bluuebunny/crossref_metadata_2025 huggingface dataset:
Complex Interplay between Sphingolipid and Sterol Metabolism Revealed by Perturbations to the Leishmania Metabolome Caused by Miltefosine
Authors: Armitage Emily G. , Alqaisi Amjed Q. I. , Godzien Joanna , Peña Imanol , Mbekeani Alison J. , Alonso-Herranz Vanesa , López-Gonzálvez Ángeles , Martín Julio , Gabarro Raquel , Denny Paul W. , Barrett Michael P. , Barbas Coral
Published: February 2018

With the World Health Organization reporting over 30,000 deaths and 200,000 to 400,000 new cases annually, visceral leishmaniasis is a serious disease affecting some of the world's poorest people. As drug resistance continues to rise, there is a huge unmet need to improve treatment. Miltefosine remains one of the main treatments for leishmaniasis, yet its mode of action (MoA) is still unknown. Understanding the MoA of this drug and parasite response to treatment could help pave the way for new and more successful treatments for leishmaniasis. A novel method has been devised to study the metabolome and lipidome ofLeishmania donovaniaxenic amastigotes treated with miltefosine. Miltefosine caused a dramatic decrease in many membrane phospholipids (PLs), in addition to amino acid pools, while sphingolipids (SLs) and sterols increased.Leishmania majorpromastigotes devoid of SL biosynthesis through loss of the serine palmitoyl transferase gene (ΔLCB2) were 3-fold less sensitive to miltefosine than wild-type (WT) parasites. Changes in the metabolome and lipidome of miltefosine-treatedL. majormirrored those ofL. donovani. A lack of SLs in the ΔLCB2 mutant was matched by substantial alterations in sterol content. Together, these data indicate that SLs and ergosterol are important for miltefosine sensitivity and, perhaps, MoA.
Alginate Oligosaccharide-Induced Modification of the
lasI-lasR
and
rhlI-rhlR
Quorum-Sensing Systems in Pseudomonas aeruginosa
Authors: Jack Alison A. , Khan Saira , Powell Lydia C. , Pritchard Manon F. , Beck Konrad , Sadh Hina , Sutton Lucy , Cavaliere Alessandra , Florance Hannah , Rye Philip D. , Thomas David W. , Hill Katja E.
Published: February 2018

Pseudomonas aeruginosa
plays a major role in many chronic infections. Its ability to readily form biofilms contributes to its success as an opportunistic pathogen and its resistance/tolerance to antimicrobial/antibiotic therapy. A low-molecular-weight alginate oligomer (OligoG CF-5/20) derived from marine algae has previously been shown to impair motility in
P. aeruginosa
biofilms and disrupt pseudomonal biofilm assembly. As these bacterial phenotypes are regulated by quorum sensing (QS), we hypothesized that OligoG CF-5/20 may induce alterations in QS signaling in
P. aeruginosa
. QS regulation was studied by using
Chromobacterium violaceum
CV026 biosensor assays that showed a significant reduction in acyl homoserine lactone (AHL) production following OligoG CF-5/20 treatment (≥2%;
P
< 0.05). This effect was confirmed by liquid chromatography-mass spectrometry analysis of C
4
-AHL and 3-oxo-C
12
-AHL production (≥2%;
P
< 0.05). Moreover, quantitative PCR showed that reduced expression of both the
las
and
rhl
systems was induced following 24 h of treatment with OligoG CF-5/20 (≥0.2%;
P
< 0.05). Circular dichroism spectroscopy indicated that these alterations were not due to steric interaction between the AHL and OligoG CF-5/20. Confocal laser scanning microscopy (CLSM) and COMSTAT image analysis demonstrated that OligoG CF-5/20-treated biofilms had a dose-dependent decrease in biomass that was associated with inhibition of extracellular DNA synthesis (≥0.5%;
P
< 0.05). These changes correlated with alterations in the extracellular production of the pseudomonal virulence factors pyocyanin, rhamnolipids, elastase, and total protease (
P
< 0.05). The ability of OligoG CF-5/20 to modify QS signaling in
P. aeruginosa
PAO1 may influence critical downstream functions such as virulence factor production and biofilm formation.
Common Hydraulic Fracturing Fluid Additives Alter the Structure and Function of Anaerobic Microbial Communities
Authors: Mumford Adam C. , Akob Denise M. , Klinges J. Grace , Cozzarelli Isabelle M.
Published: February 2018

The development of unconventional oil and gas (UOG) resources results in the production of large volumes of wastewater containing a complex mixture of hydraulic fracturing chemical additives and components from the formation. The release of these wastewaters into the environment poses potential risks that are poorly understood. Microbial communities in stream sediments form the base of the food chain and may serve as sentinels for changes in stream health. Iron-reducing organisms have been shown to play a role in the biodegradation of a wide range of organic compounds, and so to evaluate their response to UOG wastewater, we enriched anaerobic microbial communities from sediments collected upstream (background) and downstream (impacted) of an UOG wastewater injection disposal facility in the presence of hydraulic fracturing fluid (HFF) additives: guar gum, ethylene glycol, and two biocides, 2,2-dibromo-3-nitrilopropionamide (DBNPA) and bronopol (C3H6BrNO4). Iron reduction was significantly inhibited early in the incubations with the addition of biocides, whereas amendment with guar gum and ethylene glycol stimulated iron reduction relative to levels in the unamended controls. Changes in the microbial community structure were observed across all treatments, indicating the potential for even small amounts of UOG wastewater components to influence natural microbial processes. The microbial community structure differed between enrichments with background and impacted sediments, suggesting that impacted sediments may have been preconditioned by exposure to wastewater. These experiments demonstrated the potential for biocides to significantly decrease iron reduction rates immediately following a spill and demonstrated how microbial communities previously exposed to UOG wastewater may be more resilient to additional spills.

