bluuebunny/crossref_metadata_2025 huggingface dataset:
So not mothers: responsibility for surrogate orphans
Authors: Parks Jennifer A , Murphy Timothy F
Published: April 2018

The law ordinarily recognises the woman who gives birth as the mother of a child, but in certain jurisdictions, it will recognise the commissioning couple as the legal parents of a child born to a commercial surrogate. Some commissioning parents have, however, effectively abandoned the children they commission, and in such cases, commercial surrogates may find themselves facing unexpected maternal responsibility for children they had fully intended to give up. Any assumption that commercial surrogates ought to assume maternal responsibility for abandoned children runs contrary to the moral suppositions that typically govern contract surrogacy, in particular, assumptions that gestational carriers are not ‘mothers’ in any morally significant sense. In general, commercial gestational surrogates are almost entirely conceptualised as ‘vessels’. In a moral sense, it is deeply inconsistent to expect commercial surrogates to assume maternal responsibility simply because commissioning parents abandon children for one reason or another. We identify several instances of child abandonment and discuss their implications with regard to the moral conceptualisation of commercial gestational surrogates. We conclude that if gestational surrogates are to remain conceptualised as mere vessels, they should not be expected to assume responsibility for children abandoned by commissioning parents, not even the limited responsibility of giving them up for adoption or surrendering them to the state.
Gaussian Discriminant Analysis for Optimal Delineation of Mild Cognitive Impairment in Alzheimer’s Disease
Authors: Fang Chen , Li Chunfei , Cabrerizo Mercedes , Barreto Armando , Andrian Jean , Rishe Naphtali , Loewenstein David , Duara Ranjan , Adjouadi Malek
Published: April 2018

Over the past few years, several approaches have been proposed to assist in the early diagnosis of Alzheimer’s disease (AD) and its prodromal stage of mild cognitive impairment (MCI). Using multimodal biomarkers for this high-dimensional classification problem, the widely used algorithms include Support Vector Machines (SVM), Sparse Representation-based classification (SRC), Deep Belief Networks (DBN) and Random Forest (RF). These widely used algorithms continue to yield unsatisfactory performance for delineating the MCI participants from the cognitively normal control (CN) group. A novel Gaussian discriminant analysis-based algorithm is thus introduced to achieve a more effective and accurate classification performance than the aforementioned state-of-the-art algorithms. This study makes use of magnetic resonance imaging (MRI) data uniquely as input to two separate high-dimensional decision spaces that reflect the structural measures of the two brain hemispheres. The data used include 190 CN, 305 MCI and 133 AD subjects as part of the AD Big Data DREAM Challenge #1. Using 80% data for a 10-fold cross-validation, the proposed algorithm achieved an average F1 score of 95.89% and an accuracy of 96.54% for discriminating AD from CN; and more importantly, an average F1 score of 92.08% and an accuracy of 90.26% for discriminating MCI from CN. Then, a true test was implemented on the remaining 20% held-out test data. For discriminating MCI from CN, an accuracy of 80.61%, a sensitivity of 81.97% and a specificity of 78.38% were obtained. These results show significant improvement over existing algorithms for discriminating the subtle differences between MCI participants and the CN group.
Control of a 7-DOF Robotic Arm System With an SSVEP-Based BCI
Authors: Chen Xiaogang , Zhao Bing , Wang Yijun , Xu Shengpu , Gao Xiaorong
Published: April 2018

Although robot technology has been successfully used to empower people who suffer from motor disabilities to increase their interaction with their physical environment, it remains a challenge for individuals with severe motor impairment, who do not have the motor control ability to move robots or prosthetic devices by manual control. In this study, to mitigate this issue, a noninvasive brain-computer interface (BCI)-based robotic arm control system using gaze based steady-state visual evoked potential (SSVEP) was designed and implemented using a portable wireless electroencephalogram (EEG) system. A 15-target SSVEP-based BCI using a filter bank canonical correlation analysis (FBCCA) method allowed users to directly control the robotic arm without system calibration. The online results from 12 healthy subjects indicated that a command for the proposed brain-controlled robot system could be selected from 15 possible choices in 4[Formula: see text]s (i.e. 2[Formula: see text]s for visual stimulation and 2[Formula: see text]s for gaze shifting) with an average accuracy of 92.78%, resulting in a 15 commands/min transfer rate. Furthermore, all subjects (even naive users) were able to successfully complete the entire move-grasp-lift task without user training. These results demonstrated an SSVEP-based BCI could provide accurate and efficient high-level control of a robotic arm, showing the feasibility of a BCI-based robotic arm control system for hand-assistance.
Experimental and theoretical aspects of thermodynamic properties of quasi-1D and quasi-2D organic conductors and superconductors
Authors: Nakazawa Y. , Kruchinin S.
Published: April 2018

We deal with thermodynamic features of organic conductors and superconductors where itinerant [Formula: see text]-electrons/holes released from organic molecules are playing essential roles for electronic properties. Since they are low-dimensional electronic systems with relatively soft lattice framework, they show variety of phenomena related to electron correlations and electron–lattice coupling. The drastic changes of conductive and magnetic properties owing to quantum features of [Formula: see text]-electrons can be induced by external perturbations such as magnetic/electric field, pressure, etc. It is especially emphasized that the possible mechanism and relation with other phenomena of the superconductivity in [Formula: see text]-electrons system remains to be one of the interesting research areas in fundamental condensed matter science. In this review paper, we consider several topics of organic conductors and superconductors from the standpoints of thermodynamic experiments, data analyses and theories performed up to now. Starting from the overall picture of the electronic states in charge transfer complexes, thermodynamic properties of the quasi-one-dimensional systems, quasi-two-dimensional systems and [Formula: see text]–d interacting systems are reviewed. The thermodynamic parameters of the superconductive compounds in them are compared and discussed. The relations with crystal structures, electronic states, phase diagram and other experiments are also discussed in comparison with these thermodynamic properties. The possible pairing symmetries in organic superconductors and some models are mentioned in the last part. This review deals with a wide scope of theoretical and experimental topics in superconductivity in molecule-based conductive systems.
Ground effect on a self-propelled undulatory foil
Authors: Zhang Dong , Chao Liming , Pan Guang
Published: April 2018

