bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum zonulin and its diagnostic performance in non-coeliac gluten sensitivity
Authors: Barbaro Maria Raffaella , Cremon Cesare , Morselli-Labate Antonio Maria , Di Sabatino Antonio , Giuffrida Paolo , Corazza Gino Roberto , Di Stefano Michele , Caio Giacomo , Latella Giovanni , Ciacci Carolina , Fuschi Daniele , Mastroroberto Marianna , Bellacosa Lara , Stanghellini Vincenzo , Volta Umberto , Barbara Giovanni
Published: February 2020

Objective

Non-coeliac gluten sensitivity (NCGS) is characterised by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing foods, in the absence of coeliac disease (CD) and wheat allergy. No biomarkers are available to diagnose NCGS and the gold standard double-blind placebo-controlled gluten challenge is clinically impractical. The aim of our work was to investigate the role of serum zonulin as a diagnostic biomarker of NCGS and to develop a diagnostic algorithm.

Design

In a multicentre study, we enrolled 86 patients with either self-reported or double-blind confirmed NCGS, 59 patients with diarrhoea-predominant IBS (IBS-D), 15 patients with CD and 25 asymptomatic controls (AC). Zonulin serum levels were assessed and the associated diagnostic power calculated. Clinical and symptomatic data were recorded. The effect of diet on zonulin levels was evaluated in a subgroup of patients with NCGS.

Results

Compared with ACs, the NCGS, irrespective of modality of diagnosis, and patients with CD had significantly increased levels of zonulin, as did both NCGS and patients with CD compared with participants with IBS-D. Self-reported NCGS showed increased zonulin levels compared with double-blind confirmed and not-confirmed NCGS. Six-month wheat avoidance significantly reduced zonulin levels only in HLA-DQ2/8-positive participants with NCGS. The diagnostic accuracy of zonulin levels in distinguishing NCGS from IBS-D was 81%. After exclusion of CD, a diagnostic algorithm combining zonulin levels, symptoms and gender improved the accuracy to 89%.

Conclusion

Zonulin can be considered a diagnostic biomarker in NCGS and combined with demographic and clinical data differentiates NCGS from IBS-D with high accuracy. Wheat withdrawal was associated with a reduction in zonulin levels only in NCGS carrying HLA genotype.
Associations between metabolites and pancreatic cancer risk in a large prospective epidemiological study
Authors: Stolzenberg-Solomon Rachael , Derkach Andriy , Moore Steven , Weinstein Stephanie J , Albanes Demetrius , Sampson Joshua
Published: February 2020

Objective

To assess whether prediagnostic metabolites were associated with incident pancreatic ductal adenocarcinoma (PDAC) in a prospective cohort study.

Design

We conducted an untargeted analysis of 554 known metabolites measured in prediagnostic serum (up to 24 years) to determine their association with incident PDAC in a nested case-control study of male smokers (372 matched case-control sets) and an independent nested case-control study that included women and non-smokers (107 matched sets). Metabolites were measured using Orbitrap Elite or Q-Exactive high-resolution/accurate mass spectrometers. Controls were matched to cases by age, sex, race, date of blood draw, and follow-up time. We used conditional logistic regression adjusted for age to calculate ORs and 95% CIs for a 1 SD increase in log-metabolite level separately in each cohort and combined the two ORs using a fixed-effects meta-analysis.

Results

Thirty-one metabolites were significantly associated with PDAC at a false discovery rate <0.05 with 12 metabolites below the Bonferroni-corrected threshold (p<9.04×10–5). Similar associations were observed in both cohorts. The dipeptides glycylvaline, aspartylphenylalanine, pyroglutamylglycine, phenylalanylphenylalanine, phenylalanylleucine and tryptophylglutamate and amino acids aspartate and glutamate were positively while the dipeptides tyrosylglutamine and α-glutamyltyrosine, fibrinogen cleavage peptide DSGEGDFXAEGGGVR and glutathione-related amino acid cysteine-glutathione disulfide were inversely associated with PDAC after Bonferroni correction. Five top metabolites demonstrated significant time-varying associations (p<0.023) with the strongest associations observed 10–15 years after participants’ blood collection and attenuated thereafter.

Conclusion

Our results suggest that prediagnostic metabolites related to subclinical disease, γ-glutamyl cycle metabolism and adiposity/insulin resistance are associated with PDAC.
Comparison between two different next generation sequencing platforms for clinical relevant gene mutation test in solid tumours
Authors: Bessi Silvia , Pepe Francesco , Ottaviantonio Marco , Pisapia Pasquale , Malapelle Umberto , Troncone Giancarlo , Biancalani Mauro
Published: February 2020

In the present study, we analysed 44 formalin fixed paraffin embedded (FFPE) from different solid tumours by adopting two different next generation sequencing platforms: GeneReader (QIAGEN, Hilden, Germany) and Ion Torrent (Thermo Fisher Scientific, Waltham, Massachusetts, USA). We highlighted a 100% concordance between the platforms. In addition, focusing on variant detection, we evaluated a very good agreement between the two tests (Cohen’s kappa=0.84) and, when taking into account variant allele fraction value for each variant, a very high concordance was obtained (Pearson’s r=0.94). Our results underlined the high performance rate of GeneReader on FFPE samples and its suitability in routine molecular predictive practice.
Can there be wrongful life at the end of life? German courts revisit an old problem in a new context
Authors: Pfeifer Ulrich , Horn Ruth
Published: February 2020

