bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose ratio proton radiography using the proximal side of the Bragg peak
Authors: Doolan P. J. , Royle G. , Gibson A. , Lu H.‐M. , Prieels D. , Bentefour E. H. 
Published: March 2015

Purpose:In recent years, there has been a movement toward single‐detector proton radiography, due to its potential ease of implementation within the clinical environment. One such single‐detector technique is the dose ratio method in which the dose maps from two pristine Bragg peaks are recorded beyond the patient. To date, this has only been investigated on the distal side of the lower energy Bragg peak, due to the sharp falloff. The authors investigate the limits and applicability of the dose ratio method on the proximal side of the lower energy Bragg peak, which has the potential to allow a much wider range of water‐equivalent thicknesses (WET) to be imaged. Comparisons are made with the use of the distal side of the Bragg peak.Methods:Using the analytical approximation for the Bragg peak, the authors generated theoretical dose ratio curves for a range of energy pairs, and then determined how an uncertainty in the dose ratio would translate to a spread in the WET estimate. By defining this spread as the accuracy one could achieve in the WET estimate, the authors were able to generate lookup graphs of the range on the proximal side of the Bragg peak that one could reliably use. These were dependent on the energy pair, noise level in the dose ratio image and the required accuracy in the WET. Using these lookup graphs, the authors investigated the applicability of the technique for a range of patient treatment sites. The authors validated the theoretical approach with experimental measurements using a complementary metal oxide semiconductor active pixel sensor (CMOS APS), by imaging a small sapphire sphere in a high energy proton beam.Results:Provided the noise level in the dose ratio image was 1% or less, a larger spread of WETs could be imaged using the proximal side of the Bragg peak (max 5.31 cm) compared to the distal side (max 2.42 cm). In simulation, it was found that, for a pediatric brain, it is possible to use the technique to image a region with a square field equivalent size of 7.6 cm2, for a required accuracy in the WET of 3 mm and a 1% noise level in the dose ratio image. The technique showed limited applicability for other patient sites. The CMOS APS demonstrated a good accuracy, with a root‐mean‐square‐error of 1.6 mm WET. The noise in the measured images was found to be σ = 1.2% (standard deviation) and theoretical predictions with a 1.96σ noise level showed good agreement with the measured errors.Conclusions:After validating the theoretical approach with measurements, the authors have shown that the use of the proximal side of the Bragg peak when performing dose ratio imaging is feasible, and allows for a wider dynamic range than when using the distal side. The dynamic range available increases as the demand on the accuracy of the WET decreases. The technique can only be applied to clinical sites with small maximum WETs such as for pediatric brains.
Malaria Parasites Produce Volatile Mosquito Attractants
Authors: Kelly Megan , Su Chih-Ying , Schaber Chad , Crowley Jan R. , Hsu Fong-Fu , Carlson John R. , Odom Audrey R. 
Published: March 2015

ABSTRACT

The malaria parasite
Plasmodium falciparum
contains a nonphotosynthetic plastid organelle that possesses plant-like metabolic pathways. Plants use the plastidial isoprenoid biosynthesis pathway to produce volatile odorants, known as terpenes. In this work, we describe the volatile chemical profile of cultured malaria parasites. Among the identified compounds are several plant-like terpenes and terpene derivatives, including known mosquito attractants. We establish the molecular identity of the odorant receptors of the malaria mosquito vector
Anopheles gambiae
, which responds to these compounds. The malaria parasite produces volatile signals that are recognized by mosquitoes and may thereby mediate host attraction and facilitate transmission.

