bluuebunny/crossref_metadata_2025 huggingface dataset:
A Dilemma in the Communication of a UAV with its Controller
Authors: Garnaev Andrey , Trappe Wade , Petropulu Athina
Published: February 2020

In this paper, we investigate a dilemma of employing silent mode and communication mode by an unmanned aerial vehicle (UAV) in communication with its controller. In many applications, a UAV communicates with a controller to receive instructions or accurate positioning, but such active communication poses a threat that the UAV can be hijacked through spoofing. On the other hand, during a silent mode (when the UAV does not communicate with the controller), the UAV is safe from spoofing, but is not receiving updates or other important data, and can degrade the overall UAV mission. To gain insight into the UAV risk versus benefit tradeoff, a simple game-theoretic model is presented. Additionally, this paper investigates how incomplete information about the capability of the controller to quickly learn the adversary’s attack and adjust its strategy accordingly can impact the equilibrium strategies. In contrast to regular-type capability, when both the rivals maximize their payoffs simultaneously, the capability of the controller to quickly learn is modeled by having the controller apply the best-response strategy. We model this problem using a Bayesian game, where the adversary knows only a priori probabilities about what capability the controller has. Dependence of the equilibrium strategies on these a priori probabilities is illustrated.
Optimization-Based Consensus Model to Solve Multi-Criteria Large Group Decision Making Problems
Authors: Singh Anjali , Gupta Anjana
Published: February 2020

In this contribution, a consensus model is proposed to acquire a unified and converging solution of multi-criteria large group decision making problems. Unlike the iterative process and feedback mechanism based models, the suggested approach features the optimization theory to establish the consensus in one go only among the efficient experts. The time salvation characteristic of the model makes it expedient for the emergency planning and management decision problems. The algorithm is validated using the hurricane evacuation notification time problem of United States.
Effects of Fish Nets on the Nonlinear Dynamic Performance of a Floating Offshore Wind Turbine Integrated with a Steel Fish Farming Cage
Authors: Lei Y. , Zhao S. X. , Zheng X. Y. , Li W.
Published: February 2020

This paper aims to study the effects of fish nets on the nonlinear dynamic performance of a floating offshore wind turbine integrated with a steel fish farming cage (FOWT-SFFC). Fully coupled aero-hydro-servo-elastic numerical models of FOWT-SFFC, with and without nets, are constructed to probe the nonlinear time-domain stochastic response. The first-order potential flow model with quadratic drag forces is employed to calculate the hydrodynamic loading on the foundation. The effects of nets on the damping ratios of 6 degree-of-freedom motions and on their displacement response amplitude operators (RAOs) are respectively investigated in numerical decay tests and monochromatic regular waves. The results show that the nets help to increase the damping level for the whole system and reduce motion RAOs when wave periods are around the natural periods of motions, while nets play insignificant role in motions when wave periods are far away from motion natural periods. The dynamic performances of FOWT-SFFC with and without nets under random ocean waves, the combined random wind and random waves as well as current are comprehensively compared and discussed. The simulation results indicate that in wind-sea dominated conditions, the nets tend to slightly increase the dynamic responses of FOWT-SFFC, especially the components corresponding to natural periods. Nonetheless, under sea states that comprise both wind-sea waves and swell, nets help to reduce the dynamic responses of FOWT-SFFC by introducing additional damping.
3D Morphable Face Model for Face Animation
Authors: Ye Dan , Fuh Chiou-Shann
Published: February 2020

This paper employs a new technology for modeling textured 3D faces. 3D faces can either be generated automatically from one or more photographs, or modeled directly through an intuitive user interface. Users are assisted in two key problems of computer-aided face modeling. It presents two algorithms for 3D face modeling from an image sequence. The first method works by creating an initial estimate using multiframe structure from motion (SfM) reconstruction framework, which is refined by comparing against a generic face model. The comparison is carried out using an energy-function optimization strategy. Results of 3D reconstruction algorithm are presented. The second method presented reconstructs a face model by adapting a generic model to contours of a face over all the frames of an image sequence. The algorithm for pose estimation and 3D face reconstruction relies solely on contours and the system does not require knowledge of rendering parameters (e.g. light direction and intensity). Results relying on finding accurate point correspondences across frames is presented.
Geometric Feature-Based Classification of Segmented Human Chromosomes
Authors: Arora Tanvi , Dhir Renu
Published: February 2020

The chromosomes are the carriers of the geometric information, any alteration in the structure or number of these chromosomes is termed as genetic defect. These alterations cause malfunctioning in the proteins and are cause of the various underlying medical conditions that are hard to cure or detect by normal clinical procedures. In order to detect the underlying causes of these defects, the cells of the humans need to be imaged during the mitosis phase of cell division. During this phase, the chromosomes are the longest and can be easily studied and the alterations in the structure and count of the chromosomes can be analyzed easily. The chromosomes are non-rigid objects, due to which they appear in varied orientations, which makes them hard to be analyzed for the detection of structural defects. In order to detect the genetic abnormalities due to structural defects, the chromosomes need to be in straight orientation. Therefore, in this work, we propose to classify the segmented chromosomes from the metaspread images into straight, bent, touching overlapping or noise, so that the bent, touching, overlapping chromosomes can be preprocessed and straightened and the noisy objects be discarded. The classification has been done using a set of 17 different geometric features. We have proposed a Multilayer Perceptron-based classification approach to classify the chromosomes extracted from metaspread images into five distinct categories considering their orientation. The results of the classification have been analyzed using the segmented objects of the Advance Digital Imaging Research (ADIR) dataset. The proposed technique is capable of classifying the segmented chromosomes with 94.28% accuracy. The performance of the proposed technique has been compared with seven other state-of-the-art classifiers and superior results have been achieved by the proposed method.
2-Local derivations on Witt algebras
Authors: Zhao Yueqiang , Chen Yang , Zhao Kaiming
Published: February 2020