This article discusses a recent ruling by the German Federal Court concerning medical professional liability due to potentially unlawful clinically assisted nutrition and hydration (CANH) at the end of life. This case raises important ethical and legal questions regarding a third person’s right to judge the value of another person’s life and the concept of ‘wrongful life’. In our brief report, we discuss the concepts of the ‘value of life’ and wrongful life, which were evoked by the court, and how these concepts apply to the present case. We examine whether and to what extent value-of-life judgements can be avoided in medical decision-making. The wrongful-life concept is crucial to the understanding of this case. It deals with the question whether life, even when suffering is involved, could ever be worse than death. The effects of this ruling on medical and legal practice in Germany are to be seen. It seems likely that it will discourage claims for compensation following life-sustaining treatment (LST). However, it is unclear to what extent physicians’ decisions will be affected, especially those concerning withdrawal of CANH. We conclude that there is a risk that LST may come to be seen as the ‘safe’ option for the physician, and hence, as always appropriate.
Join the Lone Kidney Club: incentivising live organ donation
Authors: Glas Annet
Published: February 2020

Given the dramatic shortage of transplantable organs, demand cannot be met by established and envisioned organ procurement policies targeting postmortem donation. Live organ donation (LOD) is a medically attractive option, and ethically permissible if informed consent is given and donor beneficence balances recipient non-maleficence. Only a few legal and regulatory frameworks incentivise LOD, with the key exception of Israel’s Organ Transplant Law, which has produced significant improvements in organ donation rates. Therefore, I propose an organ procurement system that incentivises LOD by allocating additional priority points to the living donor on any transplant waiting list. I outline benefits and challenges for potential recipients, donors and society at large, and suggest measures to ensure medical protection of marginalised patient groups.
Inhibition of autophagy improves resistance and enhances sensitivity of gastric cancer cells to cisplatin
Authors: Hou Guiqin , Bai Yiru , Jia Ang , Ren Yandan , Wang Yang , Lu Jie , Wang Peng , Zhang Jianying , Lu Zhaoming
Published: February 2020

Autophagy plays critical roles in tumorigenesis, while the effects of autophagy on chemoresistance of cancer cells had great disparity. This study aims to explore the impacts of autophagy on the sensitivity and resistance of gastric cancer cells to cisplatin (DDP). We firstly demonstrated that there was stronger autophagy activity in gastric cancer SGC-7901 cells than that in DDP-resisting SGC-7901/DDP cells. Then, we discovered that inhibiting autophagy by chloroquine (CQ) significantly enhanced the proliferation-inhibiting and apoptosis-inducing effects of DDP to SGC-7901 and SGC-7901/DDP cells. Moreover, CQ could partially reverse the resistance of SGC-7901/DDP cells to DDP in a concentration-dependent manner. However, the autophagy inducer everolimus (RAD001) had no obvious effects on the sensitivity of gastric cells to DDP. Mechanistically, we demonstrated that CQ might enhance the sensitivity of SGC-7901cells and improve the resistance of SGC-7901/DDP cells to DDP through inhibiting the mTORC1 pathway, especially to SGC-7901/DDP cells. Additionally, we found interfering Beclin-1 using Beclin-1 shRNA also enhanced the proliferation-inhibiting and apoptosis-inducing effects of DDP on gastric cancer cells by inhibiting phosphorylation of Akt. Our study shows that inhibiting autophagy could improve the chemoresistance and enhanced sensitivity of gastric cancer cells to DDP and provide a rationale for the administration of cisplatin combined with CQ for treating patients with gastric cancer.
First-principles study on composition-dependent properties of quaternary InP1−x−yNxBiy alloys
Authors: Chen Yingjie , Zhu Pengfei , Wu Liyuan , Chen Xianchun , Lu Pengfei
Published: February 2020

The content of bismuth and nitrogen can strongly affect the physical properties of III–V semiconductors and have a decisive impact on their performance in applications. Using first-principles calculations, we systematically study the geometry, electronic and optical properties of [Formula: see text] aligned in special quasirandom structures (SQS). The incorporation of a small amount of N and Bi can effectively tune the band gap of pristine InP. For the same number of P atoms being substituted, co-doping mode reduced the bond length disparity and the corresponding formation energy was also smaller than that of only nitrogen doped. Since the bismuth doped increases spin-orbit splitting energy [Formula: see text], the Auger recombination and intervalence band absorption (IVBA) processes are found to be suppressed for quaternary [Formula: see text] (4.40 [Formula: see text]m), [Formula: see text] (12.04 [Formula: see text]m) and [Formula: see text] (9.12 [Formula: see text]m) alloys, which provides new feasibility in the future mid-wavelength infrared and long-wavelength infrared (MWIR/LWIR) device applications.
Characterizing the Dynamics of the Watt Governor System Under Harmonic Perturbation and Gaussian Noise
Authors: Rosa Lucas A. S. , Prebianca Flavio , Hoff Anderson , Manchein Cesar , Albuquerque Holokx A.
Published: February 2020

