bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Learning and Transfer Learning for Automatic Cell Counting in Microscope Images of Human Cancer Cell Lines
Authors: Lavitt Falko , Rijlaarsdam Demi J. , van der Linden Dennet , Weglarz-Tomczak Ewelina , Tomczak Jakub M.
Published: May 2021

In biology and medicine, cell counting is one of the most important elements of cytometry, with applications to research and clinical practice. For instance, the complete cell count could help to determine conditions for which cancer cells could grow or not. However, cell counting is a laborious and time-consuming process, and its automatization is highly demanded. Here, we propose use of a Convolutional Neural Network-based regressor, a regression model trained end-to-end, to provide the cell count. First, unlike most of the related work, we formulate the problem of cell counting as the regression task rather than the classification task. This allows not only to reduce the required annotation information (i.e., the number of cells instead of pixel-level annotations) but also to reduce the burden of segmenting potential cells and then classifying them. Second, we propose use of xResNet, a successful convolutional architecture with residual connection, together with transfer learning (using a pretrained model) to achieve human-level performance. We demonstrate the performance of our approach to real-life data of two cell lines, human osteosarcoma and human leukemia, collected at the University of Amsterdam (133 training images, and 32 test images). We show that the proposed method (deep learning and transfer learning) outperforms currently used machine learning methods. It achieves the test mean absolute error equal 12 (±15) against 32 (±33) obtained by the deep learning without transfer learning, and 41 (±37) of the best-performing machine learning pipeline (Random Forest Regression with the Histogram of Gradients features).
Polydopamine-Mediated Ag and ZnO as an Active and Recyclable SERS Substrate for Rhodamine B with Significantly Improved Enhancement Factor and Efficient Photocatalytic Degradation
Authors: Chin Hsien-Kuo , Lin Pei-Ying , Chen Jyunde , Kirankumar Rajendranath , Wen Zhi-Hong , Hsieh Shuchen
Published: May 2021

We demonstrate the development of an active multicomponent Ag/PDA/ZnO@GMF surface-enhanced Raman scattering (SERS) substrate via introducing bio-inspired polydopamine (PDA) in between a noble metal (AgNPs) and ZnO nanorods. The insertion of PDA enabled efficient charge redistribution between metal and semiconductor through their aromatic cores. The substrate exhibited a high enhancement factor (EF) of 1010 for the organic pollutant dye Rhodamine B (RhB). Subsequent exposure of a RhB-loaded substrate to an external UV light source developed an efficient pathway for RhB degradation and replenished the substrate for multiple usage cycles with remarkable photostability. Thus, enhanced performance of the substrate in terms of light-harvesting capability and high charge-separation efficiency was observed. In addition, the much larger surface area of the branched ZnO nanostructures served as a template for PDA assisted synthesis and controlled deposition of AgNPs, which further improved the SERS effect. Our work seeks to understand the contributions of the noble metal and semiconductor components and the synergistic effects of combining them with a facile charge transport medium to enable the fabrication of highly efficient SERS substrates for use in industrial and environmental applications.
Robust Control with Uncertain Disturbances for Vehicle Drift Motions
Authors: Xu Dongxin , Wang Guoye , Qu Longtao , Ge Chang
Published: May 2021

Professor drivers, including racing drivers, can drive cars to achieve drift motions by taking control of the steering angle in high tire slip ratios, which provides a way to improve the driving safety of autonomous vehicles. The existing studies can be divided into two kinds based on analysis methods, and the theory-based is chosen in this study. Because the recent theory based is most applied for planar models with neglect of the rollover accident risk, the nonlinear vehicle model is established by considering longitudinal, lateral, roll, and yaw motions and rolling safety with the nonlinear tire model UniTire. The drift motion mechanism is analyzed in steady and transient states to obtain drift motion conditions, including the velocity limitation and the relationship between sideslip angle and yaw rate, and vehicle main status parameters including the velocity, side-slip angle and yaw rate in drift conditions. The state-feedback controller is designed based on robust theory and LMI (linear matrix inequation) with uncertain disturbances to realize circle motions in drift conditions. The designed controller in simulations realizes drift circle motions aiming at analyzed status target values by matching the front-wheel steering angle with saturated tire forces, which satisfies the Lyapunov stability with robustness. Robust control in drift conditions solves the problem of how to control vehicles to perform drift motions with uncertain disturbances and improves the driving safety of autonomous vehicles.
High-Tech Defense Industries: Developing Autonomous Intelligent Systems
Authors: Reis João , Cohen Yuval , Melão Nuno , Costa Joana , Jorge Diana
Published: May 2021

