bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Class of Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Contains the Octahydro-2H-chromen-4-ol Scaffold
Authors: Li-Zhulanov Nikolai S. , Zakharenko Alexandra L. , Chepanova Arina A. , Patel Jinal , Zafar Ayesha , Volcho Konstantin P. , Salakhutdinov Nariman F. , Reynisson Jóhannes , Leung Ivanhoe K. H. , Lavrik Olga I.
Published: September 2018

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that mends topoisomerase 1-mediated DNA damage. Tdp1 is a current inhibition target for the development of improved anticancer treatments, as its inhibition may enhance the therapeutic effect of topoisomerase 1 poisons. Here, we report a study on the development of a novel class of Tdp1 inhibitors that is based on the octahydro-2H-chromene scaffold. Inhibition and binding assays revealed that these compounds are potent inhibitors of Tdp1, with IC50 and KD values in the low micromolar concentration range. Molecular modelling predicted plausible conformations of the active ligands, blocking access to the enzymatic machinery of Tdp1. Our results thus help establish a structural-activity relationship for octahydro-2H-chromene-based Tdp1 inhibitors, which will be useful for future Tdp1 inhibitor development work.
Mechanical Behaviors of Angle-Ply Black Phosphorus by Molecular Dynamics Simulations
Authors: Li Lili , Sun Rui , Yang Jie
Published: September 2018

Regular black phosphorus (BP) sheets possess strongly anisotropic properties due to the unique puckered atomistic configuration, making such BP mechanically very weak in the armchair direction. The present work aims to address this issue by proposing an angle-ply double-layer black phosphorus (DLBP) structure in which two individual atomic layers with different orientation angles are stacked up. The molecular dynamics simulations based on Stillinger-Weber potential show that the in-plane mechanical properties of such a DLBP structure, e.g., Young’s modulus and tensile strength are significantly influenced by the stacking angle of each layer. The property anisotropy of DLBP decreases as the stacking angle difference δ between two layers increases and becomes isotropic when δ = 90°. This work also shed insight into mechanisms of angle-ply layers underlying the mechanical behaviors of DLBP at the nanoscale, suggesting that the anisotropic material properties can be effectively controlled and tuned through the appropriately selected stacking angles.
Carbon Wrapped Ni3S2 Nanocrystals Anchored on Graphene Sheets as Anode Materials for Lithium-Ion Battery and the Study on Their Capacity Evolution
Authors: Guan Xianggang , Liu Xuehua , Xu Binghui , Liu Xiaowei , Kong Zhen , Song Meiyun , Fu Aiping , Li Yanhui , Guo Peizhi , Li Hongliang
Published: September 2018

Ni3S2 nanocrystals wrapped by thin carbon layer and anchored on the sheets of reduced graphene oxide (Ni3S2@C/RGO) have been synthesized by a spray-coagulation assisted hydrothermal method and combined with a calcination process. Cellulose, dissolved in Thiourea/NaOH aqueous solution is chosen as carbon sources and mixed with graphene oxide via a spray-coagulation method using graphene suspension as coagulation bath. The resulted cellulose/graphene suspension is utilized as solvent for dissolving of Ni(NO3)2 and then used as raw materials for hydrothermal preparation of the Ni3S2@C/RGO composites. The structure of the composites has been investigated and their electrochemical properties are evaluated as anode material for lithium-ion batteries. The Ni3S2@C/RGO sample exhibits increasing reversible capacities upon cycles and shows a superior rate performance as well. Such kinds of promising performance have been ascribed to the wrapping effect of carbon layer which confines the dislocation of the polycrystals formed upon cycles and the enhanced conductivity as the integration of RGO conductive substrate. Discharge capacities up to 850 and 630 mAh·g−1 at current densities of 200 and 5000 mA·g−1, respectively, are obtained. The evolution of electrochemical performance of the composites with structure variation of the encapsulated Ni3S2 nanocrystals has been revealed by ex-situ TEM and XRD measurements.
Moderation and Mediation Analysis of the Relationship between Total Protein Concentration and the Risk of Depressive Disorders in Older Adults with Function Dependence in Home Care
Authors: Nowicki Grzegorz Józef , Ślusarska Barbara , Bartoszek Agnieszka , Kocka Katarzyna , Deluga Alina , Kachaniuk Hanna , Łuczyk Marta
Published: September 2018

Due to its devastating consequences, late-life depression is an important public health problem. The aim of the study was an analysis of variables which may potentially influence the risk of depression (GDS-SF). Furthermore, the aim was to study possible mediating effects of given variables on the relationship between the total protein concentration and the risk of depression in older adults with chronic diseases, and physical function impairment. The research sample included 132 older adults with chronic conditions and physical function impairments, residing in a long-term care in residential environment. In the studied group of sensory organs, diseases proved to be a significant moderator of the relationship between GDS-SF and total serum protein concentration. A stronger relationship was observed in subjects suffering from diseases of sensory organs (b = −6.42, 95% CI= −11.27; −1.58). The Barthel index and 25(OH)D vitamin were the most significant mediators of the examined relationship. Cohort research is suggested to confirm the hypothesis.
The Ethanol Fraction of White Rose Petal Extract Abrogates Excitotoxicity-Induced Neuronal Damage In Vivo and In Vitro through Inhibition of Oxidative Stress and Proinflammation
Authors: Yon Jung-Min , Kim Yun-Bae , Park Dongsun
Published: September 2018

