bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural/mechanistic insights into the efficacy of nonclassical β‐lactamase inhibitors against extensively drug resistant Stenotrophomonas maltophilia clinical isolates
Authors: Calvopiña Karina , Hinchliffe Philip , Brem Jürgen , Heesom Kate J. , Johnson Samar , Cain Ricky , Lohans Christopher T. , Fishwick Colin W. G. , Schofield Christopher J. , Spencer James , Avison Matthew B. 
Published: September 2017

SummaryClavulanic acid and avibactam are clinically deployed serine β‐lactamase inhibitors, important as a defence against antibacterial resistance. Bicyclic boronates are recently discovered inhibitors of serine and some metallo β‐lactamases. Here, we show that avibactam and a bicyclic boronate inhibit L2 (serine β‐lactamase) but not L1 (metallo β‐lactamase) from the extensively drug resistant human pathogen Stenotrophomonas maltophilia. X‐ray crystallography revealed that both inhibitors bind L2 by covalent attachment to the nucleophilic serine. Both inhibitors reverse ceftazidime resistance in S. maltophilia because, unlike clavulanic acid, they do not induce L1 production. Ceftazidime/inhibitor resistant mutants hyperproduce L1, but retain aztreonam/inhibitor susceptibility because aztreonam is not an L1 substrate. Importantly, avibactam, but not the bicyclic boronate is deactivated by L1 at a low rate; the utility of avibactam might be compromised by mutations that increase this deactivation rate. These data rationalize the observed clinical efficacy of ceftazidime/avibactam plus aztreonam as combination therapy for S. maltophilia infections and confirm that aztreonam‐like β‐lactams plus nonclassical β‐lactamase inhibitors, particularly avibactam‐like and bicyclic boronate compounds, have potential for treating infections caused by this most intractable of drug resistant pathogens.
Can weight gain be prevented in women receiving treatment for breast cancer? A systematic review of intervention studies
Authors: Thomson Z. O. , Reeves M. M. 
Published: September 2017

SummaryBackgroundObesity and weight gain have been associated with poor disease‐specific and health‐related outcomes in women with breast cancer.ObjectivesThis review aimed to evaluate the effectiveness of weight gain prevention interventions among women with breast cancer.MethodsCompleted and ongoing trials evaluating a behaviourally based dietary intervention with or without physical activity and with a focus on weight gain prevention during treatment for breast cancer were reviewed. Weight change and body composition data were extracted. Within‐group weight change of ±1 kg and between‐group (intervention versus control) weight difference of ≥2 kg were defined as successful weight gain prevention.ResultsFive completed trials (seven intervention arms) and five ongoing trials were identified. Completed trials exclusively recruited premenopausal or premenopausal and postmenopausal women. Within‐group weight gain was prevented in two intervention arms, two arms achieved weight loss and three arms reported weight gain. Of the five comparisons with control groups, two reported significant differences in weight change between groups. Ongoing trials will provide further evidence on longer‐term outcomes, cost‐effectiveness and blood markers.ConclusionThis small but growing number of studies provides preliminary and promising evidence that weight gain can be prevented in women with breast cancer undergoing chemotherapy.
Not changes in membrane fluidity but proteotoxic stress triggers heat shock protein expression in Chlamydomonas reinhardtii
Authors: Rütgers Mark , Muranaka Ligia Segatto , Schulz‐Raffelt Miriam , Thoms Sylvia , Schurig Juliane , Willmund Felix , Schroda Michael 
Published: September 2017

AbstractA conserved reaction of all organisms exposed to heat stress is an increased expression of heat shock proteins (HSPs). Several studies have proposed that HSP expression in heat‐stressed plant cells is triggered by an increased fluidity of the plasma membrane. Among the main lines of evidence in support of this model are as follows: (a) the degree of membrane lipid saturation was higher in cells grown at elevated temperatures and correlated with a lower amplitude of HSP expression upon a temperature upshift, (b) membrane fluidizers induce HSP expression at physiological temperatures, and (c) membrane rigidifier dimethylsulfoxide dampens heat‐induced HSP expression. Here, we tested whether this holds also for Chlamydomonas reinhardtii. We show that heat‐induced HSP expression in cells grown at elevated temperatures was reduced because they already contained elevated levels of cytosolic HSP70A/90A that apparently act as negative regulators of heat shock factor 1. We find that membrane rigidifier dimethylsulfoxide impaired translation under heat stress conditions and that membrane fluidizer benzyl alcohol not only induced HSP expression but also caused protein aggregation. These findings support the classical model for the cytosolic unfolded protein response, according to which HSP expression is induced by the accumulation of unfolded proteins. Hence, the membrane fluidity model should be reconsidered.
Are tanning salons in compliance with German law? An evaluation based on a nationwide representative survey
Authors: Görig Tatiana , Schneider Sven , Greinert Rüdiger , Breitbart Eckhard W. , Diehl Katharina 
Published: September 2017