In this paper, we prove that every 2-local derivation on Witt algebras [Formula: see text] or [Formula: see text] is a derivation for all [Formula: see text]. As a consequence we obtain that every 2-local derivation on any centerless generalized Virasoro algebra of higher rank is a derivation.
Stability of Asai local factors for GL(2)
Authors: Jo Yeongseong , Krishnamurthy M.
Published: February 2020

Let [Formula: see text] be a non-archimedean local field of characteristic not equal to [Formula: see text] and let [Formula: see text] be a quadratic algebra. We prove the stability of local factors attached to irreducible admissible (complex) representations of [Formula: see text] via the Rankin–Selberg method under highly ramified twists. This includes both the Asai as well as the Rankin–Selberg local factors attached to pairs. Our method relies on expressing the gamma factor as a Mellin transform using Bessel functions.
Preparation, microstructure and dye adsorption behavior of nanostructured FeTiO3 with a magnetic recovery capacity
Authors: Wang Xiaohuan , Shi Zhiming , Wang Jun , Zhao Tao , Ji Guojun , Liu Liang
Published: February 2020

Two different morphologies of FeTiO3 (nanopowders and nanosheets) were synthesized for the selective and efficient removal of Congo red and methylene blue dyes. The FeTiO3 samples were extensively performed by XRD, TEM, EDS, XPS, BET, UV-Vis, zeta potential, FTIR, and VSM analysis. The experimental data showed that FeTiO3 nanopowders (FTO-P) and FeTiO3 nanosheets (FTO-S) were mesoporous, and each had CR adsorption quantity of 110.68[Formula: see text]mg/g and 95.33[Formula: see text]mg/g, respectively. Although FTO-S had an excellent adsorption of 76.87[Formula: see text]mg/g for MB, FTO-P showed almost no MB adsorption. The studies indicated that adsorption conform to pseudo-second-order model. The electrostatic interactions and hydrogen bonding were deemed to the mainly adsorption mechanism. The magnetic properties of samples facilitated their recovery from solution after adsorption. The study shows that FeTiO3 was an excellent adsorbent due to its remarkable and selective adsorption performance and easy magnetic separation from aqueous solution.
Magnetic Properties and Spin-Wave Excitations in Co/Mn Multilayers
Authors: Lekdadri A. , Salhi H. , Lassri H. , Moubah R.
Published: February 2020

Co/Mn multilayers were prepared using evaporation technique under ultra-high vacuum conditions and their structural and magnetic properties were studied. The temperature dependence of the spontaneous magnetization [Formula: see text] was recorded for different cobalt layer thickness ([Formula: see text]) ranging from 19[Formula: see text]Å to 70[Formula: see text]Å. Bloch’s law describes satisfactory the thermal change of magnetization for all samples. In addition, the change of the spin-wave (SW) parameter [Formula: see text] versus [Formula: see text] was discussed. The torque magnetometry was utilized to extract the effective anisotropy ([Formula: see text]) and the interlayer coupling constant ([Formula: see text]) was determined from the in-plan M–H loops. An updated model based on SW theory was applied to describe the [Formula: see text] variation and to calculate the approximate values of exchange interactions for samples with different Co-layer thicknesses.
Simultaneous Removal of Prefix and Suffix
Authors: Tamta Pawan , Pande B. P.
Published: February 2020

This work is an attempt to devise a Stemmer that can remove both prefix and suffix together from a given word in English language. For a given input word, our method considers all possible internal [Formula: see text]-grams for detection of potential stems. We frame a hypothesis where the stem length is closest to the half of the length of the input word. A standard English dictionary has been employed to identify morphologically correct [Formula: see text]-grams in the process. We apply our techniques over a random sample of 100 English words, each possessing both prefix and suffix. We also compare our proposed Stemmer with three standard algorithms from the literature. Empirical results exhibit that our technique performs better than the rest of the stemmers.
Evaluation of Advanced Ensemble Learning Techniques for Android Malware Detection
Authors: Rana Md. Shohel , Sung Andrew H.
Published: February 2020

Android is the most well-known portable working framework having billions of dynamic clients worldwide that pulled in promoters, programmers, and cybercriminals to create malware for different purposes. As of late, wide-running inquiries have been led on malware examination and identification for Android gadgets while Android has likewise actualized different security controls to manage the malware issues, including a User ID (UID) for every application, framework authorizations. In this paper, we advance and assess various kinds of machine learning (ML) by applying ensemble-based learning systems for identifying Android malware related to a substring-based feature selection (SBFS) strategy for the classifiers. In the investigation, we have broadened our previous work where it has been seen that the ensemble-based learning techniques acquire preferred outcome over the recently revealed outcome by directing the DREBIN dataset, and in this manner they give a solid premise to building compelling instruments for Android malware detection.
The Effects of Missing Data Characteristics on the Choice of Imputation Techniques
Authors: Alade Oyekale Abel , Selamat Ali , Sallehuddin Roselina
Published: February 2020

