bluuebunny/crossref_metadata_2025 huggingface dataset:
The fascinating biology behind phage display: filamentous phage assembly
Authors: Loh Belinda , Kuhn Andreas , Leptihn Sebastian
Published: December 2018

With the recently awarded Nobel Prize to the inventor of Phage Display, George Smith, the technique has once more gained attention. However, one should not forget about the biology behind the method. Almost always ignored is how the structure of this bacterial virus is assembled. In contrast to lytic phages, filamentous phages are constantly being extruded through the bacterial membranes without lysis. Such filamentous phages are found in all aquatic environments, such as rivers and lakes, in the deep sea, in arctic ice, in hot springs and, associated with their hosts, in plants and animals including humans. While most filamentous phages infect Gram‐negative hosts, inoviruses of Gram‐positive hosts have also been described. Despite being among the minority within the phage family with an estimate of less than 5%, filamentous phages are real parasites as they exist at the expense of the host, but do not kill it. In contrast to lytic bacteriophages, filamentous phages are assembled in the host’s membrane and extruded across the cellular envelope while the bacterium continues to grow. In this review, we focus on this complex and yet poorly understood process of assembly and secretion of filamentous phages.
Waterlogging‐induced adventitious root formation in cucumber is regulated by ethylene and auxin through reactive oxygen species signalling
Authors: Qi Xiaohua , Li Qianqian , Ma Xiaotian , Qian Chunlu , Wang Huihui , Ren Nannan , Shen Chenxi , Huang Shumiao , Xu Xuewen , Xu Qiang , Chen Xuehao
Published: December 2018

Development of adventitious roots (ARs) at the base of the shoot is an important adaptation of plants to waterlogging stress; however, its physiological mechanisms remain unclear. Here, we investigated the regulation of AR formation under waterlogged conditions by hormones and reactive oxygen species (ROS) in Cucumis sativus L., an agriculturally and economically important crop in China. We found that ethylene, auxin, and ROS accumulated in the waterlogged cucumber plants. On the other hand, application of the ethylene receptor inhibitor 1‐methylcyclopropene (1‐MCP), the auxin transport inhibitor 1‐naphthylphthalamic acid (NPA), or the NADPH oxidase inhibitor diphenyleneiodonium (DPI) decreased the number of ARs induced by waterlogging. Auxin enhanced the expression of ethylene biosynthesis genes, which led to ethylene entrapment in waterlogged plants. Both ethylene and auxin induced the generation of ROS. Auxin‐induced AR formation was inhibited by 1‐MCP, although ethylene‐induced AR formation was not inhibited by NPA. Both ethylene‐ and auxin‐induced AR formation were counteracted by DPI. These results indicate that auxin‐induced AR formation is dependent on ethylene, whereas ethylene‐induced AR formation is independent of auxin. They also show that ROS signals mediate both ethylene‐ and auxin‐induced AR formation in cucumber plants.
The reality of “food porn”: Larger brain responses to food‐related cues than to erotic images predict cue‐induced eating
Authors: Versace Francesco , Frank David W. , Stevens Elise M. , Deweese Menton M. , Guindani Michele , Schembre Susan M.
Published: December 2018

While some individuals can defy the lure of temptation, many others find appetizing food irresistible. The goal of this study was to investigate the neuropsychological mechanisms that increase individuals' vulnerability to cue‐induced eating. Using ERPs, a direct measure of brain activity, we showed that individuals with larger late positive potentials in response to food‐related cues than to erotic images are more susceptible to cue‐induced eating and, in the presence of a palatable food option, eat more than twice as much as individuals with the opposite brain reactivity profile. By highlighting the presence of individual brain reactivity profiles associated with susceptibility to cue‐induced eating, these findings contribute to the understanding of the neurobiological basis of vulnerability to obesity.
Integrating a Proactive Technique Into a Holistic Cyber Risk Management Approach
Authors: Marotta Angelica , McShane Michael
Published: December 2018

Cyber threats are an emerging risk posing a range of challenges to organizations of all sizes. Corporate risk managers need to understand that cyber risk management must not be a silo in the IT department. Cyber threats are the result of intelligent adaptive agents that cannot be managed by traditional risk management techniques only. The article describes the honeypot concept, which is a proactive measure for identifying and gathering information about attackers in order to develop suitable and effective countermeasures. In addition, this article proposes the integration of the honeypot concept into a cyber risk management approach based on the five preparedness mission areas of the Federal Emergency Management Agency (FEMA).
Artificial Intelligence: Implications for Social Inflation and Insurance
Authors: Kelley Kevin H. , Fontanetta Lisa M. , Heintzman Mark , Pereira Nikki
Published: December 2018

Artificial intelligence (AI) has the ability to enhance the insurance industry's value chain by altering relationships, reinventing business platforms, and expanding hidden data. Insurance companies will apply AI to greatly enhance large data analytics, evolve algorithms with transactional data faster, and combine data in new ways to discover better underwriting risks and appropriately price the risk of various insureds based on the true value of their business risks. This article explores how AI will have a significant impact on the workforce, jobs, and furthermore how the elimination of jobs will potentially exacerbate social equality gaps on a global scale, leading to a shift in culture and increased social inflation, thus impacting the insurance industry as well as its customers.
Bayesian Non-Parametric Survival Regression for Optimizing Precision Dosing of Intravenous Busulfan in Allogeneic Stem Cell Transplantation
Authors: Xu Yanxun , Thall Peter F. , Hua William , Andersson Borje S.
Published: December 2018

