bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus
Authors: Riggs Jeffrey M , Hanna Richard N , Rajan Bhargavi , Zerrouki Kamelia , Karnell Jodi L , Sagar Divya , Vainshtein Inna , Farmer Erika , Rosenthal Kimberly , Morehouse Chris , de los Reyes Melissa , Schifferli Kevin , Liang Meina , Sanjuan Miguel A , Sims Gary P , Kolbeck Roland
Published: April 2018

Objective

We investigated the mechanistic and pharmacological properties of anifrolumab, a fully human, effector-null, anti-type I interferon (IFN) alpha receptor 1 (IFNAR1) monoclonal antibody in development for SLE.

Methods

IFNAR1 surface expression and internalisation on human monocytes before and after exposure to anifrolumab were assessed using confocal microscopy and flow cytometry. The effects of anifrolumab on type I IFN pathway activation were assessed using signal transducer and activator of transcription 1 (STAT1) phosphorylation, IFN-stimulated response element–luciferase reporter cell assays and type I IFN gene signature induction. The ability of anifrolumab to inhibit plasmacytoid dendritic cell (pDC) function and plasma cell differentiation was assessed by flow cytometry and ELISA. Effector-null properties of anifrolumab were assessed in antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) assays with B cells.

Results

Anifrolumab reduced cell surface IFNAR1 by eliciting IFNAR1 internalisation. Anifrolumab blocked type I IFN-dependent STAT1 phosphorylation and IFN-dependent signalling induced by recombinant and pDC-derived type I IFNs and serum of patients with SLE . Anifrolumab suppressed type I IFN production by blocking the type I IFN autoamplification loop and inhibited proinflammatory cytokine induction and the upregulation of costimulatory molecules on stimulated pDCs. Blockade of IFNAR1 suppressed plasma cell differentiation in pDC/B cell co-cultures. Anifrolumab did not exhibit CDC or ADCC activity.

Conclusions

Anifrolumab potently inhibits type I IFN-dependent signalling, including the type I IFN autoamplification loop, and is a promising therapeutic for patients with SLE and other diseases that exhibit chronic dysfunctional type I IFN signalling.
Predicting risk of unplanned hospital readmission in survivors of critical illness: a population-level cohort study
Authors: Lone Nazir I , Lee Robert , Salisbury Lisa , Donaghy Eddie , Ramsay Pamela , Rattray Janice , Walsh Timothy S
Published: April 2018

Background

Intensive care unit (ICU) survivors experience high levels of morbidity after hospital discharge and are at high risk of unplanned hospital readmission. Identifying those at highest risk before hospital discharge may allow targeting of novel risk reduction strategies. We aimed to identify risk factors for unplanned 90-day readmission, develop a risk prediction model and assess its performance to screen for ICU survivors at highest readmission risk.

Methods

Population cohort study linking registry data for patients discharged from general ICUs in Scotland (2005–2013). Independent risk factors for 90-day readmission and discriminant ability (c-index) of groups of variables were identified using multivariable logistic regression. Derivation and validation risk prediction models were constructed using a time-based split.

Results

Of 55 975 ICU survivors, 24.1% (95%CI 23.7% to 24.4%) had unplanned 90-day readmission. Pre-existing health factors were fair discriminators of readmission (c-index 0.63, 95% CI 0.63 to 0.64) but better than acute illness factors (0.60) or demographics (0.54). In a subgroup of those with no comorbidity, acute illness factors (0.62) were better discriminators than pre-existing health factors (0.56). Overall model performance and calibration in the validation cohort was fair (0.65, 95% CI 0.64 to 0.66) but did not perform sufficiently well as a screening tool, demonstrating high false-positive/false-negative rates at clinically relevant thresholds.

Conclusions

Unplanned 90-day hospital readmission is common. Pre-existing illness indices are better predictors of readmission than acute illness factors. Identifying additional patient-centred drivers of readmission may improve risk prediction models. Improved understanding of risk factors that are amenable to intervention could improve the clinical and cost-effectiveness of post-ICU care and rehabilitation.
Stratification by interferon-γ release assay level predicts risk of incident TB
Authors: Winje Brita Askeland , White Richard , Syre Heidi , Skutlaberg Dag Harald , Oftung Fredrik , Mengshoel Anne Torunn , Blix Hege Salvesen , Brantsæter Arne Broch , Holter Ellen Kristine , Handal Nina , Simonsen Gunnar Skov , Afset Jan Egil , Bakken Kran Anne Marte
Published: April 2018

Introduction

Targeted testing and treatment of latent TB infection (LTBI) are priorities on the global health agenda, but LTBI management remains challenging. We aimed to evaluate the prognostic value of the QuantiFERON TB-Gold (QFT) test for incident TB, focusing on the interferon (IFN)-γ level, when applied in routine practice in a low TB incidence setting.

Methods

In this large population-based prospective cohort, we linked QFT results in Norway (1 January 2009–30 June 2014) with national registry data (Norwegian Surveillance System for Infectious Diseases, Norwegian Prescription Database, Norwegian Patient Registry and Statistics Norway) to assess the prognostic value of QFT for incident TB. Participants were followed until 30 June 2016. We used restricted cubic splines to model non-linear relationships between IFN-γ levels and TB, and applied these findings to a competing risk model.

