bluuebunny/crossref_metadata_2025 huggingface dataset:
STARS
Authors: Liu Rui , Liu Runze , Pugliese Andrea , Subrahmanian V. S.
Published: July 2020

Customers of virtually all online marketplaces rely upon reviews in order to select the product or service they wish to buy. These marketplaces in turn deploy review fraud detection systems so that the integrity of reviews is preserved. A well-known problem with review fraud detection systems is their underlying assumption that the majority of reviews are honest-this assumption leads to a vulnerability where an attacker can try to generate many fake reviews of a product. In this article, we consider the case where a company wishes to fraudulently promote its product through fake reviews and propose the Sockpuppet-based Targeted Attack on Reviewing Systems (STARS for short). STARS enables an attacker to enter fake reviews for a product from multiple, apparently independent, sockpuppet accounts. We show that the STARS attack enables companies to successfully promote their product against seven recent, well-known review fraud detectors on four datasets (Amazon, Epinions, and the BitcoinAlpha and OTC exchanges) by significant margins. To protect against the STARS attack, we propose a new fraud detection algorithm called RTV. RTV introduces a new class of users (called trusted users) and also considers reviews left by verified users which were not considered in existing review fraud detectors. We show that RTV significantly mitigates the impact of the STARS attack across the four datasets listed above.
A Survey of Multitier Programming
Authors: Weisenburger Pascal , Wirth Johannes , Salvaneschi Guido
Published: July 2020

Multitier programming deals with developing the components that pertain to different
tiers
in the system (e.g., client and server), mixing them in the same compilation unit. In this paradigm, the code for different tiers is then either generated at run time or it results from the compiler splitting the codebase into components that belong to different tiers based on user annotations, static analysis, types, or a combination of these. In the Web context, multitier languages aim at reducing the distinction between client and server code, by translating the code that is to be executed on the clients to JavaScript or by executing JavaScript on the server, too. Ultimately, the goal of the multitier approach is to improve program comprehension, simplify maintenance and enable formal reasoning about the properties of the
whole
distributed application.

A number of multitier research languages have been proposed over the last decade, which support various degrees of multitier programming and explore different design tradeoffs. In this article, we provide an overview of the existing solutions, discuss their positioning in the design space, and outline open research problems.
Cache What You Need to Cache
Authors: Wang Hua , Zhang Jiawei , Huang Ping , Yi Xinbo , Cheng Bin , Zhou Ke
Published: July 2020

The SSD has been playing a significantly important role in caching systems due to its high performance-to-cost ratio. Since the cache space is typically much smaller than that of the backend storage by one order of magnitude or even more, write density (defined as writes per unit time and space) of the SSD cache is therefore much more intensive than that of HDD storage, which brings about tremendous challenges to the SSD’s lifetime. Meanwhile, under social network workloads, quite a lot writes to the SSD cache are unnecessary. For example, our study on Tencent’s photo caching shows that about 61% of total photos are accessed only once, whereas they are still swapped in and out of the cache. Therefore, if we can predict these kinds of photos proactively and prevent them from entering the cache, we can eliminate unnecessary SSD cache writes and improve cache space utilization.

To cope with the challenge, we put forward a “one-time-access criteria” that is applied to the cache space and further propose a “one-time-access-exclusion” policy. Based on these two techniques, we design a prediction-based classifier to facilitate the policy. Unlike the state-of-the-art history-based predictions, our prediction is non-history oriented, which is challenging to achieve good prediction accuracy. To address this issue, we integrate a decision tree into the classifier, extract social-related information as classifying features, and apply cost-sensitive learning to improve classification precision. Due to these techniques, we attain a prediction accuracy greater than 80%. Experimental results show that the one-time-access-exclusion approach results in outstanding cache performance in most aspects. Take LRU, for instance: applying our approach improves the hit rate by 4.4%, decreases the cache writes by 56.8%, and cuts the average access latency by 5.5%.
Shapelet-transformed Multi-channel EEG Channel Selection
Authors: Dai Chenglong , Pi Dechang , Becker Stefanie I.
Published: July 2020

This article proposes an approach to select EEG channels based on EEG shapelet transformation, aiming to reduce the setup time and inconvenience for subjects and to improve the applicable performance of Brain-Computer Interfaces (BCIs). In detail, the method selects top-
k
EEG channels by solving a logistic loss-embedded minimization problem with respect to EEG shapelet learning, hyperplane learning, and EEG channel weight learning simultaneously. Especially, to learn distinguished EEG shapelets for weighting contributions of each EEG channel to the logistic loss, EEG shapelet similarity is also minimized during the procedure. Furthermore, the gradient descent strategy is adopted in the article to solve the non-convex optimization problem, which finally leads to the algorithm termed StEEGCS. In a result, classification accuracy, with those EEG channels selected by StEEGCS, is improved compared to that with all EEG channels, and classification time consumption is reduced as well. Additionally, the comparisons with several state-of-the-art EEG channel selection methods on several real-world EEG datasets also demonstrate the efficacy and superiority of StEEGCS.
Lightweight Multi-party Authentication and Key Agreement Protocol in IoT-based E-Healthcare Service
Authors: Sahu Amiya Kumar , Sharma Suraj , Puthal Deepak
Published: July 2020