Allogeneic stem cell transplantation is now part of standard care for acute leukaemia. To reduce toxicity of the pretransplant conditioning regimen, intravenous busulfan is usually used as a preparative regimen for acute leukaemia patients undergoing allogeneic stem cell transplantation. Systemic busulfan exposure, characterized by the area under the plasma concentration versus time curve, AUC, is strongly associated with clinical outcome. An AUC that is too high is associated with severe toxicities, whereas an AUC that is too low carries increased risks of recurrence of disease and failure to engraft. Consequently, an optimal AUC-interval needs to be determined for therapeutic use. To address the possibility that busulfan pharmacokinetics and pharmacodynamics vary significantly with patients’ characteristics, we propose a tailored approach to determine optimal covariate-specific AUC-intervals. To estimate these personalized AUC-intervals, we apply a flexible Bayesian non-parametric regression model based on a dependent Dirichlet process and Gaussian process. Our analyses of a data set of 151 patients identified optimal therapeutic intervals for AUC that varied substantively with age and whether the patient was in complete remission or had active disease at transplant. Extensive simulations to evaluate the dependent Dirichlet process–Gaussian process model in similar settings showed that its performance compares favourably with alternative methods. We provide an R package, DDPGPSurv, that implements the dependent Dirichlet process–Gaussian process model for a broad range of survival regression analyses.
Characterization of LRL5 as a key regulator of root hair growth in maize
Authors: Wang Chun‐Xia , Qi Chuang‐Ye , Luo Jin‐Hong , Liu Lin , He Yan , Chen Li‐Qun
Published: December 2018

Root hair, a special type of tubular‐shaped cell, outgrows from the root epidermal cell and plays important roles in the acquisition of nutrients and water, as well as interactions with biotic and abiotic stresses. Studies in the model plant Arabidopsis have revealed that root‐hair initiation and elongation are hierarchically regulated by a group of basic helix−loop−helix (bHLH) transcription factors (TFs). However, knowledge regarding the regulatory pathways of these bHLH TFs in controlling root hair growth remains limited. In this study, RNA‐seq analysis was conducted to profile the transcriptome in the elongating maize root hair and >1000 genes with preferential expression in root hair were identified. A consensus cis‐element previously featured as the potential bHLH‐TF binding sites was present in the regulatory regions for the majority of the root hair‐preferentially expressed genes. In addition, an individual change in ZmLRL5, the highest‐expressed bHLH‐TF in maize root hair resulted in a dramatic reduction in the elongation of root hair, and rendered the growth of root hair hypersensitive to translational inhibition. Moreover, RNA‐seq, yeast‐one‐hybrid and ribosome profile analysis suggested that ZmLRL5 may function as a key player in orchestrating the translational process by directly regulating the expression of translational processes/ribosomal genes during maize root hair growth.
Identification and characterization of a core set of ROS wave‐associated transcripts involved in the systemic acquired acclimation response of Arabidopsis to excess light
Authors: Zandalinas Sara I. , Sengupta Soham , Burks David , Azad Rajeev K. , Mittler Ron
Published: December 2018

Systemic acquired acclimation (SAA) plays a key role in optimizing growth and preventing damage associated with fluctuating or abrupt changes in the plant environment. To be effective, SAA has to occur at a rapid rate and depend on rapid signaling pathways that transmit signals from affected tissues to all parts of the plant. Although recent studies have identified several different rapid systemic signaling pathways that could mediate SAA, very little information is known about the extent of their involvement in mediating transcriptomic responses. Here we reveal that the systemic transcriptomic response of plants to excess light stress is extensive in its context and involves an early (2 min) and transient stage of transcript expression that includes thousands of genes. This early response is dependent on the respiratory burst oxidase homolog D protein, and the function of the reactive oxygen species (ROS) wave. We further identify a core set of transcripts associated with the ROS wave and suggest that some of these transcripts are involved in linking ROS with calcium signaling. Priming of a systemic leaf to become acclimated to a particular stress during SAA involves thousands of transcripts that display a rapid and transient expression pattern driven by the ROS wave.
Use of intravenous immunoglobulin G to treat spontaneous heparin‐induced thrombocytopenia
Authors: Irani Mehraboon , Siegal Eric , Jella Abhay , Aster Richard , Padmanabhan Anand
Published: December 2018

BACKGROUND

Spontaneous heparin‐induced thrombocytopenia (HIT) is a rare but serious prothrombotic syndrome characterized by thrombosis, thrombocytopenia, and strong platelet‐activating HIT antibodies in the absence of heparin exposure, and is frequently characterized by a suboptimal response to standard therapies. Here, we present the first report of intravenous immunoglobulin G (IVIG) use in a patient with spontaneous HIT.

STUDY DESIGN AND METHODS

Patient information, including demographic, clinical, and laboratory results, were obtained from the electronic medical record. Laboratory testing was performed in the serotonin release assay, platelet factor 4 (PF4)‐dependent P‐selectin expression assay, and PF4/polyvinylsulfonate enzyme‐linked immunosorbent assay to study the impact of IVIG on HIT antibody‐mediated platelet activation. The patient was also genotyped for a polymorphism in the IgG receptor on platelets, FcγRIIa, at amino acid position 131.