Results

The prospective analyses included 50 389 QFT results from 44 875 individuals, of whom 257 developed TB. Overall, 22% (n=9878) of QFT results were positive. TB risk increased with the IFN-γ level until a plateau level, above which further increase was not associated with additional prognostic information. The HRs for TB were 8.8 (95% CI 4.7 to 16.5), 19.2 (95% CI 11.6 to 31.6) and 31.3 (95% CI 19.8 to 49.5) times higher with IFN-γ levels of 0.35 to <1.00, 1.00 to <4.00 and >4.00 IU/mL, respectively, compared with negative tests (<0.35 IU/mL).

Conclusions

Consistently, QFT demonstrates increased risk of incident TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI.
Administration of mesenchymal stem cells during ECMO results in a rapid decline in oxygenator performance
Authors: Millar Jonathan Edward , von Bahr Viktor , Malfertheiner Maximillian V , Ki Katrina K , Redd Meredith A , Bartnikowski Nicole , Suen Jacky Y , McAuley Danny Francis , Fraser John F
Published: April 2018

Mesenchymal stem cells (MSCs) have attracted attention as a potential therapy for Acute Respiratory Distress Syndrome (ARDS). At the same time, the use of extracorporeal membrane oxygenation (ECMO) has increased among patients with severe ARDS. To date, early clinical trials of MSCs in ARDS have excluded patients supported by ECMO. Here we provide evidence from an ex-vivo model of ECMO to suggest that the intravascular administration of MSCs during ECMO may adversely impact the function of a membrane oxygenator. The addition of clinical grade MSCs resulted in a reduction of flow through the circuit in comparison to controls (0.6 ±0.35 L min-1vs 4.12 ± 0.03 L min-1, at 240 minutes) and an increase in the transoygenator pressure gradient (101±9 mmHg vs 21±4 mmHg, at 240 minutes). Subsequent immunohistochemistry analysis demonstrated quantities of MSCs highly adherent to membrane oxygenator fibres. This study highlights the potential harm associated with MSC therapy during ECMO and suggests further areas of research required to advance the translation of cell therapy in this population.
CD24 and CD49f expressions of E14.5 mouse mammary anlagen cells define putative distribution of earlier embryonic mammary stem cell activities
Authors: Song Jiazhe , Ding Fangrong , Li Song , Li Wenzhe , Li Ning , Xue Kai
Published: April 2018

Stem cell biology offers promise for understanding the origins of the mammary gland. However, the distribution of mammary stem cell (MaSC) activities at earlier embryonic stages has not been fully identified. The markers for sorting adult MaSC, CD24, CD29, and CD49f have been applied to analyze fetal MaSCs. Here we explored mammary anlagen MaSCs by investigating the expression of CD24 and CD49f. According to the comparative analysis between adult mammary gland and fetal mammary anlagen, we found that fetal mouse mammary anlagen may possess a high percentage of potential MaSCs. Flow cytometry analysis revealed 2 distinct mammary anlagen populations: Lin–CD24medand Lin–CD24high. Sphere-forming and mammary repopulating assays confirmed that the stem cell activity of E14.5 mouse mammary anlagen was restricted to the Lin–CD24medcell population. Furthermore, CD24medmammary anlagen cells were separated into Lin–CD24medCD49f+and Lin–CD24medCD49f–populations and identified, respectively. The results proved that the mammary anlagen Lin–CD24medCD49f+cell population possesses more stem cell activities than the Lin–CD24medCD49f–cell population. However, a limited numbers of stem cells and large numbers of stromal cells were identified in mammary anlagen in the Lin–CD24medcell population.
Incorporation of optimal environmental signals in the prediction of fish recruitment using random forest algorithms
Authors: Smoliński Szymon
Published: April 2018

The drivers of recruitment of selected Baltic sprat (Sprattus sprattus) and herring (Clupea harengus) stocks were investigated. Data on the interaction dynamics among fish species, the biological characteristics of the stocks, the biomass of the main predators, and the hydroclimatic environmental factors (Baltic Sea Index and sea surface temperature) were used in the analysis. The combination of random forest (Boruta algorithm) and “sliding window” approaches was tested on the simulated data and then used for the selection of relevant predictors and the optimal time window for real environmental variables. Sea surface temperature had a significant positive effect on the recruitment processes. Moreover, contrasting effects were observed in the mean Baltic Sea Index from two different time windows. The same environmental variable generated contrasting short-term and long-term effects on fish recruitment. This paper highlights the potential benefits of random forest and data mining applications for the incorporation of environmental factors in the assessment of stocks. The proposed analytical approach may be valuable for the investigations of complex environmental impacts in a broad range of ecological studies.
Determination of antimicrobial resistance to extended-spectrum cephalosporin, quinolones, and vancomycin in selected human enteric pathogens from Prince Edward Island, Canada
Authors: Awosile Babafela , German Gregory , Rodriguez-Lecompte Juan Carlos , Saab Matthew E. , Heider Luke C. , McClure J. Trenton
Published: April 2018

The aim of this study was to determine the frequency of fecal carriage of vancomycin-resistant Enterococcus spp. and Escherichia coli with reduced susceptibilities to extended-spectrum cephalosporins (ESCs) and quinolones in humans on Prince Edward Island, Canada. Convenience fecal samples from individuals on Prince Edward Island were screened phenotypically using selective culture and genotypically using multiplex polymerase chain reactions to detect E. coli and Enterococcus spp. resistant to critically important antimicrobials. Twenty-six (5.3%) of 489 individuals had E. coli with reduced susceptibility to ESCs. Twenty-five (96.2%) of the 26 isolates harbored blaTEM, 18 (69.2%) harbored blaCMY-2, 16 (61.5%) harbored blaCTX-M groups, 2 (7.7%) harbored blaSHV genes. None of the ESC-resistant E. coli was positive for carbapenem resistance. Twenty-one (8.3%) of 253 individuals had E. coli isolates with reduced quinolone susceptibility. All 21 isolates were positive for at least 1 qnr gene, with 3 (14.3%) isolates positive for qnrB, 5 (23.8%) positive for qnrS, and 13 (61.9%) positive for both qnrB and qnrS genes. All the enterococci isolates were vancomycin-susceptible. Higher susceptibility to the critically important antimicrobials was found in this study. This study can serve as a baseline for future antimicrobial resistance surveillance within this region.
TAX STRUCTURE AND ECONOMIC GROWTH: DO DIFFERENCES IN INCOME LEVEL AND GOVERNMENT EFFECTIVENESS MATTER?
Authors: YANIKKAYA HALIT , TURAN TANER
Published: April 2018