Internet of Things (IoT) is playing a promising role in e-healthcare applications in the recent decades; nevertheless, security is one of the crucial challenges in the current field of study. Many healthcare devices (for instance, a sensor-augmented insulin pump and heart-rate sensor) collect a user’s real-time data (such as glucose level and heart rate) and send them to the cloud for proper analysis and diagnosis of the user. However, the real-time user’s data are vulnerable to various authentication attacks while sending through an insecure channel. Besides that, the attacks may further open scope for many other subsequent attacks. Existing security mechanisms concentrate on two-party mutual authentication. However, an IoT-enabled healthcare application involves multiple parties such as a patient, e-healthcare test-equipment, doctors, and cloud servers that requires multi-party authentication for secure communication. Moreover, the design and implementation of a lightweight security mechanism that fits into the resource constraint IoT-enabled healthcare devices are challenging. Therefore, this article proposes a lightweight, multi-party authentication and key-establishment protocol in IoT-based e-healthcare service access network to counter the attacks in resource constraint devices. The proposed multi-party protocol has used a lattice-based cryptographic construct such as Identity-Based Encryption (IBE) to acquire security, privacy, and efficiency. The study provided all-round analysis of the scheme, such as security, power consumption, and practical usage, in the following ways. The proposed scheme is tested by a formal security tool, Scyther, to testify the security properties of the protocol. In addition, security analysis for various attacks and comparison with other existing works are provided to show the robust security characteristics. Further, an experimental evaluation of the proposed scheme using IBE cryptographic construct is provided to validate the practical usage. The power consumption of the scheme is also computed and compared with existing works to evaluate its efficiency.
A Locality Optimizer for Loop-dominated Applications Based on Reuse Distance Analysis
Authors: Lezos Christakis , Dimitroulakos Grigoris , Latifis Ioannis , Masselos Konstantinos
Published: July 2020

Source code optimization can heavily improve software code implementation quality while still being complementary to conventional compilers’ optimizations. Source code analysis tools are very useful in supporting source code optimization. This article discusses MemAssist, a source-level optimization environment for semi-automatic locality optimization of loop-dominated code. MemAssist applies reuse distance analysis and a relevant optimization algorithm to explore the design space. It generates a set of suggestions for locality optimizing loop transformations that reduce data cache miss rate and execution time. MemAssist has been used to optimize a number of applications. Experimental results show that MemAssist leads to cache miss rate reduction at all cache layers, memory accesses reduction by up to 42%, and to a speedup of up to three times. Therefore, MemAssist can be used for efficient early-stage software optimization leading to development effort and time reduction.
IL-1β Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression
Authors: Nie He , An Fangmei , Mei Jie , Yang Cheng , Zhan Qiang , Zhang Qinglin
Published: July 2020

Background. Mesenchymal stem cells (MSCs), with the powerful metabolic and functional supporting abilities for inflammatory diseases, may be an effective therapeutic strategy for acute liver failure (ALF). However, the efficacy of MSCs can still be promoted if pretreatment is applied to enhance their poor migration towards the damaged liver. The purpose of this study is to determine the effect of IL-1β pretreatment on the efficacy and homing ability of MSCs in ALF. Methods. MSCs were isolated by the whole bone marrow adherence method and characterized. The efficacy and homing ability of IL-1β-pretreated MSCs (Pre-MSCs) were examined in a rat ALF model and compared with that of MSCs and normal saline. Then, Western blot was performed to detect the c-Met and CXCR4 expression of MSCs and Pre-MSCs and followed by flow cytometry to detect the meaningful indicators. Finally, the migration abilities of different cells and different conditions were tested by the Transwell migration assay. Results. MSCs of ideal purity were successfully isolated and cultured. Comparing with MSCs, Pre-MSCs had significantly better efficacy on improving the survival rate and liver function of ALF rats. Further analyses of damaged liver tissues showed that IL-1β pretreatment significantly enhanced the efficacy of MSCs on suppressing liver necrosis. Besides, Pre-MSCs exhibited better effects in inhibiting apoptosis and activating proliferation. The results of tracing experiments with CM-Dil-labeled cells confirmed that more cells migrated to the damaged liver in the Pre-MSC group. In terms of mechanism, the CXCR4 expression was significantly enhanced by IL-1β pretreatment, and an increased migration ability towards SDF-1 that could be reversed by AMD3100 was found in Pre-MSCs. Conclusion. IL-1β pretreatment could enhance the homing ability of MSCs at least partially by increasing the expression of CXCR4 and further improve the efficacy of MSCs on ALF.
Structural Health Monitoring of Timber Using Electromechanical Impedance (EMI) Technique
Authors: Han Fang , Zhang Quanjing , Wang Chengfeng , Lu Guangtao , Jiang Jinwei
Published: July 2020