After the Cold War, the defense industries found themselves at a crossroads. However, it seems that they are gaining new momentum, as new technologies such as robotics and artificial intelligence are enabling the development of autonomous, highly innovative and disruptive intelligent systems. Despite this new impetus, there are still doubts about where to invest limited financial resources to boost high-tech defense industries. In order to shed some light on the topic, we decided to conduct a systematic literature review by using the PRISMA protocol and content analysis. The results indicate that autonomous intelligent systems are being developed by the defense industry and categorized into three different modes—fully autonomous operations, partially autonomous operations, and smart autonomous decision-making. In addition, it is also important to note that, at a strategic level of war, there is limited room for automation given the need for human intervention. However, at the tactical level of war, there is a high probability of growth in industrial defense, since, at this level, structured decisions and complex analytical-cognitive tasks are carried out. In the light of carrying out those decisions and tasks, robotics and artificial intelligence can make a contribution far superior to that of human beings.
Streptomyces Isolates from the Soil of an Ancient Irish Cure Site, Capable of Inhibiting Multi-Resistant Bacteria and Yeasts
Authors: Quinn Gerry , Abdelhameed Alyaa , Banat Aiya , Alharbi Nada , Baker Laura , Castro Helena , Dyson Paul , Facey Paul , Cobice Diego , Terra Luciana , Adu Simms , Swain Martin , Banat Ibrahim
Published: May 2021

Traditional Irish medicines are often intertwined with ritual and spirituality, making it difficult to substantiate the validity of their claims. In this manuscript, we use molecular and microscopic techniques to investigate some microorganisms that might be responsible for the reputed healing properties of an ancient Irish soil cure known as the Blessed clay from a site in Boho in the West Fermanagh Scarplands. We previously reported the isolation of an antibiotic producing bacteria from this soil. In this report, we characterize the antibiotic activity of a further six isolates of Streptomyces from this source. Two of these isolates inhibit the growth of multi-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, two inhibit the growth of the yeast Starmerella bombicola, and two have as yet undetermined activity. Genetic analysis of these Streptomyces reveals the potential to synthesize varieties of antibiotics similar to cypemycin, griseochelin, macrolactams, and candicidin. From these observations, we suggest that part of the medicinal reputation of the Blessed clay may lie in the diversity of antimicrobial producing Streptomyces isolated from this soil. These findings highlight the potential for antibiotic discovery in this area.
Additive Manufacturing and Reverse Engineering in Cranioplasty: A Personalized Approach to Minimize Skin Flap Complications
Authors: Marzola Antonio , Buonamici Francesco , Furferi Rocco , Governi Lapo , Genitori Lorenzo , Mussa Federico
Published: May 2021

Cranioplasty is a procedure performed to repair defects in the human skull bone by surgically reconstructing the shape and function of the cranium. Several complications, both intraoperative and postoperative, can affect the procedure’s outcome (e.g., inaccuracies of the reconstructed shape, infections, ulcer, necrosis). Although the design of additive manufactured implants in a preoperative stage has improved the general quality of cranioplasties, potential complications remain significant, especially in the presence of critical skin tissue conditions. In this paper, an innovative procedure to improve the chances of a positive outcome when facing critical conditions in a cranioplasty is described. The proposed approach relies on a structured planning phase articulated in a series of digital analyses and physical simulations performed on personalized medical devices that guide the surgeon in defining surgical cuts and designing the implant. The ultimate goal is to improve the chances of a positive outcome and a fast recovery for the patient. The procedure, described in extenso in the paper, was positively tested on a cranioplasty case study, which presented high risk factors.
Collaborative Robotics: Enhance Maintenance Procedures on Primary Flight Control Servo-Actuators
Authors: Raviola Andrea , Antonacci Michele , Marino Francesco , Jacazio Giovanni , Sorli Massimo , Wende Gerko
Published: May 2021