IMPORTANCEOrganic components of UOG wastewater can alter microbial communities and biogeochemical processes, which could alter the rates of essential natural attenuation processes. These findings provide new insights into microbial responses following a release of UOG wastewaters and are critical for identifying strategies for the remediation and natural attenuation of impacted environments.
Whole-Genome Sequence Analysis of Streptococcus pneumoniae Strains That Cause Hospital-Acquired Pneumonia Infections
Authors: Chang Bin , Morita Masatomo , Lee Ken-ichi , Ohnishi Makoto
Published: February 2018

Streptococcus pneumoniae
colonizes the nasopharyngeal mucus in healthy individuals and can cause otitis media, pneumonia, and invasive pneumococcal diseases. In this study, we analyzed
S. pneumoniae
strains that caused 19 pneumonia episodes in long-term inpatients with severe underlying disease in a hospital during a period of 14 months (from January 2014 to February 2015). Serotyping and whole-genome sequencing analyses revealed that 18 of the 19 pneumonia cases were caused by
S. pneumoniae
strains belonging to 3 genetically distinct groups: clonal complex 9999 (CC9999), sequence type 282 (ST282), and ST166. The CC9999 and ST282 strains appeared to have emerged separately by a capsule switch from the pandemic PMEN 1 strain (Spain
23F
-ST81). After all the long-term inpatients were inoculated with the 23-valent pneumococcal polysaccharide vaccine, no other nosocomial pneumonia infections occurred until March 2016.
Downregulation of MicroRNA eca-mir-128 in Seminal Exosomes and Enhanced Expression of CXCL16 in the Stallion Reproductive Tract Are Associated with Long-Term Persistence of Equine Arteritis Virus
Authors: Carossino Mariano , Dini Pouya , Kalbfleisch Theodore S. , Loynachan Alan T. , Canisso Igor F. , Shuck Kathleen M. , Timoney Peter J. , Cook R. Frank , Balasuriya Udeni B. R.
Published: February 2018

Equine arteritis virus (EAV) can establish long-term persistent infection in the reproductive tract of stallions and is shed in the semen. Previous studies showed that long-term persistence is associated with a specific allele of the
CXCL16
gene (
CXCL16S
) and that persistent infection is maintained despite the presence of a local inflammatory and humoral and mucosal antibody responses. In this study, we demonstrated that equine seminal exosomes (SEs) are enriched in a small subset of microRNAs (miRNAs). Most importantly, we demonstrated that long-term EAV persistence is associated with the downregulation of an SE-associated miRNA (eca-mir-128) and with an enhanced expression of CXCL16 in the reproductive tract, a putative target of eca-mir-128. The findings presented here suggest that SE eca-mir-128 is implicated in the regulation of the CXCL16/CXCR6 axis in the reproductive tract of persistently infected stallions, a chemokine axis strongly implicated in EAV persistence. This is a novel finding and warrants further investigation to identify its specific mechanism in modulating the CXCL16/CXCR6 axis in the reproductive tract of the EAV long-term carrier stallion.

IMPORTANCE
Equine arteritis virus (EAV) has the ability to establish long-term persistent infection in the stallion reproductive tract and to be shed in semen, which jeopardizes its worldwide control. Currently, the molecular mechanisms of viral persistence are being unraveled, and these are essential for the development of effective therapeutics to eliminate persistent infection. Recently, it has been determined that long-term persistence is associated with a specific allele of the
CXCL16
gene (
CXCL16S
) and is maintained despite induction of local inflammatory, humoral, and mucosal antibody responses. This study demonstrated that long-term persistence is associated with the downregulation of seminal exosome miRNA eca-mir-128 and enhanced expression of its putative target, CXCL16, in the reproductive tract. For the first time, this study suggests complex interactions between eca-mir-128 and cellular elements at the site of EAV persistence and implicates this miRNA in the regulation of the CXCL16/CXCR6 axis in the reproductive tract during long-term persistence.
Disease characteristics and management of hospitalised adolescents and adults with community-acquired pneumonia in China: a retrospective multicentre survey
Authors: Chen Liang , Zhou Fei , Li Hui , Xing Xiqian , Han Xiudi , Wang Yiming , Zhang Chunxiao , Suo Lijun , Wang Jingxiang , Yu Guohua , Wang Guangqiang , Yao Xuexin , Yu Hongxia , Wang Lei , Liu Meng , Xue Chunxue , Liu Bo , Zhu Xiaoli , Li Yanli , Xiao Ying , Cui Xiaojing , Li Lijuan , Uyeki Timothy M , Wang Chen , Cao Bin
Published: February 2018

Objectives

To describe the clinical characteristics and management of patients hospitalised with community-acquired pneumonia (CAP) in China.