The unsteady ground effect on a self-propelled undulatory foil is numerically investigated in this paper. The situation can be widely found in nature especially for fish swimming near the ground. In this study, frequency varies from 0.1 Hz to 2 Hz and distance from the ground varies from 0.2 L to 1 L. Under most kinematics, the ground has a negative effect on the performance of the foil. The swimming velocity slows down, power spend increases and swimming economy reduces. The higher frequency can produce a larger negative effect. Only at the low frequencies f = 0.1 Hz, 0.25 Hz and 0.5 Hz with distance of 0.2 L the velocity can be enhanced by 18%, 6%, 0.8%, respectively. The lift production is found to be increased. The link between the performance and the wake dynamics is also established by studying the vortex structures.
A bandpass sigma-delta modulator with the function of adjustable center-frequency
Authors: Di Xin Peng , Chen Wei Ping , Liu Xiao Wei , Fan Ling Yun
Published: April 2018

A bandpass sigma-delta modulator with the function of adjustable center-frequency is present in this paper. A method used to convert 2-order low-pass modulator to 4-order bandpass modulator is proposed to realize the design. Center-frequency that can be set to 1/6, 1/4 and 1/3 of sampling frequency is controlled according to the digital logic voltage. The bandwidth of pass-band is 200 Hz. Test results show that the average SNR is about 80 dB at different center-frequency when the sampling frequency is 64 kHz. The input signal can reach to −3 dBFs. The complexity to design a variable center-frequency bandpass modulator is greatly reduced.
High Step-Up Boost-Fly-Back Converter with Soft Switching for Photovoltaic Applications
Authors: Haghshenas Ghasem , Mehdi Mirtalaei Sayyed Mohammad , Mordmand Hamed , Shahgholian Ghazanfar
Published: April 2018

In this paper, a novel high step-up single switch DC–DC converter with soft switching is presented. The main application of this converter is the connection of photovoltaic (PV) system to a 400[Formula: see text]V DC-bus. The proposed converter achieves high step-up voltage gain with small duty cycle by a combined boost and fly-back topology. Also, its switch voltage stress is lower than the output voltage. Besides, in the proposed converter, any auxiliary switch or magnetic core has not been used — therefore, the number of converter components has not been increased much in comparison with the conventional boost-fly-back converter. The operation principles of the converter and its theoretical operation waveforms are presented. In order to evaluate the theoretical analysis, a prototype of the converter is designed and experimentally implemented. The practical results are presented for a 100[Formula: see text]W boost-fly-back converter with input voltage of 40[Formula: see text]V and output voltage of 400[Formula: see text]V. Also, the output capacitor is designed to have less than 1% ripple on output voltage.
Chaotic Motions in Forced Mixed Rayleigh–Liénard Oscillator with External and Parametric Periodic-Excitations
Authors: Miwadinou C. H. , Monwanou A. V. , Koukpemedji A. A. , Kpomahou Y. J. F. , Chabi Orou J. B.
Published: April 2018

This paper addresses the issue of a mixed Rayleigh–Liénard oscillator with external and parametric periodic-excitations. The Melnikov method is utilized to analytically determine the domain boundaries where horseshoe chaos appears. Routes to chaos are investigated through bifurcation structures, Lyapunov exponents, phase portraits and Poincaré sections. The effects of Rayleigh and Liénard parameters are analyzed. Results of analytical investigations are validated and complemented by numerical simulations.
Nonlinear Dynamics of a Multistage Gear Transmission System with Multi-Clearance
Authors: Xiang Ling , Zhang Yue , Gao Nan , Hu Aijun , Xing Jingtang
Published: April 2018

The nonlinear torsional model of a multistage gear transmission system which consists of a planetary gear and two parallel gear stages is established with time-varying meshing stiffness, comprehensive gear error and multi-clearance. The nonlinear dynamic responses are analyzed by applying the reference of backlash bifurcation parameters. The motions of the system on the change of backlash are identified through global bifurcation diagram, largest Lyapunov exponent (LLE), FFT spectra, Poincaré maps, the phase diagrams and time series. The numerical results demonstrate that the system exhibits rich features of nonlinear dynamics such as the periodic motion, nonperiodic states and chaotic states. It is found that the sun-planet backlash has more complex effect on the system than the ring-planet backlash. The motions of the system with backlash of parallel gear are diverse including some different multi-periodic motions. Furthermore, the state of the system can change from chaos into quasi-periodic behavior, which means that the dynamic behavior of the system is composed of more stable components with the increase of the backlash. Correspondingly, the parameters of the system should be designed properly and controlled timely for better operation and enhancing the life of the system.
Dynamic Network Interdiction Problem with Uncertain Data
Authors: Soleimani-Alyar Maryam , Ghaffari-Hadigheh Alireza
Published: April 2018