Electro-Hydraulic Servo-Actuators (EHSAs) are mainly used to command primary flight control surfaces in military and commercial aircraft. Since these devices are crucial for vehicle stability and maneuverability, a correct assessment of their health status is mandatory. Within this framework, a joint research project (HyDiag), held by Politecnico di Torino and Lufthansa Technik AG (LHT), aims to provide a more efficient and reliable procedure to determine the operating conditions of the EHSA. A smart and automatic sequence, able to extract several health features of the Unit Under Test (UUT), has been developed and integrated. The present paper discusses the implementation of a collaborative robot, equipped with a vision system and customized tools, for both health features extraction, and maintenance tasks on unserviceable servo-actuators. The main challenges related to the automation of such complex tasks in a real working environment are highlighted, togetherwith the advantages brought by the proposed approach. The paper also presents the first results of an ongoing experimental campaign. Specifically, it reports the enhancements of the maintenance procedures using collaborative robotics and possible future developments.
Mg,Sr-Cosubstituted Hydroxyapatite with Improved Structural Properties
Authors: Landi Elena , Guizzardi Stefano , Papa Elettra , Galli Carlo
Published: May 2021

Bone substitute materials require specific properties to make them suitable for implantation, such as biocompatibility and resistance to mechanical loads. Mg,Sr-cosubstituted hydroxyapatite (MgSr-HA) is a promising bone scaffold candidate because its structure is similar to the native bone matrix. However, MgSr-HA materials do not typically withstand thermal treatments over 800 °C, because Mg promotes HA degradation to less stable tricalcium phosphate, a compound that, albeit biocompatible, is not found in bone. We, therefore, designed an ion-exchange process to enrich sintered Sr-HA with Mg and obtain MgSr-HA porous constructs. These materials contained a 0.04–0.08 Mg/Ca molar ratio and a 0.12–0.13 Sr/Ca molar ratio, and had up to 20 MPa of compressive strength, suitable for use as bone fillers or scaffolds. Unlike previous synthetic Mg,Sr-substituted apatite powders, the proposed process did not degrade HA and thus preserved its similarity to bone structure. The obtained material thus combines the presence of bioactive Mg and Sr ions in the HA lattice with a 3D morphological/structural organization that can be customized in pore size and distribution, as well as in mechanical strength, thus potentially covering a wide range of clinical applications.
Tilia sp. Seed Oil—Composition, Antioxidant Activity and Potential Use
Authors: Poljšak Nina , Kočevar Glavač Nina
Published: May 2021

Research on new, untapped seed oil sources is receiving increased attention. In this study, 18 different seed samples of Tilia cordata and Tilia platyphyllos from various locations in Slovenia were collected and oil was extracted. The compositions of triglyceride fatty acids and unsaponifiable compounds were determined using GC-MS, while antioxidant activity was evaluated using the DPPH method. The oil content in the seeds varied significantly, from 9.1% to 21.7%. Linoleic acid (50–60%) was found to be the predominant fatty acid, followed by oleic acid (18–22%) and palmitic acid (8–9%). Characteristic cyclopropene fatty acids (sterculic, dihydrosterculic and malvalic acids) were present in the average range of 4–8.4%. Antioxidant activity ranged from 8.9% to 65.5%, and was higher, on average, for T. platyphyllos. Higher antioxidant activity was closely correlated with higher γ-tocopherol contents. Statistically significant correlations were confirmed between antioxidant activity and γ-tocopherol, between Δ-tocopherol and phytol, between stigmasterol and β-sitosterol and between squalene and malvalic acid. Tilia oil may be of great interest for cosmetic and dermal preparations. It is, however, not considered a good source of dietary fatty acids due to the undesired, significant content of omega-6 fatty acids.
High-Speed Time- and Frequency-Domain Terahertz Tomography of Glass-Fiber-Reinforced Polymer Laminates with Internal Defects
Authors: Yahng Ji-Sang , Yee Dae-Su
Published: May 2021