Design

This was a multicentre, retrospective, observational study.

Setting

13 teaching hospitals in northern, central and southern China from 1 January 2014 to 31 December 2014

Participants

Information on hospitalised patients aged ≥14 years with radiographically confirmed pneumonia with illness onset in the community was collected using standard case report forms.

Primary and secondary outcome measures

Resource use for CAP management.

Results

Of 14 793 patients screened, 5828 with radiographically confirmed CAP were included in the final analysis. Low mortality risk patients with a CURB-65 score 0–1 and Pneumonia Severity Index risk class I–II accounted for 81.2% (4434/5594) and 56.4% (2034/3609) patients, respectively. 21.7% (1111/5130) patients had already achieved clinical stability on admission. A definite or probable pathogen was identified only in 12.7% (738/5828) patients. 40.9% (1575/3852) patients without pseudomonal infection risk factors received antimicrobial overtreatment regimens. The median duration between clinical stability to discharge was 5.0 days with 30-day mortality of 4.2%.

Conclusions

These data demonstrated the overuse of health resources in CAP management, indicating that there is potential for improvement and substantial savings to healthcare systems in China.

Trial registration number

NCT02489578; Results.
Coronary artery bypass grafting in patients treated with thoracic radiation: a case–control study
Authors: Fender Erin Amanda , Chandrashekar Pranav , Liang Jackson J , Dhar Priyank R , Sio Terence T , Stulak John M , Lennon Ryan J , Slusser Joshua P , Ashman Jonathan B , Miller Robert C , Herrmann Joerg , Prasad Abhiram , Sandhu Gurpreet S
Published: February 2018

Background and aim

Thoracic radiation therapy (XRT) for cancer is associated with the development of significant coronary artery disease that may require coronary artery bypass grafting surgery (CABG). Contemporary acute surgical outcomes and long-term postoperative survival of patients with prior XRT have not been well characterised.

Methods

This was a retrospective, single-centre study of patients with a history of thoracic XRT who required CABG and who were propensity matched against 141 controls who underwent CABG over the same time period. The objectives were to assess early CABG outcomes and long-term survival in patients with prior XRT.

Results

Thirty-eight patients with a history of previous thoracic XRT underwent CABG from 1994 to 2013. The median time from XRT exposure to surgery was 7.9 years (IQR: 2.5–18.4 years). Perioperative adverse events were similar in the XRT group and controls; however, there was a trends lower utilisation of internal mammary artery (IMA) grafts in the XRT group (89%vs98%, P=0.13). After a median postoperative follow-up of 5.4 years (IQR 0.9–9.4 years), no difference in long-term all-cause mortality was observed.

Conclusion

Patients with prior thoracic XRT who undergo CABG have similar long-term all-cause mortality compared with controls. Isolated CABG after thoracic XRT is not associated with higher perioperative complications, but IMA graft use may be limited by prior XRT.
Wilson disease: more than meets the eye
Authors: Kelly Claire , Pericleous Marinos
Published: February 2018

Wilson disease is a rare but important disorder of copper metabolism, with a failure to excrete copper appropriately into bile. It is a multisystem condition with presentations across all branches of medicine. Diagnosis can be difficult and requires a high index of suspicion. It should be considered in unexplained liver disease particularly where neuropsychiatric features are also present. Treatments are available for all stages of disease. A particularly important presentation not to overlook is acute liver failure which carries a high mortality risk and may require urgent liver transplantation. Here, we provide an overview of this complex condition.
P–V criticality of conformal gravity holography in four dimensions
Authors: Pradhan Parthapratim
Published: February 2018

We examine the critical behavior, i.e. P–V criticality of conformal gravity (CG) in an extended phase space in which the cosmological constant should be interpreted as a thermodynamic pressure and the corresponding conjugate quantity as a thermodynamic volume. The main potential point of interest in CG is that there exists a nontrivial Rindler parameter [Formula: see text] in the spacetime geometry. This geometric parameter has an important role to construct a model for gravity at large distances where the parameter “[Formula: see text]” actually originates. We also investigate the effect of the said parameter on the black hole (BH) thermodynamic equation of state, critical constants, Reverse Isoperimetric Inequality, first law of thermodynamics, Hawking–Page phase transition and Gibbs free energy for this BH. We speculate that due to the presence of the said parameter, there has been a deformation in the shape of the isotherms in the P–V diagram in comparison with the charged-anti de Sitter (AdS) BH and the chargeless-AdS BH. Interestingly, we find that the critical ratio for this BH is [Formula: see text], which is greater than the charged AdS BH and Schwarzschild–AdS BH, i.e. [Formula: see text]. The symbols are defined in the main work. Moreover, we observe that the critical ratio has a constant value and it is independent of the nontrivial Rindler parameter [Formula: see text]. Finally, we derive the reduced equation of state in terms of the reduced temperature, the reduced volume and the reduced pressure, respectively.
CONTROL STRATEGIES of HEPATITIS B WITH THREE CONTROL VARIABLES
Authors: KHAN MUHAMMAD ALTAF , ISLAM SAEED , VALVERDE JOSE C. , KHAN SHER AFZAL
Published: February 2018