We investigate the disturbance on the dynamics of a Watt governor system model due to the addition of a harmonic perturbation and a Gaussian noise, by analyzing the numerical results using two distinct methods for the nonlinear dynamics characterization: (i) the well-known Lyapunov spectrum, and (ii) the 0-1 test for chaos. The results clearly show that for tiny harmonic perturbations only the smallest stable periodic structures (SPSs) immersed in chaotic domains are destroyed, whereas for intermediate harmonic perturbation amplitudes there is the emergence of quasiperiodic motion, with the existence of typical Arnold tongues and, the consequent distortion of the SPSs embedded in the chaotic region. For large enough harmonic perturbations, the SPSs immersed in chaotic domains are suppressed and the dynamics becomes essentially chaotic. Regarding the noise perturbations, it is able to suppress periodic motion even if tiny noise intensities are considered, as analyzed by a periodic attractor subject to different noise intensities. The threshold of noise amplitude for chaos generation in periodic structures is reported by both methods. Additionally, we investigate the robustness of the 0-1 test for chaos characterization in both noiseless and noise cases, and for the first time, we compare the Lyapunov exponents and 0-1 test methods in the parameter-planes. Our findings are generic due to their remarkable agreement with results previously reported for dynamical systems in other contexts.
Convolutional Neural Network Analysis of Recurrence Plots for Anomaly Detection
Authors: Chen Yun , Su Shijie , Yang Hui
Published: February 2020

Recurrence plots are widely used to represent and characterize recurrence behaviors of complex systems. Although the recurrence plot captures a great deal of useful information, very little has been done to leverage convolutional neural networks (CNNs) regarding the learning of recurrence dynamics. In this paper, we develop a new CNN approach to investigate recurrence patterns in multisensor signals for real-time anomaly detection. The proposed methodology is evaluated and validated in both simulation studies and a real-world case study for quality control of a flash welding process, which is commonly used to manufacture anchor chains in the shipbuilding industry. First, we develop a new sensing system to collect electrical-current and electrode-position profiles in the flash welding process. Second, recurrence plots are derived with multisensor signals collected from the manufacturing process of each workpiece in the anchor chain. Third, CNNs are developed to learn workpiece-to-workpiece variations in the recurrence plots. Experimental results show that the proposed CNN models of recurrence plots yield superior performance for anomaly detection of welding quality variations, improving the automation level of flash welding processes.
Mathematical Modeling of Neuronal Logic, Memory and Clocking Circuits
Authors: Lynch Stephen , Borresen Jon , Roach Paul , Kotter Mark , Slevin Mark
Published: February 2020

The differential equations used to model biological neurons and the chemical kinetics involved in synaptic excitation and inhibition have been well-established for a number of decades. For the first time, this paper presents mathematical and computational models of a neuronal binary oscillator half-adder, a neuronal Set-Reset (SR) flip-flop and a simple neuronal clocking circuit, which have all been shown to be noise resistant. In modern computers, the half-adder is the basic component to perform logic, the SR flip-flop is used to store memory and clocking circuits are used to synchronize components in parts of the computer. These novel circuits will provide the world with neuronal assays that can measure the functionality of the neurons and hence provide more information than is available with current technology. The authors are not proposing to build conventional computers with these components (they would be too slow to be practical) but the simple circuits could be used to measure the functionality of diseased circuits which are subjected to certain drugs. Neurological conditions research into Alzheimer’s disease, epilepsy and Parkinson’s disease, for example, would all benefit from this research. These assays for neuronal degradation could have major implications for the National Center for the Replacement, Refinement and Reduction of Animals in Research — otherwise known as the NC3R agenda.
Periodic Solutions of a Delayed Eco-Epidemiological Model with Infection-Age Structure and Holling Type II Functional Response
Authors: Yang Peng , Wang Yuanshi
Published: February 2020

This paper is devoted to the study of a new delayed eco-epidemiological model with infection-age structure and Holling type II functional response. Firstly, the disease transmission rate function among the predator population is treated as the piecewise function concerning the incubation period [Formula: see text] of the epidemic disease and the model is rewritten as an abstract nondensely defined Cauchy problem. Besides, the prerequisite which guarantees the presence of the coexistence equilibrium is achieved. Secondly, via utilizing the theory of integrated semigroup and the Hopf bifurcation theorem for semilinear equations with nondense domain, it is found that the model exhibits a Hopf bifurcation near the coexistence equilibrium, which suggests that this model has a nontrivial periodic solution that bifurcates from the coexistence equilibrium as the bifurcation parameter [Formula: see text] crosses the bifurcation critical value [Formula: see text]. That is, there is a continuous periodic oscillation phenomenon. Finally, some numerical simulations are shown to support and extend the analytical results and visualize the interesting phenomenon.
Multilayer Network from Multiple Entropies for Characterizing Gas-Liquid Nonlinear Flow Behavior
Authors: Gao Zhong-Ke , Lv Dong-Mei , Dang Wei-Dong , Liu Ming-Xu , Hong Xiao-Lin
Published: February 2020