Composite materials are increasingly being utilized in many products, such as aircrafts, wind blades, etc. Accordingly, the need for nondestructive inspection of composite materials is increasing and technologies that allow nondestructive inspection are being studied. Existing ultrasound methods are limited in their ability to detect defects due to high attenuation in composite materials, and radiographic examination methods could pose a danger to human health. Terahertz (THz) wave technology is an emerging approach that is useful for imaging of concealed objects or internal structures due to high transmittance in non-conductive materials, straightness, and safety to human health. Using high-speed THz tomography systems that we developed, we have obtained THz tomographic images of glass-fiber-reinforced polymer (GFRP) laminates with artificial internal defects such as delamination and inclusion. The defects have various thicknesses and sizes, and lie at different depths. We present THz tomographic images of GFRP samples to demonstrate the extent to which the defects can be detected with the THz tomography systems.
Computational Evaluation of Shock Wave Interaction with a Cylindrical Water Column
Authors: Rossano Viola , De Stefano Giuliano
Published: May 2021

Computational fluid dynamics was employed to predict the early stages of the aerodynamic breakup of a cylindrical water column, due to the impact of a traveling plane shock wave. The unsteady Reynolds-averaged Navier–Stokes approach was used to simulate the mean turbulent flow in a virtual shock tube device. The compressible flow governing equations were solved by means of a finite volume-based numerical method, where the volume of fluid technique was employed to track the air–water interface on the fixed numerical mesh. The present computational modeling approach for industrial gas dynamics applications was verified by making a comparison with reference experimental and numerical results for the same flow configuration. The engineering analysis of the shock–column interaction was performed in the shear-stripping regime, where an acceptably accurate prediction of the interface deformation was achieved. Both column flattening and sheet shearing at the column equator were correctly reproduced, along with the water body drift.
Post-Implementation ERP Software Development: Upgrade or Reimplementation
Authors: Domagała Adam , Grobler-Dębska Katarzyna , Wąs Jarosław , Kucharska Edyta
Published: May 2021

The paper deals with problems in the post-implementation phase of management Enterprise Resource Planning (ERP) systems. Proper management of the system maintenance stage is a basis for efficient system development in terms of business needs. Based on the research and analysis of collected materials, it turns out that making a decision to upgrade the system is equally crucial. We present revealed mechanisms determining the post-implementation approach to upgrade or reimplement the ERP system. The main aim is to determine the methodology and difference understanding to achieve success in the post-implementation stage. The paper shows that the systemic approach to the maintenance stage of the ERP system affects its further decisions: upgrade or reimplement. It has a direct impact on future maintenance costs and the scope of new business demands. This research is an outcome of industry–academia collaboration and based on several developed implementation systems, achieved upgrade and reimplementation projects. Based on case study analysis, we show that reimplementation means an evolution of the current ERP processes rather than another attempt to “reimplement” an unsuccessful system implementation. On the other hand, upgrades are not only a tool or system actualization but the easiest way to bolster company sustainability and to have the information system up to date. The issues discussed in the article will be used to develop changes in the implementation methodology of ERP systems.
Numerical and Experimental Analysis of Flow and Pulsation in Hump Section of Siphon Outlet Conduit of Axial Flow Pump Device
Authors: Yang Fan , Zhang Yiqi , Yuan Yao , Liu Chao , Li Zhongbin , Nasr Ahmed
Published: May 2021

In order to study the variation law of the flow field and pressure fluctuation in the hump section of the siphon outlet conduit, the flow field characteristics and frequency spectrum characteristics of the flow field were analyzed by combining a physical model test and numerical simulation under the conditions of the interaction between the axial flow pump and siphon outlet conduit, and the influence of the residual circulation at the outlet of the guide vane on the siphon outlet flow was investigated. Based on the influence of the flow field and hydraulic loss in the conduit, the equivalent surface method based on the Q criterion was used to analyze the vortex structure in the siphon outlet conduit and to analyze the internal vortex state. The results showed that with the increase of the flow rate, the intensity of the vortices in the cross-section of the hump section of the siphon outlet conduit decreased gradually, the average velocity circulation decreased gradually and the axial velocity distribution uniformity increased and tended to be stable; water flow stratification existed under three characteristic conditions with no circulation, and the hydraulic loss was greater with the circulation flow while it had a circulation under the small flow condition. Under the low flow rate conditions, the hydraulic loss was 6.6 times higher under the condition of circulation than without. Under a high flow condition, it was 1.3 times. Under the condition of a small flow rate, the vortex structure was distributed centrally at the inlet of the flow conduit, and under the other two characteristic conditions, the vortex structure mostly appeared as a strip; the pressure fluctuation in the hump section had obvious periodicity, and with the increase of the flow rate, the maximum pressure fluctuation amplitude in the hump section decreased gradually; with the decrease of the rotational speed, the pressure amplitude at the same measuring point in the hump section decreased gradually and at the optimum condition. Under the following conditions, the mean value of the pressure amplitude at the top of the hump section was reduced by 69.63%, and the mean value of the pressure amplitude at the bottom of the hump section was reduced by 63.5%. Under all the calculation conditions, the main frequency of pulsation at each measuring point of the hump section was twice the frequency of the rotation.
Emotion Recognition from ECG Signals Using Wavelet Scattering and Machine Learning
Authors: Sepúlveda Axel , Castillo Francisco , Palma Carlos , Rodriguez-Fernandez Maria
Published: May 2021