Since oxidative stress and inflammation are involved in seizure-related neurotoxicity, the neuroprotective effect of a white rose (Rosa hybrida) petal extract (WRPE) in mice that are challenged with kainic acid (KA) were examined using behavioral epileptiform seizures as well as biochemical and morphological parameters of oxidative stress and inflammation. WRPE (50–200 mg/kg) was orally administered to male ICR mice for 15 days, and intraperitoneally challenged with KA (30 mg/kg). Seizure activity, lipid peroxidation, inflammatory cytokines, and related enzymes were analyzed in the brain tissue, in addition to the morphological alterations in the hippocampal pyramidal neurons. Separately, antioxidant ingredients in WRPE were analyzed, and antioxidant, anti-inflammatory, and neuroprotective activities of WRPE were investigated in HB1.F3 human neural stem cells (NSCs) to elucidate underlying mechanisms. Total polyphenol and flavonoid contents in WRPE were 303.3 ± 15.3 mg gallic acid equivalent/g extract and 18.5 ± 2.2 mg catechin/g extract, respectively. WRPE exhibited strong radical-scavenging activities and inhibited lipid peroxidation in vitro, and protected glutamate-induced cytotoxicity in NSCs by suppressing inflammatory process. Treatment with WRPE attenuated epileptiform seizure scores to a half level in KA-challenged mice, and decreased hippocampal pyramidal neuronal injury and loss (cresyl violet and DAPI staining) as well as astrocyte activation (GFAP immunostaining). Lipid peroxidation was inhibited, and mRNA expression of antioxidant enzymes (GPx, PHGPx, SOD1, and SOD2) were recovered in the brain tissues. Inflammatory parameters (cytokines and enzymes) including NF-kB, IL-1β, TNF-α, IL-6, HMGB1, TGF-β, iNOS, COX2, and GFAP mRNAs and proteins were also down-regulated by WRPE treatment. Taken together, the results indicate that WRPE could attenuate KA-induced brain injury through antioxidative and anti-inflammatory activities.
Concepts and Challenges of Biosimilars in Breast Cancer: The Emergence of Trastuzumab Biosimilars
Authors: Uifălean Alina , Ilieş Maria , Nicoară Raul , Rus Lucia Maria , Hegheş Simona Codruţa , Iuga Cristina-Adela
Published: September 2018

With the development of anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibodies, trastuzumab-based therapy has become the standard of care among patients with early or advanced HER2-positive breast cancer. However, real-world data have shown that up to a half of patients do not receive trastuzumab or any other HER2-targeted agent, mainly due to high treatments costs. The prospect of a more enlarged access to trastuzumab treatment lies in the use of biosimilars, as the European and the US patent of the reference products has or will soon expire. Biosimilars are biologics highly similar in terms of quality characteristics, biological activity, safety and efficacy to already approved biologics. The biosimilarity of any European Union (EU)-approved biosimilar is guaranteed based on the comprehensive comparability exercise which includes comparative analytical, non-clinical and clinical studies. In the matter of biosimilars’ interchangeability and substitution, the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) have adopted different positions, triggering various discussions on the potential immunogenicity and efficacy in individual patients. As more biosimilars are gaining approval, the present review aims to offer concise information for oncologists and pharmacists about the production, approval, interchangeability, and substitution policies of biosimilars used in breast cancer therapy, with a special focus on trastuzumab.
Characteristics and Treatment Methods of Medical Waste Incinerator Fly Ash: A Review
Authors: Liu Fang , Liu Han-Qiao , Wei Guo-Xia , Zhang Rui , Zeng Tong-Tong , Liu Gui-Sheng , Zhou Jian-Hua
Published: September 2018

Medical waste incinerator fly ash (MWIFA) is quite different from municipal solid waste incinerator fly ash (MSWIFA) due to its special characteristics of high levels of chlorines, dioxins, carbon constituents, and heavy metals, which may cause irreversible harm to environment and human beings if managed improperly. However, treatment of MWIFA has rarely been specifically mentioned. In this review, various treatment techniques for MSWIFA, and their merits, demerits, applicability, and limitations for MWIFA are reviewed. Natural properties of MWIFA including the high contents of chlorine and carbonaceous matter that might affect the treatment effects of MWIFA are also depicted. Finally, several commendatory and feasible technologies such as roasting, residual carbon melting, the mechanochemical technique, flotation, and microwave treatment are recommended after an overall consideration of the special characteristics of MWIFA, balancing environmental, technological, economical information.
Detecting Short-Term Surface Melt on an Arctic Glacier Using UAV Surveys
Authors: Bash Eleanor A. , Moorman Brian J. , Gunther Allison
Published: September 2018