We examine the effects of both overall tax rate and changes in tax structure on growth by using data for more than 100 high, middle, and low income countries by employing the GMM estimation methods. In general, our results do not support the argument that overall tax rates or changes in tax structure have a significant effect on growth. However, we find that a shift from income to consumption and property taxes leads to a positive and significant effect on growth rate while a shift from consumption and property taxes to income taxes has a positive effect for low-income countries.
QCD parameter correlations from heavy quarkonia
Authors: Narison Stephan
Published: April 2018

Correlations between the QCD coupling [Formula: see text], the gluon condensate [Formula: see text] and the [Formula: see text], [Formula: see text]-quark running masses [Formula: see text] in the [Formula: see text]-scheme are explicitly studied (for the first time) from the (axial-)vector and (pseudo)scalar charmonium and bottomium ratios of Laplace sum rules (LSR) evaluated at the [Formula: see text]-subtraction stability point where perturbative (PT) @N2LO, N3LO and [Formula: see text] @NLO corrections are included. Our results clarify the (apparent) discrepancies between different estimates of [Formula: see text] from [Formula: see text] sum rule and also show the sensitivity of the sum rules on the choice of the [Formula: see text]-subtraction scale which does not permit a high-precision estimate of [Formula: see text]. We obtain from the (axial-)vector [respectively (pseudo)scalar] channels: [Formula: see text] [respectively [Formula: see text] GeV4, [Formula: see text] [respectively 1266(16)] MeV and [Formula: see text] MeV. Combined with our recent determinations from vector channel, one obtains the average: [Formula: see text] MeV and [Formula: see text] MeV. Adding the two above values of the gluon condensate to different previous estimates in Table 1, one obtains the 2018 sum rule average: [Formula: see text] GeV4. The mass-splittings [Formula: see text] give @N2LO: [Formula: see text] in good agreement with the world average.
Schrödinger field theory in curved spacetime: In-in formalism and three-point function for the inflationary background
Authors: Rostami Abasalt , Firouzjaee Javad T.
Published: April 2018

We review the Schrödinger picture of field theory in curved spacetime and using this formalism, the power spectrum of massive noninteracting, minimally coupled scalars in a fixed de Sitter background is obtained. To calculate the [Formula: see text]-point function in Schrödinger field theory, the in-in formalism is extended in the Friedmann–Lemaître–Robertson–Walker (FLRW) universe. We compute the three-point function for primordial scalar field fluctuation in the single field inflation by this in-in formalism. The results are the same as the three-point function in the Heisenberg picture.
Effects of ultra-light dark matter on the gravitational quantum well
Authors: Castorina Paolo , Iorio Alfredo , Malinsky Michal
Published: April 2018

We study the influence of a periodic perturbation of the effective masses of fermions, due to the assumed semiclassical ultra-light dark matter (ULDM) background, on the motion of neutrons in a gravitational quantum well (GQW). Our focus is on the transition probability between the lowest two energy states, with the Rabi frequency in the kHz region corresponding to the series of “sweet spot” DM masses in the [Formula: see text][Formula: see text]eV ballpark. The relevant probability is written in terms of the specific mass and of the effective coupling to the ordinary matter. These parameters can be constrained by the nonobservation of any significant deviations of the measured transition probabilities from the DM-free picture.
A Note on the Nature Diagnosability of Alternating Group Graphs Under the PMC Model and MM* Model
Authors: WANG SHIYING , ZHAO LINGQI
Published: April 2018

Many multiprocessor systems have interconnection networks as underlying topologies and an interconnection network is usually represented by a graph where nodes represent processors and links represent communication links between processors. No faulty set can contain all the neighbors of any fault-free node in the system, which is called the nature diagnosability of the system. Diagnosability of a multiprocessor system is one important study topic. As a favorable topology structure of interconnection networks, the n-dimensional alternating group graph AGn has many good properties. In this paper, we prove the following. (1) The nature diagnosability of AGn is 4n − 10 for n − 5 under the PMC model and MM* model. (2) The nature diagnosability of the 4-dimensional alternating group graph AG4 under the PMC model is 5. (3) The nature diagnosability of AG4 under the MM* model is 4.
The intramolecular hydrogen bond as a unit of molecular electronics: Molecular switching controlled by overcrowded intramolecular three-centered hydrogen bond
Authors: Afonin Andrei V. , Vashchenko Alexander V.
Published: April 2018

