bluuebunny/crossref_metadata_2025 huggingface dataset:
London ambulance source data on choking incidence for the calendar year 2016: an observational study
Authors: Pavitt Matthew J , Nevett Joanne , Swanton Laura L , Hind Matthew D , Polkey Michael I , Green Malcolm , Hopkinson Nicholas S
Published: December 2017

Introduction

Complete foreign body airway obstruction is a life-threatening emergency, but there are limited data on its epidemiology.

Methods

We conducted a retrospective analysis of data collected routinely from London Ambulance Service calls coded as being for choking was undertaken for the calendar year of 2016.

Results

There were 1916 choking episodes of significant severity to call for emergency assessment in London during 2016, 0.2% of total calls requiring an ambulance response, an average of 5.2 per day. The incidence increased at the extremes of age. Calls coded as choking occurred at times consistent with lunch and dinner and less frequently at breakfast. Peak incidence occurred at Sunday lunchtimes and on Wednesday evenings.

Conclusions

Choking is a substantial health problem for Londoners to seek emergency assistance. Choking is more frequent at the extremes of age with a higher incidence at lunch and dinner time. Greater public awareness of choking and its management could help to prevent avoidable deaths.
Geomagnetic field H, Z, and electromagnetic induction features of coronal mass ejections in association with geomagnetic storm at African longitudes
Authors: Falayi E.O. , Adepitan J.O. , Oyebanjo O.A.
Published: December 2017

The largest geomagnetic disturbance caused by a coronal mass ejection (CME) of solar cycle 24 recorded on both 17 March and 22 June 2015 with minimum disturbance storm time values of −223 and −195 nT, respectively, was investigated. This study examines the effect of CME on Earth’s geomagnetic field, which includes the time derivatives of horizontal (H) and vertical (Z) components of the geomagnetic field and the rate of induction ΔZ/ΔH at African longitudes (AAE, MBO, HBK, HER, and TAM). The results demonstrated enhancement of dH/dt and dZ/dt in the daytime over the equatorial zone (AAE and MBO) and mid-latitudes (TAM, HER, and HBK) on 17 March 2015. Nighttime enhancement was observed on 22 June 2015 over the equatorial zones and mid-latitudes. Wavelet spectrum approach is used to investigate ΔZ/ΔH variation observed at AAE, MBO, HBK, HER, and TAM. The CME may have influence on time derivatives of geomagnetic field H, Z, and electromagnetic induction at the African longitudes, which may be associated with perturbations in electric fields and currents in the equatorial and low-latitude magnetic field linked with the changes in magnetospheric convection.
Molecular analysis of anthocyanin-related genes in ornamental cabbage
Authors: Jin Si-Won , Rahim Md Abdur , Kim Hoy-Taek , Park Jong-In , Kang Jong-Goo , Nou Ill-Sup
Published: December 2017

Ornamental cabbage (Brassica oleracea var. acephala) is a winter-grown and important decorative plant of the family Brassicaceae, which displays an exceptional coloration in the central leaves of the rosette. Anthocyanins are the key determinant of the red, purple, and blue colors of vegetative and reproductive parts of many plant species including ornamental cabbage. Total anthocyanin content was measured spectrophotometrically, and the highest anthocyanin content was detected in the red followed by light-red and white ornamental cabbage lines. Anthocyanin biosynthesis is controlled by members of three different transcription factor (TF) families, such as MYB, basic helix-loop-helix (bHLH), and WD40 repeats (WDR), which function as a MBW complex. We identified three MYB, six bHLH, and one WDR TFs that regulate anthocyanin biosynthesis in ornamental cabbage. The expression of the regulatory and biosynthetic genes for anthocyanin synthesis was determined by qPCR. The tested structural genes of the anthocyanin pathway were shown to be up-regulated in the red followed by light-red ornamental cabbage lines; however, the expression levels of the late biosynthetic genes were barely detected in the white ornamental cabbage lines. Among the regulatory genes, BoPAP2 (MYB), BoTT8, BoEGL3.1, and BoMYC1.2 (bHLH), and BoTTG1 (WDR) were identified as candidates for the regulation of anthocyanin biosynthesis. This work could be useful for the breeding of novel colorful ornamental cabbage cultivars.
Gauge invariant actions for the noncommutative phase-space relativistic particle
Authors: Abreu Everton M. C. , Godinho Cresus F. L.
Published: December 2017

Our main interest here is to analyze the gauge invariance issue concerning the noncommutative relativistic particle. Since the analysis of the constraint set from Dirac’s point of view classifies it as a second-class system, it is not a gauge theory. Hence, the objective here is to obtain gauge invariant actions linked to the original one. However, we have two starting points, meaning that firstly we will begin directly from the original action and, using the Noether procedure, we have obtained a specific dual (gauge invariant) action. Following another path, we will act towards the constraints so that we have carried out the conversion of second to first-class constraints through the Batalin–Fradkin–Fradkina–Tyutin formalism, obtaining the second gauge invariant Lagrangian.
Canonical relativistic quantization of electromagnetic field in the presence of an anisotropic conductor magneto-dielectric medium
Authors: Amooshahi Majid
Published: December 2017