This paper proposes an uncertain multi-period bi-level network interdiction problem with uncertain arc capacities. It is proved that there exists an equivalence relationship between uncertain multi-period network interdiction problem and the obtained deterministic correspondent. Application of the generalized Benders’ decomposition algorithm is considered as the solution approach to the resulting mixed-integer nonlinear programming problem. Finally, a numerical example is presented to illustrate the model and the algorithm.
High-dimensional quantum key agreement protocol with pairs of single qudits
Authors: He Jianhao , Li Lvzhou , Huang Yifan , Situ Haozhen , Qiu Daowen
Published: April 2018

In this paper, we propose a high-dimensional quantum key agreement protocol where the key is encoded by pairs of single qudits which are chosen from d-level mutually unbiased bases. A security analysis is also given to show it is secure against most of the existing attacks. This protocol is useful in practice and has a higher information transmission ability because it uses high-dimensional quantum information carries.
Quasiconformal maps on a 2-step Carnot group
Authors: Gardiner Christopher James , Xie Xiangdong
Published: April 2018

We find all global quasiconformal maps (with respect to the Carnot metric) on a particular [Formula: see text]-step Carnot group. In particular, all the global quasiconformal maps of this Carnot group permute the left cosets of the center, verifying a conjecture by Xie for this particular case.
Coverage Control of Multiple Unmanned Aerial Vehicles: A Short Review
Authors: Huang Sunan , Teo Rodney Swee Huat , Leong William Wai Lun , Martinel Niki , Forest Gian Luca , Micheloni Christian
Published: April 2018

A multiple unmanned aerial vehicle (MUAV) system is a group of vehicles that are designed with the aim to perform some collective behavior. Coverage control is one of the most active research fields in MUAVs. As MUAVs are nowadays widely used in many application areas, the research in the coverage control problem has become a hot point. Although several coverage control methods have been reported, there is a lack of work highlighting the features of these methods. In this paper, we present a survey of the most relevant works in this area, classifying the types of these works and describing the main contributions in their works.
Garnet–monazite rare earth element relationships in sub-solidus metapelites: a case study from Bhutan
Authors: Warren Clare J. , Greenwood Lucy V. , Argles Tom W. , Roberts Nick M. W. , Parrish Randall R. , Harris Nigel B. W.
Published: April 2018

A key aim of modern metamorphic geochronology is to constrain precise and accurate rates and timescales of tectonic processes. One promising approach in amphibolite and granulite-facies rocks links the geochronological information recorded in zoned accessory phases such as monazite to the pressure–temperature information recorded in zoned major rock-forming minerals such as garnet. Both phases incorporate rare earth elements (REE) as they crystallize and their equilibrium partitioning behaviour potentially provides a useful way of linking time to temperature. We report REE data from sub-solidus amphibolite-facies metapelites from Bhutan, where overlapping ages, inclusion relationships and Gd/Lu ratios suggest that garnet and monazite co-crystallized. The garnet–monazite REE relationships in these samples show a steeper pattern across the heavy (H)REE than previously reported. The difference between our dataset and the previously reported data may be due to a temperature-dependence on the partition coefficients, disequilibrium in either dataset, differences in monazite chemistry or the presence or absence of a third phase that competed for the available REE during growth. We urge caution against using empirically-derived partition coefficients from natural samples as evidence for, or against, equilibrium of REE-bearing phases until monazite–garnet partitioning behaviour is better constrained.
β1-Subunit of the calcium-sensitive potassium channel modulates the pulmonary vascular smooth muscle cell response to hypoxia
Authors: Barnes Elizabeth A. , Lee Lori , Barnes Shayna L. , Brenner Robert , Alvira Cristina M. , Cornfield David N.
Published: April 2018

Accessory subunits associated with the calcium-sensitive potassium channel (BKCa), a major determinant of vascular tone, confer functional and anatomical diversity. The β1 subunit increases Ca2+ and voltagesensitivity of the BKCa channel and is expressed exclusively in smooth muscle cells. Evidence supporting the physiological significance of the β1 subunit includes the observations that murine models with deletion of the β1 subunit are hypertensive and that humans with a gain-of-function β1 mutation are at a decreased risk of diastolic hypertension. However, whether the β1 subunit of the BKCa channel contributes to the low tone that characterizes the normal pulmonary circulation or modulates the pulmonary vascular response to hypoxia remains unknown. To determine the role of the BKCa channel β1 subunit in the regulation of pulmonary vascular tone and the response to acute and chronic hypoxia, mice with deletion of the Kcnmb1 gene that encodes for the β1 subunit ( Kcnmb1−/−) were placed in chronic hypoxia (10% O2) for 21–24 days. In normoxia, right ventricular systolic pressure (RVSP) did not differ between Kcnmb1+/+ (controls) and Kcnmb1−/− mice. After exposure to either acute or chronic hypoxia, RVSP was higher in Kcnmb1−/− mice compared with Kcnmb1+/+ mice, without increased vascular remodeling. β1 subunit expression was predominantly confined to pulmonary artery smooth muscle cells (PASMCs) from vessels ≤ 150 µm. Peripheral PASMCs contracted collagen gels irrespective of β1 expression. Focal adhesion expression and Rho kinase activity were greater in Kcnmb1−/− compared with Kcnmb1+/+ PASMCs. Compromised PASMC β1 function may contribute to the heightened microvascular vasoconstriction that characterizes pulmonary hypertension.
Activation of the NF-κB pathway alters the phenotype of MSCs in the tracheal aspirates of preterm infants with severe BPD
Authors: Reicherzer Tobias , Häffner Susanne , Shahzad Tayyab , Gronbach Judith , Mysliwietz Josef , Hübener Christoph , Hasbargen Uwe , Gertheiss Jan , Schulze Andreas , Bellusci Saverio , Morty Rory E. , Hilgendorff Anne , Ehrhardt Harald
Published: April 2018

