 million and we forecast that this will increase to $24.7 million by 2020 (without inflation).Conclusion:The number of AK cryotherapy treatments increased by 160% between 1994 and 2012. we forecast that the number of treatments will increase by 30% between 2012 and 2020. The rates of non-melanoma skin cancer (NMSC) and AK appear to be increasing at the same rate. During the period 2010 to 2015 AK is anticipated to increase by 17.8% which follows a similar trend to published data that forecasts an increase in NMSC treatments of 22.3%.