Nowadays, the electromechanical impedance method has been widely used in the field of structural healthy monitoring, especially for the concrete and steel materials. However, the electromechanical impedance studies on damage detection for timber are limited due to the anisotropic and ununiform biomaterial properties. As a low‐cost and environment‐friendly building material, timber has been widely used in the construction. Thus, it is beneficial to develop electromechanical impedance technique for structural healthy monitoring of timber so as to ensure the stability and safety of the entire timber structures. In this paper, two damage factors, i.e., the damage location factor and the damage size factor of timber specimens are investigated by using the electromechanical impedance method. The method is implemented by using a patch of Lead Zirconate Titanate transducer both as an actuator to generate stress waves and a sensor to detect stress waves after propagating across the timber specimens. Then, the damage index‐root mean square deviation is employed to evaluate the damage severity of the timber specimens. The results indicate that the damage index changes consistently with the change of damage location and size factors, and the proposed method using electromechanical impedance technique can efficiently estimate the damage and its severity.
Delineation of the Germline and Somatic Mutation Interaction Landscape in Triple-Negative and Non-Triple-Negative Breast Cancer
Authors: Wu Jiande , Mamidi Tarun K. K. , Zhang Lu , Hicks Chindo
Published: July 2020

Background. Breast cancer development and progression involve both germline and somatic mutations. High-throughput genotyping and next-generation sequencing technologies have enabled discovery of genetic risk variants and acquired somatic mutations driving the disease. However, the possible oncogenic interactions between germline genetic risk variants and somatic mutations in triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (non-TNBC) have not been characterized. Here, we delineated the possible oncogenic interactions between genes containing germline and somatic mutations in TNBC and non-TNBC and investigated whether there are differences in gene expression and mutation burden between the two types of breast cancer. Methods. We addressed this problem by integrating germline mutation information from genome-wide association studies with somatic mutation information from next-generation sequencing using gene expression data as the intermediated phenotype. We performed network and pathway analyses to discover molecular networks and signalling pathways enriched for germline and somatic mutations. Results. The investigation revealed signatures of differentially expressed and differentially somatic mutated genes between TNBC and non-TNBC. Network and pathway analyses revealed functionally related genes interacting in gene regulatory networks and multiple signalling pathways enriched for germline and somatic mutations for each type of breast cancer. Among the signalling pathways discovered included the DNA repair and Androgen and ATM signalling pathways for TNBC and the DNA damage response, molecular mechanisms of cancer, and ATM and GP6 signalling pathways for non-TNBC. Conclusions. The results show that integrative genomics is a powerful approach for delineating oncogenic interactions between genes containing germline and genes containing somatic mutations in TNBC and non-TNBC and establishes putative functional bridges between genetic and somatic alterations and the pathways they control in the two types of breast cancer.
The Evolution of Thermal Conductivity and Pore Structure for Coal under Liquid Nitrogen Soaking
Authors: Li Bo , Ren Yongjie , Lv XiaoQuan
Published: July 2020

An experimental system for liquid nitrogen soaking and real‐time temperature measurement was designed and implemented to investigate the characteristics of temperature field changes in coal under liquid nitrogen soaking. Then, the heat conduction law of the coal in the process of liquid nitrogen soaking and room temperature recovery for dry and water‐saturated coal were examined. The microstructure characteristics of the coal before and after liquid nitrogen soaking were analyzed with nuclear magnetic resonance (NMR) technology. The results showed that, during the liquid nitrogen cold soaking process, the heat transfer law of the dry and water‐saturated coal samples exhibited a notable three‐stage distribution. For the room temperature recovery process, the dry and water‐saturated coal samples exhibited rapid heating characteristics, and the cooling rate gradually decreased to zero. NMR test results indicated that the liquid nitrogen soaking increased the number of micro and small pores in the coal. Thermal stress analysis revealed that the thermal stress generated by the dry coal was larger than that produced by the saturated coal, and the damage was primarily caused by thermal stress. However, the permeability of the saturated coal was better than that of the dry coal. The damage on the saturated coal was caused by the volume expansion of pores and fissures caused by water‐ice phase transition.
Supplementation of Microbial Phytase with Safflower Meal in Rainbow Trout (Oncorhynchus mykiss): The Effects on Growth, Digestibility, Environmental, and Serum Biological Parameters
Authors: Çantaş İsmail Berat , Yildirim Önder
Published: July 2020

This study aimed to determine the effects of diets replacing soybean meal with safflower meal and phytase enzyme on feed utilization, growth performance, body composition, serum biological parameters, and environmental effects of rainbow trout (Oncorhynchus mykiss). To this aim, five different isonitrogenous (44%) and isocaloric (23 kJ) experimental feeds were formulated as follows: the control group (C) containing no safflower meal and enzyme; SFM10 and SFM20 groups containing 10% and 20% of safflower meal instead of soybean meal, respectively; and SFM10 ± P1000 and SFM20 ± P2000 groups containing 10% safflower meal and 1000 IU/kg phytase and 20% safflower meal and 2000 IU/kg phytase, respectively. Juveniles (12.57 ± 3.05 g average weight) were fed for 60 days. As a result, the best growth rate and feed conversion were recorded in the SFM20 ± P2000 group with 127.07 ± 7.73% and 1.13 ± 0.020, respectively p<0.05. On the contrary, total phosphorus in SFM20 ± P2000 group trial feed was 1.20 ± 0.02, while 0.70 ± 0.08 was found in feces that is the best result between other groups. ALP, LDH, TPROT, CHOL, and triglyceride levels were not statistically different among the experimental groups. ALT, AST, glucose, and albumin levels in serum resulted to be affected by different phytase levels but without any negative effect on fish growth and fish health status. Cholesterol level in the SFM10 ± P1000 group was the highest and positively affected growth and health status of this group. In conclusion, 20% safflower meal replacement along with 2000 IU/kg microbial phytase in feeds can be considered suitable for rainbow trout due to its sustainability and reduced environmental effects due to reduced phosphorous excretion.
The Characterization of OXA-232 Carbapenemase-Producing ST437 Klebsiella pneumoniae in China
Authors: Weng Xingbei , Shi Qiucheng , Wang Sheng , Shi Yubo , Sun Dinghe , Yu Yunsong
Published: July 2020