RESULTS

A 30‐year‐old man had a thrombotic stroke and thrombocytopenia and strong HIT serologies in the absence of proximate heparin use. Direct thrombin inhibitor therapy was not associated with a prompt response. Due to severity and extent of thrombosis and persistent thrombocytopenia, he was treated with high‐dose IVIG. This treatment was associated with rapid and sustained normalization of platelet counts and a gradual improvement in thrombotic complications. Platelet activation induced by HIT antibodies in the PF4‐dependent P‐selectin expression assay (low PF4) was significantly lower after IVIG treatment, correlating well with platelet rise. Consistent with the severity of thrombosis, the patient was found to possess the 131HR polymorphism in FcγRIIa.

CONCLUSION

These results suggest that IVIG may be a useful adjunctive therapy in spontaneous HIT.
Eosinophilic cerebrospinal fluid pleocytosis associated with neural Angiostrongylus vasorum infection in a dog
Authors: Alcoverro Emili , Bersan Erika , Sanchez‐Masian Daniel , Piviani Martina
Published: December 2018

A 1‐year‐old, female intact Pug dog was presented to the Small Animal Teaching Hospital of the University of Liverpool with a 4‐week history of progressive multifocal intracranial signs. Magnetic resonance imaging (MRI) detected multiple hemorrhagic lesions in the brain. The Baermann and zinc sulfate flotation tests with centrifugation, performed on fecal samples, were positive for lungworm larvae and an antigenic test confirmed Angiostrongylus vasorum infection. Anthelmintic treatment was started with a consequent marked clinical improvement. Seventy days later, the dog was clinically normal, and no larvae were detected on the Baermann test. Repeat MRI of the brain revealed marked improvement of the hemorrhagic lesions. Cerebrospinal fluid analysis (CSF) showed marked eosinophilic pleocytosis, and anthelmintic treatment was restarted. A follow‐up CSF analysis 4 months after the first presentation revealed resolution of the eosinophilic pleocytosis. This is the first case report of marked eosinophilic pleocytosis associated with neural A vasorum infection in a dog. The CSF eosinophilic pleocytosis persisted for several weeks after treatment, even in the absence of concurrent clinical signs and with a negative A vasorum Baermann test.
Effect of oral afoxolaner on naturally occurring infestations of peacocks by the louse Goniodes pavonis
Authors: Yarto Jaramillo Enrique , Osorio Marquez Rufino , Rangel Díaz Josué , Romero Núñez Camilo , Miranda Contreras Laura , Heredia Cardenas Rafael
Published: December 2018

Background

Ectoparasitism of ornamental birds, including captive species kept in zoos, represents a serious health problem. Up to 13 different species of lice have been reported to affect peacocks worldwide and heavy infestation may cause anaemia. Because of this, alternatives to the prevailing treatments have been sought including use of isoxazolines. This class of drugs has been used successfully in poultry without adverse effects on health or production.

Objective

To evaluate the effect of afoxolaner on the peacock louse (Goniodes pavonis).

Animals

Twenty‐three peacocks (Pavo cristatus) with naturally occurring infestation with G. pavonis.

Methods and materials

The peacocks were divided in two groups; one was treated once orally with 2.5 mg/kg afoxolaner and the other group received no treatment. Samples were collected using the acetate tape technique, for identification of lice by microscopy. Concomitantly, blood samples were taken to evaluate the haematocrit before and after the intervention.

Results

Treatment with afoxolaner significantly decreased the number of peacocks positive for lice (P = 0.02) compared to the control group, in which the number of positive birds did not decrease. The haematocrit improved in the afoxolaner‐treated group from a baseline of 46.4%–54.7% at 35 days post‐treatment, whereas it decreased in untreated birds (44.6%–40.7%). No adverse effects attributed to afoxolaner treatment were observed.

Conclusions and clinical importance

Oral administration of afoxolaner is an effective treatment for G. pavonis infestation of peacocks.
Nodules and masses are associated with malignant pleural effusion in dogs and cats but many other intrathoracic CT features are poor predictors of the effusion type
Authors: Reetz Jennifer A. , Suran Jantra N. , Zwingenberger Allison L. , Stefanovski Darko
Published: December 2018

Thoracic CT may be used in the workup of patients with pleural effusion. In humans, certain pleural features on CT aid in diagnosing an underlying cause for pleural effusion, whereas this is not well studied in veterinary medicine. This retrospective cross‐sectional analytical study assessed pleural and other intrathoracic abnormalities on CT in dogs and cats with pleural effusion and explored potential discriminatory features between effusion types. Eighty‐nine dogs and 32 cats with pleural cytology and/or histopathology were categorized into malignant pleural disease (15 dogs and 11 cats), pyothorax (34 dogs and 7 cats), chylothorax (20 dogs and 11 cats), transudative (11 dogs and 2 cats), and hemorrhagic effusion (9 dogs and 1 cat). Multivariable logistic regression analysis comparing malignancy to other effusions found that older patient age (dogs: odds ratio 1.28,P = 0.015; cats: odds ratio 1.53,P = 0.005), nodular diaphragmatic pleural thickening (dogs: odds ratio 7.64,P = 0.021; cats: odds ratio 13.67,P = 0.031), costal pleural masses (dogs: odds ratio 21.50,P = 0.018; cats: odds ratio 32.74,P = 0.019), and pulmonary masses (dogs: odds ratio 44.67,P = 0.002; cats: odds ratio 18.26,P = 0.077) were associated with malignancy. In dogs, any costal pleural abnormality (odds ratio 47.55,P = 0.002) and pulmonary masses (odds ratio 10.05,P = 0.004) were associated with malignancy/pyothorax, whereas any costal pleural abnormality (odds ratio 0.14,P = 0.006) and sternal lymphadenopathy (odds ratio 0.22,P = 0.040) were inversely associated with transudates. There were, however, many overlapping abnormalities between effusion types, so further diagnostic testing remains important for diagnosis.
Impact of a void in the equine medial femoral condyle on bone stresses and peak contact pressures in a finite element model
Authors: Frazer Lance L. , Santschi Elizabeth M. , Fischer Kenneth J.
Published: December 2018