Affect detection combined with a system that dynamically responds to a person’s emotional state allows an improved user experience with computers, systems, and environments and has a wide range of applications, including entertainment and health care. Previous studies on this topic have used a variety of machine learning algorithms and inputs such as audial, visual, or physiological signals. Recently, a lot of interest has been focused on the last, as speech or video recording is impractical for some applications. Therefore, there is a need to create Human–Computer Interface Systems capable of recognizing emotional states from noninvasive and nonintrusive physiological signals. Typically, the recognition task is carried out from electroencephalogram (EEG) signals, obtaining good accuracy. However, EEGs are difficult to register without interfering with daily activities, and recent studies have shown that it is possible to use electrocardiogram (ECG) signals for this purpose. This work improves the performance of emotion recognition from ECG signals using wavelet transform for signal analysis. Features of the ECG signal are extracted from the AMIGOS database using a wavelet scattering algorithm that allows obtaining features of the signal at different time scales, which are then used as inputs for different classifiers to evaluate their performance. The results show that the proposed algorithm for extracting features and classifying the signals obtains an accuracy of 88.8% in the valence dimension, 90.2% in arousal, and 95.3% in a two-dimensional classification, which is better than the performance reported in previous studies. This algorithm is expected to be useful for classifying emotions using wearable devices.
Multi-Agent Reinforcement Learning: A Review of Challenges and Applications
Authors: Canese Lorenzo , Cardarilli Gian Carlo , Di Nunzio Luca , Fazzolari Rocco , Giardino Daniele , Re Marco , Spanò Sergio
Published: May 2021

In this review, we present an analysis of the most used multi-agent reinforcement learning algorithms. Starting with the single-agent reinforcement learning algorithms, we focus on the most critical issues that must be taken into account in their extension to multi-agent scenarios. The analyzed algorithms were grouped according to their features. We present a detailed taxonomy of the main multi-agent approaches proposed in the literature, focusing on their related mathematical models. For each algorithm, we describe the possible application fields, while pointing out its pros and cons. The described multi-agent algorithms are compared in terms of the most important characteristics for multi-agent reinforcement learning applications—namely, nonstationarity, scalability, and observability. We also describe the most common benchmark environments used to evaluate the performances of the considered methods.
CFD Assessment of the Hydrodynamic Performance of Two Impellers for a Baffled Stirred Reactor
Authors: Stuparu Adrian , Susan-Resiga Romeo , Tanasa Constantin
Published: May 2021

When converting a baffled stirred reactor to work with a different fluid, usually the original impeller must be replaced with a customized one. If the original impeller was designed for mixing liquids, its performance for liquid–solid suspensions may not be satisfactory. A case study is presented, where a two-blade original impeller is replaced with a new three-blade design. The new impeller shows clear improvements in mixing a liquid–solid suspension, while keeping the shaft power practically at the same level. As a result, a practically homogenous liquid–solid mixture is obtained, thus ensuring the required quality of the final product. The present numerical investigations employ the Eulerian multiphase model with renormalization (RNG) k–ε turbulence model to simulate the three-dimensional unsteady free-surface liquid–solid flow in a stirred tank. A sliding mesh approach was used to account for the impeller rotation within the expert code, FLUENT 16. The comparative quantitative analysis of the solid phase distribution and the relevant velocity profiles show that the new design of three-blade-impeller is significantly increasing the sedimentation time of the solid phase beyond the chemical reaction specific time. The necessary power to drive the new impeller has a slightly higher value than for the original impeller but it can be sustained by the existing driving system.
Efficacy of a Next Generation Quaternary Ammonium Chloride Sanitizer on Staphylococcus and Pseudomonas Biofilms and Practical Application in a Food Processing Environment
Authors: Shah Kundan , Muriana Peter
Published: May 2021