A canonical relativistic quantization of the electromagnetic field is introduced in the presence of an anisotropic conductor magneto-dielectric medium in a standard way in the Gupta–Bleuler framework. The medium is modeled by a continuum collection of the vector fields and a continuum collection of the antisymmetric tensor fields of the second rank in Minkowski space–time. The collection of vector fields describes the conductivity property of the medium and the collection of antisymmetric tensor fields describes the polarization and the magnetization properties of the medium. The conservation law of the total electric charges, induced in the anisotropic conductor magneto-dielectric medium, is deduced using the antisymmetry conditions imposed on the coupling tensors that couple the electromagnetic field to the medium. Two relativistic covariant constitutive relations for the anisotropic conductor magneto-dielectric medium are obtained. The constitutive relations relate the antisymmetric electric–magnetic polarization tensor field of the medium and the free electric current density four-vector, induced in the medium, to the strength tensor of the electromagnetic field, separately. It is shown that for a homogeneous anisotropic medium the susceptibility tensor of the medium satisfies the Kramers–Kronig relations. Also it is shown that for a homogeneous anisotropic medium the real and imaginary parts of the conductivity tensor of the medium satisfy the Kramers–Kronig relations and a relation other than the Kramers–Kronig relations.
A quantum framework for likelihood ratios
Authors: Bond Rachael L. , He Yang-Hui , Ormerod Thomas C.
Published: December 2017

The ability to calculate precise likelihood ratios is fundamental to science, from Quantum Information Theory through to Quantum State Estimation. However, there is no assumption-free statistical methodology to achieve this. For instance, in the absence of data relating to covariate overlap, the widely used Bayes’ theorem either defaults to the marginal probability driven “naive Bayes’ classifier”, or requires the use of compensatory expectation-maximization techniques. This paper takes an information-theoretic approach in developing a new statistical formula for the calculation of likelihood ratios based on the principles of quantum entanglement, and demonstrates that Bayes’ theorem is a special case of a more general quantum mechanical expression.
Cancer Cell Surface Negative Charges: A Bio-Physical Manifestation of the Warburg Effect
Authors: Shi Donglu
Published: December 2017

The early detection of circulating tumor cells (CTCs) in blood as part of medical diagnosis will give the doctors a head start in the provision and treatment of cancer, and therefore, with the advance in Nano technology, there is an increasing expectation of some form of early detection of circulating tumor cells at a highly sensitive level, without any biomarkers, for both early cancer diagnosis and monitoring disease progression after medical intervention. This technical note reports on the recent development in detection of highly sensitive detection of cancer cells without biomarkers. This novel concept is developed based on a hallmark cancer metabolic pattern: high glycolysis rate. Secretion of high level of lactate acid by cancer cells ultimately results in negative electrical charges on their surfaces, enabling strong binding and capturing by the positively-charged nanoprobes, and subsequent magnetic separation. When nanoprobes are incubated with cancer cells in suspension, binding takes place due to charge differences, and cancer cells are then magnetically separated. The separated cells are enumerated using a flow cytometry and identified by pathological and genome sequencing methods. Preliminary results using the approach have shown exceptionally high cancer cell capture rates, therefore potentially applicable in cancer cell detection in clinical settings.
Characterization of Surface Modification of 347 Stainless Steel upon Shot Peening
Authors: Li Kejian , Zheng Qiang , Li Chunhong , Shao Bin , Guo Donglin , Chen Dengming , Sun Jianchun , Dong Jiling , Cao Pengjun , Shin Keesam
Published: December 2017

Plastic deformations, such as those obtained by shot peening on specimen surface, are an efficient way to improve the mechanical behavior of metals. Generally, scanning electron microscopy (SEM) and electron backscattered diffraction (EBSD) are commonly used to observe the complex microstructural evolutions, such as grain refinement and phase transformation, induced by the surface treatment. In this work, the microstructure of 347 stainless steel, after ultrasonic shot peening (USP) treatments, was investigated. SEM, EBSD, transmission electron microscopy, and X-ray diffraction were used to observe the microstructural evolutions, such as grain refinement and phase transformation. Deformation depth after the USP treatment was about 200 μm. Grain size on the treated surface layer was about 100 nm, with two phases: austenite and α′-martensite. The percentages of the austenite and α′-martensite phases were 54% and 46%, respectively, which constitute an exact expression of the degree of plastic deformation on austenitic stainless steel.
Epithelial-Mesenchymal Transition in Pancreatic Cancer: A Review
Authors: Wang Shuai , Huang Shuai , Sun Yu Ling
Published: December 2017

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies and is characterized by its insensitivity to current therapy. The invasion and metastasis of solid tumors such as PDAC are complex processes involving many factors. Recent insights into the role of cancer stem cells (CSCs) and the epithelial-mesenchymal transition (EMT) in tumorigenesis have increased the knowledge base and highlighted new therapeutic targets of this disease. The process of EMT is regulated by a complex network of cytokines, transcription factors, growth factors, signaling pathways, and the tumor microenvironment, exhibiting CSC-like properties. The transition of solid cancer cells from an epithelial to a mesenchymal phenotype increases their migratory and invasive properties, thus promoting metastasis. In PDAC, the exact influence of EMT on the biological behaviors of cancer cells and its impact on clinical therapy remain controversial, but the therapeutic strategy of combining EMT inhibition with chemotherapy deserves attention. Alternatively, anti-inflammatory therapy that targets the interaction between inflammation and EMT is a valid strategy for treating the premalignant stage of tumor progression. In this review, we summarize the latest research on EMT and the potential relationship between EMT and PDAC.
Postprocessing of Accidental Scenarios by Semi-Supervised Self-Organizing Maps
Authors: Di Maio Francesco , Rossetti Roberta , Zio Enrico
Published: December 2017