Characterizing nonlinear dynamic behaviors underlying multiphase flow has attracted considerable attention from the nonlinear research field. In this paper, the authors develop a novel multiple entropy-based multilayer network (MEMN) for exploring the complex gas-liquid two-phase flow. At first, we carry out the gas-liquid flow experiments to get the multichannel measurements. Then, MEMN is constructed based on the fusion of three nonlinear entropies, namely weighted permutation entropy (WPE), wavelet packet energy entropy (WPEE), and amplitude entropy (AE). For each derived projection network of MEMN, spectral radius and global clustering coefficient are both calculated and they allow effectively uncovering the nonlinear flow behaviors in the transition of different gas-liquid flow patterns. In addition, we perform wavelet time-frequency representation for the two typical flow patterns and the results support our findings well. All these demonstrate that our MEMN framework can effectively characterize the nonlinear evolution of gas-liquid flow from the perspective of complex network theory. And this also provides a novel idea for studying nonlinear complex systems from the observed multivariate time series.
A Study of the Dynamics of a New Piecewise Smooth Map
Authors: Biswas Dhrubajyoti , Seth Soumyajit , Bor Mita
Published: February 2020

In this article, we have studied a [Formula: see text]D map, which is formed by combining the two well-known maps, i.e. the tent and the logistic maps in the unit interval, i.e. [Formula: see text]. The point of discontinuity of the map (known as border) denotes the transition from tent map to logistic map. The proposed map can behave as the piecewise smooth or nonsmooth map or both (depending on the behavior of the map just before and after the border) and the dynamics of the map has been studied using analytical tools and numerical simulations. Characterization has been done by primarily studying the Lyapunov exponents and the corresponding bifurcation diagrams. Some peculiar dynamics of this map have been shown numerically. Finally, a Simulink implementation of the proposed map has been demonstrated.
Controllable Electrochemical Synthesis of Ag Hierarchical Micro/Nanostructures with High SERS-Activity
Authors: Zhou Huayu , Wang Jingjing , Yang Qiong , Chen Menglei , Song Changsheng , Pan Jiaqi , Chen Qing , Li Chaorong
Published: February 2020

We report a one-step electrochemical deposition technique to prepare three-dimensional (3D) Ag hierarchical micro/nanostructured film consisting of well-crystallized Ag nanosheets grown on an indium tin oxide (ITO) conductive substrate. The Ag hierarchical micro/nanostructures were fabricated in the mixed solution of AgNO3 and sodium citrate in a constant current system at room temperature. Through reduction of Ag[Formula: see text] electrodeposited on the surface of ITO substrate, nanoparticles were grown to form nanosheets which further combined into 3D sphere-like microstructures. The 3D Ag micro/nanostructures have many sharp edges and nanoscale gaps which can give rise to good Raman-enhanced effect. Due to localized surface plasmon resonance (LSPR) effects, these special Ag micro/nanostructures exhibited good Raman-enhanced performance. Using Rhodamine 6G (R6G) molecules as probe molecule, we studied the influence of excitation wavelength on Raman enhancement. The results showed that the 532[Formula: see text]nm excitation wavelength is the best to obtain the strongest Raman signal and to reduce the influence of other impurity peaks. Using the as-synthesized Ag hierarchical micro/nanostructures, we can detect the 10[Formula: see text][Formula: see text]mol/L R6G aqueous solution, exhibiting great Raman-enhanced effect.
The stationary distribution and stochastic persistence for a class of disease models: Case study of malaria
Authors: Wanduku Divine
Published: February 2020

This paper presents a nonlinear family of stochastic SEIRS models for diseases such as malaria in a highly random environment with noises from the disease transmission and natural death rates, and also from the random delays of the incubation and immunity periods. Improved analytical methods and local martingale characterizations are applied to find conditions for the disease to persist near an endemic steady state, and also for the disease to remain permanently in the system over time. Moreover, the ergodic stationary distribution for the stochastic process describing the disease dynamics is defined, and the statistical characteristics of the distribution are given numerically. The results of this study show that the disease will persist and become permanent in the system, regardless of (1) whether the noises are from the disease transmission rate and/or from the natural death rates or (2) whether the delays in the system are constant or random for individuals in the system. Furthermore, it is shown that “weak” noise is associated with the existence of an endemic stationary distribution for the disease, while “strong” noise is associated with extinction of the population over time. Numerical simulation examples for Plasmodium vivax malaria are given.
On
Oanducystis
(col.) Stukalina (Crinoidea) from the Craighead Limestone Formation, Girvan district, Ayrshire
Authors: Donovan Stephen K. , Clark Neil D.L.
Published: February 2020