Current understanding of glacier mass balance changes under changing climate is limited by scarcity of in situ measurements in both time and space, as well as resolution of remote sensing products. Recent innovations in unmanned aerial vehicles (UAVs), as well as structure-from-motion photogrammetry (SfM), have led to increased use of digital imagery to derive topographic data in great detail in many fields, including glaciology. This study tested the capability of UAV surveys to detect surface changes over glacier ice during a three-day period in July 2016. Three UAV imaging missions were conducted during this time over 0.185 km 2 of the ablation area of Fountain Glacier, NU. These were processed with the SfM algorithms in Agisoft Photoscan Professional and overall accuracies of the resulting point clouds ranged from 0.030 to 0.043 m. The high accuracy of point clouds achieved here is primarily a result of a small ground sampling distance (0.018 m), and is also influenced by GPS precision. Glacier surface change was measured through differencing of point clouds and change was compared to ablation stake measurements. Surface change measured with the UAV-SfM method agreed with the coincident ablation stake measurements in most instances, with RMSE values of 0.033, 0.028, and 0.042 m for one-, two-, and three-day periods, respectively. Total specific melt over the study area measured with the UAV was 0.170 m water equivalent (w.e.), while interpolation of ablation measurements resulted in 0.144 m w.e. Using UAVs to measure small changes in glacier surfaces will allow for new investigations of distribution of mass balance measurements.
The Use of Unmanned Aerial Vehicles to Estimate Direct Tangible Losses to Residential Properties from Flood Events: A Case Study of Cockermouth Following the Desmond Storm
Authors: Rivas Casado Monica , Irvine Tracy , Johnson Sarah , Palma Marco , Leinster Paul
Published: September 2018

Damage caused by flood events is expected to increase in the coming decades driven by increased land use pressures and climate change impacts. The insurance sector needs accurate and efficient loss adjustment methodologies for flood events. These can include remote sensing approaches that enable the rapid estimation of (i) damage caused to property as well as (ii) the number of affected properties. Approaches based on traditional remote sensing methods have limitations associated with low-cloud cover presence, oblique viewing angles, and the resolution of the geomatic products obtained. Unmanned aerial vehicles (UAVs) are emerging as a potential tool for post-event assessment and provide a means of overcoming the limitations listed above. This paper presents a UAV-based loss-adjustment framework for the estimation of direct tangible losses to residential properties affected by flooding. For that purpose, features indicating damage to property were mapped from UAV imagery collected after the Desmond storm (5 and 6 December 2015) over Cockermouth (Cumbria, UK). Results showed that the proposed framework provided an accuracy of 84% in the detection of direct tangible losses compared with on-the-ground household-by-household assessment approaches. Results also demonstrated the importance of pluvial and, from eye witness reports, lateral flow flooding, with a total of 168 properties identified as flooded falling outside the fluvial flood extent. The direct tangible losses associated with these additional properties amounted to as high as £3.6 million. The damage-reducing benefits of resistance measures were also calculated and amounted to around £4 million. Differences in direct tangible losses estimated using the proposed UAV approach and the more classic loss-adjustment methods relying on the fluvial flood extent was around £1 million—the UAV approach providing the higher estimate. Overall, the study showed that the proposed UAV approach could make a significant contribution to improving the estimation of the costs associated with urban flooding, and responses to flooding events, at national and international levels.
Analysis of Livorno Heavy Rainfall Event: Examples of Satellite-Based Observation Techniques in Support of Numerical Weather Prediction
Authors: Ricciardelli Elisabetta , Di Paola Francesco , Gentile Sabrina , Cersosimo Angela , Cimini Domenico , Gallucci Donatello , Geraldi Edoardo , Larosa Salvatore , Nilo Saverio Teodosio , Ripepi Ermann , Romano Filomena , Viggiano Mariassunta
Published: September 2018

This study investigates the value of satellite-based observational algorithms in supporting numerical weather prediction (NWP) for improving the alert and monitoring of extreme rainfall events. To this aim, the analysis of the very intense precipitation that affected the city of Livorno on 9 and 10 September 2017 is performed by applying three remote sensing techniques based on satellite observations at infrared/visible and microwave frequencies and by using maps of accumulated rainfall from the weather research and forecasting (WRF) model. The satellite-based observational algorithms are the precipitation evolving technique (PET), the rain class evaluation from infrared and visible observations (RainCEIV) technique and the cloud classification mask coupling of statistical and physics methods (C-MACSP). Moreover, the rain rates estimated by the Italian Weather Radar Network are also considered to get a quantitative evaluation of RainCEIV and PET performance. The statistical assessment shows good skills for both the algorithms (for PET: bias = 1.03, POD = 0.76, FAR = 0.26; for RainCEIV: bias = 1.33, POD = 0.77, FAR = 0.41). In addition, a qualitative comparison among the three technique outputs, rain rate radar maps, and WRF accumulated rainfall maps is also carried out in order to highlight the advantages of the different techniques in providing real-time monitoring, as well as quantitative characterization of rainy areas, especially when rain rate measurements from Weather Radar Network and/or from rain gauges are not available.
Efficient Patch-Wise Semantic Segmentation for Large-Scale Remote Sensing Images
Authors: Liu Yan , Ren Qirui , Geng Jiahui , Ding Meng , Li Jiangyun
Published: September 2018