Mesenchymal stromal cells (MSCs) are released into the airways of preterm infants following lung injury. These cells display a proinflammatory phenotype and are associated with development of severe bronchopulmonary dysplasia (BPD). We aimed to characterize the functional properties of MSCs obtained from tracheal aspirates of 50 preterm infants who required invasive ventilation. Samples were separated by disease severity. The increased proliferative capacity of MSCs was associated with longer duration of mechanical ventilation and higher severity of BPD. Augmented growth depended on nuclear accumulation of NFκBp65 and was accompanied by reduced expression of cytosolic α-smooth muscle actin (α-SMA). The central role of NF-κB signaling was confirmed by inhibition of IκBα phosphorylation. The combined score of proliferative capacity, accumulation of NFκBp65, and expression of α-SMA was used to predict the development of severe BPD with an area under the curve (AUC) of 0.847. We mimicked the clinical situation in vitro, and stimulated MSCs with IL-1β and TNF-α. Both cytokines induced similar and persistent changes as was observed in MSCs obtained from preterm infants with severe BPD. RNA interference was employed to investigate the mechanistic link between NFκBp65 accumulation and alterations in phenotype. Our data indicate that determining the phenotype of resident pulmonary MSCs represents a promising biomarker-based approach. The persistent alterations in phenotype, observed in MSCs from preterm infants with severe BPD, were induced by the pulmonary inflammatory response. NFκBp65 accumulation was identified as a central regulatory mechanism. Future preclinical and clinical studies, aimed to prevent BPD, should focus on phenotype changes in pulmonary MSCs.
Recent developments in 3-D reconstruction and stereology to study the pulmonary vasculature
Authors: Mühlfeld Christian , Wrede Christoph , Knudsen Lars , Buchacker Tobias , Ochs Matthias , Grothausmann Roman
Published: April 2018

Alterations of the pulmonary vasculature are an important feature of human lung diseases such as chronic obstructive pulmonary disease, pulmonary hypertension, and bronchopulmonary dysplasia. Experimental studies to investigate the pathogenesis or a therapeutic intervention in animal models of these diseases often require robust, meaningful, and efficient morphometric data that allow for appropriate statistical testing. The gold standard for obtaining such data is design-based stereology. However, certain morphological characteristics of the pulmonary vasculature make the implementation of stereological methods challenging. For example, the alveolar capillary network functions according to the sheet flow principle, thus making unbiased length estimations impossible and requiring other strategies to obtain mechanistic morphometric data. Another example is the location of pathological changes along the branches of the vascular tree. For developmental defects like in bronchopulmonary dysplasia or for pulmonary hypertension, it is important to know whether certain segments of the vascular tree are preferentially altered. This cannot be overcome by traditional stereological methods but requires the combination of a three-dimensional data set and stereology. The present review aims at highlighting the great potential while discussing the major challenges (such as time consumption and data volume) of this combined approach. We hope to raise interest in the potential of this approach and thus stimulate solutions to overcome the existing challenges.
Beneficial impacts of regular exercise on platelet function in sedentary older adults: evidence from a randomized 6-mo walking trial
Authors: Haynes Andrew , Linden Matthew D. , Robey Elisa , Naylor Louise H. , Ainslie Philip N. , Cox Kay L. , Lautenschlager Nicola T. , Green Daniel J.
Published: April 2018

Platelet activation, including the formation of monocyte platelet aggregates (MPAs), contributes to atherosclerosis, thrombus formation, and acute coronary syndromes. Regular participation in exercise can lower cardiovascular risk, but little is known regarding the impact of exercise training on platelet function. We investigated the effect of 6 mo of walking exercise on platelet function in sedentary older adults without significant cardiovascular disease. Twenty-seven participants were randomly allocated to 6 mo of either: no-exercise ( n = 13) or 3 × 50 min/wk of supervised center-based walking ( n = 14). Circulating and agonist-induced MPAs were assessed using flow cytometry before [ month 0 (0M)] and after [ month 6 (6M)] the intervention. Circulating MPAs increased from 0M (3.7 ± 1.0%) to 6M (4.7 ± 1.6%) in the no-exercise group ( P = 0.009), whereas a nonsignificant decrease was observed in the walking group (0M 4.3 ± 1.7 vs. 6M 3.7 ± 1.2 %, P = 0.052). The change in MPAs between groups was significant ( P = 0.001). There were no differences between groups in platelet responses to agonists across the interventions (all P > 0.05). Collectively, these data suggest that the absence of regular exercise may increase MPAs, which are cellular mediators involved in atherosclerosis, while regular walking inhibits such increases. The thrombotic function of platelets appears to be relatively unaltered by exercise training. This study provides novel data related to the cardioprotective effects associated with participation in exercise.