Only two nominal species of crinoid, the diplobathrid camerates
Diabolocrinus craigheadensis
Ramsbottom and
Diabolocrinus globularis
(Nicholson and Etheridge), have been described from the Ordovician (Chatfieldian; Sandbian) Craighead Limestone Formation, Craighead Quarry, near Girvan, Ayrshire. In contrast, columnal morphotaxa are represented by over 20 taxa including those in open nomenclature. Two thecae from Craighead Quarry and referred to
Diabolocrinus
sp. or spp. preserve features of the stem facet that are similar to specimens referred to
Oanducystis
(col.) spp. from the same locality. These columnal morphotaxa are synonymized with
Diabolocrinus
and left in open nomenclature. However,
Diabolocrinus
is limited to Laurentia, whereas the remaining morphospecies of
Oanducystis
(col.) Stukalina are limited to Kazakhstan and Estonia.
Challenging endocrinology students with a critical-thinking workbook
Authors: Daemicke Alexandra K. , Galt Nicholas J. , Samonds Karen E. , Bergan-Roller Heather E.
Published: February 2020

A central goal of science education is to help students develop higher order thinking skills to enable them to face the challenges of life. Accordingly, science instructors are now urged to craft their classrooms such that they serve as not only spaces for disseminating information, but also an arena through which students are encouraged to think scientifically and develop critical-thinking skills. This project aimed to develop a workbook that helps postsecondary students learn endocrinology and engages them in critical thinking. Each of the five chapters focuses on a different topic rooted within core biological concepts relevant to endocrinology. Such topics were identified on cross-referencing seminal reports on science education. Tenants of Numrich’s Sequence of Critical-Thinking Tasks were used to guide the development of chapter sections with the intent of engaging students in critical thinking over time by way of practice and scaffolded guidance. Chapter sections of modeling, event sequencing, clinical application, research and communication, and simulation, target different skills presented in Numrich’s framework. Students’ learning, experiences, and behaviors were used to evaluate the workbook and inform the revision of the workbook into the publicly available second edition.
Determinants of self-regulated learning skills: the roles of tutors and students
Authors: Demirören Meral , Turan Sevgi , Taşdelen Teker Gülşen
Published: February 2020

Problem-based learning (PBL) is an instructional method that offers students the opportunity to develop self-regulatory strategies as an explicit learning outcome. As a multifaceted PBL environment, the guidance of tutors is important to students as they develop self-regulatory learning (SRL) skills and self-efficacy, the most focused motivational element in SRL. The present study examines the relationship between academic achievement and PBL self-efficacy levels, as well as the role played by tutors. A cross-sectional study was conducted with third- year medical students ( n = 257; 75%). The SRL perception (SRLP) scale, the self-efficacy for PBL scale (SPBL), tutor evaluation scale (TES), and an achievement test were used to gather data in this study. In every scale, participant scores were higher than the midpoint, which is 3. There were positive correlations between SRL, self-efficacy, and the tutoring scores of tutors. As the correlation between SRLP and achievement was not significant, achievement was removed from the regression equation, and only SPBL and TES results were used. The results of the regression analysis indicated that SPBL and TES explained 36% of the variance. The level of self-efficacy in PBL predicted the students’ SRL abilities, as did tutor evaluations. The findings show that students used their SRL skills and had beliefs about their ability to learn effectively in the PBL context. Both the tutors’ tutoring skills and the students’ self-efficacy made important contributions to improving the students’ self-regulated learning skills.
DNA damage-free iPS cells exhibit potential to yield competent cardiomyocytes
Authors: Miller Jessica M. , Mardhekar Nikhil M. , Pretorius Danielle , Krishnamurthy Prasanna , Rajasekaran Namakkal Soorappan , Zhang Jianyi , Kannappan Ramaswamy
Published: February 2020

DNA damage accrued in induced pluripotent stem cell (iPSC)-derived cardiomyocytes during in vitro culture practices lessens their therapeutic potential. We determined whether DNA-damage-free iPSCs (DdF-iPSCs) can be selected using stabilization of p53, a transcription factor that promotes apoptosis in DNA-damaged cells, and differentiated them into functionally competent DdF cardiomyocytes (DdF-CMs). p53 was activated using Nutlin-3a in iPSCs to selectively kill the DNA-damaged cells, and the stable DdF cells were cultured further and differentiated into CMs. Both DdF-iPSCs and DdF-CMs were then characterized. We observed a significant decrease in the expression of reactive oxygen species and DNA damage in DdF-iPSCs compared with control (Ctrl) iPSCs. Next-generation RNA sequencing and Ingenuity Pathway Analysis revealed improved molecular, cellular, and physiological functions in DdF-iPSCs. The differentiated DdF-CMs had a compact beating frequency between 40 and 60 beats/min accompanied by increased cell surface area. Additionally, DdF-CMs were able to retain the improved molecular, cellular, and physiological functions after differentiation from iPSCs, and, interestingly, cardiac development network was prominent compared with Ctrl-CMs. Enhanced expression of various ion channel transcripts in DdF-CMs implies DdF-CMs are of ventricular CMs and mature compared with their counterparts. Our results indicated that DdF-iPSCs could be selected through p53 stabilization using a small-molecule inhibitor and differentiated into ventricular DdF-CMs with fine-tuned molecular signatures. These iPSC-derived DdF-CMs show immense clinical potential in repairing injured myocardium.