Carbapenem-resistant Klebsiella pneumoniae (CRKP) was epidemic around the world and become a global threat to public health. The most important carbapenem-resistant mechanism is producing carbapenemases, especially Klebsiella pneumoniae carbapenemase (KPC), which is prevalent in the international clonal complex CC11. The high-risk multidrug-resistant CC11 is widespread worldwide, and KPC-producing and (New Delhi metallo) NDM-producing strains had been reported in this clonal complex before; moreover, cases with the CC11 strain faced more severe forms of drug resistance and treatment challenges than other clonal complexes. In this study, we identified an OXA-232-producing ST437 Klebsiella pneumoniae isolate in China, which belonged to CC11. The isolate was resistant to β-lactams, aminoglycosides, and fluoroquinolones but susceptible to fosfomycin, tigecycline, and colistin. The blaOXA-232 gene was located on a 6141 bp ColKP3-type nonconjugative plasmid, and the plasmid was transformed by chemical transformation successfully. This is the first report of OXA-232-producing ST437 K. pneumoniae in China, a new clone of high-risk multidrug-resistant CC11.
Real-World Experience with Dolutegravir-Based Two-Drug Regimens
Authors: Ward Douglas , Ramgopal Moti , Riedel David J. , Garris Cindy , Dhir Shelly , Waller John , Roberts Jenna , Mycock Katie , Oglesby Alan , Collins Bonnie , Dominguez Megan , Pike James , Mrus Joseph
Published: July 2020

Background. Dolutegravir-based 2-drug regimens (DTG 2DRs) are now accepted as alternatives to 3-drug regimens for HIV antiretroviral treatment (ART); however, literature on physician drivers for prescribing DTG 2DR is sparse. This study evaluated treatment patterns of DTG 2DR components in clinical practice in the US. Methods. This was a retrospective chart review in adult patients in care in the US with HIV-1 who received DTG 2DR prior to July 31, 2017, with follow-up until January 30, 2018. Primary objectives of the study were to determine reasons for patients initiating DTG 2DR and to describe the demographics and clinical characteristics. All analyses were descriptive. Results. Overall, 278 patients received DTG 2DR (male: 70%; mean age: 56 years). Most patients were treatment experienced (98%), with a mean 13.5 years of prior ART. DTG was most commonly paired with darunavir (55%) or rilpivirine (27%). The most common physician-reported reasons for initiating DTG 2DR were treatment simplification/streamlining (30%) and avoidance of potential long-term toxicities (20%). Before starting DTG 2DR, 42% of patients were virologically suppressed; of those, 95% maintained suppression while on DTG 2DR. Of the 50% of patients with detectable viral load before DTG 2DR, 79% achieved and maintained virologic suppression on DTG 2DR during follow-up. There were no virologic data for 8% of patients prior to starting DTG 2DR. Only 15 patients discontinued DTG 2DR, of whom 4 (27%) discontinued due to virologic failure. Conclusions. Prior to commercial availability of the single-tablet 2DRs, DTG 2DR components were primarily used in treatment-experienced patients for treatment simplification and avoidance of long-term toxicities. Many of these patients achieved and maintained virologic suppression, with low discontinuation rates.
Improved Shrinkage Estimator of Large-Dimensional Covariance Matrix under the Complex Gaussian Distribution
Authors: Zhang Bin
Published: July 2020

Estimating the covariance matrix of a random vector is essential and challenging in large dimension and small sample size scenarios. The purpose of this paper is to produce an outperformed large-dimensional covariance matrix estimator in the complex domain via the linear shrinkage regularization. Firstly, we develop a necessary moment property of the complex Wishart distribution. Secondly, by minimizing the mean squared error between the real covariance matrix and its shrinkage estimator, we obtain the optimal shrinkage intensity in a closed form for the spherical target matrix under the complex Gaussian distribution. Thirdly, we propose a newly available shrinkage estimator by unbiasedly estimating the unknown scalars involved in the optimal shrinkage intensity. Both the numerical simulations and an example application to array signal processing reveal that the proposed covariance matrix estimator performs well in large dimension and small sample size scenarios.
Posterior Ankle Arthroscopy for Osteochondromatosis of the Posterior Ankle Extra-Articular Space with a Longitudinal Tear of Flexor Hallucis Longus
Authors: Tonogai Ichiro , Sairyo Koichi
Published: July 2020