SummaryBackgroundGiven the evidence for increased skin cancer risk due to the sunbed use, a regulation of hazardous artificial ultraviolet radiation (UVR regulation) was passed in Germany in 2012. The aim of this study was to explore the advisory services in tanning studios as reported by sunbed users and to evaluate the information provided by the personnel of tanning salons after the UVR regulation was enacted.MethodsThe first wave of the representative National Cancer Aid Monitoring on Sunbed Use included a subgroup of 357 German citizens between 14 and 45 years who had used sunbeds since the UVR regulation was implemented. The participants provided data on sunbed use and related issues in telephone interviews.ResultsAlthough sunbed operators are mandated to offer their customers certain services at least once since the implementation of the UVR regulation, 15.4% of sunbed users were never advised to use protective eyewear during tanning and 13.1% were not provided with eyewear during their last sunbed use. Overall, 66.0% were never offered to develop a tanning schedule, 56.9% were never advised on the risks of UVR, 43.4% were never offered a determination of their skin type and 40.0% of users were never advised on how to use a sunbed safely.ConclusionsThe data showed that 3 years after the UVR regulation was enacted, compliance with this legislation is still not optimal. Binding wording in the legal text and making them applicable to unsupervised sunbeds as well is necessary to extend the impact of this legislation.
On Solving Endogeneity with Invalid Instruments: An Application to Investment Equations
Authors: Galvao Antonio F. , Montes–Rojas Gabriel , Olmo Jose , Song Suyong 
Published: September 2017

SummaryRegression models relating investment demand with firms’ Tobin's q and cash flow are fraught with measurement errors which, in turn, cause endogeneity bias. We propose an alternative solution to this problem based on modelling the interaction between the endogenous Tobin's q and the error term in the investment equation as a function of lagged values of Tobin's q. We then study the identification conditions and asymptotic properties of the resulting estimator. Our analysis of a panel of US firms reveals a larger effect of Tobin's q on firms’ investment demand than that obtained by using available estimators in the literature. Moreover, the estimates highlight the importance of cash flow. We find mixed evidence on the relationship between investment demand and firms’ cash flow with respect to different measures of financial constraints. Nevertheless, this evidence is more supportive of the view that firms’ cash flows have a weaker correlation to investment demand when financial conditions tighten.
Racialized physical space as cultural product
Authors: Bonam Courtney M. , Taylor Valerie J. , Yantis Caitlyn 
Published: September 2017

AbstractWe argue for incorporating physical space into the psychological study of race. Specifically, we review historical and sociological work explaining how physical space (e.g., houses, rivers, neighborhoods, and nations) has been used to construct race and racial hierarchy, leaving physical space structurally racialized. This structural racialization, we propose, has led people to think of physical space in racial terms, creating mental images of race that include physical space characteristics. We explain how these mental images may influence race‐related psychological processes (e.g., person perception and social identity threat). We also detail evidence that these mental images of racialized space shape how people perceive and interact with space, in ways that likely reinforce its structural racialization. We therefore frame physical space as a cultural product, situating it within the mutually constitutive nature of culture and psyche. This expanded approach to studying race can facilitate a fuller understanding of all the ways in which psychological processes contribute to racial inequality.
Low velocity impact behaviour of a hybrid carbon‐epoxy/cork laminate
Authors: Silva F.G.A. , de Moura M.F.S.F. , Magalhães A.G. 
Published: September 2017