One major characteristic of data is completeness. Missing data is a significant problem in medical datasets. It leads to incorrect classification of patients and is dangerous to the health management of patients. Many factors lead to the missingness of values in databases in medical datasets. In this paper, we propose the need to examine the causes of missing data in a medical dataset to ensure that the right imputation method is used in solving the problem. The mechanism of missingness in datasets was studied to know the missing pattern of datasets and determine a suitable imputation technique to generate complete datasets. The pattern shows that the missingness of the dataset used in this study is not a monotone missing pattern. Also, single imputation techniques underestimate variance and ignore relationships among the variables; therefore, we used multiple imputations technique that runs in five iterations for the imputation of each missing value. The whole missing values in the dataset were 100% regenerated. The imputed datasets were validated using an extreme learning machine (ELM) classifier. The results show improvement in the accuracy of the imputed datasets. The work can, however, be extended to compare the accuracy of the imputed datasets with the original dataset with different classifiers like support vector machine (SVM), radial basis function (RBF), and ELMs.
Neural Decision Tree Towards Fully Functional Neural Graph
Authors: Xiao Han , Xu Ge
Published: February 2020

Though the traditional algorithms could be embedded into neural architectures with the proposed principle of [H. Xiao, Hungarian layer: Logics empowered neural architecture, arXiv: 1712.02555], the variables that only occur in the condition of branch could not be updated as a special case. To tackle this issue, we multiply the conditioned branches with Dirac symbol (i.e., [Formula: see text]), then approximate Dirac symbol with the continuous functions (e.g., [Formula: see text]). In this way, the gradients of condition-specific variables could be worked out in the back-propagation process, approximately, making a fully functional neural graph. Within our novel principle, we propose the neural decision tree (NDT), which takes simplified neural networks as decision function in each branch and employs complex neural networks to generate the output in each leaf. Extensive experiments verify our theoretical analysis and demonstrate the effectiveness of our model.
Modeling Plant Metabolism: From Network Reconstruction to Mechanistic Models
Authors: Clark Teresa J. , Guo Longyun , Morgan John , Schwender Jorg
Published: February 2020

Mathematical modeling of plant metabolism enables the plant science community to understand the organization of plant metabolism, obtain quantitative insights into metabolic functions, and derive engineering strategies for manipulation of metabolism. Among the various modeling approaches, metabolic pathway analysis can dissect the basic functional modes of subsections of core metabolism, such as photorespiration, and reveal how classical definitions of metabolic pathways have overlapping functionality. In the many studies using constraint-based modeling in plants, numerous computational tools are currently available to analyze large-scale and genome-scale metabolic networks. For 13C-metabolic flux analysis, principles of isotopic steady state have been used to study heterotrophic plant tissues, while nonstationary isotope labeling approaches are amenable to the study of photoautotrophic and secondary metabolism. Enzyme kinetic models explore pathways in mechanistic detail, and we discuss different approaches to determine or estimate kinetic parameters. In this review, we describe recent advances and challenges in modeling plant metabolism.
Temperature, Dynamics, and Enzyme-Catalyzed Reaction Rates
Authors: Arcus Vickery L. , Mulholland Adrian J.
Published: February 2020

We review the adaptations of enzyme activity to different temperatures. Psychrophilic (cold-adapted) enzymes show significantly different activation parameters (lower activation enthalpies and entropies) from their mesophilic counterparts. Furthermore, there is increasing evidence that the temperature dependence of many enzyme-catalyzed reactions is more complex than is widely believed. Many enzymes show curvature in plots of activity versus temperature that is not accounted for by denaturation or unfolding. This is explained by macromolecular rate theory: A negative activation heat capacity for the rate-limiting chemical step leads directly to predictions of temperature optima; both entropy and enthalpy are temperature dependent. Fluctuations in the transition state ensemble are reduced compared to the ground state. We show how investigations combining experiment with molecular simulation are revealing fundamental details of enzyme thermoadaptation that are relevant for understanding aspects of enzyme evolution. Simulations can calculate relevant thermodynamic properties (such as activation enthalpies, entropies, and heat capacities) and reveal the molecular mechanisms underlying experimentally observed behavior.
Regulatory T Cells and Human Disease
Authors: Sakaguchi Shimon , Mikami Norihisa , Wing James B. , Tanaka Atsushi , Ichiyama Kenji , Ohkura Naganari
Published: February 2020

Naturally occurring CD4+regulatory T cells (Tregs), which specifically express the transcription factor FoxP3 in the nucleus and CD25 and CTLA-4 on the cell surface, are a functionally distinct T cell subpopulation actively engaged in the maintenance of immunological self-tolerance and homeostasis. Recent studies have facilitated our understanding of the cellular and molecular basis of their generation, function, phenotypic and functional stability, and adaptability. It is under investigation in humans how functional or numerical Treg anomalies, whether genetically determined or environmentally induced, contribute to immunological diseases such as autoimmune diseases. Also being addressed is how Tregs can be targeted to control physiological and pathological immune responses, for example, by depleting them to enhance tumor immunity or by expanding them to treat immunological diseases. This review discusses our current understanding of Treg immunobiology in normal and disease states, with a perspective on the realization of Treg-targeting therapies in the clinic.
Caspases in Cell Death, Inflammation, and Pyroptosis
Authors: Kesavardhana Sannula , Malireddi R.K. Subbarao , Kanneganti Thirumala-Devi
Published: February 2020