Foodborne pathogens are known to adhere strongly to surfaces and can form biofilms in food processing facilities; therefore, their potential to contaminate manufactured foods underscores the importance of sanitation. The objectives of this study were to (1) examine the efficacy of a new-generation sanitizer (Decon7) on Staphylococcus and Pseudomonas biofilms, (2) identify biofilm bacteria from workers’ boots in relation to previous sanitizer chemistry, (3) validate the efficacy of Decon7 on biofilm from workers’ boots from an abattoir/food processing environment, and (4) compare the sensitivity of isolated boot biofilm bacteria to new- and early (Bi-Quat)-generation QAC sanitizers. Decon7 was applied at two concentrations (5%, 10%) and was shown to be effective within 1 min of exposure against enhanced biofilms of Staphylococcus spp. and Pseudomonas spp. in 96-well microplates. Decon7 was also used to treat workers’ boots that had accumulated high levels of biofilm bacteria due to ineffective sanitization. Bacteria isolated before enzyme/sanitizer treatment were identified through 16S rRNA PCR and DNA sequencing. All treatments were carried out in triplicate and analyzed by one-way RM-ANOVA or ANOVA using the Holm–Sidak test for pairwise multiple comparisons to determine significant differences (p < 0.05). The data show a significant difference between Decon7 sanitizer treatment and untreated control groups. There was a ~4–5 log reduction in Staphylococcus spp. and Pseudomonas spp. (microplate assay) within the first 1 min of treatment and also a > 3-log reduction in the bacterial population observed in the biofilms from workers’ boots. The new next-generation QAC sanitizers are more effective than prior QAC sanitizers, and enzyme pre-treatment can facilitate biofilm sanitizer penetration on food contact surfaces. The rotation of sanitizer chemistries may prevent the selective retention of chemistry-tolerant microorganisms in processing facilities.
Operational Forecasting of Tropical Cyclone Rapid Intensification at the National Hurricane Center
Authors: DeMaria Mark , Franklin James L. , Onderlinde Matthew J. , Kaplan John
Published: May 2021

Although some recent progress has been made in operational tropical cyclone (TC) intensity forecasting, the prediction of rapid intensification (RI) remains a challenging problem. To document RI forecast progress, deterministic and probabilistic operational intensity models used by the National Hurricane Center (NHC) are briefly reviewed. Results show that none of the deterministic models had RI utility from 1991 to about 2015 due to very low probability of detection, very high false alarm ratio, or both. Some ability to forecast RI has emerged since 2015, with dynamical models being the best guidance for the Atlantic and statistical models the best RI guidance for the eastern North Pacific. The first probabilistic RI guidance became available in 2001, with several upgrades since then leading to modest skill in recent years. A tool introduced in 2018 (DTOPS) is currently the most skillful among NHC’s probabilistic RI guidance. To measure programmatic progress in forecasting RI, the Hurricane Forecast Improvement Program has introduced a new RI metric that uses the traditional mean absolute error but restricts the sample to only those cases where RI occurred in the verifying best track or was forecast. By this metric, RI forecasts have improved by ~20–25% since the 2015–2017 baseline period.
Increased Levels of IL-16 in the Central Nervous System during Neuroinflammation Are Associated with Infiltrating Immune Cells and Resident Glial Cells
Authors: Hridi Shehla U , Barbour Mark , Wilson Chelsey , Franssen Aimee JPM , Harte Tanith , Bushell Trevor J , Jiang Hui-Rong
Published: May 2021