In this paper, we present a compartmental mathematical model of hepatitis B virus with optimal control strategies. First, we formulate the model applying the optimal control techniques which use control variables in the form of isolation, educational campaign and vaccination. We derive the conditions under which it is optimal to eradicate the disease and examine the impact of possible vaccination treatment strategies on disease transmission. When such an elimination is impossible, we use the techniques of Pontryagin’s Maximum Principle to derive the necessary conditions for the optimal control problem. The numerical results show that some effective vaccination and control can reduce the disease spread in the community.
A Finite Element Formulation for Crack Problem in Couple-Stress Elasticity
Authors: Homayounfard Milad , Daneshmehr Alireza , Salari Arvand
Published: February 2018

In this research, we investigated the crack behavior in the Mode I fracture in a plane strain state, considering the size effects and under the couple-stress theory using finite element method (FEM). First, using the eigenfunction expansion technique, we provided the stress, couple-stress, displacement, strain, and curvature fields at the crack-tip. Then, using the FEM, fundamental parameters that determine the stress and couple-stress fields at the crack-tip (i.e., stress intensity factor and couple-stress intensity factor) were obtained. In the formulation of FEM, we used a mixed variational method, in which displacement and rotation are considered as independent variables, and their kinematic constraints are applied using Lagrange multipliers. Based on this formulation, it was possible to implement the classical quarter-point elements for the crack-tip. The results show that under the framework of the couple-stress theory, energy release rate can still be considered as the fundamental measure and determinant parameter for the crack behavior, but the stress intensity factor alone cannot appropriately describe the crack behavior.
Left ventricular volume analysis as a basic tool to describe cardiac function
Authors: Kerkhof Peter L. M. , Kuznetsova Tatiana , Ali Rania , Handly Neal
Published: February 2018

The heart is often regarded as a compression pump. Therefore, determination of pressure and volume is essential for cardiac function analysis. Traditionally, ventricular performance was described in terms of the Starling curve, i.e., output related to input. This view is based on two variables (namely, stroke volume and end-diastolic volume), often studied in the isolated (i.e., denervated) heart, and has dominated the interpretation of cardiac mechanics over the last century. The ratio of the prevailing coordinates within that paradigm is termed ejection fraction (EF), which is the popular metric routinely used in the clinic. Here we present an insightful alternative approach while describing volume regulation by relating end-systolic volume (ESV) to end-diastolic volume. This route obviates the undesired use of metrics derived from differences or ratios, as employed in previous models. We illustrate basic principles concerning ventricular volume regulation by data obtained from intact animal experiments and collected in healthy humans. Special attention is given to sex-specific differences. The method can be applied to the dynamics of a single heart and to an ensemble of individuals. Group analysis allows for stratification regarding sex, age, medication, and additional clinically relevant covariates. A straightforward procedure derives the relationship between EF and ESV and describes myocardial oxygen consumption in terms of ESV. This representation enhances insight and reduces the impact of the metric EF, in favor of the end-systolic elastance concept advanced 4 decades ago.
Pulmonary IL-1β expression in early life causes permanent changes in lung structure and function in adulthood
Authors: Hogmalm Anna , Bry Maija , Bry Kristina
Published: February 2018

Chorioamnionitis, mechanical ventilation, oxygen therapy, and postnatal infection promote inflammation in the newborn lung. The long-term consequences of pulmonary inflammation during infancy have not been well characterized. The aim of this study was to examine the impact of inflammation during the late saccular to alveolar stages of lung development on lung structure and function in adulthood. To induce IL-1β expression in the pulmonary epithelium of mice with a tetracycline-inducible human IL-1β transgene, doxycycline was administered via intraperitoneal injections to bitransgenic pups and their littermate controls on postnatal days (PN) 0, 0.5, and 1. Lung structure, inflammation, and airway reactivity were studied in adulthood. IL-1β production in early life resulted in increased numbers of macrophages and neutrophils on PN21, but inflammation subsided by PN42. Permanent changes in alveolar structure, i.e., larger alveoli and thicker alveolar walls, were present from PN21 to PN84. Lack of alveolar septation thus persisted after IL-1β production and inflammation had ceased. Early IL-1β production caused goblet cell hyperplasia, enhanced calcium-activated chloride channel 3 (CLCA3) protein expression, and increased airway reactivity in response to methacholine on PN42. Lymphoid follicles were present adjacent to small airways in the lungs of adult bitransgenic mice, and levels of the B cell chemoattractant CXC-motif ligand (CXCL) 13 were elevated in the lungs of bitransgenic mice compared with controls. In conclusion, IL-1β-induced pulmonary inflammation in early life causes a chronic lung disease in adulthood.
Mechanical Properties of Scrap Tire Crumbs‐Clayey Soil Mixtures Determined by Laboratory Tests
Authors: Li ShanShan , Li Dayong
Published: February 2018