Caspases are a family of conserved cysteine proteases that play key roles in programmed cell death and inflammation. In multicellular organisms, caspases are activated via macromolecular signaling complexes that bring inactive procaspases together and promote their proximity-induced autoactivation and proteolytic processing. Activation of caspases ultimately results in programmed execution of cell death, and the nature of this cell death is determined by the specific caspases involved. Pioneering new research has unraveled distinct roles and cross talk of caspases in the regulation of programmed cell death, inflammation, and innate immune responses. In-depth understanding of these mechanisms is essential to foster the development of precise therapeutic targets to treat autoinflammatory disorders, infectious diseases, and cancer. This review focuses on mechanisms governing caspase activation and programmed cell death with special emphasis on the recent progress in caspase cross talk and caspase-driven gasdermin D–induced pyroptosis.
The Innate Biologies of Adaptive Antigen Receptors
Authors: Hayday Adrian C. , Vantourout Pierre
Published: February 2020

Nonclonal innate immune responses mediated by germ line–encoded receptors, such as Toll-like receptors or natural killer receptors, are commonly contrasted with diverse, clonotypic adaptive responses of lymphocyte antigen receptors generated by somatic recombination. However, the Variable (V) regions of antigen receptors include germ line–encoded motifs unaltered by somatic recombination, and theoretically available to mediate nonclonal, innate responses, that are independent of or largely override clonotypic responses. Recent evidence demonstrates that such responses exist, underpinning the associations of particular γδ T cell receptors (TCRs) with specific anatomical sites. Thus, TCRγδ can make innate and adaptive responses with distinct functional outcomes. Given that αβ T cells and B cells can also make nonclonal responses, we consider that innate responses of antigen receptor V-regions may be more widespread, for example, inducing states of preparedness from which adaptive clones are better selected. We likewise consider that potent, nonclonal T cell responses to microbial superantigens may reflect subversion of physiologic innate responses of TCRα/β chains.
Chromatosome Structure and Dynamics from Molecular Simulations
Authors: Öztürk Mehmet Ali , De Madhura , Cojocaru Vlad , Wade Rebecca C.
Published: February 2020

Chromatosomes are fundamental units of chromatin structure that are formed when a linker histone protein binds to a nucleosome. The positioning of the linker histone on the nucleosome influences the packing of chromatin. Recent simulations and experiments have shown that chromatosomes adopt an ensemble of structures that differ in the geometry of the linker histone–nucleosome interaction. In this article we review the application of Brownian, Monte Carlo, and molecular dynamics simulations to predict the structure of linker histone–nucleosome complexes, to study the binding mechanisms involved, and to predict how this binding affects chromatin fiber structure. These simulations have revealed the sensitivityof the chromatosome structure to variations in DNA and linker histone sequence, as well as to posttranslational modifications, thereby explaining the structural variability observed in experiments. We propose that a concerted application of experimental and computational approaches will reveal the determinants of chromatosome structural variability and how it impacts chromatin packing.
Resveratrol Prevents Right Ventricle Remodeling and Dysfunction in Monocrotaline-Induced Pulmonary Arterial Hypertension with a Limited Improvement in the Lung Vasculature
Authors: Vázquez-Garza Eduardo , Bernal-Ramírez Judith , Jerjes-Sánchez Carlos , Lozano Omar , Acuña-Morín Edgar , Vanoye-Tamez Mariana , Ramos-González Martín R. , Chapoy-Villanueva Héctor , Pérez-Plata Luis , Sánchez-Trujillo Luis , Torre-Amione Guillermo , Ramírez-Rivera Alicia , García-Rivas Gerardo
Published: February 2020

Pulmonary arterial hypertension (PAH) is a life-threatening disease that is characterized by an increase in pulmonary vascular pressure, leading to ventricular failure and high morbidity and mortality. Resveratrol, a phenolic compound and a sirtuin 1 pathway activator, has known dietary benefits and is used as a treatment for anti-inflammatory and cardiovascular diseases. Its therapeutic effects have been published in the scientific literature; however, its benefits in PAH are yet to be precisely elucidated. Using a murine model of PAH induced by monocrotaline, the macroscopic and microscopic effects of a daily oral dose of resveratrol in rats with PAH were evaluated by determining its impact on the lungs and the right and left ventricular function. While most literature has focused on smooth muscle cell mechanisms and lung pathology, our results highlight the relevance of therapy-mediated improvement of right ventricle and isolated cardiomyocyte physiology in both ventricles. Although significant differences in the pulmonary architecture were not identified either micro- or macroscopically, the effects of resveratrol on right ventricular function and remodeling were observed to be beneficial. The values for the volume, diameter, and contractility of the right ventricular cardiomyocytes returned to those of the control group, suggesting that resveratrol has a protective effect against ventricular dysfunction and pathological remodeling changes in PAH. The effect of resveratrol in the right ventricle delayed the progression of findings associated with right heart failure and had a limited positive effect on the architecture of the lungs. The use of resveratrol could be considered a future potential adjunct therapy, especially when the challenges to making a diagnosis and the current therapy limitations for PAH are taken into consideration.
Adaptive Fixed-Time Terminal Sliding Mode Control on SE(3) for Coupled Spacecraft Tracking Maneuver
Authors: Gong Kejie , Liao Ying , Wang Yong
Published: February 2020