We report a rare case of osteochondromatosis of the posterior ankle extra-articular space with a longitudinal tear of flexor hallucis longus (FHL). A 77-year-old woman was referred to our hospital with an approximately 4-year history of pain and swelling in the right posterior ankle joint without obvious trauma. The pain had worsened in the previous 2 years. On presentation, she had tenderness at the posteromedial and posterolateral ankle. Imaging revealed several ossified loose bodies in the posterior ankle extra-articular space. We removed the loose bodies, performed tenosynovectomy around the FHL, and released the FHL tendon using a posterior arthroscopic technique via standard posterolateral and posteromedial portals. A longitudinal tear and fibrillation were detected in the FHL. The patient was able to return to her daily activities approximately 3 weeks after surgery. At the 1-year follow-up visit, she continued to have minor discomfort and slight swelling on the posteromedial aspect of the right ankle but had no recurrence of the ossified loose bodies. To our knowledge, this is the first report of osteochondromatosis of the posterior ankle extra-articular space with a longitudinal tear of the FHL that was treated by removal of loose bodies, tenosynovectomy around the FHL, and release of the FHL tendon via posterior ankle arthroscopy.
Estimating a Finite Population Mean Using Transformed Data in Presence of Random Nonresponse
Authors: Bii Nelson Kiprono , Onyango Christopher Ouma , Odhiambo John
Published: July 2020

Developing finite population estimators of parameters such as mean, variance, and asymptotic mean squared error has been one of the core objectives of sample survey theory and practice. Sample survey practitioners need to assess the properties of these estimators so that better ones can be adopted. In survey sampling, the occurrence of nonresponse affects inference and optimality of the estimators of finite population parameters. It introduces bias and may cause samples to deviate from the distributions obtained by the original sampling technique. To compensate for random nonresponse, imputation methods have been proposed by various researchers. However, the asymptotic bias and variance of the finite population mean estimators are still high under this technique. In this paper, transformation of data weighting technique is suggested. The proposed estimator is observed to be asymptotically consistent under mild assumptions. Simulated data show that the estimator proposed is much better than its rival estimators for all the different mean functions simulated.
Risk Modeling and Quantification of a Platoon in Mixed Traffic Based on the Mass-Spring-Damper Model
Authors: Jiang Luo , Ji Jie , Ren Yue , Wang Hong , Huang Yanjun
Published: July 2020

Connected and automated vehicle (CAV) technologies have great potential to improve road safety. However, an emerging type of mixed traffic flow with human-driven vehicles (HDVs) and CAVs has also arisen in recent years. To improve the overall safety of this mixed traffic flow, a novel car-following model is proposed to control the driving behaviors of the above two types of vehicles in a platoon from the perspective of a mechanical system, mass-spring-damper (MSD) system. Furthermore, a quantitative index is proposed by incorporating the psychological field theory into the MSD model. The errors of spacing and speed in the car-following processes can be expressed as the accumulation of the virtual total energy, and the magnitude of the energy is used to reflect the danger level of vehicles in the mixed platoon. At the same time, the optimization model of minimum total energy is solved under the constraints of vehicle dynamics and the mechanical characteristics of the MSD system, and the optimal solutions are used as the parameters of the MSD car-following model. Finally, a mixed platoon composed of 3 CAVs and 2 HDVs without performing lane changing is tested using the driver-in-the-loop test platform. The test results show that, in the mixed platoon, CAVs can optimally adjust the intervehicle spacing by making full use of the braking distance, which also provides sufficient reaction time for the driver of HDV to avoid rear-end collisions. Furthermore, in the early stage of the emergency braking, the spacing error is the dominant factor influencing the car-following behaviors, but in the later stage of emergency braking, the speed error becomes the decisive factor of the car-following behaviors. These results indicate that the proposed car-following model and quantitative index are of great significance for improving the overall safety of the mixed traffic flow with CAVs and HDVs.
Chaotic Behaviour and Bifurcation in Real Dynamics of Two-Parameter Family of Functions including Logarithmic Map
Authors: Sajid Mohammad
Published: July 2020

The focus of this research work is to obtain the chaotic behaviour and bifurcation in the real dynamics of a newly proposed family of functions fλ,ax=x+1−λxlnax;x>0, depending on two parameters in one dimension, where assume that λ is a continuous positive real parameter and a is a discrete positive real parameter. This proposed family of functions is different from the existing families of functions in previous works which exhibits chaotic behaviour. Further, the dynamical properties of this family are analyzed theoretically and numerically as well as graphically. The real fixed points of functions fλ,ax are theoretically simulated, and the real periodic points are numerically computed. The stability of these fixed points and periodic points is discussed. By varying parameter values, the plots of bifurcation diagrams for the real dynamics of fλ,ax are shown. The existence of chaos in the dynamics of fλ,ax is explored by looking period-doubling in the bifurcation diagram, and chaos is to be quantified by determining positive Lyapunov exponents.
A Multilevel Mobile Fog Computing Offloading Model Based on UAV-Assisted and Heterogeneous Network
Authors: Chen Zhixiong , Xiao Nan , Han Dongsheng
Published: July 2020

The mobile fog computing (MFC) network that integrates unmanned aerial vehicles (UAV) fully exerts its advantages of flexible deployment, load balance, and rapid response. Under complex network environment, proposing a reasonable offloading model and according resource optimization of the MFC network is important to satisfy high-requirement offloading standard. In this paper, a multilevel MFC offloading model where UAV and fog nod undertake relay nodes and offloading computing nodes are established for computation-intensive and latency-critical tasks, considering heterogeneous network selection , dynamic channel quality and central cloud access . With the total system utility optimality function including reward function maximization as the goal, the MDP algorithm is applied to solve the best offloading decision of the computing task and the balanced load mode of the MFC network. Finally, the simulation section verifies the excellent performance of the proposed multilevel MFC offloading model in network resource utilization. Simulation results show that the model can optimize the relative position of service nodes in MFC network and ensure the offloading reliability of terminal equipment.
Mesenchymal Stem/Stromal Cell-Mediated Mitochondrial Transfer and the Therapeutic Potential in Treatment of Neurological Diseases
Authors: Han Deqiang , Zheng Xin , Wang Xueyao , Jin Tao , Cui Li , Chen Zhiguo
Published: July 2020