IMPORTANCE
Malaria is a key global health concern. Mosquitoes that transmit malaria are more attracted to malaria parasite-infected mammalian hosts. These studies aimed to understand the chemical signals produced by malaria parasites; such an understanding may lead to new transmission-blocking strategies or noninvasive malaria diagnostics.
Manganese Homeostasis in Group A Streptococcus Is Critical for Resistance to Oxidative Stress and Virulence
Authors: Turner Andrew G. , Ong Cheryl-lynn Y. , Gillen Christine M. , Davies Mark R. , West Nicholas P. , McEwan Alastair G. , Walker Mark J. 
Published: March 2015

ABSTRACTStreptococcus pyogenes(group A Streptococcus [GAS]) is an obligate human pathogen responsible for a spectrum of human disease states. Metallobiology of human pathogens is revealing the fundamental role of metals in both nutritional immunity leading to pathogen starvation and metal poisoning of pathogens by innate immune cells. Spy0980 (MntE) is a paralog of the GAS zinc efflux pump CzcD. Through use of an isogenicmntEdeletion mutant in the GAS serotype M1T1 strain 5448, we have elucidated that MntE is a manganese-specific efflux pump required for GAS virulence. The 5448ΔmntEmutant had significantly lower survival following infection of human neutrophils than did the 5448 wild type and the complemented mutant (5448ΔmntE::mntE). Manganese homeostasis may provide protection against oxidative stress, explaining the observedex vivoreduction in virulence. In the presence of manganese and hydrogen peroxide, 5448ΔmntEmutant exhibits significantly lower survival than wild-type 5448 and the complemented mutant. We hypothesize that MntE, by maintaining homeostatic control of cytoplasmic manganese, ensures that the peroxide response repressor PerR is optimally poised to respond to hydrogen peroxide stress. Creation of a 5448ΔmntE-ΔperRdouble mutant rescued the oxidative stress resistance of the double mutant to wild-type levels in the presence of manganese and hydrogen peroxide. This work elucidates the mechanism for manganese toxicity within GAS and the crucial role of manganese homeostasis in maintaining GAS virulence.IMPORTANCEManganese is traditionally viewed as a beneficial metal ion to bacteria, and it is also established that most bacteria can tolerate high concentrations of this transition metal. In this work, we show that in group A Streptococcus, mutation of themntElocus, which encodes a transport protein of the cation diffusion facilitator (CDF) family, results in accumulation of manganese and sensitivity to this transition metal ion. The toxicity of manganese is indirect and is the result of a failure of the PerR regulator to respond to oxidative stress in the presence of high intracellular manganese concentrations. These results highlight the importance of MntE in manganese homeostasis and maintenance of an optimal manganese/iron ratio in GAS and the impact of manganese on resistance to oxidative stress and virulence.
Contribution of Resistance-Nodulation-Cell Division Efflux Systems to Antibiotic Resistance and Biofilm Formation in Acinetobacter baumannii
Authors: Yoon Eun-Jeong , Nait Chabane Yassine , Goussard Sylvie , Snesrud Erik , Courvalin Patrice , Dé Emmanuelle , Grillot-Courvalin Catherine 
Published: March 2015

ABSTRACT

Acinetobacter baumannii
is a nosocomial pathogen of increasing importance due to its multiple resistance to antibiotics and ability to survive in the hospital environment linked to its capacity to form biofilms. To fully characterize the contribution of AdeABC, AdeFGH, and AdeIJK resistance-nodulation-cell division (RND)-type efflux systems to acquired and intrinsic resistance, we constructed, from an entirely sequenced susceptible
A. baumannii
strain, a set of isogenic mutants overexpressing each system following introduction of a point mutation in their cognate regulator or a deletion for the pump by allelic replacement. Pairwise comparison of every derivative with the parental strain indicated that AdeABC and AdeFGH are tightly regulated and contribute to acquisition of antibiotic resistance when overproduced. AdeABC had a broad substrate range, including β-lactams, fluoroquinolones, tetracyclines-tigecycline, macrolides-lincosamides, and chloramphenicol, and conferred clinical resistance to aminoglycosides. Importantly, when combined with enzymatic resistance to carbapenems and aminoglycosides, this pump contributed in a synergistic fashion to the level of resistance of the host. In contrast, AdeIJK was expressed constitutively and was responsible for intrinsic resistance to the same major drug classes as AdeABC as well as antifolates and fusidic acid. Surprisingly, overproduction of AdeABC and AdeIJK altered bacterial membrane composition, resulting in decreased biofilm formation but not motility. Natural transformation and plasmid transfer were diminished in recipients overproducing AdeABC. It thus appears that alteration in the expression of efflux systems leads to multiple changes in the relationship between the host and its environment, in addition to antibiotic resistance.