Objective

To predict bone and medial meniscal stresses and contact pressures in an equine stifle with a medial femoral condyle (MFC) intact or with a 2‐cm3 subchondral bone void, under varying degrees of internal femoral rotation (IFR).

Study design

Finite element model (FEM) of a cadaveric equine stifle loaded to 8000 N.

Methods

The FEM was constructed from computed tomography (CT) of the right, extended stifle of a yearling. The CT image was segmented into relevant anatomic structures and meshed into 4‐node tetrahedrons. Bone material properties were assigned according to Hounsfield units, soft tissue properties were estimated from published data, and the model was loaded to 8000 N in 155° extension.

Results

The main stresses found in the intact MFC were in compression, with very small areas of shear and tension. Adding a 2‐cm3 MFC void increased peak compression stress by 25%, shear by 50%, and tension by 200%. An MFC void also increased tension and shear placed on the medial meniscus by 30%. Under load, IFR of 2.5° and 5° increased MFC peak stresses 8%‐21%.

Conclusion

A 2‐cm3 MFC void in an equine stifle FEM increased stress in the bone and meniscus. Internal femoral rotation slightly increased predicted bone stress.

Clinical significance

Increases in bone and meniscal stress predicted in an MFC with a void provide evidence to understand the persistence of voids and mechanism of damage to the medial meniscus.
A Review of Available Methods for the Assessment of Fluid Added Mass, Damping, and Stiffness With an Emphasis on Hydraulic Turbines
Authors: Dehkharqani Arash Soltani , Aidanpää Jan-Olov , Engström Fredrik , Cervantes Michel J.
Published: December 2018

Fluid added mass, damping, and stiffness are highly relevant parameters to consider when evaluating the dynamic response of a submerged structure in a fluid. The prediction of these parameters for hydraulic turbines has been approached relatively recently. Complex fluid-structure analyses including three-dimensional flow and the need for experiments during operation are the main challenges for the numerical and experimental approaches, respectively. The main objective of this review is to address the impact of different parameters, for example, flow velocity, cavitation, nearby solid structure, and rotational speed on the fluid added mass and damping of Kaplan/Propeller and Francis turbine runners. The fluid added stiffness is also discussed in the last section of the paper. Although studies related to hydraulic turbines are the main objective of this paper, the literature on hydrofoils is also taken into consideration to provide valuable information on topics such as individual runner blades. In this literature survey, the analytical, numerical, and experimental approaches used to determine fluid added parameters are discussed, and the pros and the cons of each method are addressed.
Parametric Study of a Unmanned Aerial Vehicle Ingestion Into a Business Jet Size Fan Assembly Model
Authors: Lyons Troy , D'Souza Kiran
Published: December 2018

This work investigated the damage severity of an unmanned aerial vehicle (UAV) ingestion into fan models of a midsized business jet engine. The ingestion of the quadcopter UAV model into the fan was carried out in ls-dyna. The material models used for the quadcopter and the fan were previously validated, and the fan's durability was simulated through simulated bird ingestions. The results of this work show that UAVs will cause significantly more damage than birds due mostly to the hard components typically used in motors, batteries, and cameras. Particular parameters of the ingestion studied include the phase of flight of the plane, impact location and orientation, and fan blade thickness.
Nanoparticle Redistribution in PC3 Tumors Induced by Local Heating in Magnetic Nanoparticle Hyperthermia: In Vivo Experimental Study
Authors: Gu Qimei , Joglekar Tejashree , Bieberich Charles , Ma Ronghui , Zhu Liang
Published: December 2018

In magnetic nanoparticle hyperthermia, a required thermal dosage for tumor destruction greatly depends on nanoparticle distribution in tumors. The objective of this study is to conduct in vivo experiments to evaluate whether local heating using magnetic nanoparticle hyperthermia changes nanoparticle concentration distribution in prostatic cancer (PC3) tumors. In vivo animal experiments were performed on grafted PC3 tumors implanted in mice to investigate whether local heating via exposing the tumor to an alternating magnetic field (5 kA/m and 192 kHz) for 25 min resulted in nanoparticle spreading from the intratumoral injection site to tumor periphery. Nanoparticle redistribution due to local heating is evaluated via comparing microCT images of resected tumors after heating to those in the control group without heating. A previously determined calibration relationship between microCT Hounsfield unit (HU) values and local nanoparticle concentrations in the tumors was used to determine the distribution of volumetric heat generation rate (q‴MNH) when the nanoparticles were subject to the alternating magnetic field. sas,matlab, and excel were used to process the scanned data to determine the total heat generation rate and the nanoparticle distribution volumes in individual HU ranges. Compared to the tumors in the control group, nanoparticles in the tumors in the heating group occupied not only the vicinity of the injection site, but also tumor periphery. The nanoparticle distribution volume in the high q‴MNH range (>1.8 × 106 W/m3) is 10% smaller in the heating group, while in the low q‴MNH range of 0.6–1.8 × 106 W/m3, it is 95% larger in the heating group. Based on the calculated heat generation rate in individual HU ranges, the percentage in the HU range larger than 2000 decreases significantly from 46% in the control group to 32% in the heating group, while the percentages in the HU ranges of 500–1000 and 1000–1500 in the heating group are much higher than that in the control group. Heating PC3 tumors for 25 min resulted in significant nanoparticle migration from high concentration regions to low concentration regions in the tumors. The volumetric heat generation rate distribution based on nanoparticle distribution before or after local heating can be used in the future to guide simulation of nanoparticle redistribution and its induced temperature rise in PC3 tumors during magnetic nanoparticle hyperthermia, therefore, accurately predicting required thermal dosage for safe and effective thermal therapy.
Structure–property relationships for wet dentin adhesive polymers
Authors: Parthasarathy Ranganathan , Misra Anil , Song Linyong , Ye Qiang , Spencer Paulette
Published: December 2018