Mesenchymal stem/stromal cells (MSCs) are multipotent stem cells that can be derived from various tissues. Due to their regenerative and immunomodulatory properties, MSCs have been extensively researched and tested for treatment of different diseases/indications. One mechanism that MSCs exert functions is through the transfer of mitochondria, a key player involved in many biological processes in health and disease. Mitochondria transfer is bidirectional and has an impact on both donor and recipient cells. In this review, we discussed how MSC-mediated mitochondrial transfer may affect cellular metabolism, survival, proliferation, and differentiation; how this process influences inflammatory processes; and what is the molecular machinery that mediates mitochondrial transfer. In the end, we summarized recent advances in preclinical research and clinical trials for the treatment of stroke and spinal cord injury, through application of MSCs and/or MSC-derived mitochondria.
Plasma Gelsolin Inhibits CD8+ T-cell Function and Regulates Glutathione Production to Confer Chemoresistance in Ovarian Cancer
Authors: Asare-Werehene Meshach , Communal Laudine , Carmona Euridice , Han Youngjin , Song Yong Sang , Burger Dylan , Mes-Masson Anne-Marie , Tsang Benjamin K.
Published: July 2020

Although initial treatment of ovarian cancer is successful, tumors typically relapse and become resistant to treatment. Because of poor infiltration of effector T cells, patients are mostly unresponsive to immunotherapy. Plasma gelsolin (pGSN) is transported by exosomes (small extracellular vesicle, sEV) and plays a key role in ovarian cancer chemoresistance, yet little is known about its role in immunosurveillance. Here, we report the immunomodulatory roles of sEV-pGSN in ovarian cancer chemoresistance. In chemosensitive conditions, secretion of sEV-pGSN was low, allowing for optimal CD8+ T-cell function. This resulted in increased T-cell secretion of IFNγ, which reduced intracellular glutathione (GSH) production and sensitized chemosensitive cells to cis-diaminedichloroplatinum (CDDP)-induced apoptosis. In chemoresistant conditions, increased secretion of sEV-pGSN by ovarian cancer cells induced apoptosis in CD8+ T cells. IFNγ secretion was therefore reduced, resulting in high GSH production and resistance to CDDP-induced death in ovarian cancer cells. These findings support our hypothesis that sEV-pGSN attenuates immunosurveillance and regulates GSH biosynthesis, a phenomenon that contributes to chemoresistance in ovarian cancer.

Significance:

These findings provide new insight into pGSN-mediated immune cell dysfunction in ovarian cancer chemoresistance and demonstrate how this dysfunction can be exploited to enhance immunotherapy.
Calibration of Pathogenicity Due to Variant-Induced Leaky Splicing Defects by Using BRCA2 Exon 3 as a Model System
Authors: Tubeuf Hélène , Caputo Sandrine M. , Sullivan Teresa , Rondeaux Julie , Krieger Sophie , Caux-Moncoutier Virginie , Hauchard Julie , Castelain Gaia , Fiévet Alice , Meulemans Laëtitia , Révillion Françoise , Léoné Mélanie , Boutry-Kryza Nadia , Delnatte Capucine , Guillaud-Bataille Marine , Cleveland Linda , Reid Susan , Southon Eileen , Soukarieh Omar , Drouet Aurélie , Di Giacomo Daniela , Vezain Myriam , Bonnet-Dorion Françoise , Bourdon Violaine , Larbre Hélène , Muller Danièle , Pujol Pascal , Vaz Fátima , Audebert-Bellanger Séverine , Colas Chrystelle , Venat-Bouvet Laurence , Solano Angela R. , Stoppa-Lyonnet Dominique , Houdayer Claude , Frebourg Thierry , Gaildrat Pascaline , Sharan Shyam K. , Martins Alexandra
Published: July 2020

BRCA2 is a clinically actionable gene implicated in breast and ovarian cancer predisposition that has become a high priority target for improving the classification of variants of unknown significance (VUS). Among all BRCA2 VUS, those causing partial/leaky splicing defects are the most challenging to classify because the minimal level of full-length (FL) transcripts required for normal function remains to be established. Here, we explored BRCA2 exon 3 (BRCA2e3) as a model for calibrating variant-induced spliceogenicity and estimating thresholds for BRCA2 haploinsufficiency. In silico predictions, minigene splicing assays, patients' RNA analyses, a mouse embryonic stem cell (mESC) complementation assay and retrieval of patient-related information were combined to determine the minimal requirement of FL BRCA2 transcripts. Of 100 BRCA2e3 variants tested in the minigene assay, 64 were found to be spliceogenic, causing mild to severe RNA defects. Splicing defects were also confirmed in patients' RNA when available. Analysis of a neutral leaky variant (c.231T>G) showed that a reduction of approximately 60% of FL BRCA2 transcripts from a mutant allele does not cause any increase in cancer risk. Moreover, data obtained from mESCs suggest that variants causing a decline in FL BRCA2 with approximately 30% of wild-type are not pathogenic, given that mESCs are fully viable and resistant to DNA-damaging agents in those conditions. In contrast, mESCs producing lower relative amounts of FL BRCA2 exhibited either null or hypomorphic phenotypes. Overall, our findings are likely to have broader implications on the interpretation of BRCA2 variants affecting the splicing pattern of other essential exons.