In this paper, a reaching law-based adaptive fixed-time terminal sliding mode control law, which is used for coupled spacecraft tracking maneuver in the presence of large inertia parametric uncertainties and external disturbances, is proposed. The coupled 6-DOF kinematics and dynamics for spacecraft motion are modeled on Lie group SE(3). The relative configuration is expressed by a local coordinate (exponential coordinate) of SE(3). In order to estimate the inertia parameters and external disturbances, we also propose a novel adaptive update law, which can make the control law be applied without the inertia parameters of the spacecraft a priori. Fixed-time convergence property of the closed-loop feedback system is proved in the framework of Lyapunov. Numerical simulations are performed to demonstrate the performances of the proposed control scheme for coupled spacecraft tracking maneuver.
Possible Mechanisms Involved in the Cooccurrence of Oral Lichen Planus and Hashimoto’s Thyroiditis
Authors: Wu Peiyao , Luo Shuhan , Zhou Tao , Wang Rui , Qiu Xuemei , Yuan Peiyang , Yang Yuqing , Han Qi , Jiang Lu
Published: February 2020

Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disorder mediated by T cells, with a multifactorial etiology. Hashimoto’s thyroiditis (HT) is a common autoimmune disease characterized by hypothyroidism. Although many clinical studies conducted over the past several decades have reported the cooccurrence of OLP and HT, the underlying mechanism remains unclear. This review summarizes potential mechanisms that might be involved in the cooccurrence of OLP and HT. We find that OLP and HT share a common or overlapping pathogenesis in terms of immune, heredity, environmental, and hormonal factors, which might cause cooccurrence. Furthermore, considering the latency of HT, a routine screen for thyroid diseases, particularly HT, is suggested for confirmed OLP patients.
An fMRI Study of the Effects of Vibroacoustic Stimulation on Functional Connectivity in Patients with Insomnia
Authors: Zabrecky George , Shahrampour Shiva , Whitely Cutler , Alizadeh Mahdi , Conklin Chris , Wintering Nancy , Doghramji Karl , Zhan Tingting , Mohamed Feroze , Newberg Andrew , Monti Daniel
Published: February 2020

Background. It is well known that vibratory and auditory stimuli from vehicles such as cars and trains can help induce sleep. More recent literature suggests that specific types of vibratory and acoustic stimulation might help promote sleep, but this has not been tested with neuroimaging. Thus, the purpose of this study was to observe the effects of vibroacoustic stimulation (providing both vibratory and auditory stimuli) on functional connectivity changes in the brain using resting state functional magnetic resonance imaging (rs-fMRI), and compare these changes to improvements in sleep in patients with insomnia. Methods. For this study, 30 patients with insomnia were randomly assigned to receive one month of a vibroacoustic stimulation or be placed in a waitlist control. Patients were evaluated pre- and postprogram with qualitative sleep questionnaires and measurement of sleep duration with an actigraphy watch. In addition, patients underwent rs-fMRI to assess functional connectivity. Results. The results demonstrated that those patients receiving the vibroacoustic stimulation had significant improvements in measured sleep minutes as well as in scores on the Insomnia Severity Index questionnaire. In addition, significant changes were noted in functional connectivity in association with the vermis, cerebellar hemispheres, thalamus, sensorimotor area, nucleus accumbens, and prefrontal cortex. Conclusions. The results of this study show that vibroacoustic stimulation alters the brain’s functional connectivity as well as improves sleep in patients with insomnia.
Tumor Mutational Burden and PTEN Alterations as Molecular Correlates of Response to PD-1/L1 Blockade in Metastatic Triple-Negative Breast Cancer
Authors: Barroso-Sousa Romualdo , Keenan Tanya E. , Pernas Sonia , Exman Pedro , Jain Esha , Garrido-Castro Ana C. , Hughes Melissa , Bychkovsky Brittany , Umeton Renato , Files Janet L. , Lindeman Neal I. , MacConaill Laura E. , Hodi F. Stephen , Krop Ian E. , Dillon Deborah , Winer Eric P. , Wagle Nikhil , Lin Nancy U. , Mittendorf Elizabeth A. , Van Allen Eliezer M. , Tolaney Sara M.
Published: February 2020

Purpose:

Few patients with metastatic triple-negative breast cancer (mTNBC) benefit from immune checkpoint inhibitors (ICI). On the basis of immunotherapy response correlates in other cancers, we evaluated whether high tumor mutational burden (TMB) ≥10 nonsynonymous mutations/megabase and PTEN alterations, defined as nonsynonymous mutations or 1 or 2 copy deletions, were associated with clinical benefit to anti-PD-1/L1 therapy in mTNBC.

Experimental Design:

We identified patients with mTNBC, who consented to targeted DNA sequencing and were treated with ICIs on clinical trials between April 2014 and January 2019 at Dana-Farber Cancer Institute (Boston, MA). Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were correlated with tumor genomic features.