AbstractThis work addresses low velocity impact behaviour of monolithic cross‐ply carbon‐epoxy and hybrid carbon‐epoxy/cork laminates. The [04, 904]s layup was selected due to its high mismatch bending between different oriented layers, which is a critical aspect concerning large delamination development at these critical interfaces. The effect of a cork layer inserted at the most critical interface on low velocity impact behaviour of the carbon‐epoxy laminate is discussed. Impact response and resulting damage profiles of monolithic and hybrid laminates are compared, and advantages of the hybrid solution are underlined. A numerical analysis including cohesive zone modelling was also performed to assess the damage profiles obtained for the two laminates analysed. The model revealed to be effective for a better comprehension of damage mechanism for both studied cases.
Bacterial contamination of platelet components not detected by BacT/ALERT®
Authors: Abela M. A. , Fenning S. , Maguire K. A. , Morris K. G. 
Published: September 2017

SUMMARYObjectivesTo investigate the possible causes for false negative results in BacT/ALERT® 3D Signature System despite bacterial contamination of platelet units.BackgroundThe Northern Ireland Blood Transfusion Service (NIBTS) routinely extends platelet component shelf life to 7 days. Components are sampled and screened for bacterial contamination using an automated microbial detection system, the BacT/ALERT® 3D Signature System. We report on three platelet components with confirmed bacterial contamination, which represent false negative BacT/ALERT® results and near‐miss serious adverse events.MethodsNIBTS protocols for risk reduction of bacterial contamination of platelet components are described. The methodology for bacterial detection using BacT/ALERT® is outlined. Laboratory tests, relevant patient details and relevant follow‐up information are analysed.ResultsIn all three cases, Staphylococcus aureus was isolated from the platelet residue and confirmed on terminal sub‐culture using BacT/ALERT®. In two cases, S. aureus with similar genetic makeup was isolated from the donors.ConclusionRisk reduction measures for bacterial contamination of platelet components are not always effective. Automated bacterial culture detection does not eliminate the risk of bacterial contamination. Visual inspection of platelet components prior to release, issue and administration remains an important last line of defence.
Identification and Characterization of the Major Porin of Desulfovibrio vulgaris Hildenborough
Authors: Zeng Lucy , Wooton Etsuko , Stahl David A. , Walian Peter J. 
Published: September 2017

ABSTRACT

Due in large part to their ability to facilitate the diffusion of a diverse range of solutes across the outer membrane (OM) of Gram-negative bacteria, the porins represent one of the most prominent and important bacterial membrane protein superfamilies. Notably, for the Gram-negative bacterium
Desulfovibrio vulgaris
Hildenborough, a model organism for studies of sulfate-reducing bacteria, no genes for porins have been identified or proposed in its annotated genome. Results from initial biochemical studies suggested that the product of the DVU0799 gene, which is one of the most abundant proteins of the
D. vulgaris
Hildenborough OM and purified as a homotrimeric complex, was a strong porin candidate. To investigate this possibility, this protein was further characterized biochemically and biophysically. Structural analyses via electron microscopy of negatively stained protein identified trimeric particles with stain-filled depressions and structural modeling suggested a β-barrel structure for the monomer, motifs common among the known porins. Functional studies were performed in which crude OM preparations or purified DVU0799 was reconstituted into proteoliposomes and the proteoliposomes were examined for permeability against a series of test solutes. The results obtained establish DVU0799 to be a pore-forming protein with permeability properties similar to those observed for classical bacterial porins, such as those of
Escherichia coli
. Taken together, these findings identify this highly abundant OM protein to be the major porin of
D. vulgaris
Hildenborough. Classification of DVU0799 in this model organism expands the database of functionally characterized porins and may also extend the range over which sequence analysis strategies can be used to identify porins in other bacterial genomes.