NEW & NOTEWORTHY Culture-stress-induced DNA damage in stem cells lessens their performance. A robust small-molecule-based approach, by stabilizing/activating p53, to select functionally competent DNA-damage-free cells from a heterogeneous population of cells is demonstrated. This protocol can be adopted by clinics to select DNA-damage-free cells before transplanting them to the host myocardium. The intact DNA-damage-free cells exhibited with fine-tuned molecular signatures and improved cellular functions. DNA-damage-free cardiomyocytes compared with control expressed superior cardiomyocyte functional properties, including, but not limited to, enhanced ion channel signatures. These DNA-intact cells would better engraft, survive, and, importantly, improve the cardiac function of the injured myocardium.
A Prediction Model for Concrete Cracks due to Chloride‐Induced Corrosion
Authors: Wang Jiao , Li Ling , Zhang X. G. , Zhao Yangang
Published: February 2020

The nonhomogeneity of concrete leads to randomness in the development and extension of cracks. Scholars have proposed different models to analyze the development of cracks. Different from existing works on crack development, in this paper, we establish a crack spacing model on the basis of the mechanical equilibrium relation of differential elements. We also establish a mechanical equilibrium model considering that the shrinkage of concrete is constrained by the bonding force of reinforced concrete. Then, on the basis of the equilibrium condition, we propose an analytical model of spacing between the first crack and the second crack at the interface of steel and concrete due to corrosion expansion. This calculation model has only three variables: tensile strength, effective constraint length of the reinforcement, and bond force. In addition, the parameters are clearly defined. We verified the development of cracks at the interface between steel bar and concrete under chloride corrosion at different locations in a steel bar by comparing it with existing simulations and experimental results. The analytical model proposed in this paper has an accuracy of 92%, indicating that our expression for crack spacing can effectively predict the location of cracks.
Wind Pressure Coefficients Zoning Method Based on an Unsupervised Learning Algorithm
Authors: Li Danyu , Liu Bin , Cheng Yongfeng
Published: February 2020

Damage of the cladding structures usually occurs from the wind-sensitive part, which can cause the damaged conditions to obviously vary from different areas especially on a large roof surface. It is necessary to design optimization due to the difference of wind loads by defining more accurate wind pressure coefficient (WPC) zones according to the wind vulnerability analysis. The existing wind pressure coefficient zoning methods (WPCZM) have successfully been used to characterize the simple roof shapes. But the solutions for the complex and irregular roof shapes generally rely on the empirical judgment which is defective to the wind loading analysis. In this study, a classification concept for WPC values on the roof surface is presented based on the unsupervised learning algorithm, which is not limited by the roof geometry and can realize the multitype WPC zoning more accurately. As a typical unsupervised learning algorithm, an improved K-means clustering is proposed to develop a new WPCZM to verify the above concept. And a method to determine the optimal K-value is presented by using the K-means clustering test and clustering validity indices to overcome the difficulty of obtaining the cluster number in the traditional methods. As an example, the most unfavorable pressure and suction WPC zones are studied on a flat roof structure with single wind direction and full wind direction based on the data obtained from the wind tunnel test. As another example, the mean pressure coefficient zones are studied on a saddle roof structure under 0- and 45-degree wind direction based on the data obtained by the wind tunnel test. And the proposed WPCZM is illustrated and verified.
Electrode Afterload: A Valuable Technique in a Case of Short Electrode Insertion
Authors: Riemann C. , Scholz S. , Sudhoff H. , Todt I.
Published: February 2020

Introduction. The location of the electrode inside the cochlea is important for speech performance. However, many variables, including array length, insertion depth, and individual anatomy, may affect the intracochlear position of the electrode. Insertion deeper than 20 mm and revision surgery are critical situations in which residual hearing and electrode integrity may be at risk. This case report challenges this hypothesis and raises the following question: is it possible to achieve a better speech understanding with an electrode afterload without compromising residual hearing? Case Report. A 73-year-old female patient showed up for evaluation of hearing loss. The patient was operated four times in an external hospital due to cholesteatoma formation in the right ear. Related to a poor aided speech understanding, a CI-surgery was performed. 5 months after the surgery, the subject returned with poor speech understanding. A revision surgery was performed, where the first white marker of the electrode was seen in the round window (20 mm). The electrode was inserted 4 mm deeper into the cochlea. After six and twelve months, the results of the Freiburger monosyllabic speech test improved till 25% and 45%, respectively. Discussion. Hearing preservation is possible with a revisional deeper insertion from 20 mm to 24 mm. In this case, a partial obliteration of an open cavity made the electrode surgically easily accessible. This allowed the deeper insertion during the revision surgery. In a regular surgical field with a posterior tympanotomy, the revision surgery is more challenging and brings the electrode into the risk of an iatrogenic destruction. Conclusion. This case of an electrode afterload after having inserted the electrode initially to mm, demonstrates that hearing can be preserved and speech perception can improve after performing this maneuver.
Empirical Study on the Transparency of Security Risk Information in Chinese Listed Pharmaceutical Enterprises Based on the ANP-DS Method
Authors: Wang Jining , Guo Chong , Chen Tingqiang
Published: February 2020