Dentin adhesive systems for composite tooth restorations are composed of hydrophilic/hydrophobic monomers, solvents, and photoinitiators. The adhesives undergo phase separation and concomitant compositional change during their application in the wet oral environment; phase separation compromises the quality of the hybrid layer in the adhesive/dentin interface. In this work, the adhesive composition in the hybrid layer can be represented using the phase boundaries of a ternary phase diagram for the hydrophobic monomer/hydrophilic monomer/water system. The polymer phases, previously unaccounted for, play an important role in determining the mechanical behavior of the bulk adhesive, and the chemomechanical properties of the phases are intimately related to the effects produced by differences in the hydrophobic–hydrophilic composition. As the composition of the polymer phases varies from hydrophobic-rich to hydrophilic-rich, the amount of the adsorbed water and the nature of polymer–water interaction vary nonlinearly and strongly correlate with the change in elastic moduli under wet conditions. The failure strain, loss modulus, and glass transition temperature vary nonmonotonically with composition and are explained based upon primary and secondary transitions observed in dynamic mechanical testing. Due to the variability in composition, the assignment of mechanical properties and the choice of suitable constitutive models for polymer phases in the hybrid layer are not straightforward. This work investigates the relationship between composition and chemomechanical properties of the polymer phases formed on the water-adhesive phase boundary using quasistatic and dynamic mechanical testing, mass transfer experiments, and vibrational spectroscopy.
Changing Molecular Markers of Antimalarial Drug Sensitivity across Uganda
Authors: Asua Victor , Vinden Joanna , Conrad Melissa D. , Legac Jennifer , Kigozi Simon P. , Kamya Moses R. , Dorsey Grant , Nsobya Samuel L. , Rosenthal Philip J.
Published: December 2018

The potential spread of antimalarial drug resistance to Africa, in particular for artemisinins and key partner drugs, is a major concern. We surveyed
Plasmodium falciparum
genetic markers associated with drug sensitivity on 3 occasions at ∼6-month intervals in 2016 and 2017 at 10 sites representing a range of epidemiological settings in Uganda.
Isavuconazole in the Treatment of Coccidioidal Meningitis
Authors: Heidari Arash , Quinlan Miriam , Benjamin David J. , Laurence Brett , Mu Anandit , Ngai Tiffany , Hoffman Wes J. , Cohen Stuart H. , McHardy Ian , Johnson Royce , Thompson George R.
Published: December 2018

Patients with coccidioidal meningitis require lifelong antifungal therapy. Cumulative toxicity and lack of antifungal efficacy require salvage therapy in the treatment of some patients.
Emergence of OXA-232 Carbapenemase-Producing
Klebsiella pneumoniae
That Carries a pLVPK-Like Virulence Plasmid among Elderly Patients in China
Authors: Shu Lingbin , Dong Ning , Lu Jun , Zheng Zhiwei , Hu Jie , Zeng Wenqing , Sun Qiaoling , Chan Edward Wai-Chi , Zhou Hongwei , Hu Fupin , Chen Sheng , Zhang Rong
Published: December 2018

This study reported the clonal dissemination of OXA-232-producing sequence type 15 (ST15) carbapenem-resistant
Klebsiella pneumoniae
among elderly patients in China. All patients were immunocompromised, suffered from multiple underlying diseases, and were hospitalized for a prolonged period; however, they slowly recovered on antimicrobial therapy.
Gain-of-Function Mutations in the Phospholipid Flippase MprF Confer Specific Daptomycin Resistance
Authors: Ernst Christoph M. , Slavetinsky Christoph J. , Kuhn Sebastian , Hauser Janna N. , Nega Mulugeta , Mishra Nagendra N. , Gekeler Cordula , Bayer Arnold S. , Peschel Andreas
Published: December 2018

Ever since daptomycin was introduced to the clinic, daptomycin-resistant isolates have been reported. In most cases, the resistant isolates harbor point mutations in MprF, which produces and flips the positively charged phospholipid LysPG. This has led to the assumption that the resistance mechanism relies on the overproduction of LysPG, given that increased LysPG production may lead to increased electrostatic repulsion of positively charged antimicrobial compounds, including daptomycin. Here we show that the resistance mechanism is highly specific and relies on a different process that involves a functional MprF flippase, suggesting that the resistance-conferring mutations may enable the flippase to accommodate daptomycin or an unknown component that is crucial for its activity. Our report provides a new perspective on the mechanism of resistance to a major antibiotic.
Intrinsic Class D β-Lactamases of
Clostridium difficile
Authors: Toth Marta , Stewart Nichole K. , Smith Clyde , Vakulenko Sergei B.
Published: December 2018