Some laboratory tests, such as Proctor compaction test, direct shear and cyclic direct shear tests, consolidation test, and unconfined compression test, were performed on scrap tire crumbs‐clayey soil mixtures to study the mechanical properties of the mixtures. The results show that (1) the maximum dry unit weight and the corresponding optimum moisture content of the mixtures decrease rapidly with the increase of scrap tire crumbs content (CSTC), showing good potential for using the mixtures as lightweight fill material; (2) it is not possible to prepare the mixture when CSTC exceeds 30% due to the occurrence of cracks in the mixture after removing from a mould; and (3) the shear strength of mixtures approximately increases by 20% when CSTC is up to 30%, while the residual strength decreases by 15%, compared with that of pure clayey soil. During shearing, the dilation of the mixtures occurs, particularly under the condition of a high CSTC and a low vertical pressure. Besides, the compressive strength and consolidation settlement of the mixtures decrease with CSTC increasing. The results indicate that it is possible for scrap tire crumbs used to improve clayey soil, which is suitable to act as a fill material.
Relative Risk Chart Score for the Assessment of the Cardiovascular Risk in Young Patients with Ankylosing Spondylitis
Authors: Rueda-Gotor Javier , Genre Fernanda , Corrales Alfonso , Blanco Ricardo , Fuentevilla Patricia , Portilla Virginia , Expósito Rosa , Arnaiz Cristina Mata , Pina Trinitario , González-Juanatey Carlos , Rodriguez-Rodriguez Luis , González-Gay Miguel A.
Published: February 2018

Objective. To determine if the use of the relative risk (RR) chart score may help to identify young ankylosing spondylitis (AS) patients at high risk of cardiovascular (CV) disease. Methods. 73 AS patients younger than 50 years were assessed. CV risk was calculated according to the total cholesterol systematic coronary risk evaluation (TC-SCORE) and the RR chart score. C-reactive protein (CRP) value at disease diagnosis and carotid ultrasound data were also analyzed. Results. Twenty (27.4%) patients exhibited carotid plaques being classified into the category of very high CV risk. None of them was found to have a high/very high TC-SCORE. CRP > 3 mg/L at disease diagnosis was associated with the presence of carotid plaques (odds ratio 5.66, p=0.03). Whereas only 5 (14.2%) of the 35 patients with RR = 1 had carotid plaques, 15 (39.5%) of 38 with RR > 1 showed plaques. A model that included the performance of carotid US in patients with RR > 1 who had CRP > 3 mg/L allowed us to identify 60% of very high risk patients, with a specificity of 77.4%. Conclusions. RR chart score assessment may help to identify young AS patients at high risk of CV disease.
Prognostic Significance of Blood, Serum, and Ascites Parameters in Patients with Malignant Peritoneal Mesothelioma or Peritoneal Carcinomatosis
Authors: Su Shan-shan , Zheng Guo-qi , Yin Wen-jie , Liang Yu-fei , Liu Ying-ying , Song Hui , Sun Ning-ning , Yang Yu-xin
Published: February 2018

To determine effects of the biochemical and cytological properties of blood, serum, and ascites on survival of patients with malignant peritoneal effusion (MPeE), including malignant peritoneal mesothelioma (MPeM) and peritoneal carcinomatosis (PC), we conducted a retrospective study of patients with MPeE and healthy controls. Potential prognostic factors were identified as follows: age, sex, blood neutrophil-to-lymphocyte ratio (NLR), serum parameters, ascites parameters, serum-ascites albumin gradient, and the ascites-serum LDH ratio. Compared to those of the control group, serum albumin levels were significantly lower, and the NLR and serum LDH levels were significantly higher in the MPeE group. Overall survival (OS) was longer in patients with MPeM compared to that in patients with PC. Compared with patients in the MPeM, patients with PC had higher NLRs, ascites glucose levels, serum-ascites albumin gradients, and serum LDH levels. In contrast, their ascites albumin levels and ascites-serum LDH ratios were lower. Univariate analyses indicated that the NLR, serum LDH levels, ascites LDH levels, ascites coenocyte levels, and the ascites coenocyte-to-monocyte ratios affected the OS. Multivariate analyses identified only serum and ascites LDH levels as independent prognostic factors.
Protocomputing Architecture over a Digital Medium Aiming at Real‐Time Video Processing
Authors: Tanibata Aoi , Schmid Alexandre , Takamaeda-Yamazaki Shinya , Ikebe Masayuki , Motomura Masato , Asai Tetsuya
Published: February 2018

A protocomputational architecture is presented that implements the ancient reaction‐diffusion model as a microelectronic hardware. A digital medium is selected for the physical mapping of the protoarchitecture as a way to benefit from reliable advanced integrated circuits fabrication technologies. The extraction of dense motion vector fields from textureless objects in a video sequence is selected as a realistic application. Real‐time video processing results at 30 fps are achieved using an FPGA physical implementation of the proposed protoarchitecture.
Approaches to Addressing Service Selection Ties in Ad Hoc Mobile Cloud Computing
Authors: Akinola Ayotuyi Tosin , Adigun Matthew Olusegun
Published: February 2018