Integrated Deterministic and Probabilistic Safety Analysis (IDPSA) of dynamic systems calls for the development of efficient methods for accidental scenarios generation. The necessary consideration of failure events timing and sequencing along the scenarios requires the number of scenarios to be generated to increase with respect to conventional PSA. Consequently, their postprocessing for retrieving safety relevant information regarding the system behavior is challenged because of the large amount of generated scenarios that makes the computational cost for scenario postprocessing enormous and the retrieved information difficult to interpret. In the context of IDPSA, the interpretation consists in the classification of the generated scenarios as safe, failed, Near Misses (NMs), and Prime Implicants (PIs). To address this issue, in this paper we propose the use of an ensemble of Semi-Supervised Self-Organizing Maps (SSSOMs) whose outcomes are combined by a locally weighted aggregation according to two strategies: a locally weighted aggregation and a decision tree based aggregation. In the former, we resort to the Local Fusion (LF) principle for accounting the classification reliability of the different SSSOM classifiers, whereas in the latter we build a classification scheme to select the appropriate classifier (or ensemble of classifiers), for the type of scenario to be classified. The two strategies are applied for the postprocessing of the accidental scenarios of a dynamic U-Tube Steam Generator (UTSG).
Complexity Analysis of Resting-State fMRI in Adult Patients with Attention Deficit Hyperactivity Disorder: Brain Entropy
Authors: Akdeniz Gülsüm
Published: December 2017

Objective. Complexity analysis of functional brain structure data represents a new multidisciplinary approach to examining complex, living structures. I aimed to construct a connectivity map of visual brain activities using resting-state functional magnetic resonance imaging (fMRI) data and to characterize the level of complexity of functional brain activity using these connectivity data. Methods. A total of 25 healthy controls and 20 patients with attention deficit hyperactivity disorder (ADHD) participated. fMRI preprocessing analysis was performed that included head motion correction, temporal filtering, and spatial smoothing process. Brain entropy (BEN) was calculated using the Shannon entropy equation. Results. My findings demonstrated that patients exhibited reduced brain complexity in visual brain areas compared to controls. The mean entropy value of the ADHD group was 0.56±0.14, compared to 0.64±0.11 in the control group. Conclusion. My study adds an important novel result to the growing literature pertaining to abnormal visual processing in ADHD that my ADHD patients had lower BEN values, indicating more-regular functional brain structure and abnormal visual information processing.
Performance Investigation of Air Velocity Effects on PV Modules under Controlled Conditions
Authors: Ali Muzaffar , Iqbal Muhammad Hasan , Sheikh Nadeem Ahmed , Ali Hafiz M. , Shehryar Manzoor M. , Khan Muhammad Mahabat , Tamrin Khairul Fikri
Published: December 2017

Junction temperature of PV modules is one of the key parameters on which the performance of PV modules depends. In the present work, an experimental investigation was carried out to analyze the effects of air velocity on the performance of two PV modules, that is, monocrystalline silicon and polycrystalline silicon under the controlled conditions of a wind tunnel in the presence of an artificial solar simulator. The parameters investigated include the surface temperature variation, power output, and efficiency of PV modules under varying air velocity from near zero (indoor lab. conditions) to 15 m/s. Additionally, the results were also determined at two different module angular positions: at 0° angle, that is, parallel to air direction and at 10° angle with the direction of coming air to consider the effects of tilt angles. Afterwards, the thermal analysis of the modules was performed using Ansys-Fluent in which junction temperature and heat flux of modules were determined by applying appropriate boundary conditions, such as air velocity, heat flux, and solar radiation. Finally, the numerical results are compared with the experiment in terms of junction temperatures of modules and good agreement was found. Additionally, the results showed that the maximum module temperature drops by 17.2°C and the module efficiency and power output increased from 10 to 12% with increasing air velocity.
A Topology on Milnor’s Group of a Topological Field and Continuous Joint Determinants
Authors: Myung Sung
Published: December 2017

For the tuple set of commuting invertible matrices with coefficients in a given field, the joint determinants are defined as generalizations of the determinant map for the square matrices. We introduce a natural topology on Milnor’s K-groups of a topological field as the quotient topology induced by the joint determinant map and investigate the existence of a nontrivial continuous joint determinant by utilizing this topology, generalizing the author’s previous results on the continuous joint determinants for the commuting invertible matrices over R and C.
Academic Activities Transaction Extraction Based on Deep Belief Network
Authors: Wang Xiangqian , Huang Fang , Wan Wencong , Zhang Chengyuan
Published: December 2017

Extracting information about academic activity transactions from unstructured documents is a key problem in the analysis of academic behaviors of researchers. The academic activities transaction includes five elements: person, activities, objects, attributes, and time phrases. The traditional method of information extraction is to extract shallow text features and then to recognize advanced features from text with supervision. Since the information processing of different levels is completed in steps, the error generated from various steps will be accumulated and affect the accuracy of final results. However, because Deep Belief Network (DBN) model has the ability to automatically unsupervise learning of the advanced features from shallow text features, the model is employed to extract the academic activities transaction. In addition, we use character-based feature to describe the raw features of named entities of academic activity, so as to improve the accuracy of named entity recognition. In this paper, the accuracy of the academic activities extraction is compared by using character-based feature vector and word-based feature vector to express the text features, respectively, and with the traditional text information extraction based on Conditional Random Fields. The results show that DBN model is more effective for the extraction of academic activities transaction information.
The Optimal Dividend Payout Model with Terminal Values and Its Application
Authors: Luo Xiankang , Chen Peimin , Ma Jiangming
Published: December 2017