NEW & NOTEWORTHY Monocyte-platelet aggregates contribute to atherosclerosis and exercise can lower cardiovascular risk. This is the first study to discover that a lack of regular physical activity is associated with increased monocyte-platelet aggregates over a 6-mo intervention period. In contrast, walking exercise inhibits increased monocyte-platelet aggregates in the circulation. This study highlights a novel pathway by which regular participation in exercise exerts its cardioprotective effects.
Left Functional Pneumonectomy Caused by a Very Rare Giant Intrathoracic Cystic Lesion in a Patient with Gorham–Stout Syndrome: Case Report and Review of the Literature
Authors: Tasis Nikolaos , Tsouknidas Ioannis , Ioannidis Argyrios , Nassiopoulos Konstantinos , Filippou Dimitrios
Published: April 2018

Gorham–Stout syndrome is an uncommon entity, with few cases reported in bibliography. It consists of osteolytic manifestations affecting various bones and replacing them with lymphangiomatous tissue. With pathophysiology unknown, Gorham–Stout disease affects also cardiorespiratory system usually causing lytic lesions to the bones of the thoracic cage or directly invading the thoracic duct. This is a case report of a unique respiratory manifestation of the disease and a review of its cardiorespiratory complications.
Optimum Assembly Sequence Planning System Using Discrete Artificial Bee Colony Algorithm
Authors: Özmen Özkan , Batbat Turgay , Özen Tolgan , Sinanoğlu Cem , Güven Ayşegül
Published: April 2018

Assembly refers both to the process of combining parts to create a structure and to the product resulting therefrom. The complexity of this process increases with the number of pieces in the assembly. This paper presents the assembly planning system design (APSD) program, a computer program developed based on a matrix-based approach and the discrete artificial bee colony (DABC) algorithm, which determines the optimum assembly sequence among numerous feasible assembly sequences (FAS). Specifically, the assembly sequences of three-dimensional (3D) parts prepared in the computer-aided design (CAD) software AutoCAD are first coded using the matrix-based methodology and the resulting FAS are assessed and the optimum assembly sequence is selected according to the assembly time optimisation criterion using DABC. The results of comparison of the performance of the proposed method with other methods proposed in the literature verify its superiority in finding the sequence with the lowest overall time. Further, examination of the results of application of APSD to assemblies consisting of parts in different numbers and shapes shows that it can select the optimum sequence from among hundreds of FAS.
Traumatic Penile Pain: A Case of Dorsal Vein Thrombophlebitis after Intercourse
Authors: Kennebrew Garry J. , Daggett Benjamin , Ritz Reis B.
Published: April 2018

Dorsal Vein thrombosis, also known as Mondor’s disease of the penis, is a superficial thrombophlebitis first described in the literature by Falco in 1955. Mondor’s disease refers to a superficial thrombophlebitis of any locale. Diagnosis can be made clinically with palpation of a mobile, cord-like thickening on dorsum of penis without associated evidence of inflammation, infection, or dermatologic changes. Bedside ultrasonography with color Doppler can aid in the diagnosis of penile thrombophlebitis by revealing a noncompressible superficial vessel with normal surrounding flow. The following case presentation details the etiology, diagnosis, and management of a particularly rare disease process.
Analysis of Behavioral Economics in Crowdsensing: A Loss Aversion Cooperation Model
Authors: Li Deng , Qiu Liying , Liu Jiaqi , Xiao Congwen
Published: April 2018

The existing incentive mechanisms of crowdsourcing construct the expected utility function based on the assumption of rational people in traditional economics. A large number of studies in behavioral economics have demonstrated the defects of the traditional utility function and introduced a new parameter called loss aversion coefficient to calculate individual utility when it suffers a loss. In this paper, combination of behavioral economics and a payment algorithm based on the loss aversion is proposed. Compared with usual incentive mechanisms, the node utility function is redefined by the loss aversion characteristic of the node. Experimental results show that the proposed algorithm can get a higher rate of cooperation with a lower payment price and has good scalability compared with the traditional incentive mechanism.
From Oxidative Stress Damage to Pathways, Networks, and Autophagy via MicroRNAs
Authors: Engedal Nikolai , Žerovnik Eva , Rudov Alexander , Galli Francesco , Olivieri Fabiola , Procopio Antonio Domenico , Rippo Maria Rita , Monsurrò Vladia , Betti Michele , Albertini Maria Cristina
Published: April 2018

Oxidative stress can alter the expression level of many microRNAs (miRNAs), but how these changes are integrated and related to oxidative stress responses is poorly understood. In this article, we addressed this question by using in silico tools. We reviewed the literature for miRNAs whose expression is altered upon oxidative stress damage and used them in combination with various databases and software to predict common gene targets of oxidative stress‐modulated miRNAs and affected pathways. Furthermore, we identified miRNAs that simultaneously target the predicted oxidative stress‐modulated miRNA gene targets. This generated a list of novel candidate miRNAs potentially involved in oxidative stress responses. By literature search and grouping of pathways and cellular responses, we could classify these candidate miRNAs and their targets into a larger scheme related to oxidative stress responses. To further exemplify the potential of our approach in free radical research, we used our explorative tools in combination with ingenuity pathway analysis to successfully identify new candidate miRNAs involved in the ubiquitination process, a master regulator of cellular responses to oxidative stress and proteostasis. Lastly, we demonstrate that our approach may also be useful to identify novel candidate connections between oxidative stress‐related miRNAs and autophagy. In summary, our results indicate novel and important aspects with regard to the integrated biological roles of oxidative stress‐modulated miRNAs and demonstrate how this type of in silico approach can be useful as a starting point to generate hypotheses and guide further research on the interrelation between miRNA‐based gene regulation, oxidative stress signaling pathways, and autophagy.
UbiCompass: An IoT Interaction Concept
Authors: Alce Günter , Espinoza Andreas , Hartzell Ted , Olsson Staffan , Samuelsson Dennis , Wallergård Mattias
Published: April 2018