Significance:

These findings demonstrate that BRCA2 tumor suppressor function tolerates substantial reduction in full-length transcripts, helping to determine the pathogenicity of BRCA2 leaky splicing variants, some of which may not increase cancer risk.
NudCD1 Promotes the Proliferation and Metastasis of Non-Small Cell Lung Cancer Cells through the Activation of IGF1R-ERK1/2
Authors: He Bin , Xia Shihui , Zhang Zengwang
Published: July 2020

Background: NudC domain containing 1 (NudCD1) is an oncoprotein related to diverse cancers. This study aims to investigate the expression, role, and regulatory mechanism of NudCD1 in non-small cell lung cancer (NSCLC). Methods: qRT-PCR, Western blot, and immunohistochemistry were performed to detect the expressions of NudCD1 in NSCLC tissues and cell lines. The correlation between NudCD1 expression and clinical features was determined by the χ2 test. Besides, shRNA was used to construct the NudCD1 low expression model of NCI-H1299 and NCI-H460 cells, and CCK-8 and transwell assay were conducted to monitor the changes of proliferation, migration, and invasion of cancer cells. The expression levels of epithelial-mesenchymal transition markers and IGF1R-ERK1/2 signaling pathway proteins were detected by Western blot. Results: The expression of NudCD1 in NSCLC was higher than that in normal tissues, and the increased expression of NudCD1 was significantly correlated with increased T stage and lymph node metastasis. Moreover, patients with high expression of NudCD1 had worse prognosis. NudCD1 knockdown was proven to impede the proliferation but facilitate the migration and invasion of cancer cells. Furthermore, knockdown of NudCD1 resulted in an increase in the expression of E-cadherin and a decrease in the expression of vimentin. We also observed that NudCD1 overexpression promoted the phosphorylation of IGF1R and ERK1/2 proteins. Conclusion: NudCD1 promotes the proliferation and metastasis of NSCLC cells via activation of IGF1R-ERK1/2, which indicates that NudCD1 may be a potential therapy target of NSCLC.
A Comparison of Serial Position Effects in Patients with Mild Cognitive Impairment due to Parkinson’s Disease or to Alzheimer’s Disease
Authors: Meyer Antonia , Handabaka Ivana , Ehrensperger Michael M. , Gschwandtner Ute , Hatz Florian , Monsch Andreas U. , Stieglitz Rolf D. , Fuhr Peter
Published: July 2020

Objective: The first (primacy region) and last (recency region) items of a word list are generally better memorized than items from the middle region. The recency effect depends on short-term memory (STM) and the primacy effect on long-term memory (LTM), where verbal information is transferred from STM into LTM by maintenance rehearsal. We compared the serial position effects (SPE) between patients with mild cognitive impairment (MCI) due to Parkinson’s disease (PD), i.e., PD-MCI, and patients with MCI due to Alzheimer’s disease (AD-MCI), and evaluated the influence of SPE and frontostriatal deficits on verbal memory recall. Methods: Four similar groups of subjects participated in the study: 26 PD-MCI patients, 26 cognitively normal patients with PD (PD-CN), 26 AD-MCI patients, and 26 normal controls (NC). Verbal episodic memory, verbal span, attentional capacity, executive functions, and verbal working memory performance were assessed. Measures for primacy and recency regions were defined at the first trial of a 16-items word list. Hierarchical regression models were used to investigate the contribution of frontostriatal deficits beyond SPE on verbal memory recall performance (“long-delay free recall”) in PD and AD patients. Results: Primacy effects were significantly diminished in both PD-MCI and AD-MCI patients relative to NC and PD-CN (all p < 0.01). Compared to PD-MCI patients, AD-MCI patients exhibited significantly worse “delayed-recall ‘savings’.” Reduced primacy effect was predictive for decreased recall performance in PD and AD. The conducted hierarchical regression model revealed that in PD, but not in AD patients, performance of attention and executive function significantly increased the prediction of free recalled words. Conclusions: Reduced recall performance is likely due to impaired transition of newly learned material from STM into LTM in AD and in PD. Whereas AD-MCI patients suffer from a storage deficit, the similarly reduced recall performance found in patients with PD-MCI may additionally be related to deficient attentional and executive capacity.
Comparison of Circulating Levels of Uremic Toxins in Hemodialysis Patients Treated with Medium Cut-Off Membranes and High-Flux Membranes: Theranova in Sisli Hamidiye Etfal (THE SHE) Randomized Control Study
Authors: Sevinc Mustafa , Hasbal Nuri Baris , Yilmaz Vuslat , Basturk Taner , Ahbap Elbis , Sakaci Tamer , Ozcafer Perin Nazif , Unsal Abdulkadir
Published: July 2020