Results:

Sixty-two women received anti-PD-1/L1 inhibitors alone (23%) or combined with targeted therapy (19%) or chemotherapy (58%). High TMB (18%) was associated with significantly longer PFS (12.5 vs. 3.7 months; P = 0.04), while PTEN alterations (29%) were associated with significantly lower ORR (6% vs. 48%; P = 0.01), shorter PFS (2.3 vs. 6.1 months; P = 0.01), and shorter OS (9.7 vs. 20.5 months; P = 0.02). Multivariate analyses confirmed that these associations were independent of performance status, prior lines of therapy, therapy regimen, and visceral metastases. The survival associations were additionally independent of PD-L1 in patients with known PD-L1 and were not found in mTNBC cohorts treated with chemotherapy (n = 90) and non-ICI regimens (n = 169).

Conclusions:

Among patients with mTNBC treated with anti-PD-1/L1 therapies, high TMB and PTEN alterations were associated with longer and shorter survival, respectively. These observations warrant validation in larger datasets.
Congenital Anomalies of the Kidney and Urinary Tract in Children with Congenital Heart Defects
Authors: Jiang Dapeng , Wang Qi , Shi Zhengzhou , Sun Jie
Published: February 2020

Background/Aims: To investigate the incidence and clinical characteristics of congenital anomalies of the kidney and urinary tract (CAKUT) in children with congenital heart defects (CHD). Methods: We retrospectively analyzed the clinical data of children with CHD with CAKUT admitted to the Shanghai Children’s Medical Center affiliated with the Shanghai Jiao Tong University School of Medicine between September 2018 and March 2019. Patients underwent routine examinations for liver, kidney, and coagulation function, and urinary tract ultrasonography, and we summarized patients’ clinical manifestations and imaging abnormalities. Results: A total of 1,410 children with CHD were diagnosed and treated in our hospital. The total number of patients with abnormal urogenital systems was 104, and hydronephrosis was the most common abnormality, followed by vesicoureteral reflux and duplication of the kidney and ureter. The overall prevalence of CAKUT was 7.4%. There was no statistically significant difference for maternal age, sex, parity, gestational age, and history of medication during pregnancy between the patients with CAKUT and those without CAKUT. Conclusion: The incidence of CAKUT in our patients with CHD was significantly higher than that in the general population. We recommend urinary ultrasonography as a routine examination for children with CHD for early detection of CAKUT, to avoid missed diagnoses, and to initiate appropriate treatment.
Pretreatment Heterogeneous Enhancement Pattern of Hepatocellular Carcinoma May Be a Useful New Predictor of Early Response to Lenvatinib and Overall Prognosis
Authors: Kawamura Yusuke , Kobayashi Masahiro , Shindoh Junichi , Kobayashi Yuta , Kasuya Kayoko , Sano Tomoya , Fujiyama Shunichiro , Hosaka Tetsuya , Saitoh Satoshi , Sezaki Hitomi , Akuta Norio , Suzuki Fumitaka , Suzuki Yoshiyuki , Ikeda Kenji , Arase Yasuji , Hashimoto Masaji , Kumada Hiromitsu
Published: February 2020

Objective: The aim of this study was to evaluate the performance of pretreatment computed tomography (CT) enhancement of hepatocellular carcinoma (HCC) as a potential predictor of response to lenvatinib and its relevance to survival outcomes. Methods: We evaluated 51 consecutive patients who received lenvatinib treatment for unresectable HCC. On imaging analysis, pretreatment arterial/portal phase dynamic CT images were classified as follows: type 2, homogeneous enhancement pattern with increased arterial blood flow; type 3, heterogeneous enhancement pattern with a septum-like structure; and type 4, heterogeneous enhancement pattern with irregularly shaped ring structures. Treatment response was evaluated using modified Response Evaluation Criteria in Solid Tumors at 2–12 weeks after initiation of lenvatinib, and the correlations between the CT enhancement patterns and response to lenvatinib or survival outcomes were investigated. Results: Of the 51 patients, 38 (75%) experienced an objective response (OR). ORs were significantly more common in heterogeneously enhanced HCC (types 3 and 4) than in homogeneous HCC (type 2) (83 vs. 53%, respectively; p = 0.037). Multivariate analysis revealed that pretreatment heterogeneous enhancement pattern is an independent predictor for response to lenvatinib (odds ratio, 4.75; p = 0.042). Presence of OR was associated with longer progression-free survival (PFS) (hazard ratio, 0.36; p = 0.017), and patients with oncologically aggressive type 3 and 4 tumors showed similar PFS to those harboring type 2 tumors (p = 0.455), reflecting that OR was more common in type 3 or 4 tumors compared with type 2 tumors. Although postprogression survival was extremely poor in patients with type 4 tumors (p = 0.064), overall survival after introduction of lenvatinib was not statistically different among the three groups of patients (p = 0.053). Conclusion: The CT enhancement pattern of HCC may predict response to lenvatinib. OR seems to occur more frequently in HCC with oncologically aggressive features and may contribute to prolonged survival through a prolonged progression-free interval, even in an oncologically poor-risk group of patients.
Squamous Cell Carcinoma of a Thyroglossal Duct Cyst and the Role of a Level IA Neck Dissection
Authors: Henry Laura , Mignone Robert , Pepek Joseph , Julien Christopher , Rajasekaran Karthik
Published: February 2020