C. difficile
is a spore-forming anaerobic bacterium which causes infection of the large intestine with high mortality rates. The
C. difficile
infection is difficult to prevent and treat, as the pathogen is resistant to many antimicrobial agents. Prolonged use of β-lactam antibiotics for treatment of various infectious diseases triggers the infection, as these drugs suppress the abundance of protective gut bacteria, allowing the resistant
C. difficile
bacteria to multiply. While resistance of
C. difficile
to β-lactam antibiotics plays the major role in the development of the disease, the mechanism of resistance is unknown. The significance of our research is in the discovery in
C. difficile
of β-lactamases, enzymes that destroy β-lactam antibiotics. These findings ultimately can help to combat deadly
C. difficile
infections.
Exoribonuclease-Resistant RNAs Exist within both Coding and Noncoding Subgenomic RNAs
Authors: Steckelberg Anna-Lena , Vicens Quentin , Kieft Jeffrey S.
Published: December 2018

During infection, viruses often produce subgenomic RNAs (sgRNAs) that either serve as the template for protein synthesis or act as “riboregulators” that interact with and influence the viral and cellular machinery. Recently, a mechanism for producing sgRNAs was found that depends on the presence of specifically structured RNA elements (xrRNAs). However, the degree to which this mechanism is used, where the elements are found, their structural diversity, and what types of sgRNAs are produced by this pathway were unclear. This article describes the discovery of these structured RNA elements in two large families of plant viruses and shows that they are used to produce both protein-coding sgRNAs and “riboregulatory” RNAs. These discoveries provide evidence that xrRNA-based RNA maturation pathways may be more widespread than previously anticipated and that they are involved in producing a variety of RNAs of diverse functions.
Genome-Guided Identification of Organohalide-Respiring
Deltaproteobacteria
from the Marine Environment
Authors: Liu Jie , Häggblom Max M.
Published: December 2018

The marine environment is a major reservoir for both anthropogenic and natural organohalides, and reductive dehalogenation is thought to be an important process in the overall cycling of these compounds. Here we demonstrate that the capacity of organohalide respiration appears to be widely distributed in members of marine
Deltaproteobacteria
. The identification of reductive dehalogenase genes in diverse
Deltaproteobacteria
and the confirmation of their dehalogenating activity through functional assays and transcript analysis in select isolates extend our knowledge of organohalide-respiring
Deltaproteobacteria
diversity. The presence of functional reductive dehalogenase genes in diverse
Deltaproteobacteria
implies that they may play an important role in organohalide respiration in the environment.
Finer-Scale Phylosymbiosis: Insights from Insect Viromes
Authors: Leigh Brittany A. , Bordenstein Sarah R. , Brooks Andrew W. , Mikaelyan Aram , Bordenstein Seth R.
Published: December 2018

Viruses are the most abundant biological entity on the planet and interact with microbial communities with which they associate. The virome of animals is often dominated by bacterial viruses, known as bacteriophages or phages, which can (re)structure bacterial communities potentially vital to the animal host. Beta diversity relationships of animal-associated bacterial communities in laboratory and wild populations frequently parallel animal phylogenetic relationships, a pattern termed phylosymbiosis. However, little is known about whether viral communities also exhibit this eco-evolutionary pattern. Metagenomics of purified viruses from recently diverged species of
Nasonia
parasitoid wasps reared in the lab indicates for the first time that the community relationships of the virome can also exhibit complete phylosymbiosis. Therefore, viruses, particularly bacteriophages here, may also be influenced by animal evolutionary changes either directly or indirectly through the tripartite interactions among hosts, bacteria, and phage communities. Moreover, we report several new bacteriophage genomes from the common gut bacteria in
Nasonia
.
Species Designations Belie Phenotypic and Genotypic Heterogeneity in Oral Streptococci
Authors: Velsko Irina M. , Chakraborty Brinta , Nascimento Marcelle M. , Burne Robert A. , Richards Vincent P.
Published: December 2018

Representative type strains are commonly used to characterize bacterial species, yet species are phenotypically and genotypically heterogeneous. Conclusions about strain physiology and activity based on a single strain therefore may be inappropriate and misleading. When selecting strains for probiotic use, the assumption that all strains within a species share the same desired probiotic characteristics may result in selection of a strain that lacks the desired traits, and therefore makes a minimally effective or ineffective probiotic. Health-associated oral streptococci are promising candidates for anticaries probiotics, but strains need to be carefully selected based on observed phenotypes. We characterized the genotypes and anticaries phenotypes of strains from 10 species of oral streptococci and demonstrate poor correlation between genotype and phenotype across all species.
The personal and social experiences of community-dwelling younger adults after stroke in Australia: a qualitative interview study
Authors: Shipley Jessica , Luker Julie , Thijs Vincent , Bernhardt Julie
Published: December 2018

Objectives

To examine the personal and social experiences of younger adults after stroke.

Design

Qualitative study design involving in-depth semi-structured interviews and rigorous qualitative descriptive analysis informed by social constructionism.

Participants

Nineteen younger stroke survivors aged 18 to 55 years at the time of their first-ever stroke.