Introduction: Removal of uremic toxins is a main objective of hemodialysis; however, whether high-flux and medium cut-off (MCO) membranes differ as regards removal of middle and large uremic toxins is not clear. Objective: To compare medium cut-off and high-flux dialyzers as regards their intra- and interdialysis effect on circulating levels of middle and large uremic toxins and serum albumin. Methods: Fifty-two patients were randomized to have hemodialysis with either 3 months of high-flux dialyzer followed by 3 months of MCO or vice versa. Blood samples were taken before and after dialysis at the first and last sessions of each dialyzer for analyses of middle and large uremic toxins including inflammatory mediators and vascular endothelial growth factor (VEGF), and serum albumin. Results: Reduction rates were higher, and postdialysis levels of β-2 microglobulin, free kappa and lambda light chains, and myoglobulin were lower at the first and last sessions with MCO dialyzers compared to high-flux dialyzers (p < 0.05 for all). Last session predialysis levels of β-2 microglobulin, free kappa light chain, and free lambda light chain were lower than first session predialysis levels in MCO dialyzers as compared to high-flux dialyzers (p < 0.05 for all). Last session levels of interleukin-6, interleukin-10, interleukin-17, and interferon-gamma did not differ between dialyzers (p > 0.05 for all). VEGF level was lower in the MCO group compared to the high-flux group (p = 0.043). Last session level of serum albumin with MCO dialyzers was lower than that with high-flux dialyzers (3.62 [3.45–3.88] vs. 3.78 [3.58–4.02] g/L) (p = 0.04) and 6.7% lower (p < 0.001) than at the first session of MCO dialyzers. Conclusion: The decline in circulating levels of several middle and large uremic toxins including VEGF following hemodialysis was more pronounced when using MCO membranes as compared to high-flux membranes while their effect on inflammatory molecules was similar.
What Are the Minimal Detectable Changes in SDMT and Verbal Fluency Tests for Assessing Changes in Cognitive Performance in Persons with Multiple Sclerosis and Non-Multiple Sclerosis Controls?
Authors: Magnin Eloi , Sagawa Yoshimasa , Moulin Thierry , Decavel Pierre
Published: July 2020

Introduction: Cognitive impairment is frequent in persons with multiple sclerosis (PwMS) and can impact on activities of daily living. The capacity to differentiate real changes from background statistical noise induced by human, instrumentational, and environmental variations inherent to the evaluation would improve cognitive assessments. Objective: To assess the short-term reproducibility of cognitive tests in non-multiple sclerosis (non-MS) persons and PwMS. Methods: Sixty-two PwMS and 19 non-MS persons performed 2 measurements, 1 week apart, of the Symbol Digit Modalities Test (SDMT) and phonological and semantic verbal fluency. Test-retest reliability was evaluated by the intraclass correlation coefficients (ICC) and agreement by standard error of measurement (SEM) and minimum detectable change (MDC). Results: The reliability of the cognitive variables studied had moderate to high ICC values (ICC > 0.8) in both populations. The threshold to consider a significant cognitive modification evaluated by SEM and MDC was lower in PwMS compared with non-MS persons. Conclusions: SDMT and verbal fluency have good short-term reproducibility in PwMS. Specific SEM and MDC cutoffs based on the same design of evaluation (especially retest timing) and to the targeted pathological population (MS vs. healthy) should systematically be used to consider cognitive modification as significant in research protocol as well as in clinical practice.
Risk Factors of In-Hospital Mortality in Patients Treated for Pneumonia at a Tertiary Care Centre in Switzerland
Authors: Elsener Christian , Beeler Patrick E. , Battegay Edouard , Bello Braimoh , Thienemann Friedrich
Published: July 2020

Background: Little is known about risk factors upon hospital admission that are associated with in-hospital death of patients hospitalized for bacterial pneumonia. Identifying such factors may help to optimize the treatment and lower the mortality of these patients. Objectives: The aim of the study was to characterize baseline characteristics of patients hospitalized for bacterial pneumonia in Switzerland and to identify risk factors associated with all-cause in-hospital mortality. Methods: Routinely collected electronic health record data of patients discharged from a large Swiss tertiary care hospital between August 2009 and 2017 were analysed. Potential risk factors such as patient demographics, physical examination findings, vital signs, laboratory results, and comorbidities were considered within ±24 h of admission. Univariable and multivariable logistic regression models identified risk factors for in-hospital death. The area under the receiver operating characteristic (ROC) curve was used to compare the identified factors to existing pneumonia scoring systems. Results: Out of 1,781 hospital stays with initial and main diagnosis of bacterial pneumonia, 85 patients (4.85%) died (33.9% female, median age 62.3 years [interquartile range, 52–75]). Age, low systolic blood pressure, underweight, a missing value for body mass index, decreased haemoglobin level, raised C-reactive protein, high urea, high lactate dehydrogenase, concomitant pleural effusion, and cancer were independently associated with in-hospital death. The area under the ROC curve was 0.89 for the multivariable model containing the identified predictors. Conclusions: Our data are consistent with previous trials characterizing patients hospitalized for pneumonia. Additionally, we identified new and independent risk factors associated with in-hospital death among patients treated for bacterial pneumonia. Findings need to be further validated in larger multicentre cohorts.