For some firms with large nonliquid assets, preferred shareholders can still get back a little bit of money when the firms finish disbursement of loans at the status of bankruptcy. For such a situation, to investigate the optimal dividend policy, a stochastic dynamic dividend model with nonzero terminal bankruptcy values is put forward in this paper. Moreover, an analytic solution for the optimal objective function of the discounted dividends is provided and verified. An important application of this result is that it can be employed to construct the solution for the optimal value function on the dividend problem with bailouts at bankruptcy. Further, the relationship for the solutions of these two different problems is demonstrated. In the end, some numerical examples are provided to support our theoretical results and the corresponding economic interpretations are illustrated.
Preservation of Postharvest Quality of Leafy Amaranth (Amaranthus spp.) Vegetables Using Evaporative Cooling
Authors: Ambuko Jane , Wanjiru F. , Chemining’wa G. N. , Owino W. O. , Mwachoni Eliakim
Published: December 2017

Leafy vegetables are very highly perishable and must be utilized immediately after harvest. Their fast deterioration is attributed to various biological and environmental factors with temperature playing a central role. Evaporative cooling is a low-cost temporary storage technology that offers smallholder vegetable farmers an alternative to expensive cold rooms. The present study sought to determine the effectiveness of evaporative cooling using zero energy brick cooler (ZEBC) and evaporative charcoal cooler (ECC), to preserve the postharvest quality of leafy amaranth vegetables. Freshly harvested vegetables were separated into bundles weighing 300 grams and stored under ZEBC, ECC, and ambient room conditions (control). Real time changes in temperature and relative humidity (RH) as well as changes in quality attributes (physiological weight loss (PWL), wilting index, hue angle, and vitamin C) were determined during the storage period. The temperature difference between the ZEBC and ECC versus the ambient air ranged between 4 and 10°C. Significantly higher RH (80–100%) was recorded in both evaporative cooling chambers. At the end of storage, higher PWL (47.6%) was recorded at ambient room conditions compared to 10.5 and 6.7% under ZEBC and ECC, respectively. A rapid decline in vitamin C (51%) was reported in vegetables stored at ambient room conditions. Overall, there was better vegetable quality preservation under ECC and ZEBC.
A Gradual Approach for Multimodel Journey Planning: A Case Study in Izmir, Turkey
Authors: Dalkılıç Feriştah , Doğan Yunus , Birant Derya , Kut Recep Alp , Yılmaz Reyat
Published: December 2017

Planning a journey by integrating route and timetable information from diverse sources of transportation agencies such as bus, ferry, and train can be complicated. A user-friendly, informative journey planning system may simplify a plan by providing assistance in making better use of public transportation. In this study, we presented the service-oriented, multimodel Intelligent Journey Planning System, which we developed to assist travelers in journey planning. We selected Izmir, Turkey, as the pilot city for this system. The multicriteria problem is one of the well-known problems in transportation networks. Our study proposes a gradual path-finding algorithm to solve this problem by considering transfer count and travel time. The algorithm utilizes the techniques of efficient algorithms including round based public transit optimized router, transit node routing, and contraction hierarchies on transportation graph. We employed Dijkstra’s algorithm after the first stage of the path-finding algorithm by applying stage specific rules to reduce search space and runtime. The experimental results show that our path-finding algorithm takes 0.63 seconds of processing time on average, which is acceptable for the user experience.
Combined Sector and Channel Hopping Schemes for Efficient Rendezvous in Directional Antenna Cognitive Radio Networks
Authors: Al-Mqdashi AbdulMajid M. , Sali A. , Noordin Nor K. , Hashim Shaiful J. , Nordin Rosdiadee
Published: December 2017

Rendezvous is a prerequisite and important process for secondary users (SUs) to establish data communications in cognitive radio networks (CRNs). Recently, there has been a proliferation of different channel hopping- (CH-) based schemes that can provide rendezvous without relying on any predetermined common control channel. However, the existing CH schemes were designed with omnidirectional antennas which can degrade their rendezvous performance when applied in CRNs that are highly crowded with primary users (PUs). In such networks, the large number of PUs may lead to the inexistence of any common available channel between neighboring SUs which result in a failure of their rendezvous process. In this paper, we consider the utilization of directional antennas in CRNs for tackling the issue. Firstly, we propose two coprimality-based sector hopping (SH) schemes that can provide efficient pairwise sector rendezvous in directional antenna CRNs (DIR-CRNs). Then, we propose an efficient CH scheme that can be combined within the SH schemes for providing a simultaneous sector and channel rendezvous. The guaranteed rendezvous of our schemes are proven by deriving the theoretical upper bounds of their rendezvous delay metrics. Furthermore, extensive simulation comparisons with other related rendezvous schemes are conducted to illustrate the significant outperformance of our schemes.
Melatonin and Angelman Syndrome: Implications and Mathematical Model of Diurnal Secretion
Authors: Paprocka Justyna , Kijonka Marek , Wojcieszek Piotr , Pęcka Marcin , Emich-Widera Ewa , Sokół Maria
Published: December 2017