Squamous cell carcinoma of a thyroglossal duct cyst is exceedingly rare, with less than 30 cases reported across the literature. Herein, we present a case of squamous cell carcinoma (SCC) of a thyroglossal duct cyst (TGDC) and discuss the utility of a level IA neck dissection in these cases. In 2018, a 62-year-old female presented to a university-affiliated otolaryngologist with symptoms of dysphagia and a palpable anterior midline neck mass. MRI demonstrated a 3.1 × 2.0-cm mass concerning an invasive TGDC. She was referred to our institution for further management. Preoperative imaging demonstrated an invasive TGDC but no pathological nodes. A Sistrunk procedure and a IA neck dissection were performed. Pathology demonstrated one pathological node in the neck dissection specimen. In summary, a bilateral IA neck dissection was performed on a clinically node zero (N0) patient, and a pathological node was ultimately identified. We hope that by introducing this idea of a IA neck dissection for SCC of a TGDC, we can prompt further investigation into the utility of this procedure for these uniquely rare cases.
Communication Attitude of Kannada-Speaking School-Age Children Who Do and Do Not Stutter
Authors: Veerabhadrappa Rakesh Chowkalli , Vanryckeghem Martine , Maruthy Santosh
Published: February 2020

Background: A large body of evidence suggests that the Communication Attitude Test (CAT) is a reliable and valid tool for assessing the speech-associated attitude of school-age children who stutter (CWS). Objective: The purpose of the present study was to adapt and validate the CAT for the Kannada-speaking school-age CWS. Methods: The original version of the CAT was forward- and back-translated by the first author. The Communication Attitude Test Kannada (CAT-K) was then administered to 293 children who do not stutter (CWNS) and 100 CWS. All children were native speakers of the Kannada language and were between the ages of 7 and 14 years. The Stuttering Severity Instrument-fourth edition (SSI-4) was used to estimate the severity of stuttering. Results: The data revealed that, in comparison to CWNS, the CWS’ mean CAT-K score was significantly higher, and a significant effect of stuttering severity and age on mean attitude scores was observed. In addition, results showed that the CAT-K is a reliable and valid test. Conclusion: The findings suggest the presence of a negative attitude in Kannada-speaking CWS and that the CAT-K is a useful tool in the assessment of Kannada school-age CWS. Given the need for speech-language pathologists to address a speech-associated negative attitude in CWS, incorporating the CAT-K as part of the diagnostic assessment of stuttering is valuable.
Translation and Validation of a Chinese Version of the Parental Self-Efficacy with Eczema Care Index
Authors: Cheng Nam Sze , Chau Janita Pak Chun , Hon Kam Lun Ellis , Chow Chung Mo , Choi Kai Chow , Lo Suzanne Hoi Shan , Leung Ting Fan
Published: February 2020

Background: Parental self-efficacy has been found to be a critical determinant of the efficacy of interventions intended to enhance the parental management of childhood eczema. Objectives: The psychometric properties of a translated Chinese version of the Parental Self-Efficacy with Eczema Care Index (C-PASECI) were examined. Methods: The PASECI was translated in a 2-stage process involving both forward and backward translation. Subsequently, the psychometric properties of the C-PASECI were examined in a cohort of 147 Chinese parents or caregivers of children with eczema. Specifically, the internal consistency, 2-day test-retest reliability and construct validity were assessed. Results: The C-PASECI received a Cronbach’s αof 0.97, and the intraclass correlation coefficients of each item ranged from 0.93 to 0.99. Negative correlations were observed among the C-PASECI, Children’s Dermatology Life Quality Index and Scoring Atopic Dermatitis Scale scores, indicating the acceptable convergent validity of the C-PASECI. The moderate correlation observed between the C-PASECI and General Self-Efficacy Scale (Pearson’s r = 0.53, p < 0.001) reflected the acceptable concurrent validity of the C-PASECI. The results of confirmatory factor analysis supported the factorial validity of the C-PASECI. Conclusion: The C-PASECI appears to be a reliable and valid measure of parental self-efficacy in Chinese parents or caregivers of children with eczema.
Primary Idiopathic Complex Aphthosis: Diagnosis and Successful Treatment with Montelukast in a 44-Year-Old Filipino Female
Authors: Aquino Terese Monette , Jamora Maria Jasmin
Published: February 2020

Recurrent aphthous stomatitis (RAS) is an oral condition characterized by frequent attacks of painful oral ulcers. Complex aphthosis (CA) is a severe form of RAS described as the almost constant presence of ≥3 oral ulcers with or without genital aphthosis. Management of primary CA varies, but most patients warrant the use of systemic agents. Because of prolonged treatment, it is preferred to use systemic medications with the least side effects. Herein, we present a case of a primary idiopathic CA. Workup and examination were done to exclude Adamantiades-Behçet’s disease and other diseases. The patient was shifted to montelukast after poor tolerance to colchicine. Favorable control of CA was noted during the 5-month follow-up period while the patient was on montelukast.
Transformation of Seborrheic Keratosis into Bowenoid Actinic Keratosis via Three Steps of Histological Change in a Patient with Rheumatoid Arthritis Treated with Multiple Immunosuppressants
Authors: Oka Masahiro , Yamamoto Yuki , Fujii Miki
Published: February 2020