The ad hoc mobile cloud (AMC) allows mobile devices to connect together through a wireless connection or any other means and send a request for web services from one to another within the mobile cloud. However, one of the major challenges in the AMC is the occurrence of dissatisfaction experienced by the users. This is because there are many services with similar functionalities but varying nonfunctional properties. Moreover, another resultant cause of user dissatisfaction being coupled with runtime redundancy is the attainment of similar quality computations during service selection, often referred to as “service selection ties.” In an attempt to address this challenge, service selection mechanisms for the AMC were developed in this work. This includes the use of selected quality of service properties coupled with user feedback data to determine the most suitable service. These mechanisms were evaluated using the experimental method. The evaluation of the mechanisms mainly focused on the metrics that evaluate the satisfaction of users' interest via the quantitative evaluation. The experiments affirmed that the use of the shortest distance can help to break selection ties between potential servicing nodes. Also, a continuous use of updated and unlimited range of users' assessments enhances an optimal service selection.
Typhoid Fever due to Extended Spectrum β-Lactamase-Producing Salmonella enterica Serovar Typhi: A Case Report and Literature Review
Authors: Ahamed Riyaaz Abdul Azeez , Perera Vindya , Sivakumaran Sabaratnam , de Silva Nelun
Published: February 2018

Emergence of cephalosporin-resistant strains of Salmonella enterica serovar Typhi is a cause of concern in the management of enteric fever. Cephalosporin resistance in Salmonella species is mainly due to the production of extended-spectrum β-lactamases (ESBLs). The majority of ESBLs in Salmonella enterica serovar Typhi are derivatives of the TEM, SHV, and CTX-M β-lactamase families. Of these, CTX-M appears to be predominant. This paper discusses the detection and molecular characterization of an ESBL-producing Salmonella enterica serovar Typhi strain isolated from a patient who was admitted to a private hospital in Sri Lanka. The three main types of β-lactamases such as TEM, SHV, and CTX-M were identified in this isolate. This case report from Sri Lanka contributes to the knowledge of the increasingly reported cases of typhoid fever due to Salmonella enterica serovar Typhi resistant to β-lactamase by ESBL production.
Minimizing Harmonic Distortion Impact at Distribution System with Considering Large‐Scale EV Load Behaviour Using Modified Lightning Search Algorithm and Pareto‐Fuzzy Approach
Authors: Syed Nasir S. N. , Jamian J. J. , Mustafa M. W.
Published: February 2018

This research is focusing on optimal placement and sizing of multiple variable passive filter (VPF) to mitigate harmonic distortion due to charging station (CS) at 449 bus distribution network. There are 132 units of CS which are scheduled based on user behaviour within 24 hours, with the interval of 15 minutes. By considering the varying of CS patterns and harmonic impact, Modified Lightning Search Algorithm (MLSA) is used to find 22 units of VPF coordination, so that less harmonics will be injected from 415 V bus to the medium voltage network and power loss is also reduced. Power system harmonic flow, VPF, CS, battery, and the analysis will be modelled in MATLAB/m‐file platform. High Performance Computing (HPC) is used to make simulation faster. Pareto‐Fuzzy technique is used to obtain sizing of VPF from all nondominated solutions. From the result, the optimal placements and sizes of VPF are able to reduce the maximum THD for voltage and current and also the total apparent losses up to 39.14%, 52.5%, and 2.96%, respectively. Therefore, it can be concluded that the MLSA is suitable method to mitigate harmonic and it is beneficial in minimizing the impact of aggressive CS installation at distribution network.
Numerical Modeling of Wave-Current Flow around Cylinders Using an Enhanced Equilibrium Bhatnagar-Gross-Krook Scheme
Authors: Xing Liming , Liu Haifei , Ding Yu , Huang Wei
Published: February 2018

Flow around cylinders is a classic issue of fluid mechanics and it has great significance in engineering fields. In this study, a two-dimensional hydrodynamic lattice Boltzmann numerical model is proposed, coupling wave radiation stress, bed shear stress, and wind shear stress, which is able to simulate wave propagation of flow around cylinders. It is based on shallow water equations and a weight factor is applied for the force term. An enhanced equilibrium Bhatnagar-Gross-Krook (BGK) scheme is developed to treat the wave radiation stress term in collision step. This model is tested and verified by two cases: the first case is the flow around a single circular cylinder, where the flow is driven by current, wave, or both wave and current, respectively, and the second case is the solitary waves moving around cylinders. The results illustrate the correctness of this model, which could be used to analyze the detailed flow pattern around a cylinder.
Abstract ES1-2: Guidelines for postmastectomy radiotherapy
Authors: Recht A
Published: February 2018

A joint panel of the American Society of Clinical Oncology (ASCO), American Society for Radiation Oncology (ASTRO), and Society of Surgical Oncology (SSO) convened in 2015 to develop an update of the prior ASCO guideline (J Clin Oncol 2001;19:1539-1569) concerning the use of postmastectomy radiation therapy (PMRT). This effort focused on common scenarios where there have been substantial controversy. Their conclusions and supporting evidence have been published (J Clin Oncol 2016;34:4431-4442).