IMPORTANCE
Increased expression of chromosomal genes for RND-type efflux systems plays a major role in bacterial multidrug resistance.
Acinetobacter baumannii
has recently emerged as an important human pathogen responsible for epidemics of hospital-acquired infections. Besides its remarkable ability to horizontally acquire resistance determinants, it has a broad intrinsic resistance due to low membrane permeability, endogenous resistance genes, and antibiotic efflux. The study of isogenic mutants from a susceptible
A. baumannii
clinical isolate overproducing or deleted for each of the three major RND-type pumps demonstrated their major contribution to intrinsic resistance and to the synergism between overproduction of an efflux system and acquisition of a resistance gene. We have also shown that modulation of expression of the structural genes for the efflux systems results in numerous alterations in membrane-associated cellular functions, in particular, in a decrease in biofilm formation and resistance gene acquisition.
Acupuncture for erectile dysfunction: a systematic review protocol
Authors: Cui Xiaoming , Li Xiaoli , Peng Weina , Zhou Jing , Yu Jinna , Ye Yongming , Liu Zhishun 
Published: March 2015

IntroductionThis systematic review protocol aims to provide a protocol for assessing the safety and effectiveness of acupuncture for the treatment of erectile dysfunction(ED). Previous systematic reviews did not draw convincing conclusions owing to high heterogeneity and few included randomised controlled trials, so it is necessary to reassess the efficacy and safety of acupuncture for ED.Methods and analysisEight electronic databases will be searched: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed, EMBASE, PsycInfo, the Chinese Biomedical Literature Database (CBM), the Chinese Medical Current Content (CMCC) and the China National Knowledge Infrastructure (CNKI). Related Chinese literature will be searched in other Chinese databases. All relevant randomised controlled trials in English or Chinese without any restrictions of publication type will be included. The main outcome measure will be improvements in sexual activity assessed by validated questionnaires. Assessment of risk of bias, data synthesis and subgroup analysis will be carried out using Review Manager 5.3.Ethics and disseminationThe results of the systematic review will be disseminated via publication in a peer-reviewed journal and presented at a relevant conference. The data we will use do not include individual patient data, so ethical approval is not required.Trial registration numberPROSPERO CRD42014013575.
The prevalence, risk factors and short-term outcomes of delirium in Thai elderly emergency department patients
Authors: Sri-on Jiraporn , Tirrell Gregory Philip , Vanichkulbodee Alissala , Niruntarai Supa , Liu Shan W 
Published: March 2015

BackgroundWe sought to determine the prevalence of delirium in a Thai emergency department (ED). The secondary objective was to identify risk factors and short-term outcomes in delirious elderly ED patients.MethodsThis was a prospective cross-sectional study in the ED of an urban tertiary care hospital. Patients aged ≥65 years who presented to the ED were included. We excluded patients who had severe dementia, were not responsive to verbal stimuli, had severe trauma and were blind, deaf, aphasic or unable to speak Thai. Delirium was determined using the Confusion Assessment Method for the Intensive Care Unit. We collected 30-day mortality rate, hospital length of stay and revisit rate as short-term outcomes.ResultsWe had a final sample size of 232 patients; 27 (12%) were delirious in the ED, of which 16 (59%) were not recognised to be delirious by the emergency physician. Multivariable logistic regression analysis showed dementia (adjusted OR (AOR) 13.1; 95% CI 2.9 to 59.6), auditory impairment (AOR 4.8; 95% CI 1.6 to 13.8) and ED diagnosis of metabolic derangement (AOR 6.5; 95% CI 1.6 to 26.8) were associated with delirium in the ED. Delirium was associated with a higher mortality rate than those without delirium (15% vs 2%, p=0.004).ConclusionsIn one middle-income country, elderly ED patients were delirious >10% of the time. Delirium was underdiagnosed and was associated with an increased 30-day mortality rate. Delirium screening needs to be improved, potentially focusing on high-risk patients.
Age‐dependent expression of osteochondrosis‐related genes in equine leukocytes
Authors: Mendoza L. , Piquemal D. , Lejeune J. P. , Vander Heyden L. , Noguier F. , Bruno R. , Sandersen C. , Serteyn D. 
Published: March 2015