The main aim of the study was to compare the melatonin rhythms in subjects with Angelman syndrome (n=9) and in children with (n=80) and without (n=40) epilepsy (nonepileptic patients diagnosed with peripheral nerve palsies, myopathy, and back pain) using our mathematical model of melatonin circadian secretion. The characteristics describing the diurnal hormone secretion such as minimum melatonin concentration, release amplitude, phase shift of melatonin release, and sleep duration as well as the dim light melatonin onset (DLMO) of melatonin secretion and theγshape parameter allow analyzing the fit and deducing about how much the measured melatonin profile differs from a physiological bell-shaped secretion. The estimated sleep duration and phase shift of melatonin release as well as the DMLO offsets at 25% and 50% relative thresholds are the key characteristic of Angelman syndrome children. As revealed from theγshape parameter, the melatonin secretion profiles are disturbed in majority of the AG subjects revealing rather a triangular course instead of the bell-like one.
PMDP: A Framework for Preserving Multiparty Data Privacy in Cloud Computing
Authors: Li Ji , Wei Jianghong , Liu Wenfen , Hu Xuexian
Published: December 2017

The amount of Internet data is significantly increasing due to the development of network technology, inducing the appearance of big data. Experiments have shown that deep mining and analysis on large datasets would introduce great benefits. Although cloud computing supports data analysis in an outsourced and cost-effective way, it brings serious privacy issues when sending the original data to cloud servers. Meanwhile, the returned analysis result suffers from malicious inference attacks and also discloses user privacy. In this paper, to conquer the above privacy issues, we propose a general framework for Preserving Multiparty Data Privacy (PMDP for short) in cloud computing. The PMDP framework can protect numeric data computing and publishing with the assistance of untrusted cloud servers and achieve delegation of storage simultaneously. Our framework is built upon several cryptography primitives (e.g., secure multiparty computation) and differential privacy mechanism, which guarantees its security against semihonest participants without collusion. We further instantiate PMDP with specific algorithms and demonstrate its security, efficiency, and advantages by presenting security analysis and performance discussion. Moreover, we propose a security enhanced framework sPMDP to resist malicious inside participants and outside adversaries. We illustrate that both PMDP and sPMDP are reliable and scale well and thus are desirable for practical applications.
Analysis of Contact Part of Error Tooth Surface and Dynamic Performance Prediction for Involute Gear
Authors: Liu Xinrong , Wang Zhonghou
Published: December 2017

Aiming at the problem of constructing digital model of involute gear with error, the method of linear interpolation combined with area weight interpolation is proposed. Based on the non‐feature discrete data block technique, the true tooth surface discrete data obtained by the coordinate measuring instrument is divided into blocks, and then the interpolation method is used to interpolate the nonmeasurement area to construct the real tooth surface with errors. The contact part and dynamic performance of the gear are predicted by using the constructed error tooth surface. The contact error of the tooth surface and the transmission error of the gear are verified by the test, and the reliability of the judgment result is judged by measuring the vibration in the direction of the gear meshing line. Compared with the example, this method not only reduces the computational complexity of the interpolation algorithm, but also improves the accuracy of the tooth interpolation data points and the smoothness of the error tooth surface.
Research on the Effectiveness Evaluation Model of the Prison Physical Protection System Based on Grey Analytic Hierarchy Process
Authors: Yin Ke
Published: December 2017

In order to improve the rationality and validity of the physical protection system effectiveness evaluation in prison, this paper discusses the main factors that affect the system performance in the prison security system construction process and explores the key points in evaluating the effectiveness of searching system. The author of this paper has constructed an evaluation index system that accurately reflects the physical protection system in prison and comes up with an evaluation model and algorithm based on the gray level analysis by verifying the rationality of effectiveness evaluation model of prison physical protection system and the validity of the evaluation method.
Lateral Ramus Cortical Bone Plate in Alveolar Cleft Osteoplasty with Concomitant Use of Buccal Fat Pad Derived Cells and Autogenous Bone: Phase I Clinical Trial
Authors: Khojasteh Arash , Kheiri Lida , Behnia Hossein , Tehranchi Azita , Nazeman Pantea , Nadjmi Nasser , Soleimani Masoud
Published: December 2017

Tissue regeneration has become a promising treatment for craniomaxillofacial bone defects such as alveolar clefts. This study sought to assess the efficacy of lateral ramus cortical plate with buccal fat pad derived mesenchymal stem cells (BFSCs) in treatment of human alveolar cleft defects. Ten patients with unilateral anterior maxillary cleft met the inclusion criteria and were assigned to three treatment groups. First group was treated with anterior iliac crest (AIC) bone and a collagen membrane (AIC group), the second group was treated with lateral ramus cortical bone plate (LRCP) with BFSCs mounted on a natural bovine bone mineral (LRCP+BFSC), and the third group was treated with AIC bone, BFSCs cultured on natural bovine bone mineral, and a collagen membrane (AIC+BFSC). The amount of regenerated bone was measured using cone beam computed tomography 6 months postoperatively. AIC group showed the least amount of new bone formation (70±10.40%). LRCP+BFSC group demonstrated defect closure and higher amounts of new bone formation (75±3.5%) but less than AIC+BFSC (82.5±6.45%), suggesting that use of BFSCs within LRCP cage and AIC may enhance bone regeneration in alveolar cleft bone defects; however, the differences were not statistically significant. This clinical trial was registered at clinicaltrial.gov with NCT02859025 identifier.
The Role of the Innate Immune System in Oncolytic Virotherapy
Authors: Phan Tuan Anh , Tian Jianjun Paul
Published: December 2017