Interleukin (IL)-16, a CD4+ immune cell specific chemoattractant cytokine, has been shown to be involved in the development of multiple sclerosis, an inflammatory demyelinating disease of the central nervous system (CNS). While immune cells such as T cells and macrophages are reported to be the producers of IL-16, the cellular source of IL-16 in the CNS is less clear. This study investigates the correlation of IL-16 expression levels in the CNS with the severity of neuroinflammation and determines the phenotype of cells which produce IL-16 in the CNS of experimental autoimmune encephalomyelitis (EAE) mice. Our data show that IL-16 expression is significantly increased in the brain and spinal cord tissues of EAE mice compared to phosphate buffered saline (PBS) immunised controls. Dual immunofluorescence staining reveals that the significantly increased IL-16+ cells in the CNS lesions of EAE mice are likely to be the CD45+ infiltrating immune cells such as CD4+ or F4/80+ cells and the CNS resident CD11b+ microglia and GFAP+ astrocytes, but not NeuN+ neurons. Our data suggest cytokine IL-16 is closely involved in EAE pathology as evidenced by its increased expression in the glial and infiltrating immune cells, which impacts the recruitment and activation of CD4+ immune cells in the neuroinflammation.
Anatomo-Functional Origins of the Cortical Silent Period: Spotlight on the Basal Ganglia
Authors: Zeugin David , Ionta Silvio
Published: May 2021

The so-called cortical silent period (CSP) refers to the temporary interruption of electromyographic signal from a muscle following a motor-evoked potential (MEP) triggered by transcranial magnetic stimulation (TMS) over the primary motor cortex (M1). The neurophysiological origins of the CSP are debated. Previous evidence suggests that both spinal and cortical mechanisms may account for the duration of the CSP. However, contextual factors such as cortical fatigue, experimental procedures, attentional load, as well as neuropathology can also influence the CSP duration. The present paper summarizes the most relevant evidence on the mechanisms underlying the duration of the CSP, with a particular focus on the central role of the basal ganglia in the “direct” (excitatory), “indirect” (inhibitory), and “hyperdirect” cortico-subcortical pathways to manage cortical motor inhibition. We propose new methods of interpretation of the CSP related, at least partially, to the inhibitory hyperdirect and indirect pathways in the basal ganglia. This view may help to explain the respective shortening and lengthening of the CSP in various neurological disorders. Shedding light on the complexity of the CSP’s origins, the present review aims at constituting a reference for future work in fundamental research, technological development, and clinical settings.
The Efficacy of Transcranial Direct Current Stimulation in Enhancing Surgical Skill Acquisition: A Preliminary Meta-Analysis of Randomized Controlled Trials
Authors: Hung Chao-Ming , Zeng Bing-Yan , Zeng Bing-Syuan , Sun Cheuk-Kwan , Cheng Yu-Shian , Su Kuan-Pin , Wu Yi-Cheng , Chen Tien-Yu , Lin Pao-Yen , Liang Chih-Sung , Hsu Chih-Wei , Chu Che-Sheng , Chen Yen-Wen , Wu Ming-Kung , Tseng Ping-Tao
Published: May 2021

The application of transcranial direct current stimulation (tDCS) to targeted cortices has been found to improve in skill acquisition; however, these beneficial effects remained unclear in fine and complicated skill. The aim of the current meta-analysis was to investigate the association between tDCS application and the efficacy of surgical performance during surgical skill training. We included randomized controlled trials (RCTs) investigating the efficacy of tDCS in enhancing surgical skill acquisition. This meta-analysis was conducted under a random-effect model. Six RCTs with 198 participants were included. The main result revealed that tDCS was associated with significantly better improvement in surgical performance than the sham control (Hedges’ g = 0.659, 95% confidence intervals (95%CIs) = 0.383 to 0.935, p < 0.001). The subgroups of tDCS over the bilateral prefrontal cortex (Hedges’ g = 0.900, 95%CIs = 0.419 to 1.382, p < 0.001) and the primary motor cortex (Hedges’ g = 0.599, 95%CIs = 0.245 to 0.953, p = 0.001) were both associated with significantly better improvements in surgical performance. The tDCS application was not associated with significant differences in error scores or rates of local discomfort compared with a sham control. This meta-analysis supported the rationale for the tDCS application in surgical training programs to improve surgical skill acquisition.
Differential Diagnosis of Chorea—HIV Infection Delays Diagnosis of Huntington’s Disease by Years
Authors: Achenbach Jannis , Faissner Simon , Saft Carsten
Published: May 2021