The equilibrium geometry of the 2,5-bis-[2-(pyridin-2-yl)-vinyl]-1[Formula: see text]-pyrrole calculated at the MP2/6-311[Formula: see text]G([Formula: see text],[Formula: see text]) level of theory evidences the breaking of one of the components in the three-centered intramolecular hydrogen bond due to the steric strain. For this reason, the three-centered intramolecular hydrogen bonding turns out to be asymmetric interaction involving the major and minor components. However, the reversible switching between these components under an external impact is also possible. Two different stable states with unequal geometric and electronic structure are observed in the derivatives of the 2,5-bis-[2-(pyridin-2-yl)-vinyl]-1[Formula: see text]-pyrrole. These molecules represent novel molecular switches operating due to the pendulum-like transition between the nonequivalent two-centered components of the overcrowded three-centered intramolecular hydrogen bond. Implantation of hydrogen bond as a unit of the molecular scale device enhances potential of molecular electronics and could serve as a step towards the construction of artificial biological ensembles.
Super-Yang–Mills theory on a Lorentz breaking background
Authors: Ullah Farman , Ganai Prince A , Haritha Cheralan P. , Mawlong Barilang
Published: April 2018

In this paper, we will analyze a super-Yang–Mills Theory on a Lorentz breaking background. This theory will be analyzed using aether superspace formalism. We will also study the quantum symmetries of this theory. Thus, we will analyze this theory both in linear and nonlinear gauges. We will also study the effects of adding a bare mass term in the Curci–Ferrari gauge.
Computational analysis on actuator failures of flexible aircraft
Authors: Yang Shi-Bin , Wang Li-Bao , Xu Dan
Published: April 2018

A coupled model of aeroservoelasticity and hydraulic actuator used for failure simulation is presented. The mathematical model composites rigid-body modes, elastic modes, control surface modes, unsteady aerodynamic forces and failure models (jam, loss of control (LOC), oscillatory failure, and hydraulic fluid leakage). A clear framework of coupling method of airplane aeroelastic equation and control surface dynamic equation is provided to study the impacts of surface failures on rigid-elastic motion of airplane. The coupled model is shown to be effective in evaluation of gust response in both discrete gust and continuous turbulence conditions compared with results obtained from the 3-order simplified actuator. Examples of gust load alleviation (GLA) system with LOC of ailerons are given. Results show that total loss of function of GLA system is caused by the LOC. With continuous turbulence excitation, the failure loads is several times larger than that without GLA system.
Online Sequencing of Non-Decomposable Macrotasks in Expert Crowdsourcing
Authors: Schmitz Heinz , Lykourentzou Ioanna
Published: April 2018

We introduce the problem of Task Assignment and Sequencing, which models online optimization in expert crowdsourcing settings that involve non-decomposable macrotasks. Non-decomposition is a property of certain types of complex problems, like the formulation of an R&D approach or the definition of a research methodology, which cannot be handled through the "divide-and-conquer" approach typically used in microtask crowdsourcing. In contrast to splitting the macrotask to multiple microtasks and allocating them to several workers in parallel, our model supports the sequential improvement of the macrotask one worker at a time, across distinct time slots of a given timeline, until a sufficient quality level is achieved. Our model assumes an online environment where expert workers are available only at specific time slots and worker/task arrivals are not known
a priori
. With respect to this setting, we propose TAS-ONLINE, an online algorithm that aims to complete as many tasks as possible within budget, required quality, and a given timeline, without any future input information regarding job release dates or worker availabilities. Experimental results comparing TAS-ONLINE to five benchmarks show that it achieves more completed jobs, lower flow times, and higher job quality. This work bears practical implications for providing performance and quality guarantees to expert crowdsourcing platforms that wish to integrate non-decomposable macrotasks into their offered services.
Quantifying Controversy on Social Media
Authors: Garimella Kiran , Morales Gianmarco De Francisci , Gionis Aristides , Mathioudakis Michael
Published: April 2018

Which topics spark the most heated debates on social media? Identifying those topics is not only interesting from a societal point of view but also allows the filtering and aggregation of social media content for disseminating news stories. In this article, we perform a systematic methodological study of controversy detection by using the content and the network structure of social media.

Unlike previous work, rather than studying controversy in a single hand-picked topic and using domain-specific knowledge, we take a general approach to study topics
in any domain
. Our approach to quantifying controversy is based on a graph-based three-stage pipeline, which involves (i) building a
conversation graph
about a topic, (ii) partitioning the conversation graph to identify potential sides of the controversy, and (iii) measuring the amount of controversy from characteristics of the graph.

We perform an extensive comparison of controversy measures, different graph-building approaches, and data sources. We use both controversial and non-controversial topics on Twitter, as well as other external datasets. We find that our new random-walk-based measure outperforms existing ones in capturing the intuitive notion of controversy and show that content features are vastly less helpful in this task.
HiNFS
Authors: Chen Youmin , Shu Jiwu , Ou Jiaxin , Lu Youyou
Published: April 2018

Persistent memory provides data persistence at main memory with emerging non-volatile main memories (NVMMs). Recent persistent memory file systems aggressively use
direct access
, which directly copy data between user buffer and the storage layer, to avoid the double-copy overheads through the OS page cache. However, we observe they all suffer from slow writes due to NVMMs’ asymmetric read-write performance and much slower performance than DRAM.