The complexity of the immune responses is a major challenge in current virotherapy. This study incorporates the innate immune response into our basic model for virotherapy and investigates how the innate immunity affects the outcome of virotherapy. The viral therapeutic dynamics is largely determined by the viral burst size, relative innate immune killing rate, and relative innate immunity decay rate. The innate immunity may complicate virotherapy in the way of creating more equilibria when the viral burst size is not too big, while the dynamics is similar to the system without innate immunity when the viral burst size is big.
Accurate 2-D AOA Estimation and Ambiguity Resolution for a Single Source under Fixed Uniform Circular Arrays
Authors: Zuo Le , Pan Jin
Published: December 2017

This paper presents an analytic algorithm for accurate two-dimensional (2-D) angle of arrival (AOA) estimation of a single source under fixed uniform circular arrays (UCAs). Algebraic and explicit formulations for 2-D AOA estimation are first developed in the Fourier domain. It is shown that three is the minimum number of antennas for 2-D AOA estimation based on phase measurement. Then a signal model for phase extraction is established with equivalent phase noises through observations of signal samples corrupted by additive Gaussian white noise. Under fixed UCAs, 2-D AOA estimation of a single source would suffer from phase ambiguity, and hence, ambiguity resolution is also addressed in the Fourier domain by integer search. Numerical examples are provided to verify the effectiveness and appealing performance of the proposed 2-D AOA estimation algorithm.
Single-Cell RNA-seq Reveals a Subpopulation of Prostate Cancer Cells with Enhanced Cell-Cycle–Related Transcription and Attenuated Androgen Response
Authors: Horning Aaron M. , Wang Yao , Lin Che-Kuang , Louie Anna D. , Jadhav Rohit R. , Hung Chia-Nung , Wang Chiou-Miin , Lin Chun-Lin , Kirma Nameer B. , Liss Michael A. , Kumar Addanki P. , Sun LuZhe , Liu Zhijie , Chao Wei-Ting , Wang Qianben , Jin Victor X. , Chen Chun-Liang , Huang Tim H.-M.
Published: December 2017

Increasing evidence suggests the presence of minor cell subpopulations in prostate cancer that are androgen independent and poised for selection as dominant clones after androgen deprivation therapy. In this study, we investigated this phenomenon by stratifying cell subpopulations based on transcriptome profiling of 144 single LNCaP prostate cancer cells treated or untreated with androgen after cell-cycle synchronization. Model-based clustering of 397 differentially expressed genes identified eight potential subpopulations of LNCaP cells, revealing a previously unappreciable level of cellular heterogeneity to androgen stimulation. One subpopulation displayed stem-like features with a slower cell doubling rate, increased sphere formation capability, and resistance to G2–M arrest induced by a mitosis inhibitor. Advanced growth of this subpopulation was associated with enhanced expression of 10 cell-cycle–related genes (CCNB2, DLGAP5, CENPF, CENPE, MKI67, PTTG1, CDC20, PLK1, HMMR, and CCNB1) and decreased dependence upon androgen receptor signaling. In silico analysis of RNA-seq data from The Cancer Genome Atlas further demonstrated that concordant upregulation of these genes was linked to recurrent prostate cancers. Analysis of receiver operating characteristic curves implicates aberrant expression of these genes and could be useful for early identification of tumors that subsequently develop biochemical recurrence. Moreover, this single-cell approach provides a better understanding of how prostate cancer cells respond heterogeneously to androgen deprivation therapies and reveals characteristics of subpopulations resistant to this treatment.

Significance: Illustrating the challenge in treating cancers with targeted drugs, which by selecting for drug resistance can drive metastatic progression, this study characterized the plasticity and heterogeneity of prostate cancer cells with regard to androgen dependence, defining the character or minor subpopulations of androgen-independent cells that are poised for clonal selection after androgen-deprivation therapy. Cancer Res; 78(4); 853–64. ©2017 AACR.
Targeting CDK6 and BCL2 Exploits the “MYB Addiction” of Ph+ Acute Lymphoblastic Leukemia
Authors: De Dominici Marco , Porazzi Patrizia , Soliera Angela Rachele , Mariani Samanta A. , Addya Sankar , Fortina Paolo , Peterson Luke F. , Spinelli Orietta , Rambaldi Alessandro , Martinelli Giovanni , Ferrari Anna , Iacobucci Ilaria , Calabretta Bruno
Published: December 2017

Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) is currently treated with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy. However, most patients develop resistance to TKI through BCR-ABL1–dependent and –independent mechanisms. Newly developed TKI can target Ph+ ALL cells with BCR-ABL1–dependent resistance; however, overcoming BCR-ABL1–independent mechanisms of resistance remains challenging because transcription factors, which are difficult to inhibit, are often involved. We show here that (i) the growth of Ph+ ALL cell lines and primary cells is highly dependent on MYB-mediated transcriptional upregulation of CDK6, cyclin D3, and BCL2, and (ii) restoring their expression in MYB-silenced Ph+ ALL cells rescues their impaired proliferation and survival. Levels of MYB and CDK6 were highly correlated in adult Ph+ ALL (P = 0.00008). Moreover, Ph+ ALL cells exhibited a specific requirement for CDK6 but not CDK4 expression, most likely because, in these cells, CDK6 was predominantly localized in the nucleus, whereas CDK4 was almost exclusively cytoplasmic. Consistent with their essential role in Ph+ ALL, pharmacologic inhibition of CDK6 and BCL2 markedly suppressed proliferation, colony formation, and survival of Ph+ ALL cells ex vivo and in mice. In summary, these findings provide a proof-of-principle, rational strategy to target the MYB "addiction" of Ph+ ALL.

Significance: MYB blockade can suppress Philadelphia chromosome-positive leukemia in mice, suggesting that this therapeutic strategy may be useful in patients who develop resistance to imatinib and other TKIs used to treat this disease. Cancer Res; 78(4); 1097–109. ©2017 AACR.
Neddylation Blockade Diminishes Hepatic Metastasis by Dampening Cancer Stem-Like Cells and Angiogenesis in Uveal Melanoma
Authors: Jin Yanli , Zhang Ping , Wang Yun , Jin Bei , Zhou Jingfeng , Zhang Jing , Pan Jingxuan
Published: December 2017

Purpose: Liver metastasis is the major and direct cause of death in patients with uveal melanoma (UM). There is no effective therapy for patients with metastatic UM. Improved treatments of hepatic metastatic patients with UM were urgently needed. Inspired by readily detectable key components in the neddylation pathway in UM cells, we aimed at exploring whether neddylation pathway was a therapeutic target for liver metastatic UM.

Experimental Design: Expression of key proteins in the neddylation pathway in UM was detected by Western blotting, real-time quantitative RT-PCR (qRT-PCR), and immunohistochemical staining. Cellular proliferation, apoptosis, cell cycle, migration, and cancer stem-like cells (CSCs) properties were examined upon treatment with MLN4924, a potent and selective NAE inhibitor. Antitumor activity and frequency of CSCs were determined by using a NOD-SCID mouse xenograft model. Liver metastasis was evaluated by use of a NOD-scid-IL2Rg−/− mouse model.

Results: NAE1 expression was readily detectable in UM. Inhibition of the neddylation pathway by MLN4924 repressed the CSCs properties in UM (capacities of tumorsphere formation and serially replating, aldehyde dehydrogenase-positive cells, and frequency of CSC) through Slug protein degradation. MLN4924 treatment disturbed the paracrine secretion of NF-κB-mediated VEGF-C and its dependent angiogenesis. The inhibitory effect of neddylation blockade on proliferation, which was confirmed by xenografted UM tumor in NOD-SCID mice, was involved in activation of ATM-Chk1-Cdc25C DNA damage response, and G2–M phase arrest. Neddylation inhibition profoundly inhibited hepatic metastasis in UM.

Conclusions: Our studies validate the neddylation pathway as a promising therapeutic target for the treatment of patients with hepatic metastasis of UM. Clin Cancer Res; 24(15); 3741–54. ©2017 AACR.

See related commentary by Yang et al., p. 3477
Neoadjuvant Chemotherapy Exerts Selection Pressure Towards Luminal Phenotype Breast Cancer
Authors: Galli Giulia , Bregni Giacomo , Cavalieri Stefano , Porcu Luca , Baili Paolo , Hade Amash , Di Salvo Francesca , Sant Milena , Agresti Roberto , Gennaro Massimiliano , Folli Secondo , De Santis Maria C. , Paolini Biagio , Carcangiu Maria L. , de Braud Filippo , Di Cosimo Serena
Published: December 2017

Background: Breast cancer (BC) phenotype after neoadjuvant chemotherapy (NAC) has not been extensively described and few data exist on whether expression of the primary tumor hormone receptors, HER2 and Ki-67 changes as a result of chemotherapy. Materials and Methods: We analyzed specimens from all BC patients treated with anthracycline/taxane-based NAC at our Institution between January 2010 and March 2015 (n = 325). The expression of estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki-67 was determined in pre- and post-NAC specimens. McNemar's test was used to compare paired proportions. Results: Among patients with residual disease after NAC, basal phenotype was luminal A, luminal B, HER2 positive and triple negative in 44, 111, 74 and 27 cases, respectively. PR-positive tumors decreased from 68.0% in the initial biopsy sample to 61.7% in the surgical specimen (p = 0.024). A Ki-67 of < 20% increased from 23.6% to 45% (p < 0.001). ER expression changed from positive to negative in 5% and from negative to positive in 16.7% of cases. Overall, 30% of cases underwent subtype changes, 79% of them towards luminal differentiation. Conclusions: The switch towards luminal phenotype suggests some kind of endocrine effect of NAC. Our findings raise renewed interest in combinatorial cytotoxic chemotherapy with concomitant or rather sequential endocrine therapy, either alone or with targeted agents.
Evaluation of Novel Anticaries Adhesive in a Secondary Caries Animal Model
Authors: Wu Tianmu , Li Bolei , Zhou Xuedong , Hu Yao , Zhang Huajin , Huang Yingkang , Xu Hockin H.K. , Guo Qiang , Li Mingyun , Feng Mingye , Peng Xian , Weir Michael D , Cheng Lei , Ren Biao
Published: December 2017