We report a case of seborrheic keratosis (SK) that transformed into bowenoid actinic keratosis (AK) via three steps of histological change in a 77-year-old woman. The patient presented with a multiple-year history of a brownish lesion on the right cheek. She reported that some months earlier she had noted a pinkish lesion developing within the brownish lesion. She had also been treated with several immunosuppressants for rheumatoid arthritis for many years. Physical examination revealed a nodule measuring 13 × 12 mm on the lateral side of the right upper cheek. The lesion comprised three regions: a brownish hyperkeratotic region in the upper portion; a pinkish region in the lower portion; and a slightly dented, band-like region between the other two regions. Histopathologically, the specimen consisted of four zones: SK comprising basaloid cells; SK composed of squamoid cells; atrophic AK; and bowenoid AK. The zones of SK with basaloid cells and squamoid cells clinically corresponded to the brownish hyperkeratotic region. Atrophic and bowenoid AK zones corresponded to the dented, band-like region and pinkish region, respectively. Collectively, the nodular skin lesion was diagnosed as SK associated with atrophic and bowenoid AK within the SK lesion. The present case suggests that bowenoid AK developed from SK by malignant transformation via three steps of histological change. The facts that our patient had received treatment with several immunosuppressants and that no other AK lesions were evident around the AK support the notion that in this case, bowenoid AK developed from SK by malignant transformation.
Electrophysiological Characterization of C9ORF72-Associated Amyotrophic Lateral Sclerosis: A Retrospective Study
Authors: Pegat Antoine , Bouhour Françoise , Mouzat Kevin , Vial Christophe , Pegat Benoit , Leblanc Pascal , Broussolle Emmanuel , Millecamps Stéphanie , Lumbroso Serge , Bernard Emilien
Published: February 2020

Objective: C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS). The aim of the present study was to determine whether C9ORF72-associated ALS (C9-ALS) patients present distinctive electrophysiological characteristics that could differentiate them from non C9ORF72-associated ALS (nonC9-ALS) patients. Methods: Clinical and electrodiagnostic data from C9-ALS patients and nonC9-ALS patients were collected retrospectively. For electroneuromyography, the mean values of motor conduction, myography, and the mean values of sensory conduction were considered. Furthermore, the proportion of ALS patients with electrophysiological sensory neuropathy was determined. Results: No significant difference was observed between 31 C9-ALS patients and 22 nonC9-ALS patients for mean motor conduction and myography. For sensory conduction analyses, mean sensory conduction was not significantly different between both groups. In total, 38% of ­C9-ALS patient and 21% of nonC9-ALS patients presented electrophysiological sensory neuropathy (p = 0.33). In ­C9-ALS patients with electrophysiological sensory neuropathy, 80% (8/10) were male and 67% (6/9) presented spinal onset compare to 25% (4/16, p = 0.014) male and 25% (4/16, p = 0.087) with spinal onset in those without electrophysiological sensory neuropathy. Conclusion: Although not different from nonC9-ALS, these results suggest that sensory involvement is a frequent feature of C9-ALS patients, expanding the phenotype of the disease beyond the motor and cognitive domains.
Successful Treatment of Allopurinol-Induced Severe Skin Reactions with Double Filtration Plasmapheresis: A Case Report
Authors: Xie Pan , Tao Min , Zhao Hongwen , Sheng Yuxiu , Qiu Jun , Xu Yan , Li Huanna , Wang Huan , Cao Ge , Ronco Claudio , Peng Kanfu
Published: February 2020

Severe cutaneous adverse reactions (SCAR) are uncommon and acute and frequently represent a drug reaction. For years, allopurinol use has remained the highest risk factor for SCARs worldwide. There are multiple risk factors for allopurinol-induced SCARs, including genetic and non-genetic factors. Renal failure has been found to be an important factor resulting in allopurinol-induced SCARs with greater severity and poorer prognosis. An 80-year-old female was admitted to our hospital after administration of allopurinol in December 2018. She developed erythaematous skin of the epidermis of the hips, which rapidly extended over the trunk and limbs, resulting in itching and flaking. The presumptive diagnosis was a drug-induced SCAR. Despite treatment with glucocorticoids and kidney support therapy, the skin lesions extended over the entire body. Fortunately, the progression of pruritic erythema was stopped by double-filtration plasmapheresis (DFPP). DFPP was discontinued after the signs of skin inflammation were no longer visible. Her skin, but not kidney function, recovered after 10 days of hospitalization. She tolerated DFPP well without development of any severe complications. We present here a case of allopurinol-induced SCAR, which was successfully treated with DFPP.
Unbalanced X;Autosome Translocations May Lead to Mild Phenotypes and Are Associated with Autoimmune Diseases
Authors: Ciaccio Claudia , Redaelli Serena , Bentivegna Angela , Marelli Susan , Crosti Francesca , Sala Elena M. , Cavallari Ugo
Published: February 2020

Unbalanced X;autosome translocations are a rare occurrence with a wide variability in clinical presentation in which the X chromosome unbalance is usually mitigated by a favorable X inactivation pattern. In most cases, this compensation mechanism is incomplete, and the patients show a syndromic clinical presentation. We report the case of a family with 4 women, of 3 different generations, carrying an unbalanced X;7 translocation with a derivative X;7 chromosome and showing a skewed X inactivation pattern with a preferential activation of the normal X. None of the carriers show intellectual disability, and all of them have a very mild clinical presentation mainly characterized by gynecological/hormonal issues and autoimmune disorders. We underline the necessity of family testing for a correct genetic consultation, especially in the field of prenatal diagnosis. We indeed discuss the fact that X;autosome translocations may lead to self-immunization, as skewed X chromosome inactivation has already been proved to be related to autoimmune disorders.