Frequent outbreaks of drug safety incidents pose a massive threat to public health and safety, while the transparency of security risk information in medical enterprises is not optimistic. Therefore, this study uses the analytic network process (Dempster-Shafer method) to construct a transparent comprehensive evaluation model for security risk information in listed pharmaceutical enterprises from the perspective of government supervision and listed pharmaceutical enterprises. On the basis of 59,305 data obtained by 303 enterprises listed in the Chinese biomedical sector, this research conducted an empirical study on the transparency of safety risk information in Chinese listed pharmaceutical enterprises. The current study found that the transparency of security risk information in Chinese listed pharmaceutical enterprises is generally between “general” and “relatively good” and tends to be “relatively good.” However, administrative punishment information, adverse drug reaction reporting systems, and production processes need continuous improvement.
Efficacy of Tocilizumab in Limbic Encephalitis with Anti-CASPR2 Antibodies
Authors: Benucci Maurizio , Tramacere Luciana , Infantino Maria , Manfredi Mariangela , Grossi Valentina , Damiani Arianna , Gobbi Francesca Li , Piccininni Maristella , Zaccara Gaetano , Cincotta Massimo
Published: February 2020

We report the case of a 64-year-old man who presented with subacute memory, balance impairment, behavioral and mood changes, and epileptic seizures. Magnetic resonance imaging (MRI) showed bilateral hippocampal abnormalities. Brain [18F]-FDG fluorodeoxyglucose positron emission tomography (PET) revealed hypometabolism in both the temporal lobe as well as in the left insular and parietal regions. The clinical and neuroradiological picture and the detection of anti-CASPR2 antibodies in serum oriented the diagnosis towards autoimmune limbic encephalitis. Intravenous high-dose steroid and immunoglobulin treatments were ineffective. We did not use rituximab for the presence of antibodies to HbcAg positivity. Tocilizumab given intravenously 8 mg/kg once a month for six months and then subcutaneously 162 mg every week for six months resulted in clinical and neuroradiological improvement. These data support the efficacy of tocilizumab in autoimmune limbic encephalitis associated with anti-CASPR2 antibodies, which has been sporadically reported in the literature.
Interleukin-9 Deletion Relieves Vascular Dysfunction and Decreases Blood Pressure via the STAT3 Pathway in Angiotensin II-Treated Mice
Authors: Yang Yunzhao , Tang Shaoqun , Zhai Chunchun , Zeng Xin , Liu Qingjian , Xu Cheng , Chen Hexiang
Published: February 2020

Background. Multiple interleukin (IL) family members were reported to be closely related to hypertension. We aimed to investigate whether IL-9 affects angiotensin II- (Ang II-) induced hypertension in mice. Methods. Mice were treated with Ang II, and IL-9 expression was determined. In addition, effects of IL-9 knockout (KO) on blood pressure were observed in Ang II-infused mice. To determine whether the effects of IL-9 on blood pressure was mediated by the signal transducer and activator of the transcription 3 (STAT3) pathway, Ang II-treated mice were given S31-201. Furthermore, circulating IL-9 levels in patients with hypertension were measured. Results. Ang II treatment increased serum and aortic IL-9 expression in a dose-dependent manner; IL-9 levels were the highest in the second week and continued to remain high into the fourth week after the treatment. IL-9 KO downregulated proinflammatory cytokine expression, whereas it upregulated anti-inflammatory cytokine levels, relieved vascular dysfunction, and decreased blood pressure in Ang II-infused mice. IL-9 also reduced smooth muscle 22α (SM22α) expression and increased osteopontin (OPN) levels both in mice and in vitro. The effects of IL-9 KO on blood pressure and inflammatory response were significantly reduced by S31-201 treatment. Circulating IL-9 levels were significantly increased in patients with the hypertension group than in the control group, and elevated IL-9 levels positively correlated with both systolic blood pressure and diastolic blood pressure in patients with hypertension. Conclusions. IL-9 KO alleviates inflammatory response, prevents phenotypic transformation of smooth muscle, reduces vascular dysfunction, and lowers blood pressure via the STAT3 pathway in Ang II-infused mice. IL-9 might be a novel target for the treatment and prevention of clinical hypertension.
Remote Aircraft Target Recognition Method Based on Superpixel Segmentation and Image Reconstruction
Authors: Chen Yantong , Li Yuyang , Wang Junsheng
Published: February 2020

Satellite images are always with complex background and shadow areas. These factors can lead to target segmentation break up and recognition with a low accuracy. Aiming at solving these problems, we proposed an aircraft recognition method based on superpixel segmentation and reconstruction. First, we need to estimate the orientation of an aircraft by using histograms of oriented gradients. And then, an improved Simple Linear Iterative Cluster (SLIC) superpixel segmentation algorithm is provided. By comparing texture feature instead of color feature space, we cluster the pixels that are with the same features. Last, through target template images and orientation, we reconstruct the superpixels. Also, the lowest error matching ratio is the recognized target. The test results show that the algorithm is robust to noise and recognize more aircrafts. Especially, when the satellite images with complex background and shadow areas, our method recognizes accuracy better than other methods. It can satisfy the demand of satellite image aircraft recognition.
Natural Products and Their Bioactive Compounds: Neuroprotective Potentials against Neurodegenerative Diseases
Authors: Mohd Sairazi Nur Shafika , Sirajudeen K. N. S.
Published: February 2020