The Panel unanimously agreed that PMRT reduces the risks of local-regional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with 1-3 positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. The Panel however could not find sufficient evidence to recommend a specific formula or method of how to combine clinical, pathologic, and biologic data to calculate the risk of LRF. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT or not requires a great deal of clinical judgement. The Panel agreed clinicians making such recommendations for an individual patient should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase the risks of complications from PMRT.

When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the Panel recommended that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know that additional axillary nodes are involved.

Patients with axillary nodal involvement following neoadjuvant systemic therapy should receive PMRT. The role of PMRT in other patients with clinical Stage I or II breast cancer is uncertain.

Finally, the Panel recommended that radiation therapy generally be given to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast when PMRT is used. However, there may be subgroups that will have limited, if any, benefits from treating both these nodal areas compared to treating only one of them or, perhaps, treating only the chest wall or reconstructed breast. There is insufficient evidence at this time to define such subgroups in detail.

This lecture will address selected elements of the data leading to the Panel's decisions.

Citation Format: Recht A. Guidelines for postmastectomy radiotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES1-2.
Abstract ES2-3: Managing increased breast cancer risk based on high and moderate penetrance gene mutations
Authors: Garber JE
Published: February 2018

Genetic testing in the modern era increasingly examines multiple genes using next generation technologies. Most assays include the high penetrance genes, which confer lifetime breast cancer risk greater than 5-fold, include BRCA1/2, TP53, CDH1 and PALB2. Moderate penetrance genes are associated with lifetime breast cancer risk in the range of 2-3 fold, and include ATM, NF1, CHEK2 (mutation-specific) and NBN, with BARD1 and others potentially joining the group. Substantial data has emerged from studies of women with BRCA1/2 mutations, evaluating the performance of screening technologies, such as mammogram, breast MRI and ultrasound, and the efficacy of risk-reducing breast and ovarian/fallopian tube surgical procedures. Guidelines exist in the NCCN (US) and ESMO guidelines in Europe, among others, trying to provide recommendations for the age at which to initiate screening or undergo risk-reducing salpingo-oophorectomies, for example. Data are increasing on the moderate penetrance genes but there is still much reliance on extrapolation from the high-penetrance genes, which should be done thoughtfully. One approach is to estimate the age at which lifetime breast cancer risk equals the risk from a high penetrance gene when screening is to begin and initiate imaging surveillance at that time. For example, initiation of annual breast imaging would be at age 40 for ATM (RR 2.8) instead of age 25 as is done for BRCA1/2 or age 20 as for TP53. However, there are no data that this is the correct age at which to initiate screening, so this practical suggestion must meet criteria for reasonableness as well as effectiveness. Other source of data may include more precise gene-specific risk estimates from focused genetic epidemiology studies, and ongoing data from studies of prospectively identified mutation carriers. Further understanding of the mechanisms of carcinogenicity for mutation carriers may also help to provide insights that can guide therapeutic and preventive approaches. For example, the work on RANK ligand by Lindeman et al has led to the development of a definitive breast cancer prevention trial examining the RANK-Ligand inhibitor Denosumab in BRCA1 mutation carriers, entitled BRCA-P, being led by C. Singer of the ABCSG and Dr. Lindeman, and to be conducted in sites around the world. Other approaches are in development and will be discussed.

Citation Format: Garber JE. Managing increased breast cancer risk based on high and moderate penetrance gene mutations [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES2-3.
Abstract ES3-3: Progress, paradigms, and pathways of long non-coding RNAs in cancer
Authors: Yang L
Published: February 2018

Despite recent advances in cancer research, many cancer types continue to be deficient of FDA-approved targeted therapies and also have poor prognoses. One of the fundamental challenges in developing targeted therapies against cancer lies in the absence of characterized molecular mechanisms that underlie tumor initiation and progression. These setbacks demand improved identification of biomarkers for human cancer, among which long non-coding RNAs (lncRNAs) show promise. It has become increasingly apparent that lncRNAs are aberrantly expressed in a broad spectrum of cancers and that they play key roles in promoting and maintaining cancer characteristics, demonstrating their clinical potential as biomarkers and therapeutic targets. In this review, we focus on the recent discoveries of lncRNAs in cancer signaling pathways as key signal transduction mediators. We review the functional roles of lncRNAs as protein, RNA and lipid binding partners in regulating cellular responses to extracellular signals and discuss their clinical potential as diagnostic indicators, stratification markers, and therapeutic targets of combinatorial treatments. Specifically, the following topics will be discussed: 1) Somatic mutations or disease-associated SNPs of lncRNAs implicate lncRNAs as cancer risk genes; 2) Through RNA-protein, RNA-RNA, RNA-lipid interactions, lncRNAs modulate cancer signaling pathways and consequences; 3) Dysregulation of lncRNAs lead to hyper- or hypo-activation of cellular pathways, leading to resistance to current targeted therapies; 4) Targeting lncRNA alone or a co-targeting strategy may help overcome the targeted therapy resistance.