Lately, different wearable form factors have reached the consumer domain. Wearables enable at-a-glance access to information and can continually sense the surrounding environment. Internet of Things (IoT) researchers have focused on the main enabling factors: the integration of several technologies and communication solutions. Less effort has been devoted to exploring how not-so-tech-savvy end users can discover and directly interact with the numerous connected things predicted by the IoT vision. This paper presents a novel IoT interaction concept called UbiCompass. A functional, smartwatch face prototype of the UbiCompass was developed and integrated with an existing smart home system, in which five different connected devices could be controlled using simple interaction. It was then compared to a traditional smartphone mobile application in a controlled experiment. The results show statistically significant differences in favor of the proposed concept. This highlights the potential the UbiCompass has as an IoT interaction concept.
CCNV Space-Times as Potential Supergravity Solutions
Authors: Coley A. , McNutt D. , Pelavas N.
Published: April 2018

It is of interest to study supergravity solutions preserving a nonminimal fraction of supersymmetries. A necessary condition for supersymmetry to be preserved is that the space-time admits a Killing spinor and hence a null or time-like Killing vector field. Any space-time admitting a covariantly constant null vector (CCNV) field belongs to the Kundt class of metrics and more importantly admits a null Killing vector field. We investigate the existence of additional non-space-like isometries in the class of higher-dimensional CCNV Kundt metrics in order to produce potential solutions that preserve some supersymmetries.
Circulating MicroRNAs as Biomarkers of Gestational Diabetes Mellitus: Updates and Perspectives
Authors: Guarino Elisa , Delli Poggi Chiara , Grieco Giuseppina Emanuela , Cenci Valeria , Ceccarelli Elena , Crisci Isabella , Sebastiani Guido , Dotta Francesco
Published: April 2018

Gestational diabetes mellitus (GDM) is defined as any degree of carbohydrate intolerance, with onset or first recognition during second or third trimester of gestation. It is estimated that approximately 7% of all pregnancies are complicated by GDM and that its prevalence is rising all over the world. Thus, the screening for abnormal glucose levels is generally recommended as a routine component of care for pregnant women. However, additional biomarkers are needed in order to predict the onset or accurately monitor the status of gestational diabetes. Recently, microRNAs, a class of small noncoding RNAs demonstrated to modulate gene expression, have been proven to be secreted by cells of origin and can be found in many biological fluids such as serum or plasma. Such feature renders microRNAs as optimal biomarkers and sensors of in situ tissue alterations. Furthermore, secretion of microRNAs via exosomes has been reported to contribute to tissue cross talk, thus potentially represents, if disrupted, a mechanistic cause of tissue/cell dysfunction in a specific disease. In this review, we summarized the recent findings on circulating microRNAs and gestational diabetes mellitus with particular focus on the potential use of microRNAs as putative biomarkers of disease as well as a potential cause of GDM complications and β cell dysfunction.
Nonparametric Blind Signal Detection Based on Logarithmic Moments in Very Impulsive Noise
Authors: Luo Jinjun , Wang Shilian , Zhang Eryang , Man Xin
Published: April 2018

The detection problem in impulsive noise modeled by the symmetric alpha stable SαS distribution is studied. The traditional detectors based on the second or higher order moments fail in SαS noise, and the method based on the fractional lower order moments (FLOMs) performs poorly when the noise distribution has small values of characteristic exponent. In this paper, a detector based on the logarithmic moments is investigated. The analytical expressions of the false alarm and detection probabilities are derived in nonfading channels as well as Rayleigh fading channels. The effect of noise uncertainty on the performance is discussed. Simulation results show that the logarithmic detector performs better than the FLOM and Cauchy detectors in very impulsive noise. In addition, the logarithmic detector is a nonparametric method and avoids estimating the parameter of the noise distribution, which makes the logarithmic detector easier to implement than the FLOM detector.
Isolated Pancreatic Tuberculosis Mimicking Pancreatic Cancer: A Diagnostic Challenge
Authors: Bhurwal Abhishek , Haq Muhammad Masoodul , Sapru Sunil , Tortora Matthew , Ramasamy Dhanasekaran
Published: April 2018

Isolated pancreatic tuberculosis is an exceedingly rare condition, even in areas of the world where the disease is highly prevalent. Abdominal tuberculosis is a common form of extrapulmonary tuberculosis but involvement of the pancreas is very rare. We report a case of isolated pancreatic tuberculosis presenting as a pancreatic mass in a patient with persistent abdominal pain and jaundice. Clinically and radiologically, the mass mimicked a malignant pancreatic tumor with a vastly different prognostic implication and therapeutic approach. Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) can provide valuable diagnostic information in this scenario. After the tissue showed evidence of acid-fast bacilli and the cultures showed growth of Mycobacterium tuberculosis, antituberculosis therapy was initiated. Conservative management is usually successful in alleviating symptoms and leading to a cure. The excellent response to ATT makes it imperative that these patients are diagnosed early and managed appropriately to avoid unnecessary surgery and associated morbidity.
Effect of a Sodium and Calcium DL-β-Hydroxybutyrate Salt in Healthy Adults
Authors: Fischer Tobias , Och Ulrike , Klawon Ira , Och Tim , Grüneberg Marianne , Fobker Manfred , Bordewick-Dell Ursula , Marquardt Thorsten
Published: April 2018