Setting

Participants were recruited from urban and rural settings across Australia. Interviews took place in a clinic room of the Florey Institute of Neuroscience and Mental Health (Melbourne, Australia), over an online conference platform or by telephone.

Results

Four main themes emerged from the discourses: (1) psycho-emotional experiences after young stroke; (2) losing pre-stroke life construct and relationships; (3) recovering and adapting after young stroke; and (4) invalidated by the old-age, physical concept of stroke. While these themes ran through the narratives of all participants, data analysis also drew out interesting variation between individual experiences.

Conclusions

For many younger adults, stroke is an unexpected and devastating life event that profoundly diverts their biography and presents complex and continued challenges to fulfilling age-normative roles. While adaptation, resilience and post-traumatic growth are common, this study suggests that more bespoke support is needed for younger adults after stroke. Increasing public awareness of young stroke is also important, as is increased research attention to this problem.
Scoping review of priority setting of research topics for musculoskeletal conditions
Authors: Bourne Allison M , Johnston Renea V , Cyril Sheila , Briggs Andrew M , Clavisi Ornella , Duque Gustavo , Harris Ian A , Hill Catherine , Hiller Claire , Kamper Steven J , Latimer Jane , Lawson Andrew , Lin Chung-Wei Christine , Maher Christopher , Perriman Diana , Richards Bethan L , Smitham Peter , Taylor William John , Whittle Sam , Buchbinder Rachelle
Published: December 2018

Objective

Describe research methods used in priority-setting exercises for musculoskeletal conditions and synthesise the priorities identified.

Design

Scoping review.

Setting and population

Studies that elicited the research priorities of patients/consumers, clinicians, researchers, policy-makers and/or funders for any musculoskeletal condition were included.

Methods and analysis

We searched MEDLINE and EMBASE from inception to November 2017 and the James Lind Alliance top 10 priorities, Cochrane Priority Setting Methods Group, and Cochrane Musculoskeletal and Back Groups review priority lists. The reported methods and research topics/questions identified were extracted, and a descriptive synthesis conducted.

Results

Forty-nine articles fulfilled our inclusion criteria. Methodologies and stakeholders varied widely (26 included a mix of clinicians, consumers and others, 16 included only clinicians, 6 included only consumers or patients and in 1 participants were unclear). Only two (4%) reported any explicit inclusion criteria for priorities. We identified 294 broad research priorities from 37 articles and 246 specific research questions from 17 articles, although only four (24%) of the latter listed questions in an actionable format. Research priorities for osteoarthritis were identified most often (n=7), followed by rheumatoid arthritis (n=4), osteoporosis (n=4) and back pain (n=4). Nearly half of both broad and specific research priorities were focused on treatment interventions (n=116 and 111, respectively), while few were economic (n=8, 2.7% broad and n=1, 0.4% specific), implementation (n=6, 2% broad and n=4, 1.6% specific) or health services and systems research (n=15, 5.1% broad and n=9, 3.7% specific) priorities.

Conclusions

While many research priority-setting studies in the musculoskeletal field have been performed, methodological limitations and lack of actionable research questions limit their usefulness. Future studies should ensure they conform to good priority-setting practice to ensure that the generated priorities are of maximum value.

PROSPERO registration number

CRD42017059250.
Precision-Exercise-Prescription in patients with lung cancer undergoing surgery: rationale and design of the PEP study trial
Authors: Ulrich Cornelia M , Himbert Caroline , Boucher Kenneth , Wetter David W , Hess Rachel , Kim Jaewhan , Lundberg Kelly , Ligibel Jennifer A , Barnes Christopher A , Rushton Bailee , Marcus Robin , Finlayson Samuel R G , LaStayo Paul C , Varghese Thomas K
Published: December 2018

Introduction

Lung cancer is a significant burden on societies worldwide, and the most common cause of death in patients with cancer overall. Exercise intervention studies in patients with lung cancer have consistently shown benefits with respect to physical and emotional functioning. However, to date, exercise training has not been consistently implemented into clinical practice given that interventions have been costly and not aligned with clinical care.

Methods/design

The Precision-Exercise-Prescription (PEP) study is a prospective randomised controlled trial comparing the effectiveness and feasibility of a personalised intervention exercise programme among patients with lung cancer undergoing surgery. Two-hundred patients who are diagnosed with stage primary or secondary lung cancer and are eligible to undergo surgical treatment at Huntsman Cancer Institute comprise the target population. Patients are randomised to either the (1) outpatient precision-exercise intervention group or (2) delayed intervention group. The intervention approach uses Motivation and Problem Solving, a hybrid behavioural treatment based on motivational interviewing and practical problem solving. The dosage of the exercise intervention is personalised based on the individual’s Activity Measure for Post-Acute-Care outpatient basic mobility score, and incorporates four exercise modes: mobility, callisthenics, aerobic and resistance. Exercise is implemented by physical therapists at study visits from presurgery until 6 months postsurgery. The primary endpoint is the level of physical function assessed by 6 min walk distance at 2 months postsurgery. Secondary outcomes include patient-reported outcomes (eg, quality of life, fatigue and self-efficacy) and other clinical outcomes, including length of stay, complications, readmission, pulmonary function and treatment-related costs up to 6 months postsurgery.

Ethics/dissemination

The PEP study will test the clinical effectiveness and feasibility of a personalised exercise intervention in patients with lung cancer undergoing surgery. Outcomes of this clinical trial will be presented at national and international conferences and symposia and will be published in international, peer-reviewed journals. Ethics approval was obtained at the University of Utah (IRB 00104671).