We investigated the anticaries properties of an adhesive containing dimethylaminododecyl methacrylate (DMADDM) in vivo via a secondary caries animal model. Cavities were prepared in the maxillary first molars of Wistar rats. DMADDM-containing adhesives were applied on one side and commercial adhesives on the opposite side as a control. After a 3-week feeding period to induce secondary caries, the molars were harvested for the evaluation of the secondary caries. Lesion depth (LD) and mineral loss (ML) were measured via a micro-CT method, and a modified Keyes scoring method yielded scores for the caries lesions. Statistical analysis was divided into 2 parts: a correlation analysis between 2 evaluations with one-way ANOVA and a least-significant differences (LSD) test, and an evaluation of anticaries adhesives with a paired samples t test. The results showed that: (1) secondary caries was successfully produced in rats; (2) there was a correlation between the modified Keyes scoring method and micro-CT in the evaluation of the secondary caries; (3) the adhesive containing DMADDM significantly reduced both LD and ML (according to micro-CT), and also lowered the scores (based on the modified Keyes scoring method). This suggests that the novel DMADDM adhesive could perform an anticaries function in vivo via the secondary caries animal model which was also developed and testified in research. Secondary caries is one of the major reasons leading to the failure of caries restoration treatment. As a solution, anticaries adhesives perform well in biofilm inhibition in vitro. However, the lack of secondary caries animal models limits the evaluation of anticaries adhesives in vivo.
A Multicenter Clinical Evaluation of Data Logging in Cochlear Implant Recipients Using Automated Scene Classification Technologies
Authors: Cristofari Eliana , Cuda Domenico , Martini Alessandro , Forli Francesca , Zanetti Diego , Di Lisi Diego , Marsella Pasquale , Marchioni Daniele , Vincenti Vincenzo , Aimoni Claudia , Paludetti Gaetano , Barezzani Maria Grazia , Leone Carlo Antonio , Quaranta Nicola , Bianchedi Marco , Presutti Livio , Della Volpe Antonio , Redaelli de Zinis Luca Oscar , Cantore Italo , Frau Giuseppe Nicolò , Orzan Eva , Galletti Francesco , Vitale Silvano , Raso Ferdinando , Negri Maurizio , Trabalzini Franco , Livi Walter , Piccioni Lucia Oriella , Ricci Giampietro , Malerba Paolo
Published: December 2017

Currently, there are no studies assessing everyday use of cochlear implant (CI) processors by recipients by means of objective tools. The Nucleus 6 sound processor features a data logging system capable of real-time recording of CI use in different acoustic environments and under various categories of loudness levels. In this study, we report data logged for the different scenes and different loudness levels of 1,366 CI patients, as recorded by SCAN. Monitoring device use in cochlear implant recipients of all ages provides important information about the listening conditions encountered in recipients' daily lives that may support counseling and assist in the further management of their device settings. The findings for this large cohort of active CI users confirm differences between age groups concerning device use and exposure to various noise environments, especially between the youngest and oldest age groups, while similar levels of loudness were observed.
Short-Term Outcomes following Hepatectomy in Elderly Patients with Hepatocellular Carcinoma: An Analysis of 10,805 Septuagenarians and 2,381 Octo- and Nonagenarians in Japan
Authors: Okinaga Hiroko , Yasunaga Hideo , Hasegawa Kiyoshi , Fushimi Kiyohide , Kokudo Norihiro
Published: December 2017

Background: As the population is aging, the indication for hepatocellular carcinoma (HCC) resection in patients aged over 80 years will increase. Japan is facing the most aging society worldwide. We examined the safety of hepatectomy in octogenarians and nonagenarians using large-scale data from the Diagnosis Procedure Combination database, a national administrative database in Japan. Method: We conducted a survey to collect data for all inpatients from 2007 and 2012. We identified 27,094 patients who underwent hepatectomy for HCC. Patients' age was divided into the following five categories: ≤59, 60-69, 70-79, 80-84, and ≥85 years (n = 5,099, 8,809, 10,805, 2,011, and 370, respectively). The primary outcomes of hepatectomy were in-hospital death within 90 days and complications. Logistic regression analyses were performed to analyze the impact of age on the outcomes with the adjustment of other individual-level factors. Results: The mortality and morbidity rates were 2.6 and 23.4%, respectively. Compared with patients in their 70s, the mortality rate was significantly lower in patients aged ≤59 years (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.26-0.45; p < 0.01) and in those in their 60s (OR, 0.63; 95% CI, 0.53-0.74; p < 0.01). However, no significant difference was observed in patients aged 80-84 years (OR, 1.03; 95% CI, 0.78-1.385; p = 0.844) and those aged ≥85 years (OR, 0.95; 95% CI, 0.50-1.79; p = 0.870). Based on the multivariate logistic regression analysis, age ≥70 years, male gender, low hospital volume, and surgical procedure were identified as independent predictors of mortality. Conclusions: The operative risk for hepatectomy gradually increases with age until patients are in their 70s, and it appears to reach a plateau among septuagenarian. Indeed, age over 70 years can also be a risk factor for HCC. By considering the aging risk, surgeons can attain good outcome after hepatectomy even in octo- and nonagenarian patients.