Efficient and accurate semantic segmentation is the key technique for automatic remote sensing image analysis. While there have been many segmentation methods based on traditional hand-craft feature extractors, it is still challenging to process high-resolution and large-scale remote sensing images. In this work, a novel patch-wise semantic segmentation method with a new training strategy based on fully convolutional networks is presented to segment common land resources. First, to handle the high-resolution image, the images are split as local patches and then a patch-wise network is built. Second, training data is preprocessed in several ways to meet the specific characteristics of remote sensing images, i.e., color imbalance, object rotation variations and lens distortion. Third, a multi-scale training strategy is developed to solve the severe scale variation problem. In addition, the impact of conditional random field (CRF) is studied to improve the precision. The proposed method was evaluated on a dataset collected from a capital city in West China with the Gaofen-2 satellite. The dataset contains ten common land resources (Grassland, Road, etc.). The experimental results show that the proposed algorithm achieves 54.96% in terms of mean intersection over union (MIoU) and outperforms other state-of-the-art methods in remote sensing image segmentation.
Development of a Non-Invasive On-Chip Interconnect Health Sensing Method Based on Bit Error Rates
Authors: Shin Insun , Koo Kyoungmin , Kwon Daeil
Published: September 2018

Electronic products and systems are widely used in industrial network systems, control devices, and data acquisition devices across many industry sectors. Failures of such electronic systems might lead to unexpected downtime, loss of productivity, additional work for repairs, and delay in product and service development. Thus, developing an appropriate sensing technique is necessary, because it is the first step in system fault diagnosis and prognosis. Many sensing techniques often require external and additional sensing devices, which might disturb system operation and consequently increase operating costs. In this study, we present an on-chip health sensing method for non-destructive and non-invasive interconnect degradation detection. Bit error rate (BER), which represents data integrity during digital signal transmission, was selected to sense interconnect health without connecting external sensing devices. To verify the health sensing performance, corrosion tests were conducted with in situ monitoring of the BER and direct current (DC) resistance. The eye size, extracted from the BER measurement, showed the highest separation between the intact and failed interconnect, as well as a gradual transition, compared with abrupt changes in the DC resistance, during interconnect degradation. These experimental results demonstrate the potential of the proposed sensing method for on-chip interconnect health monitoring applications without disturbing system operation.
Reconstructed Order Analysis-Based Vibration Monitoring under Variable Rotation Speed by Using Multiple Blade Tip-Timing Sensors
Authors: Chen Zhongsheng , Liu Jianhua , Zhan Chi , He Jing , Wang Weimin
Published: September 2018

On-line vibration monitoring is significant for high-speed rotating blades, and blade tip-timing (BTT) is generally regarded as a promising solution. BTT methods must assume that rotating speeds are constant. This assumption is impractical, and blade damages are always formed and accumulated during variable operational conditions. Thus, how to carry out BTT vibration monitoring under variable rotation speed (VRS) is a big challenge. Angular sampling-based order analyses have been widely used for vibration signals in rotating machinery with variable speeds. However, BTT vibration signals are well under-sampled, and Shannon’s sampling theorem is not satisfied so that existing order analysis methods will not work well. To overcome this problem, a reconstructed order analysis-based BTT vibration monitoring method is proposed in this paper. First, the effects of VRS on BTT vibration monitoring are analyzed, and the basic structure of angular sampling-based BTT vibration monitoring under VRS is presented. Then a band-pass sampling-based engine order (EO) reconstruction algorithm is proposed for uniform BTT sensor configuration so that few BTT sensors can be used to extract high EOs. In addition, a periodically non-uniform sampling-based EO reconstruction algorithm is proposed for non-uniform BTT sensor configuration. Next, numerical simulations are done to validate the two reconstruction algorithms. In the end, an experimental set-up is built. Both uniform and non-uniform BTT vibration signals are collected, and reconstructed order analysis are carried out. Simulation and experimental results testify that the proposed algorithms can accurately capture characteristic high EOs of synchronous and asynchronous vibrations under VRS by using few BTT sensors. The significance of this paper is to overcome the limitation of conventional BTT methods of dealing with variable blade rotating speeds.
Unobtrusive Photoplethysmographic Monitoring Under the Foot Sole while in a Standing Posture
Authors: Hong Seunghyeok , Park Kwang Suk
Published: September 2018

Photoplethysmography (PPG) of the foot sole could provide additional health-related information compared with traditional PPG of the finger or wrist. Previously, foot PPG required the procedural binding of a light-emitting diode (LED)-photodetector (PD) pair. We achieved PPG of the foot sole without binding any sensors to the foot while the participant stood in a natural standing position on the testing device. Foot PPG was performed using multiple LED-PD pairs to overcome motion artefacts caused by stabilization. We identified regions of the sole suitable for reliable sensor positioning with optimal LED-PD pairs on the basis of the estimated heart rate (HR) and signal quality index derived by dynamic time warping (wSQI). The first experiment included four participants with direct skin-to-sensor contact, and the results showed a mean HR estimation error of 0.01 beats/min and a wSQI of 0.909. The extended experiment with 53 participants, which involved including a gap between the skin and sensors to consider real-life applications, yielded a mean HR estimation error of 0.638 beats/min and a wSQI of 0.751. Based on the selection ratio of optimal LED-PD pairs, the best region of the sole for PPG was the midfoot, except the medial longitudinal arch. In conclusion, we confirmed that foot PPG using multiple LED-PD pairs is appropriate for HR evaluation and further applications.
The Simplification of Biological Diversity in International and EU Law
Authors: Josefsson Henrik
Published: September 2018