In this article, we propose HiNFS, a high-performance file system for non-volatile main memory, to combine both
buffering
and
direct access
for fine-grained file system operations. HiNFS uses an
NVMM-aware Write Buffer
to buffer the lazy-persistent file writes in DRAM, while performing direct access to NVMM for eager-persistent file writes. It directly reads file data from both DRAM and NVMM, by ensuring read consistency with a combination of the
DRAM Block Index
and
Cacheline Bitmap
to track the latest data between DRAM and NVMM. HiNFS also employs a
Buffer Benefit Model
to identify the eager-persistent file writes before issuing I/Os. Evaluations show that HiNFS significantly improves throughput by up to 184% and reduces execution time by up to 64%comparing with state-of-the-art persistent memory file systems PMFS and EXT4-DAX.
Advances in Multicompartment Mesoporous Silica Micro/Nanoparticles for Theranostic Applications
Authors: Liu Jian , Liu Tingting , Pan Jian , Liu Shaomin , Lu G.Q. (Max)
Published: April 2018

Mesoporous silica nanoparticles (MSNs) are promising functional nanomaterials for a variety of biomedical applications, such as bioimaging, drug/gene delivery, and cancer therapy. This is due to their low density, low toxicity, high biocompatibility, large specific surface areas, and excellent thermal and mechanical stability. The past decade has seen rapid advances in the development of MSNs with multiple compartments. These include hierarchical porous structures and core-shell, yolk-shell, and Janus structured particles for efficient diagnosis and therapeutic applications. We review advances in this area, covering the categories of multicompartment MSNs and their synthesis methods, with an emphasis on hierarchical structures and the incorporation of multiple functions. We classify multicompartment mesoporous silica micro/nanostructures, ranging from core-shell and yolk-shell structures to Janus and raspberry-like nanoparticles, and discuss their synthesis methods. We review applications of these multicompartment MSNs, including bioimaging, targeted drug/gene delivery, chemotherapy, phototherapy, and in vitro diagnostics. We also highlight the latest trends and new opportunities.
Social Norms and the Environment
Authors: Nyborg Karine
Published: April 2018

Social norms affect environmental quality. But what exactly is a social norm? Environmental economists studying the topic draw on diverse scholarly traditions and may not have the same phenomenon in mind when using the concept. For example, social norms may refer to common, but not necessarily socially approved, behaviors; to internalized ethical rules; or to one of several equilibria in a coordination game. I first discuss some of the definitions used in the environmental economics literature. Then, I outline a simple framework for analysis of voluntary contributions to public goods. Using this framework, I illustrate differences and similarities between altruism, moral norms, and social norms and discuss implications for environmental policies. In particular, when a social norm represents one of several stable equilibria, policy can potentially invoke abrupt and dramatic behavioral changes.
Novel Treatment of Disseminated Coccidioidomycosis in a Dog with Voriconazole
Authors: Raghu Chantel , Reagh Christopher
Published: April 2018

A dog with disseminated coccidioidomycosis involving the vertebral, cutaneous, and pulmonary systems was treated successfully with voriconazole after failing traditional therapy with fluconazole and terbinafine. This report is the first to describe the successful management of refractory coccidioidomycosis with voriconazole in a dog.
Robust Optimal Design of Quantum Electronic Devices
Authors: Morales Ociel , Periago Francisco , Vallejo José A.
Published: April 2018

We consider the optimal design of a sequence of quantum barriers, in order to manufacture an electronic device at the nanoscale such that the dependence of its transmission coefficient on the bias voltage is linear. The technique presented here is easily adaptable to other response characteristics. There are two distinguishing features of our approach. First, the transmission coefficient is determined using a semiclassical approximation, so we can explicitly compute the gradient of the objective function. Second, in contrast with earlier treatments, manufacturing uncertainties are incorporated in the model through random variables; the optimal design problem is formulated in a probabilistic setting and then solved using a stochastic collocation method. As a measure of robustness, a weighted sum of the expectation and the variance of a least-squares performance metric is considered. Several simulations illustrate the proposed technique, which shows an improvement in accuracy over 69% with respect to brute-force, Monte-Carlo-based methods.
Prevalence, Predictive Factors, and Characteristics of Osteoporosis in Hyperthyroid Patients
Authors: Ale Ayotunde O. , Ogbera Anthonia O. , Ebili Henry O. , Adeyemo Olusola L. , Afe Taiwo O.
Published: April 2018

Objective. The osteoporosis in thyroid disorder has the lowest report especially in sub-Saharan Africa. This study aims to determine the prevalence, predictive factors, and characteristics of osteoporosis in hyperthyroid patients. Method. Forty (40) hyperthyroid patients and healthy controls ages 21–50 years were recruited in this study. Questionnaires were administered to capture bio- and clinical data. Biochemical tests included blood, thyroid functions, intact parathyroid hormone, corrected calcium, and 25-hydroxyvitamin D tests. Bone mineral density (BMD) was also evaluated. Data were analyzed using the SPSS 21. A p value < 0.05 was regarded as significant. Results. Osteoporosis was observed in 18 (45%) of study subjects, 13 (72.2%) females and 5 (27.8%) males, respectively. The BMD of the hyperthyroid patients had a negative correlation with free triiodothyronine, FT3 (r=−0.49, p=0.005), FT4 (r=−0.33, p=0.009), corrected calcium (r=−0.31, p=0.039), alkaline phosphatase (r=−0.53, p<0.001), and osteocalcin (r=−0.61, p<0.001). Conversely, a positive association with thyroid-stimulating hormone (TSH) (r=0.54, p<0.001) was observed. Multiple regression showed osteocalcin (p<0.001) and TSH (p=0.015) as independent predictors of osteoporosis. Conclusion. Thyrotoxicosis is a risk factor for osteoporosis occurrence, and we recommend routine screening for this bone disease in persons over 20 years old with this disorder.
Modeling and Simulation for the Investigation of Radar Responses to Electronic Attacks in Electronic Warfare Environments
Authors: Park So Ryoung , Nam Ilku , Noh Sanguk
Published: April 2018