Introduction:Osteochondrosis (OC) is a developmental disease in horses which has a significant impact on the horse's welfare and performance. The early disturbance in the process of endochondral ossification progresses to inflammatory and repair processes in older horses. Previously, differentially expressed genes in leukocytes of OC‐affected horses have been identified. The aim of the present study is to detect age‐related changes in these differentially expressed genes.Materials and Methods:The expression of OC‐related genes was analysed by real‐time PCR and subsequent statistical analysis (ΔΔCT) in the leukocytes of 135 Belgian Warmblood horses divided into three different age groups: <12 months (n=47), 18–24 months (n=50) >30 months (n=38).Results:Relative expression of genes of horses less than 12 months of age showed significant induction of the genes MGAT4A, PRKCG, MHCI, ApoB, ApoB3G, B4GALT6 and a significantly lower expression of the genes OAS3. Horses of 18–24 months of age, showed a significantly higher expression of the genes TBC1D9, MGAT4A, IFIH1, MHCIIa and MMP1. Horses of more than 30 months of age showed a significantly higher expression of the genes MGAT4A, HP, SECTM1 compared with their age‐matched control groups.Conclusions:The study demonstrates that OC‐related genes are differentially expressed in horses of different ages compared with their age‐matched controls. Some of the genes may be implicated in cell signalling and differentiation as well as carbohydrate and lipid metabolism and inflammation. However, the causal relationship between the differentially expressed genes and the development and progression of the OC lesions needs to be determined.
An Evaluation-Driven Decision Procedure for G3i
Authors: Ferrari Mauro , Fiorentini Camillo , Fiorino Guido 
Published: March 2015

It is well known that G3i, the sequent calculus for intuitionistic propositional logic where weakening and contraction are absorbed into the rules, is not terminating. Indeed, due to the contraction in the rule for left implication, the naïve goal-oriented proof-search strategy, consisting in applying the rules of the calculus bottom up until possible, can generate branches of infinite length. The usual solution to this problem is to support the proof-search procedure with a loop checking mechanism that prevents the generation of infinite branches by storing and analyzing some information regarding the branch under development.In this article, we propose a new technique based on evaluation functions. An evaluation function is a lightweight computational mechanism that, analyzing only the current goal of the proof search, allows one to drive the application of rules to guarantee termination and to avoid useless backtracking. We describe an evaluation-driven proof-search procedure that given a sequent σ returns either a G3i-derivation of σ or a countermodel for σ. We prove that such a procedure is terminating and correct, and that the depth of the G3i-trees generated during proof search is quadratic in the size of σ. Finally, we discuss the overhead time introduced by evaluation functions in the proof-search procedure.
Why Is It Hard to Obtain a Dichotomy for Consistent Query Answering?
Authors: Fontaine Gaëlle 
Published: March 2015

A database may for various reasons become inconsistent with respect to a given set of integrity constraints. In the late 1990s, the formal approach of consistent query answering was proposed in order to query such databases. Since then, a lot of efforts have been spent to classify the complexity of consistent query answering under various classes of constraints. It is known that for the most common constraints and queries, the problem is in coNP and might be coNP-hard, yet several relevant tractable classes have been identified. Additionally, the results that emerged suggested that given a set of key constraints and a conjunctive query, the problem of consistent query answering is either in PTime or is coNP-complete. However, despite all the work, as of today this dichotomy remains a conjecture.
The main contribution of this article is to explain why it appears so difficult to obtain a dichotomy result in the setting of consistent query answering. Namely, we prove that such a dichotomy with respect to common classes of constraints and queries is harder to achieve than a dichotomy for the constraint satisfaction problem, which is a famous open problem since the 1990s.
Quantification of Age-Related Differences in Reaching and Circle-Drawing using a Robotic Rehabilitation Device
Authors: Pacilli Alessandra , Germanotta Marco , Rossi Stefano , Cappa Paolo 
Published: March 2015