Background. Ketone body therapy and supplementation are of high interest for several medical and nutritional fields. The intake of ketone bodies is often discussed in relation to rare metabolic diseases, such as multiple acyl-CoA dehydrogenase deficiency (MADD), that have no alternatives for treatment. Case reports showed positive results of therapy using ketone bodies. The number of ketone body salts offered on the wellness market is increasing steadily. More information on the kinetics of intake, safety, and tolerance of these products is needed.Methods. In a one-dose kinetic study, six healthy subjects received an intervention (0.5 g/kg bw) using a commercially available ketone body supplement. The supplement contained a mixture of sodium and calcium D-/L-β-hydroxybutyrate (βHB) as well as food additives. The blood samples drawn in the study were tested for concentrations of D-βHB, glucose, and electrolytes, and blood gas analyses were done. Data on sensory evaluation and observed side effects of the supplement were collected. The product also went through chemical food analysis.Results. The supplement led to a significant increase of D-βHB concentration in blood 2.5 and 3 h after oral intake (p=0.033;  p=0.043). The first significant effect was measured after 2 h with a mean value of 0.598 ± 0.300 mmol/L at the peak, which was recorded at 2.5 h. Changes in serum electrolytes and BGA were largely unremarkable. Taking the supplement was not without side effects. One subject dropped out due to gastrointestinal symptoms and two others reported similar but milder problems.Conclusions. Intake of a combination of calcium and sodium D-/L-βHB salt shows a slow resorption with a moderate increase of D-βHB in serum levels. An influence ofβHB salts on acid-base balance could not be excluded by this one-dose study. Excessive regular consumption without medical observation is not free of adverse effects. The tested product can therefore not be recommended unconditionally.
FDA Approval Summary: Niraparib for the Maintenance Treatment of Patients with Recurrent Ovarian Cancer in Response to Platinum-Based Chemotherapy
Authors: Ison Gwynn , Howie Lynn J. , Amiri-Kordestani Laleh , Zhang Lijun , Tang Shenghui , Sridhara Rajeshwari , Pierre Vadryn , Charlab Rosane , Ramamoorthy Anuradha , Song Pengfei , Li Fang , Yu Jingyu , Manheng Wimolnut , Palmby Todd R. , Ghosh Soma , Horne Hisani N. , Lee Eunice Y. , Philip Reena , Dave Kaushalkumar , Chen Xiao Hong , Kelly Sharon L. , Janoria Kumar G. , Banerjee Anamitro , Eradiri Okponanabofa , Dinin Jeannette , Goldberg Kirsten B. , Pierce William F. , Ibrahim Amna , Kluetz Paul G. , Blumenthal Gideon M. , Beaver Julia A. , Pazdur Richard
Published: April 2018

The FDA approved niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, on March 27, 2017, for maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response to platinum-based chemotherapy. Approval was based on data from the NOVA trial comparing niraparib with placebo in two independent cohorts, based on germline BRCA mutation status (gBRCAm vs. non-gBRCAm). Progression-free survival (PFS) in each cohort was the primary endpoint. In the gBRCAm cohort, estimated median PFS on niraparib was 21 months versus 5.5 months on placebo [HR, 0.26; 95% confidence interval (CI), 0.17–0.41; P < 0.0001]. In the non-gBRCAm cohort, estimated median PFS for niraparib and placebo was 9.3 and 3.9 months, respectively (HR, 0.45; 95% CI, 0.34–0.61; P < 0.0001). Common adverse reactions (>20% and higher incidence in the niraparib arm) with niraparib included thrombocytopenia, anemia, neutropenia, nausea, constipation, vomiting, mucositis, fatigue, decreased appetite, headache, insomnia, nasopharyngitis, dyspnea, rash, and hypertension. There were five cases of myelodysplastic syndrome and acute myeloid leukemia (1.4%) in patients treated with niraparib compared with two cases (1.1%) on placebo. Niraparib is the first PARP inhibitor approved as maintenance therapy for patients with ovarian, fallopian tube, or primary peritoneal cancer, with improvement in PFS, regardless of gBRCAm status. Clin Cancer Res; 24(17); 4066–71. ©2018 AACR.

See related commentary by Konstantinopoulos and Matulonis, p. 4062
Secretory IgM Exacerbates Tumor Progression by Inducing Accumulations of MDSCs in Mice
Authors: Tang Chih-Hang Anthony , Chang Shiun , Hashimoto Ayumi , Chen Yi-Ju , Kang Chang Won , Mato Anthony R. , Del Valle Juan R. , Gabrilovich Dmitry I. , Hu Chih-Chi Andrew
Published: April 2018

Chronic lymphocytic leukemia (CLL) cells can secrete immunoglobulin M. However, it is not clear whether secretory IgM (sIgM) plays a role in disease progression. We crossed the Eμ-TCL1 mouse model of CLL, in which the expression of human TCL1 oncogene was driven by the V(H) promoter-Ig(H)-Eμ enhancer, with MD4 mice whose B cells produced B-cell receptor (membrane-bound IgM) and sIgM with specificity for hen egg lysozyme (HEL). CLL cells that developed in these MD4/Eμ-TCL1 mice reactivated a parental Ig gene allele and secreted IgM, and did not recognize HEL. The MD4/Eμ-TCL1 mice had reduced survival, increased myeloid-derived suppressor cells (MDSC), and decreased numbers of T cells. We tested whether sIgM could contribute to the accumulation of MDSCs by crossing μS–/– mice, which could not produce sIgM, with Eμ-TCL1 mice. The μS–/–/Eμ-TCL1 mice survived longer than Eμ-TCL1 mice and developed decreased numbers of MDSCs which were less able to suppress proliferation of T cells. We targeted the synthesis of sIgM by deleting the function of XBP-1s and showed that targeting XBP-1s genetically or pharmacologically could lead to decreased sIgM, accompanied by decreased numbers and reduced functions of MDSCs in MD4/Eμ-TCL1 mice. Additionally, MDSCs from μS–/– mice grafted with Lewis lung carcinoma were inefficient suppressors of T cells, resulting in slower tumor growth. These results demonstrate that sIgM produced by B cells can upregulate the functions of MDSCs in tumor-bearing mice to aggravate cancer progression. In a mouse model of CLL, production of secretory IgM led to more MDSCs, fewer T cells, and shorter survival times for the mice. Thus, secretory IgM may aggravate the progression of this cancer. Cancer Immunol Res; 6(6); 696–710. ©2018 AACR.
Non-Cardiac Chest Pain
Authors: Frieling Thomas
Published: April 2018