Trial registration number

NCT03306992.
Prevalence and prognostic implication of iron deficiency and anaemia in patients with severe aortic stenosis
Authors: Kvaslerud Anette Borger , Hussain Amjad Iqbal , Auensen Andreas , Ueland Thor , Michelsen Annika E , Pettersen Kjell Ingar , Aukrust Pål , Mørkrid Lars , Gullestad Lars , Broch Kaspar
Published: December 2018

Objective

The aim of this study was to evaluate the prevalence and prognostic implication of iron deficiency (ID) and anaemia in patients with severe aortic stenosis (AS).

Methods

In an observational study of consecutive patients referred for aortic valve replacement (AVR), we assessed a wide range of biomarkers of iron status, including the definition of ID commonly applied in patients with chronic heart failure (ferritin <100 µg/L or ferritin 100–299 µg/L with a transferrin saturation <20%). The endpoints were short-term (one-year) and long-term (median 4.7 years, IQR: 3.8–5.5) mortality and major adverse cardiovascular events (MACE) within the first year after inclusion.

Results

464 patients were included in this substudy. 91 patients (20%) received conservative treatment and 373 patients (80%) received AVR. ID was detected in 246 patients (53%). 94 patients (20%) had anaemia. Patients with ID had an overall worse clinical profile than patients without ID. During follow-up, 129 patients (28%) died. Neither ID as defined above, soluble transferrin receptor nor hepcidin were associated with short-term or long-term mortality or MACE independent on treatment allocation. Anaemia was associated with one-year mortality in conservatively treated patients.

Conclusions

ID and anaemia are prevalent in patients with severe AS. In our cohort, ID did not provide independent prognostic information on top of conventional risk factors. More studies are required to determine how to correctly diagnose ID in patients with AS.

Trial registration number

NCT01794832.
Performance of the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis in a geographically distant National Register-based cohort: an external validation
Authors: Ljung Lotta , Ueda Peter , Liao Katherine P , Greenberg Jeffrey D , Etzel Carol J , Solomon Daniel H , Askling Johan
Published: December 2018

Background

Cardiovascular (CV) risk stratification for patients with rheumatoid arthritis (RA) should facilitate evidence-based management. Prior work has derived an internally validated a CV risk score, the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis (ERS-RA), using US data. The aim of this study was to perform an external validation among unselected patients with RA from Europe.

Methods

Three large, partially overlapping, cohorts of patients with RA from the Swedish Rheumatology Quality register were identified for external validation, two with information on smoking and two with close to 10 years of median follow-up. The 10 -year rate of first CV events was assessed using the Kaplan-Meier method. The performance of ERS-RA was assessed using C-index and comparisons of observed versus predicted risks.

Results

The C-index for ERS-RA varied across the three RA cohorts, from 0.75 to 0.78. Predicted risks corresponded well to observed risks among individuals with ≤10 % observed 10- year CV risk, but underestimated risk in individuals with a higher observed risk. In the absence of data on smoking, ERS-RA underestimated the CV risk by 3.3%, whereas in the cohorts including data on smoking, the calibration was within 1% (0.06% and 0.7%). In the clinically relevant risk intervals (<5%, 5.0%–<7.5%, 7.5%–<10%), ERS-RA performed well.

Conclusions

In an unselected Swedish population with RA, ERS-RA performed well, although the 10-year CV risk was underestimated in high-risk groups and in the absence of data on smoking. ERS-RA could be considered as a risk stratification tool for targeted preventive interventions in clinical rheumatology practice.
Dysregulation of insulin levels in Chagas heart disease is associated with altered adipocytokine levels
Authors: Dabarian André Luiz , Mady Charles , Barbosa-Ferreira João Marcos , Ianni Barbara Maria , Hotta Viviane Tiemi , Ramires Félix José Alvarez , Lopes Heno Ferreira , Buck Paula de Cássia , Pessoa Fernanda Gallinaro , Fonseca Keila Cardoso Barbosa , Nogueira Adriana Ramos , Fernandes Fábio
Published: December 2018

Metabolic, inflammatory, and autonomic nervous system (ANS) dysfunction are present in patients with heart failure. However, whether these changes are due to left ventricular dysfunction or heart failure etiology is unknown. We evaluated metabolism and inflammatory activity in patients with idiopathic dilated cardiomyopathy (IDC) and Chagas cardiomyopathy (CHG) and their correlation with the ANS. Forty-six patients were divided into 3 groups: IDC, CHG, and control. We evaluated adiponectin, leptin, insulin, interleukin-6, and tumor necrosis factor-alpha. ANS were analyzed by heart rate variability in time and frequency domains on a 24-hour Holter monitor. Levels of glucose, cholesterol, leptin, and adiponectin did not show differences between groups. Insulin levels were lower in CHG group (5.4 ± 3.3 μU/mL) when compared with control (8.0 ± 4.9 μU/mL) and IDC (9.9 ± 5.0 μU/mL) groups (p = 0.007). Insulin was positively associated with LFr/HFr ratio (r = 0.562; p = 0.029) and with the LFr component (r = 0.562; p = 0.029) and negatively associated with adiponectin (r = –0.603; p = 0.017) in CHG group. The addition of an adiponectin unit reduced average insulin by 0.332 μg/mL. Insulin levels were decreased in the CHG group when compared with the IDC group and were associated with ANS indexes and adiponectin levels.