Every system that manages or assesses biodiversity rests on a simplification of its complexity. The simplification of biodiversity is debatable and difficult; even, for example, regarding the elements on which the assessment and management should focus. Nevertheless, within law, there are assessment and management schemes that are based on a simplified understanding of the meaning of [the construct of] ‘biodiversity’. For example, the Ecosystem Approach, European Union (EU) Habitats Directive, and the EU Water Framework Directive try to assess the status of different biodiversity elements based on their different ‘biodiversity’ simplifications. As the conservation of biodiversity is a vital global question, it is important to include the right elements within the ‘biodiversity’ construct to achieve no net loss. Based on international and EU law, I conceptualize a consistent legal simplification of ‘biodiversity’.
An Efficient Approach for Coordination of Dual-Channel Closed-Loop Supply Chain Management
Authors: Arshad Muhammad , Khalid Qazi Salman , Lloret Jaime , Leon Antonio
Published: September 2018

In this paper, a closed-loop supply chain composed of dual-channel retailers and manufacturers, a dynamic game model under the direct recovery, and an entrusted third-party recycling mode of the manufacturer is constructed. The impact of horizontal fairness concern behavior is introduced on the pricing strategies and utility of decision makers under different recycling models. The equilibrium strategy at fair neutrality is used as a reference to compare offline retails sales. Research shows that in the closed-loop supply chain of dual-channel sales, whether in the case of fair neutrality or horizontal fairness concerns, the manufacturer’s direct recycling model is superior to the entrusted third-party recycling, and the third-party recycling model is transferred by the manufacturer. In the direct recycling model, the horizontal fairness concern of offline retailers makes two retailers in the positive supply chain compete to lower the retail price in order to increase market share. Manufacturers will lower the wholesale price to encourage competition, and the price will be the horizontal fairness concern coefficient, which is negatively correlated. In the reverse supply chain, manufacturers increase the recycling rate of used products. This pricing strategy increases the utility of manufacturers and the entire supply chain system compared to fair neutral conditions, while two retailers receive diminished returns. Manufacturers, as channel managers to encourage retailers to compete for price cuts, can be coordinated through a three-way revenue sharing contract to achieve Pareto optimality.
Generalized Neutrosophic Soft Expert Set for Multiple-Criteria Decision-Making
Authors: Uluçay Vakkas , Şahin Memet , Hassan Nasruddin
Published: September 2018

Smarandache defined a neutrosophic set to handle problems involving incompleteness, indeterminacy, and awareness of inconsistency knowledge, and have further developed it neutrosophic soft expert sets. In this paper, this concept is further expanded to generalized neutrosophic soft expert set (GNSES). We then define its basic operations of complement, union, intersection, AND, OR, and study some related properties, with supporting proofs. Subsequently, we define a GNSES-aggregation operator to construct an algorithm for a GNSES decision-making method, which allows for a more efficient decision process. Finally, we apply the algorithm to a decision-making problem, to illustrate the effectiveness and practicality of the proposed concept. A comparative analysis with existing methods is done and the result affirms the flexibility and precision of our proposed method.
Relationships between the Toxicities of Radix Aconiti Lateralis Preparata (Fuzi) and the Toxicokinetics of Its Main Diester-Diterpenoid Alkaloids
Authors: Yang Mengbi , Ji Xiaoyu , Zuo Zhong
Published: September 2018

The processed lateral root of Aconitum carmichaelii Deb (Aconiti Radix lateralis praeparata or Fuzi) is a potent traditional herbal medicine extensively used in treatment of cardiovascular diseases, rheumatism arthritis, and bronchitis in many Asian countries. Although Fuzi has promising therapeutic effects, its toxicities are frequently observed. Three main C19-diester-diterpenoid alkaloids (DDAs) are believed to be the principal toxins of the herb. Although toxicokinetic profiles of the toxic DDAs have already been examined in several studies, they have seldom been correlated with the toxicities of Fuzi. The current article aimed to investigate the relationship between the up-to-date toxicokinetic data of the toxic DDAs and the existing evidence of the toxic effects of Fuzi. Relationships between the cardiac toxicity and the plasma and heart concentration of DDAs in mice and rats were established. Based on our findings, clinical monitoring of the plasma concentrations of DDAs of Fuzi is recommended to prevent potential cardiac toxicities. Additionally, caution with respect to potential hepatic and renal toxicity induced by Fuzi should be exercised. In addition, further analyses focusing on the preclinical tissue distribution profile of DDAs and on the long-term toxicokinetic-toxicity correlation of DDAs are warranted for a better understanding of the toxic mechanisms and safer use of Fuzi.
Organic and Peptidyl Constituents of Snake Venoms: The Picture Is Vastly More Complex Than We Imagined
Authors: Villar-Briones Alejandro , Aird Steven D.
Published: September 2018