IMPORTANCE
Porins are membrane proteins that form transmembrane pores for the passive transport of small molecules across the outer membranes of Gram-negative bacteria. The present study identified and characterized the major porin of the model sulfate-reducing bacterium
Desulfovibrio vulgaris
Hildenborough, observing its preference for anionic sugars over neutral ones. Its predicted architecture appears to be novel for a classical porin, as its core β-barrel structure is of a type typically found in solute-specific channels. Broader use of the methods employed here, such as assays for channel permeability and electron microscopy of purified samples, is expected to help expand the database of confirmed porin sequences and improve the range over which sequence analysis-based strategies can be used to identify porins in other Gram-negative bacteria. Functional characterization of these critical gatekeeping proteins from divergent
Desulfovibrio
species should offer an improved understanding of the physiological features that determine their habitat range and supporting activities.
An Alternative STAT Signaling Pathway Acts in Viral Immunity in
Caenorhabditis elegans
Authors: Tanguy Mélanie , Véron Louise , Stempor Przemyslaw , Ahringer Julie , Sarkies Peter , Miska Eric A. 
Published: September 2017

ABSTRACT

Across metazoans, innate immunity is vital in defending organisms against viral infection. In mammals, antiviral innate immunity is orchestrated by interferon signaling, activating the STAT transcription factors downstream of the JAK kinases to induce expression of antiviral effector genes. In the nematode
Caenorhabditis elegans
, which lacks the interferon system, the major antiviral response so far described is RNA interference (RNAi), but whether additional gene expression responses are employed is not known. Here we show that, despite the absence of both interferon and JAK, the
C. elegans
STAT homolog STA-1 orchestrates antiviral immunity. Intriguingly, mutants lacking STA-1 are less permissive to antiviral infection. Using gene expression analysis and chromatin immunoprecipitation, we show that, in contrast to the mammalian pathway, STA-1 acts mostly as a transcriptional repressor. Thus, STA-1 might act to suppress a constitutive antiviral response in the absence of infection. Additionally, using a reverse genetic screen, we identify the kinase SID-3 as a new component of the response to infection, which, along with STA-1, participates in the transcriptional regulatory network of the immune response. Our work uncovers novel physiological roles for two factors in viral infection: a SID protein acting independently of RNAi and a STAT protein acting in
C. elegans
antiviral immunity. Together, these results illustrate the complex evolutionary trajectory displayed by innate immune signaling pathways across metazoan organisms.

IMPORTANCE
Since innate immunity was discovered, a diversity of pathways has arisen as powerful first-line defense mechanisms to fight viral infection. RNA interference, reported mostly in invertebrates and plants, as well as the mammalian interferon response and JAK/STAT pathway are key in RNA virus innate immunity. We studied infection by the Orsay virus in
Caenorhabditis elegans
, where RNAi is known to be a potent antiviral defense. We show that, in addition to its RNAi pathway,
C. elegans
utilizes an alternative STAT pathway to control the levels of viral infection. We identify the transcription factor STA-1 and the kinase SID-3 as two components of this response. Our study defines
C. elegans
as a new example of the diversity of antiviral strategies.
Risk factors for amendment in type, duration and setting of prescribed outpatient parenteral antimicrobial therapy (OPAT) for adult patients with cellulitis: a retrospective cohort study and CART analysis
Authors: Quirke Michael , Curran Emma May , O’Kelly Patrick , Moran Ruth , Daly Eimear , Aylward Seamus , McElvaney Gerry , Wakai Abel 
Published: September 2017

AbstractPurpose of the studyTo measure the percentage rate and risk factors for amendment in the type, duration and setting of outpatient parenteral antimicrobial therapy (OPAT) for the treatment of cellulitis.Study designA retrospective cohort study of adult patients receiving OPAT for cellulitis was performed. Treatment amendment (TA) was defined as hospital admission or change in antibiotic therapy in order to achieve clinical response. Multivariable logistic regression (MVLR) and classification and regression tree (CART) analysis were performed.ResultsThere were 307 patients enrolled. TA occurred in 36 patients (11.7%). Significant risk factors for TA on MVLR were increased age, increased Numerical Pain Scale Score (NPSS) and immunocompromise. The median OPAT duration was 7 days. Increased age, heart rate and C reactive protein were associated with treatment prolongation. CART analysis selected age &lt;64.5 years, female gender and NPSS &lt;2.5 in the final model, generating a low-sensitivity (27.8%), high-specificity (97.1%) decision tree.ConclusionsIncreased age, NPSS and immunocompromise were associated with OPAT amendment. These identified risk factors can be used to support an evidence-based approach to patient selection for OPAT in cellulitis. The CART algorithm has good specificity but lacks sensitivity and is shown to be inferior in this study to logistic regression modelling.
Redo surgery using IntraLase femtosecond laser for treating a decentered laser in situ keratomileusis flap
Authors: Lei Yulin , Hou Jie , Zheng Xiuyun 
Published: September 2017