Background: Although robotic therapy is at the forefront of upper limb rehabilitation, there is limited information about the importance of selecting age-matched subjects to evaluate recovery of arm movement during rehabilitation.Objective: This study aims to quantify differences in the arm motion of healthy children and adults when they interact with a planar robot, in order to determine whether an age-matched control group is necessary in clinical studies involving pediatric patients.Methods: Ten children (aged 7 to 10 years) and ten adults (aged 23 to 25 years) performed, at self-selected speed and accuracy, planar-reaching and circle-drawing movements with a robotic device. We analyzed the motor performances for the two groups quantifying the participants' dexterity in completing two chosen tasks. The measurement of the entire upper limb was obtained by merging the data provided by the robot with that of an optical tracking system.Results: Children drew circles with less smoothness than adults but with the same accuracy and joint coordination. During planar reaching task, children optimized only the coordination but performed the movement with less accuracy and smoothness than adults.Conclusions: Our findings provide evidence that age-matched healthy children should be used to quantify the recovery of robot-mediated therapy in children with upper limb impairments.
Three-Dimensional Biomechanical Analysis of the Bovine Humerus
Authors: Bouza-Rodríguez José Benito , Miramontes-Sequeiros Luz Calia 
Published: March 2015

There are few reports on the biomechanical analysis of the animal humerus. In this study, a three-dimensional finite element model of the bovine humerus was created, and loaded with the physiological forces acting when the cow is falling or jumping (weight and impact forces). Subsequently the corresponding stress and strain distribution in the humerus for different inclined positions of bone was determined.The highest stress concentration occurred in the distal humeral diaphysis, both when only the reaction and load transfer forces were considered and when muscle forces were included too, although when muscle forces were included these maximum stresses decreased. In the distal humeral diaphysis, an increase was also observed in the cortical thickness; this may be a bone adaptation to reduce the maximum stresses. By understanding these bone adaptation processes at regional level, non-pharmacological treatments to some bone pathologies could be developed, mainly the ones characterized by loss of bone mass.Furthermore, taking into account both the humerus fracture strength and the maximum force that muscles can make without breaking, it is deduced that during jumping or falling the cow must maintain the humerus as vertical as possible to better bear the impact. This is in congruity with what was observed.The interest of this study is in improving the knowledge of animal humerus biomechanics and its application in orthopaedic design and surgical treatments.
Modified Newton‐Raphson Method to Tune Feedback Gains of Control System for Standing by Functional Neuromuscular Stimulation Following Spinal Cord Injury
Authors: Nataraj Raviraj , Audu Musa L. , Triolo Ronald J. 
Published: March 2015

Background: Functional neuromuscular stimulation (FNS) can restore standing capabilities following spinal cord injury.
Feedback control of these systems can optimize performance by reducing the required upper extremity support. However, tuning
these control systems can be intensive and clinically inconvenient.Objective: This case study investigated a clinical method to efficiently tune feedback gains for a control system utilizing
feedback of total body center of mass acceleration to modulate stimulation levels to targeted paralyzed musculature of the lower
extremities and trunk.Methods: Gains for this control system were tuned to minimize the stabilization loading by one arm against internal postural
perturbations volitionally‐generated during manipulation of an object using the other arm. An algorithm based on a modified
form of the Newton‐Raphson method was employed to find the optimal feedback gains with lower subject effort than that to
determine the original tuning curves.Results: This method accurately (<6.2% error) approximated the optimal gains with 70% fewer manipulations by the subject.Conclusions: These results suggest that optimal feedback gains for the specific FNS control system can be determined
systematically with considerably less effort than heuristic gain tuning. This demonstrates the potential for devising simple,
convenient methods for effective system re‐tuning during clinical usage.