Small metabolites and peptides in 17 snake venoms (Elapidae, Viperinae, and Crotalinae), were quantified using liquid chromatography-mass spectrometry. Each venom contains >900 metabolites and peptides. Many small organic compounds are present at levels that are probably significant in prey envenomation, given that their known pharmacologies are consistent with snake envenomation strategies. Metabolites included purine nucleosides and their bases, neurotransmitters, neuromodulators, guanidino compounds, carboxylic acids, amines, mono- and disaccharides, and amino acids. Peptides of 2–15 amino acids are also present in significant quantities, particularly in crotaline and viperine venoms. Some constituents are specific to individual taxa, while others are broadly distributed. Some of the latter appear to support high anabolic activity in the gland, rather than having toxic functions. Overall, the most abundant organic metabolite was citric acid, owing to its predominance in viperine and crotaline venoms, where it chelates divalent cations to prevent venom degradation by venom metalloproteases and damage to glandular tissue by phospholipases. However, in terms of their concentrations in individual venoms, adenosine, adenine, were most abundant, owing to their high titers in Dendroaspis polylepis venom, although hypoxanthine, guanosine, inosine, and guanine all numbered among the 50 most abundant organic constituents. A purine not previously reported in venoms, ethyl adenosine carboxylate, was discovered in D. polylepis venom, where it probably contributes to the profound hypotension caused by this venom. Acetylcholine was present in significant quantities only in this highly excitotoxic venom, while 4-guanidinobutyric acid and 5-guanidino-2-oxopentanoic acid were present in all venoms.
Simulating Hydrological Impacts under Climate Change: Implications from Methodological Differences of a Pan European Assessment
Authors: Koutroulis Aristeidis G. , Papadimitriou Lamprini V. , Grillakis Manolis G. , Tsanis Ioannis K. , Wyser Klaus , Caesar John , Betts Richard A.
Published: September 2018

The simulation of hydrological impacts in a changing climate remains one of the main challenges of the earth system sciences. Impact assessments can be, in many cases, laborious processes leading to inevitable methodological compromises that drastically affect the robustness of the conclusions. In this study we examine the implications of different CMIP5-based regional and global climate model ensembles for projections of the hydrological impacts of climate change. We compare results from three different assessments of hydrological impacts under high-end climate change (RCP8.5) across Europe, and we focus on how methodological differences affect the projections. We assess, as systematically as possible, the differences in runoff projections as simulated by a land surface model driven by three different sets of climate projections over the European continent at global warming of 1.5 °C, 2 °C and 4 °C relative to pre-industrial levels, according to the RCP8.5 concentration scenario. We find that these methodological differences lead to considerably different outputs for a number of indicators used to express different aspects of runoff. We further use a number of new global climate model experiments, with an emphasis on high resolution, to test the assumption that many of the uncertainties in regional climate and hydrological changes are driven predominantly by the prescribed sea surface temperatures (SSTs) and sea-ice concentrations (SICs) and we find that results are more sensitive to the choice of the atmosphere model compared to the driving SSTs. Finally, we combine all sources of information to identify robust patterns of hydrological changes across the European continent.
Risk Factors and Prevention of Peritoneal Dialysis-Related Peritonitis
Authors: Gadola Liliana , Poggi Carla , Dominguez Patricia , Poggio María V. , Lungo Eliana , Cardozo Claudia
Published: September 2018

Background

Peritonitis is a major complication and the main cause of peritoneal dialysis (PD) failure. The aim of the present study was to evaluate peritonitis risk factors and its prevention with a new peritoneal educational program (NPEP).

Methods

We performed a retrospective analysis of a cohort of chronic PD patients, older than 16 years, who began PD in the period 1 January 1999 to 31 December 2015 at a Uruguayan PD center, with follow-up until 31 December 2016.

Results

The population included 222 cases (219 patients, 128 men), median age 59 (interquartile range [IQR] 47.0 – 72.0) years, median time on PD 17.5 (IQR 6.0 – 36.2) months. Ninety-five patients suffered 1 or more episodes of peritonitis, and they had been on PD for a longer period and had nasal-positive culture more frequently. A NPEP started in September 2008; patients who trained with it, as well as younger patients, had longer peritonitis-free survival. After the NPEP, global peritonitis rates decreased significantly (from 0.48 to 0.29 episodes/patient-year, respectively), particularly gram-positive bacteria and Staphylococcus aureus / coagulase-negative (CoNS) (from 0.26 to 0.12 and 0.21 to 0.07 episodes/patient-year, respectively). In the multivariate Cox analysis of peritonitis risk factors, survival to first peritonitis was significantly associated only with age (hazard ratio [HR] 1.024, 95% confidence interval [CI] 1.007 – 1.397, p = 0.007) and the NPEP (HR 0.600, 95% CI 0.394 – 0.913, p = 0.017).