Objective Decentered flaps are rarely reported after femtosecond laser-assisted in situ keratomileusis flap procedures. We present a patient with a decentered flap after preparation of a corneal flap using the Femto LDV technique. Methods The 22-year-old man required a redo operation because of a decentered corneal flap. It was performed the same day at the patient's insistence and with his consent. The new corneal flap for the redo surgery was prepared using the femtosecond laser technique and IntraLase. Results Uncorrected visual acuity for each eye was 1.2 during the 12-month follow-up. The results of the Femtosecond laser technique showed good predictability and repeatability regarding the preparation of corneal flaps, but it still may cause some intraoperative complications. Conclusion Once redo surgery is needed, the size and depth of the initially prepared flap should be determined using anterior segment optical coherence tomography to pre-set the parameters for preparation of the redo flap.
Should Emergency Endoscopy be Performed in All Patients With Suspected Colonic Diverticular Hemorrhage?
Authors: Uehara Takeshi , Matsumoto Satohiro , Miyatani Hiroyuki , Mashima Hirosato 
Published: September 2017

Objective:We attempted to develop a scoring system for facilitating decision making regarding the performance of emergency endoscopy in patients with colonic diverticular hemorrhage.Methods:This study involved analysis of the data of 178 patients who presented with hematochezia and were diagnosed as having colonic diverticular hemorrhage by colonoscopy. The patients were divided into 2 groups depending on whether the bleeding source was identified or not at the initial endoscopy (source-identified and source-not-identified groups), and on the basis of the results obtained, we established a scoring system for predicting successful identification of the bleeding source.Results:The percentages of patients on oral anticoagulant therapy or with a Charlson comorbidity index of ≥6, serum C-reactive protein level of ≥1 mg/dL, or extravasation of contrast medium visualized on contrast-enhanced computed tomographic (CT) images were all significantly higher in the identified than in the nonidentified group. Multivariate analysis identified extravasation of contrast medium on contrast-enhanced CT images (odds ratio [OR]: 10.6; 95% confidence interval [CI]: 2.7-42.2) and use of anticoagulants (OR: 4.5; 95% CI: 1.5-13.5) as independent predictors of successful identification of the bleeding source at the initial endoscopy in patients with colonic diverticular hemorrhage. On the basis of these results, we established a scoring system, which showed a sensitivity of 80% and specificity of 81% for successful identification of the bleeding source at the initial endoscopy.Conclusions:Herein, we propose a scoring system as a useful tool for determining whether emergency endoscopy is indicated in individual patients with suspected colonic diverticular hemorrhage.
The Role of the Accessory Malleolar Ossicles and Malleolar Avulsion Fractures in Lateral Ankle Ligament Reconstruction
Authors: Reiner Matthew M. , Sharpe Jonathan J. 
Published: September 2017

While it is well known that ankle sprains are one of the most common injuries in the United States, predictive factors regarding failure of conservative treatment are not well known. There are many biomechanical and epidemiological factors that play a role in recurrence and failure of conservative treatment, but most cases are able to be treated with immobilization and/or rest, ice, elevation, physical therapy, and bracing. We propose that one important risk factor is often overlooked simply due to the fact that a vast majority of these cases resolve without the need for surgery. Accessory ossicles and avulsion fractures of the malleoli or talus may represent a predisposition or marker for ligamentous damage that may lead to the need for lateral ankle ligament repair or reconstruction in the future. We have identified 61 consecutive patients who underwent lateral ankle ligament repair or reconstruction by the primary surgeon from the years 2007 to 2017. Out of those patients who met our inclusion and exclusion criteria, 66% had the presence of osseous pathology consisting of accessory ossicles or avulsion fractures of the medial or lateral malleolus or talus. The proportion of osseous pathology seen with lateral ankle ligament repair or reconstruction was higher than what has been previously reported in both operative and nonoperative settings. This may help identify a risk factor for failure of conservative treatment in patients presenting with acute ankle sprains or ankle instability especially in the active cohort. Levels of Evidence: Level IV: Case series