An electronic warfare (EW) simulator is presented to investigate and evaluate the tracking performance of radar system under the electronic attack situations. The EW simulator has the input section in which the characteristic parameters of radar threat, radar warning receiver, jammer, electromagnetic wave propagation, and simulation scenario can be set up. During the process of simulation, the simulator displays the situations of simulation such as the received signal and its spectrum, radar scope, and angle tracking scope and also calculates the transient and root-mean-squared tracking errors of the range and angle tracking system of radar. Using the proposed EW simulator, we analyze the effect of concealment according to the noise and signal powers under the noise jamming and also analyze the effect of deception by calculating errors between the desired value and the estimated one under the deceptive jamming. Furthermore, the proposed EW simulator can be used to figure out the feature of radar threats based on the information collected from the EW receiver and also used to carry out the electronic attacks efficiently in electronic warfare.
Prevalence of Helicobacter pylori cagA and iceA Genes and Their Association with Gastrointestinal Diseases
Authors: Abu-Taleb Ashwak M. F. , Abdelattef Randa S. , Abdel-Hady Amina A. , Omran Farida H. , El-korashi Lobna A. , Abdel-aziz El-hady Hoda , El-Gebaly Ahmed M.
Published: April 2018

H. pylori infection causes peptic ulcer, chronic gastritis, mucosa-associated lymphoid tissue lymphoma, and gastric carcinoma. It has several virulence factors such as cytotoxin-associated gene A(cagA) and the induced by contact with epithelium antigen (iceA). We aimed to explore the relationship between cagA and iceA of H. pylori and gastrointestinal diseases. One hundred and eighteen patients who attended Gastrointestinal Endoscopy Unit at Zagazig University Hospitals, Egypt, were included in this study. Two gastric biopsies were collected and evaluated by rapid urease test (RUT) and PCR. cagA and iceA genes were amplified by PCR. We found that 54 patients (45.76%) were positive by both RUT and PCR. cagA and iceA genes were present in 57.4% and 46.29% of the studied patients, respectively. cagA was the most prevalent gene in gastritis (33.3%) and peptic ulcer (68.7%). iceA1/iceA2 positive genes were the most prevalent in gastric cancer (75%). iceA1 gene was present in 38.7% of cagA positive cases, but iceA2 gene was present in 45.2% of cagA positive cases. iceA1/iceA2 positive genes were present in 29% of cagA positive cases. In conclusion, cagA and iceA genes could be used as markers for severe gastrointestinal diseases. iceA gene was strongly related to cagA gene.
Invasive Lobular Carcinoma of the Breast with Extracellular Mucin: Case Report of a New Variant of Lobular Carcinoma of the Breast
Authors: Boukhechba M. , Kadiri H. , El Khannoussi B.
Published: April 2018

Invasive carcinoma of no special type (NST) or ductal carcinoma is the largest group of invasive breast cancers. Invasive lobular carcinoma (ILC) is the second most common histological type; it comprises 5%–15% of all invasive breast cancers. Historically, lobular neoplasia and invasive lobular carcinoma may produce intracellular mucin that pushes the nucleus to one side, creating the characteristic signet ring cell morphology. The extracellular mucin secretion is essentially described in mucinous breast carcinoma. Mucinous differentiation can be seen in small areas of NST carcinoma, but recently a few cases of invasive lobular carcinoma with extracellular mucin are reported in the literature. It is important for pathologists to recognize this new entity because it mimics a NST carcinoma, as such a diagnosis may require a different approach in clinical management and surveillance. We report a new case of ILC with extracellular mucin and a review of the literature.
Three MYO15A Mutations Identified in One Chinese Family with Autosomal Recessive Nonsyndromic Hearing Loss
Authors: Zhang Fengguo , Xu Lei , Xiao Yun , Li Jianfeng , Bai Xiaohui , Wang Haibo
Published: April 2018

Hearing impairment is one of the most common sensory disease, of which more than 50% is attributed to a genetic etiology. The goal of this research is to explore the genetic cause of a Chinese deafness pedigree who was excluded of GJB2, SLC26A4, or MtDNA12SrRNA variants. Three variants, c.3971C>A (p.A1324D), c.4011insA (p.Q1337Qfs∗22), and c.9690+1G>A, in the MYO15A gene were identified by targeted capture sequencing and Sanger sequencing, and the first two of them were novel. These variants were cosegregated with the disease in this family and absent in 200 normal hearing persons. They were concluded to be pathogenic mutations by phylogenetic analysis and structure modeling. Thus, the combined use of SNPScan assay and targeted capture sequencing is a high-efficiency and cost-effective screening procedure for hereditary hearing loss. Genetic counseling would be important for this family, and our finding would be a great supplement to the mutation spectrum of MYO15A.
N-3 Polyunsaturated Fatty Acids Stimulate Bile Acid Detoxification in Human Cell Models
Authors: Cieślak Anna , Trottier Jocelyn , Verreault Mélanie , Milkiewicz Piotr , Vohl Marie-Claude , Barbier Olivier
Published: April 2018