In recent years, natural products, which originate from plants, animals, and fungi, together with their bioactive compounds have been intensively explored and studied for their therapeutic potentials for various diseases such as cardiovascular, diabetes, hypertension, reproductive, cancer, and neurodegenerative diseases. Neurodegenerative diseases, including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis are characterized by the progressive dysfunction and loss of neuronal structure and function that resulted in the neuronal cell death. Since the multifactorial pathological mechanisms are associated with neurodegeneration, targeting multiple mechanisms of actions and neuroprotection approach, which involves preventing cell death and restoring the function to damaged neurons, could be promising strategies for the prevention and therapeutic of neurodegenerative diseases. Natural products have emerged as potential neuroprotective agents for the treatment of neurodegenerative diseases. This review focused on the therapeutic potential of natural products and their bioactive compounds to exert a neuroprotective effect on the pathologies of neurodegenerative diseases.
Energy-Efficient Robust Control for Direct Drive and Energy Recuperation Hydraulic Servo System
Authors: Wang Weiping , Zhao Jiyun
Published: February 2020

During the vertical cyclic actuation process of heavy materials handling, the gravitational potential energy will be converted to heat in the form of throttle in the traditional hydraulic system. Therefore, large energy dissipation is inevitable is this process. In order to achieve energy recuperation, as well as precise trajectory tracking, a direct drive and energy recuperation system is developed. To be specific, the function of direct drive and energy recovery is realized via the three-chamber actuator and a hydraulic accumulator. Moreover, the optimized parameters are obtained by the simulated annealing algorithm. To further reduce the energy consumption, the variable supply pressure control circuit is introduced into the system. Furthermore, the prescribed tracking performance is guaranteed by the proposed robust controller. To compensate for the uncertainties, both in the variable supply pressure control circuit and the robust controller, the RBF neural network is employed to approximate the unknown function. The presented approach theoretically possesses the ability to minimize the energy consumption while maintaining satisfied tracking accuracy. The results demonstrate that the proposed approach can save nearly 90 percent of the energy, and the maximum tracking error is 2 mm.
Percutaneous Atrial Septal Defect Closure Using the Occlutech Figulla Device in Adults: More than 800 Patient-Years of Follow-Up
Authors: Snijder R. J. R. , Renes L. E. , Bosshardt D. , Suttorp M. J. , ten Berg J. M. , Post M. C.
Published: February 2020

Purpose. The Occlutech Figulla occluder has been proven safe and effective at midterm follow-up after percutaneous atrial septal defect (ASD) closure. We describe the safety and efficacy at long-term follow-up in adults. Methods. All consecutive adult patients that underwent ASD closure between 2008 and 2015 were included. All complications were registered. Residual left-to-right shunt (LRS) was diagnosed using color-Doppler transthoracic echocardiography (TTE). Right-to-left shunting was diagnosed using contrast TTE. Successful closure was defined as no LRS at follow-up. Results. In total, 166 patients (mean age 56.7 ± 16.1 years; 62% female) underwent percutaneous ASD closure using the Occlutech Flex I (70%) or Flex II (30%) device (diameter 24 mm; range 10–40 mm) under general anaesthesia and transoesophageal echocardiographic guidance. Long-term follow-up data were available for 144 patients (87%) with a mean follow-up of 5.9 ± 2.6 years, a total of 814 patient-years. During hospitalization, device embolization occurred in three patients (1.8%) with successful extraction in all. During the long-term follow-up, 15 patients (9.8%) suffered new-onset atrial fibrillation and stroke occurred in 2.1%. There was no residual LRS at 12-month follow-up. No device embolization occurred during the long-term follow-up. Conclusion. Percutaneous ASD closure using the Occlutech device appears to be safe at long-term follow-up with a high successful closure rate at one year.
Fragility of Bridge Columns under Vehicle Impact Using Risk Analysis
Authors: Kim Kyeongjin , Lee Jaeha
Published: February 2020

In this study, risk analysis was conducted to evaluate the vulnerability of bridge columns to vehicle impact. A three‐step risk analysis procedure was used. The first step involved a Preliminary Risk Analysis (PRA), which was an initial screening step to determine whether a bridge column requires second‐step analysis or not. The second step was a Simplified Risk Analysis (SRA), which involved determining the level of risk (low, moderate, or high) for a bridge column. The third step comprised a Detailed Risk Analysis (DRA). Computer simulation was based on the results of SRA. In this study, the risk level of 8,267 bridges in South Korea was evaluated, and a resulting total of 58 bridge columns in the Risk Level High (RLH) category were selected as a result of SRA. These bridge columns were classified into five types based on their slenderness ratio. Using these five types of bridge column, DRA was conducted. As expected, larger deformations of the bridge column were observed if the vehicle velocity and slenderness ratio were both increased. Using the bridge columns in the categories of response high and response moderate under vehicle impact, fragility curves were proposed using statistical data of material strength and the few results of the numerical analysis.