Background: Non-cardiac chest pain (NCCP) is recurrent angina pectoris-like pain without evidence of coronary heart disease in conventional diagnostic evaluation. The prevalence of NCCP is up to 70% and may be detected (in this order) at all levels of the medical health care system (general practitioner, emergency department, chest pain unit, coronary care). Reduction of quality of life due to NCCP is comparable, and partially even higher, to that caused by cardiac chest pain. Reasons for psychological strain are symptom recurrence in approximately 50%, nonspecific diagnosis with resulting uncertainty, and insufficient integration of other medical disciplines in the diagnostic workup. Methods and Results: The management of patients with chest pain has to be multidisciplinary because non-cardiac causes may be frequently encountered. Especially gastroenterological expertise is required since the cause of chest pain is gastroesophageal reflux disease (GERD) in 50-60%, hypercontractile esophageal motility disorders with nutcracker/jackhammer esophagus or diffuse esophageal spasm or achalasia in 15-18%, and other esophageal alterations (e.g., infectious esophageal inflammation, drug-induced ulcers, rings, webs, eosinophilic esophagitis) in 32-35%. Conclusion: This review highlights the importance of regular interdisciplinary ward rounds and management of chest pain units.
Different Characteristics, Clinical Outcomes, and Left Atrial Reverse Remodeling in Patients with Mitral Stenosis Maintaining Sinus Rhythm for at Least 10 Years after Successful Percutaneous Mitral Valvuloplasty
Authors: Cho In-Jeong , Kim Soo-Jin  , Han Donghee  , Kim Darae , Shim Chi Young , Hong Geu-Ru  , Chang Hyuk-Jae 
Published: April 2018

Background: We aimed to investigate the characteristics and echocardiographic changes in patients with severe mitral stenosis (MS) who maintained sinus rhythm (SR) for at least 10 years after successful percutaneous mitral balloon valvuloplasty (PMV). Methods: We retrospectively reviewed 107 patients who had successful PMV and follow-up echocardiography for at least 10 years without mitral valve surgery. Preprocedural, immediate postprocedural (PMV), and long-term follow-up echocardiography (at least 10 years after PMV) data were reviewed. Results: The mean follow-up time after PMV was 15 ± 4 years for SR patients (n = 50) and 16 ± 4 years (p = 0.172) for atrial fibrillation (AF) patients (n = 57). The left atrial diameter was significantly decreased in SR patients in the follow-up echocardiography images compared to its pre-PMV value (46.7 ± 6.3 vs. 43.3 ± 6.2 mm, respectively), whereas it was significantly increased in patients with AF (53.9 ± 7.1 vs. 58.1 ± 8.7 mm). In multivariate analysis, preprocedural AF (odds ratio [OR] 14.50, p = 0.001) and LA diameter ≥50 mm (OR 8.81, p < 0.001) were independently associated with increased risk for the presence of AF after successful PMV. Conclusion: Very long-term maintenance of SR after successful PMV was associated with preprocedural SR and LA diameter < 50 mm.
Comparison of Different Compression to Ventilation Ratios (2: 1, 3: 1, and 4: 1) during Cardiopulmonary Resuscitation in a Porcine Model of Neonatal Asphyxia
Authors: Pasquin Matteo P. , Cheung Po-Yin , Patel Sparsh , Lu Min , Lee Tze-Fun , Wagner Michael , O’Reilly Megan , Schmölzer Georg M.
Published: April 2018

Background: High-quality chest compression is essential during neonatal cardiopulmonary resuscitation (CPR). However, the optimal compression to ventilation ratio (C:V) that should be used during neonatal CPR to optimize coronary and cerebral perfusion while providing adequate ventilation remains unknown. Objective: We hypothesized that different C:V ratios (e.g., 2: 1 or 4: 1) will reduce the time to return of spontaneous circulation (ROSC) in severely asphyxiated piglets. Methods: Thirty-one newborn piglets (1–4 days old) were anesthetized, intubated, instrumented, and exposed to 50-min normocapnic hypoxia followed by asphyxia. Piglets were randomized into 4 groups: 2: 1 (n = 8), 3: 1 (n = 8), 4: 1 (n = 8) C:V ratio, or a sham group (n = 7). Cardiac function, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment. Results: Thirty-one piglets were included in the study, and there was no difference in the duration of asphyxia or the degree of asphyxiation (as indicated by pH, PaCO2, and lactate) among the different groups. The median (IQR) time to ROSC was similar between the groups with 127 (82–210), 96 (88–126), and 119 (83–256) s in the 2: 1, 3: 1, and 4: 1 C:V ratio groups, respectively (p = 0.67 between groups). Similarly, there was no difference in 100% oxygen requirement or epinephrine administration between the experimental groups. Conclusions: Different C:V ratios resulted in similar ROSC, mortality, oxygen, and epinephrine administration during resuscitation in a porcine model of neonatal asphyxia.