Conclusion

A multidisciplinary peritoneal educational program may improve peritonitis rates, independently of other risk factors.
Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids
Authors: Lajkó Eszter , Spring Sarah , Hegedüs Rózsa , Biri-Kovács Beáta , Ingebrandt Sven , Mező Gábor , Kőhidai László
Published: September 2018

Background:Peptide hormone-based targeted tumor therapy is an approved strategy to selectively block the tumor growth and spreading. The gonadotropin-releasing hormone receptors (GnRH-R) overexpressed on different tumors (e.g., melanoma) could be utilized for drug-targeting by application of a GnRH analog as a carrier to deliver a covalently linked chemotherapeutic drug directly to the tumor cells. In this study our aim was (i) to analyze the effects of GnRH-drug conjugates on melanoma cell proliferation, adhesion and migration, (ii) to study the mechanisms of tumor cell responses, and (iii) to compare the activities of conjugates with the free drug.

Results:In the tested conjugates, daunorubicin (Dau) was coupled to8Lys of GnRH-III (GnRH-III(Dau=Aoa)) or its derivatives modified with4Lys acylated with short-chain fatty acids (acetyl group in [4Lys(Ac)]-GnRH-III(Dau=Aoa) and butyryl group in [4Lys(Bu)]-GnRH-III(Dau=Aoa)). The uptake of conjugates by A2058 melanoma model cells proved to be time dependent. Impedance-based proliferation measurements with xCELLigence SP system showed that all conjugates elicited irreversible tumor growth inhibitory effects mediated via a phosphoinositide 3-kinase-dependent signaling. GnRH-III(Dau=Aoa) and [4Lys(Ac)]-GnRH-III(Dau=Aoa) were shown to be blockers of the cell cycle in the G2/M phase, while [4Lys(Bu)]-GnRH-III(Dau=Aoa) rather induced apoptosis. In short-term, the melanoma cell adhesion was significantly increased by all the tested conjugates. The modification of the GnRH-III in position 4 was accompanied by an increased cellular uptake, higher cytotoxic and cell adhesion inducer activity. By studying the cell movement of A2058 cells with a holographic microscope, it was found that the migratory behavior of melanoma cells was increased by [4Lys(Ac)]-GnRH-III(Dau=Aoa), while the GnRH-III(Dau=Aoa) and [4Lys(Bu)]-GnRH-III(Dau=Aoa) decreased this activity.

Conclusion:Internalization and cytotoxicity of the conjugates showed that GnRH-III peptides could guard Dau to melanoma cells and promote antitumor activity. [4Lys(Bu)]-GnRH-III(Dau=Aoa) possessing the butyryl side chain acting as a “second drug” proved to be the best candidate for targeted tumor therapy due to its cytotoxicity and immobilizing effect on tumor cell spreading. The applicability of impedimetry and holographic phase imaging for characterizing cancer cell behavior and effects of targeted chemotherapeutics with small structural differences (e.g., length of the side chain in4Lys) was also clearly suggested.
Psychometric Comparison of the Hearing in Noise Test and the American English Matrix Test
Authors: Harianawala Jumana , Galster Jason , Hornsby Benjamin
Published: September 2018

Background:The hearing in noise test (HINT) is the most popular adaptive test used to evaluate speech in noise performance, especially in context of hearing aid features. However, the number of conditions that can be tested on the HINT is limited by a small speech corpus. The
American English Matrix test (AEMT) is a new alternative adaptive speech in noise test with a larger speech corpus. The study examined the relationships between the performance of hearing aid wearers on the HINT and the AEMT.Purpose:To examine whether there was a difference in performance
of hearing aid wearers on the HINT and the AEMT. A secondary purpose, given the AEMT’s steep performance-intensity function, was to determine whether the AEMT is more sensitive to changes in speech recognition resulting from directional (DIR) microphone processing in hearing aids.Research
Design:A repeated measures design was used in this study. Multiple measurements were made on each subject. Each measurement involved a different experimental condition.Study Sample:Ten adults with hearing loss participated in this study.Data Collection and Analysis:All participants
completed the AEMT and HINT, using adaptive and fixed test formats while wearing hearing aids. Speech recognition was assessed in two hearing aid microphone settings—omnidirectional and fixed DIR. All testing was conducted via sound field presentation. Performance on HINT and AEMT were
systematically compared across all test conditions using a linear model with repeated measures.Results:The results of this study revealed that adult hearing aid users perform differently on the HINT and AEMT, with adaptive AEMT testing yielding significantly better (more negative) thresholds
than the HINT. Slopes of performance intensity functions obtained by testing at multiple fixed signal-to-noise ratios, revealed a somewhat steeper slope for the HINT compared with the AEMT. Despite this steeper slope, the benefit provided by DIR microphones was not significantly different
between the two speech tests.Conclusions:The observation of similar DIR benefits of the HINT and AEMT suggests that the HINT and AEMT are equally sensitive to changes in speech recognition thresholds following intervention. Therefore, the decision to use the AEMT or the HINT will depend
on the purpose of the study and/or the technology being investigated. Other test related factors such as available sentence corpus, learning effects and test time will also influence test selection.
Negative Side Effects Associated with Hearing Aid Use in Adults with Hearing Loss
Authors: Manchaiah Vinaya , Abrams Harvey , Bailey Abram , Andersson Gerhard
Published: September 2018