Cholestasis is characterized by the accumulation of toxic bile acids (BAs) in liver cells. The present study aimed to evaluate the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs), such as docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, on BA homeostasis and toxicity in human cell models. The effects of EPA and/or DHA on the expression of genes involved in the maintenance of BA homeostasis were analyzed in human hepatoma (HepG2) and colon carcinoma (Caco-2) cells, as well as in primary culture of human intestinal (InEpC) and renal (RPTEC) cells. Extracellular BA species were quantified in culture media using LC-MS/MS. BA-induced toxicity was evaluated using caspase-3 and flow cytometry assays. Gene expression analyses of HepG2 cells reveal that n-3 PUFAs reduce the expression of genes involved in BA synthesis (CYP7A1, CYP27A1) and uptake (NTCP), while activating genes encoding metabolic enzymes (SULT2A1) and excretion transporters (MRP2, MRP3). N-3 PUFAs also generate a less toxic BA pool and prevent the BA-dependent activation of apoptosis in HepG2 cells. Conclusion. The present study reveals that n-3 PUFAs stimulate BA detoxification.
A Novel and Inexpensive Approach for Force Sensing Based on FSR Piezocapacitance Aimed at Hysteresis Error Reduction
Authors: Matute Arnaldo , Paredes-Madrid Leonel , Moreno Gelman , Cárdenas Fabián , Palacio Carlos A.
Published: April 2018

Force-sensing resistors (FSRs) are inexpensive alternatives to load cells. They are suitable for applications where noninvasive devices are needed to measure force, stress, or pressure. However, they have been proved to be hysteresis prone and offer nonrepeatable readings due to their highly voltage-dependent electrical resistance. A piezocapacitive effect has been found as an alternative phenomenon that is able to offer force-dependent readings of capacitance with less hysteresis error. Also, this capacitance is not dependent on voltage, which also improves repeatability in force measurements. Since measuring capacitance is more expensive than resistance, the least costly conditioning circuitry is desired. An inexpensive alternative using an LM555 that oscillates depending on capacitance is here presented. Hysteresis and repeatability errors have been reduced for a widespread-used force-sensing resistor brand.
Sex and Geographic Differences in the Prevalence of Reported Childhood Motor Disability and Their Trends in Taiwan
Authors: Tsai Cheng-Fang , Guo How-Ran , Tseng Yen-Cheng , Lai Der-Chung
Published: April 2018

Motor disability (MD) is not uncommon in children, but data at the national level are scarce. As the Taiwan government certifies and registers disabled residents for providing services on a routine basis, the registry provides a unique opportunity for studying MD. Using data from the registry, we calculated the prevalence of MD by age, sex, and geographic area and assessed the changes from 2004 to 2010. We excluded cases under 3 years old because the government discourages the certification at this age. We found that cases between 3 and 17 years old decreased from 8187 to 6022 per year from 2004 to 2010 and the prevalence generally decreased every year in all age groups. There were more boy cases than girl cases every year, and the prevalence rate ratios ranged from 1.26 to 1.39 (p<0.05 in all years), with a decreasing trend over time (p<0.01). Rural areas had higher prevalence in all the years, and the prevalence rate ratio decreased from 1.31 to 1.23 (p<0.05 in all years), with a decreasing trend over time (p<0.05). Further studies identifying the risk factors contributing to the decreases might help in the prevention of MD in the future.
The Use of Modified Templates in Early and Advanced Stage Nonseminomatous Germ Cell Tumor
Authors: Masterson Timothy A. , Cary Clint
Published: April 2018

The surgical management of both early and advanced stage germ cell tumors of the testis remains a complex process of surgical decision making to maximize oncologic control while minimizing morbidity. Over the past 5 decades, the evolution of the surgical template for retroperitoneal lymphadenectomy (RPLND) has resulted in important modifications to achieve these goals. In this review, we will characterize the historical motivating factors that led to the modified template, outline patient and clinical factors in selecting these approaches in both early and advanced stage disease, and briefly discuss future horizons for their implementation.
Differentiation Model Establishment and Differentiation-Related Protein Screening in Primary Cultured Human Sebocytes
Authors: Zhang Man-Feng , Cai Xiao-Lin , Jing Kai-Peng , Pi Xiao-Xue , Liao Pei-Yu , Li Shi-Jie , Wen-Li  , Cai Chuan-Chuan , Quan Juan-Hua , Fan Yi-Ming , Ge-Shi
Published: April 2018

Sebocyte differentiation is a continuous process, but its potential molecular mechanism remains unclear. We aimed to establish a novel sebocyte differentiation model using human primary sebocytes and to identify the expression profiles of differentiation-associated proteins. Primary human sebocytes were cultured on Sebomed medium supplemented with 2% serum for 7 days. Flow cytometry showed that S phase cells were decreased time-dependently, while G1 and subG1 (apoptosis) phase cells increased under serum starvation. Transmission electron microscopy and Oil Red O staining revealed a gradual increase of intracellular lipid accumulation. Expression of proliferation marker was diminished, while expression of differentiation, apoptosis, and lipogenic markers elevated gradually during 7-day culture. iTRAQ analysis identified 3582 expressed proteins in this differentiation model. Compared with day 0, number of differentially expressed proteins was 132, 54, 321, and 96 at days 1, 3, 5, and 7, respectively. Two overexpressed proteins (S100 calcium binding protein P and ferredoxin reductase) and 2 downexpressed proteins (adenosine deaminase and keratin 10) were further confirmed by Western blot and immunohistochemistry.
Rifampicin in Nontuberculous Mycobacterial Infections: Acute Kidney Injury with Hemoglobin Casts
Authors: Kora Rishi , Brodsky Sergey V. , Nadasdy Tibor , Agra Dean , Satoskar Anjali A.
Published: April 2018