Citation Format: Yang L. Progress, paradigms, and pathways of long non-coding RNAs in cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES3-3.
Abstract ES4-1: Her2 testing - 2017 guidelines for HER2 testing
Authors: Jenkins RB
Published: February 2018

Currently the use of anti-HER2 directed therapy (HDT) is predicated on the identification of HER2-postive breast cancers. Immunohistochemistry (IHC) and in situ hybridization (ISH) are the most common (and FDA-approved methods) for detecting HER2-positive breast cancers. While IHC and ISH are generally robust testing modalities, both can be subject to various pre-analytic, analytic and post-analytic issues/problems. In response to these issues/problems, ASCO and CAP formed a joint HER2 Guideline Committee. The initial guidelines of this committee were released in 2007 and a first revision of the guidelines was released in 2013. Since 2013, additional issues with HER2 testing have arisen and the ASCO/CAP Committee will be releasing a second revision to the guidelines in late 2017 or early 2018. This educational presentation will discuss HER2 testing – with a focus on fluorescent in situ hybridization (FISH). It will outline the 2013 ASCO/CAP guidelines and describe some of the issues that have arisen with these guidelines. The presentation will conclude with a discussion of the pending 2017/2018 ASCO/CAP guidelines for HER2 testing.

Citation Format: Jenkins RB. Her2 testing - 2017 guidelines for HER2 testing [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES4-1.
Abstract ES4-2: Adjuvant therapy for HER2-positive breast cancers: is less more?
Authors: O'Regan RM
Published: February 2018

The use of trastuzumab-based chemotherapy has dramatically improved outcome for patients with early stage HER2-positive breast cancer. Given the excellent outcomes seen to date and the toxicities associated with therapy, it is critical to establish whether additional therapies can further improve outcome, and conversely if there are patients who would have a favorable outcome with less therapy.

The addition of pertuzumab to trastuzumab-based chemotherapy results in improved survival for patients with metastatic HER2-positive breast cancer and higher response rates in the pre-operative setting. Although results of the AFFINITY trial demonstrated improved outcome for adding pertuzumab to trastuzumab-based chemotherapy, the benefit was largely restricted to patients with node-positive breast cancer. Additionally, it is unclear if patients treated pre-operatively require the continued addition of pertuzumab to trastuzumab. Neratinib, a pan-HER tyrosine kinase inhibitor, reduces recurrence rate when used following adjuvant trastuzumab, but the benefit appears restricted to hormone receptor-positive breast cancers and diarrhea is a significant issue with this agent. In contrast, de-escalating treatment for patients with stage 1 HER2-positive breast cancer with the use of paclitaxel and trastuzumab is associated with extremely favorable outcomes.

To date, the treatment of HER2-positive early stage breast cancer has not taken hormone receptor status into account when selecting HER2-directed therapies. Breast cancers that express both hormone receptors and HER2 are heterogeneous and a significant proportion have a luminal A phenotype, suggesting the possibility that combined estrogen receptor and HER2 inhibition may be especially important, given the crosstalk between these pathways. Further evaluation of non-chemotherapeutic approaches in triple positive breast cancers is justified.

Citation Format: O'Regan RM. Adjuvant therapy for HER2-positive breast cancers: is less more? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES4-2.
Abstract ES4-3: Can we improve treatment tailoring in advanced HER2+ breast cancer?
Authors: Piccart MJ
Published: February 2018

In the 1980s the importance of HER2 signalling to the aberrant behaviour of certain breast cancer cells was recognized for the first time. The intervening 3 decades have seen an immense international translational and clinical research effort that at first identified a hitherto unknown subtype of breast cancer – HER2-positive breast cancer - and then went on to entirely transform the natural history of this aggressive disease. For women with metastatic HER2-positive breast cancer, this has meant in practical terms a doubling of median overall survival and 5-year survival rate. First with the advent of trastuzumab, followed closely by lapatinib, pertuzumab and T-DM1, the lives of thousands of women have been made both longer and better. Nevertheless, metastatic HER2-positive breast cancer remains an incurable disease and new therapeutic options are needed. Additionally, the rapid changes in treatment standards 5 years ago have left unanswered numerous questions, including about the “real-life” benefit of pertuzumab and T-DM1 since both the CLEOPATRA and EMILIA trials were conducted on populations that no longer exist in practice. Furthermore, despite significant research efforts with translational research and new imaging techniques, in both the advanced and early settings, no predictive biomarkers has been clinically validated to help decision making for this patient population and therefore a more refined approach to treatment tailoring remains beyond our reach. Finally, better understanding of resistance to currently existing anti-HER2 agents and of the role played by the microenvironment (e.g. immune system) and of interconnected signalling pathways (e.g. PI3K-mTOR-AKT) is at the core of clinical trials exploring new drugs and new regimens, including the combination of anti-HER2 agents and anti-PD-1/PDL-1, PI3K inhibitors and CDK 4/6 inhibitors, as well as new host of pan-HER inhibitors, drug antibody conjugates and bi-specific antibodies which may in coming years further push the boundaries of what we can do for our patients.

Citation Format: Piccart MJ. Can we improve treatment tailoring in advanced HER2+ breast cancer? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES4-3.