Background:The low uptake of hearing aids in the United States has been attributed to a number of reasons, including low perceived hearing disability, limited perceived benefit and cost. Another possible reason may be related to negative side effects associated with hearing aid
use.Purpose:The present study was aimed at determining and classifying the negative side effects associated with hearing aid use in adults with hearing loss.Research Design:The study used a cross-sectional survey design.Study Sample:Five hundred and twelve participants
completed an electronic survey.Data Collection and Analysis:The data was collected using the negative side effects of hearing aids (NSE-HAs) questionnaire. Data were analyzed using Chi square analysis, principal components analysis, and calculation of Cronbach’s alpha.Results:Some
individuals reported negative side effects for all 32 items. However, careful examination of results suggests that, as a whole, reported negative side effects tend to be mild with mean scores falling close to the lower quartile of the total scores. Chi square test results suggest that the
variables of age, gender, duration of hearing loss, self-reported hearing disability, and duration of hearing aid use seem to be significantly associated with the reported negative side effects. The NSE-HAs questionnaire was found to have a complex structure as indicated by the principal components
analysis. However, good internal consistency was found in both the full scale and subscales.Conclusions:The present study suggests that, although a large number of adults with hearing loss who use hearing aids experience some degree of negative side effects, those effects tend to be
mild.
Monitoring Hearing in an Infectious Disease Clinic with mHealth Technologies
Authors: Brittz Marize , Heinze Barbara , Mahomed-Asmail Faheema , Swanepoel De Wet , Stoltz Anton
Published: September 2018

Background:Decentralized detection and monitoring of hearing loss can be supported by new mobile health technologies using automated testing that can be facilitated by minimally trained persons. These may prove particularly useful in an infectious disease (ID) clinic setting
where the risk of hearing loss is high.Purpose:To evaluate the clinical utility of mobile and automated audiometry hearing health technology in an ID clinic setting.Research Design:Smartphone-automated pure-tone audiometry (PTA) (hearTest™) and speech-in-noise testing (SA
English digits-in-noise [DIN] test) were compared with manual audiometry (2, 4, and 8 kHz). Smartphone-automated PTA and the DIN test were repeated to determine the test‐retest reliability.Study Sample:Two hundred subjects (73% female and 27% male) were enrolled. Fifty participants
were retested with the smartphone applications. Participants ranged from an age of 18 to 55 years with a mean age of 44.4 (8.7 standard deviation).Data Analysis:Threshold comparisons were made between smartphone audiometry testing and manual audiometry. Smartphone-automated PTA, manual
audiometry, and test‐retest measures were compared (Wilcoxon signed ranked test). Spearman rank correlation test was used to determine the relationship between the smartphone applications and manual audiometry, as well as for test‐retest reliability.Results:Within all
participants, 88.2% of thresholds corresponded within 10 dB or less between smartphone audiometry and manual audiometry. There was a significant difference (p < 0.05) between the right ear at 4 and 8 kHz and in the left ear at 2 and 4 kHz between smartphone and manual audiometry,
respectively. No significant difference was noted (p < 0.05) between test and retest measures of smartphone technology.Conclusions:Smartphone audiometry with calibrated headphones provides reliable results in an ID clinic setting and can be used as a baseline and monitoring
tool at ID clinics.
Hormones and Hearing: Central Auditory Processing in Women
Authors: Trott Skylar , Cline Trey , Weihing Jeffrey , Beshear Deidra , Bush Matthew , Shinn Jennifer
Published: September 2018

Background:Estrogen has been identified as playing a key role in many organ systems. Recently, estrogen has been found to be produced in the human brain and is believed contribute to central auditory processing. After menopause, a low estrogen state, many women report hearing
loss but demonstrate no deficits in peripheral hearing sensitivity, which support the notion that estrogen plays an effect on central auditory processing. Although animal research on estrogen and hearing loss is extensive, there is little in the literature on the human model.Purpose:The
aim of this study was to evaluate relationships between hormonal changes and hearing as it relates to higher auditory function in pre- and postmenopausal (Post-M) females.Research Design:A prospective, group comparison study.Study Sample:Twenty eight women between the ages of
18 and 70 at the University of Kentucky were recruited.Data Collection and Analysis:Participants were separated into premenopausal and peri-/Post-M groups. Participants had normal peripheral hearing sensitivity and underwent a behavioral auditory processing battery and electrophysiological
evaluation. An analysis of variance was performed to address the aims of the study.Results:Results from the study demonstrated statistically significant difference between groups, where Post-M females had difficulties in spatial hearing abilities as reflected on the Listening in Spatialized
Noise Test‐Sentences test. In addition, measures on the auditory brainstem response and the middle latency response reflected statistically significant differences between groups with Post-M females having longer latencies.Conclusions:Results from the present study demonstrated
significant differences between groups, particularly listening in noise. Females who present with auditory complaints in spite of normal hearing thresholds should have a more extensive audiological evaluation to further evaluate possible central deficits.