Rifampicin is a key component of multidrug regimens not only for tuberculosis, but also nontuberculous mycobacterial infections (NTM) which are on the rise worldwide. Knowledge of the toxicity profile is important. Hepatotoxicity is a well-known side effect of Rifampicin necessitating regular liver function monitoring during therapy. Acute kidney injury (AKI) is a relatively rare complication, usually resulting from allergic interstitial nephritis (AIN). Rifampicin-induced intravascular hemolysis resulting in hemoglobinuria and AKI is even more uncommon, especially in Western countries with low prevalence of mycobacterial infections. Rifampicin-induced antibodies are implicated and this complication preferentially occurs during intermittent drug treatment protocols or when Rifampicin is restarted after a long drug-free interval. Awareness of this drug complication and its unique timing is important especially among emergency room physicians where patients with AKI may first present. It is equally important for nephrologists and pathologists. We describe one such case with detailed clinical course of the patient and interesting biopsy findings of ATN with intratubular hemoglobin casts.
Disruption of IFN-I Signaling Promotes HER2/Neu Tumor Progression and Breast Cancer Stem Cells
Authors: Castiello Luciano , Sestili Paola , Schiavoni Giovanna , Dattilo Rosanna , Monque Domenica M. , Ciaffoni Fiorella , Iezzi Manuela , Lamolinara Alessia , Sistigu Antonella , Moschella Federica , Pacca Anna Maria , Macchia Daniele , Ferrantini Maria , Zeuner Ann , Biffoni Mauro , Proietti Enrico , Belardelli Filippo , Aricò Eleonora
Published: April 2018

Type I interferon (IFN-I) is a class of antiviral immunomodulatory cytokines involved in many stages of tumor initiation and progression. IFN-I acts directly on tumor cells to inhibit cell growth and indirectly by activating immune cells to mount antitumor responses. To understand the role of endogenous IFN-I in spontaneous, oncogene-driven carcinogenesis, we characterized tumors arising in HER2/neu transgenic (neuT) mice carrying a nonfunctional mutation in the IFNI receptor (IFNAR1). Such mice are unresponsive to this family of cytokines. Compared with parental neu+/− mice (neuT mice), IFNAR1−/− neu+/− mice (IFNAR-neuT mice) showed earlier onset and increased tumor multiplicity with marked vascularization. IFNAR-neuT tumors exhibited deregulation of genes having adverse prognostic value in breast cancer patients, including the breast cancer stem cell (BCSC) marker aldehyde dehydrogenase-1A1 (ALDH1A1). An increased number of BCSCs were observed in IFNAR-neuT tumors, as assessed by ALDH1A1 enzymatic activity, clonogenic assay, and tumorigenic capacity. In vitro exposure of neuT+ mammospheres and cell lines to antibodies to IFN-I resulted in increased frequency of ALDH+ cells, suggesting that IFN-I controls stemness in tumor cells. Altogether, these results reveal a role of IFN-I in neuT-driven spontaneous carcinogenesis through intrinsic control of BCSCs. Cancer Immunol Res; 6(6); 658–70. ©2018 AACR.
Sarcoid-Like Granulomatosis of the Lung Related to Immune-Checkpoint Inhibitors: Distinct Clinical and Imaging Features of a Unique Immune-Related Adverse Event
Authors: Nishino Mizuki , Sholl Lynette M. , Awad Mark M. , Hatabu Hiroto , Armand Philippe , Hodi F. Stephen
Published: April 2018

With the rapidly expanding role of immune-checkpoint inhibitor therapy in advanced cancer treatment, an increasing number of new immune-related adverse events (irAEs) are being reported. The present report describes sarcoid-like granulomatosis of the lung as a distinct type of irAE with characteristic clinical, imaging, and histologic features. In patients treated with immune-checkpoint inhibitors, sarcoid-like granulomatosis of the lung presented with a focal area of consolidation in the lung, which was often nodular or round, in the absence of new or enlarging lymphadenopathy on imaging. Histologic examination demonstrated nonnecrotizing granulomas and an absence of malignant cells. The patients were free of new or worsening respiratory symptoms, despite the development of lung parenchymal consolidations. Holding the immune-checkpoint inhibitors led to the spontaneous resolution of the findings, without any specific treatment for the abnormality. Awareness of the manifestations of sarcoid-like granulomatosis of the lung as a distinct type of irAE will improve management of patients treated with immune-checkpoint inhibitors. Cancer Immunol Res; 6(6); 630–5. ©2018 AACR.
Secondary Caries in situ Models: A Systematic Review
Authors: Hollanders Audrey C.C. , Kuper Nicolien K. , Maske Tamires T. , Huysmans Marie-Charlotte D.N.J.M.
Published: April 2018

In situ caries research serves as a bridge between clinical research and laboratory studies. In this kind of research, volunteers wear a removable intraoral splint or prosthesis containing research samples. Many different in situ models exist to investigate secondary caries. This systematic review compared currently existing secondary caries models and their lesion progression per day values. Materials and Methods: Three databases (Medline, Embase, and Cochrane) were searched for relevant literature. Bias risk was assessed and model parameters and caries-related outcomes were extracted by 2 independent researchers. Where possible, caries-related outcomes were normalized by estimating lesion progression per day by dividing lesion depth extracted from microradiographic or microhardness data by the number of days the study lasted. Results: The literature search identified 335 articles. After eliminating duplicates and selection, 31 articles were included. The models differed greatly on factors such as sample location, presence of fluoride in the model, and analysis methods. Three main groups could be identified by sample placement; 68% of models placed samples palatally in the upper jaw, and the lower jaw model could be divided into the buccal (26%) and approximal (6%) areas. Average lesion progression in enamel next to composite was 4.3 ± 2.8 µm (range1.1–8.8 µm/day). Discussion: Studies conducted with palatal models showed caries progression rates 2–5 times higher than the estimated clinical progression rates. Lesion progression per day could be a useful tool for future comparison of models and establishing a standardized model.