Background: There is a broad range of potential differential diagnoses for chorea. Besides rare, inherited neurodegenerative diseases such as Huntington’s disease (HD) chorea can accompany basal ganglia disorders due to vasculitis or infections, e.g., with the human immunodeficiency virus (HIV). The clinical picture is complicated by the rare occurrence of HIV infection and HD. Methods: First, we present a case suffering simultaneously from HIV and HD (HIV/HD) focusing on clinical manifestation and disease onset. We investigated cross-sectional data regarding molecular genetic, motoric, cognitive, functional, and psychiatric disease manifestation of HIV/HD in comparison to motor-manifest HD patients without HIV infection (nonHIV/HD) in the largest cohort of HD patients worldwide using the registry study ENROLL-HD. Data were analyzed using ANCOVA analyses controlling for covariates of age and CAG repeat length between groups in IBM SPSS Statistics V.25. Results: The HD diagnosis in our case report was delayed by approximately nine years due to the false assumption that the HIV infection might have been the cause of chorea. Out of n = 21,116 participants in ENROLL-HD, we identified n = 10,125 motor-manifest HD patients. n = 23 male participants were classified as suffering from HIV infection as a comorbidity, compared to n = 4898 male non-HIV/HD patients. Except for age, with HIV/HD being significantly younger (p < 0.050), we observed no group differences regarding sociodemographic, genetic, educational, motoric, functional, and cognitive parameters. Male HIV/HD patients reported about a 5.3-year-earlier onset of HD symptoms noticed by themselves compared to non-HIV/HD (p < 0.050). Moreover, patients in the HIV/HD group had a longer diagnostic delay of 1.8 years between onset of symptoms and HD diagnosis and a longer time regarding assessment of first symptoms by the rater and judgement of the patient (all p < 0.050). Unexpectedly, HIV/HD patients showed less irritability in the Hospital Anxiety and Depression Scale (all p < 0.05). Conclusions: The HD diagnosis in HIV-infected male patients is secured with a diagnostic delay between first symptoms noticed by the patient and final diagnosis. Treating physicians therefore should be sensitized to think of potential alternative diagnoses in HIV-infected patients also afflicted by movement disorders, especially if there is evidence of subcortical atrophy and a history of hyperkinesia, even without a clear HD-family history. Those patients should be transferred for early genetic testing to avoid further unnecessary diagnostics and improve sociomedical care.
Population-Based Study of Prevalence, Bother and Behavior Related to Treatment for Lower Urinary Tract Symptoms and Overactive Bladder among Polish Neurogenic Patients
Authors: Przydacz Mikolaj , Chlosta Marcin , Golabek Tomasz , Chlosta Piotr
Published: May 2021

Background: The aim of this study was to perform a cross-sectional study of Polish neurogenic patients to measure, at the population level, the prevalence, bother and behavior associated with treatment for lower urinary tract symptoms (LUTS) and overactive bladder (OAB). Methods: This epidemiological study was based on data from LUTS POLAND, a computer-assisted and population-representative telephone survey. Participants were classified by age, sex and place of residence. Results: LUTS POLAND includes 6005 completed interviews, of which 1166 (19.4%) were for individuals who had ever received any treatment by neurologists and/or neurosurgeons. Among these neurogenic participants, LUTS prevalence was 72.3%, statistically higher than for non-neurogenic respondents. At the population level, neurogenic patients had about a 20% higher risk for LUTS presence than non-neurogenic participants (relative risk: 1.17–1.21). LUTS prevalence did not differ between men and women. Frequency was the most common of the LUTS. Forty percent of neurogenic respondents described having more than one LUTS subtype (i.e., storage, voiding, and/or post-micturition symptom subtype), and more than 50% of respondents reported OAB symptoms. Both storage and voiding symptoms were bothersome, and many neurogenic individuals (42.3–51.0%) expressed anxiety about bladder function affecting quality of life. Only one-third (34.9–36.6%) of neurogenic participants had sought treatment for their LUTS, and the majority of such individuals received and maintained treatment. Conclusions: LUTS and OAB symptoms were highly prevalent and bothersome among Polish neurogenic patients at the population level. Because the scale of seeking treatment for LUTS was low, Polish neurogenic patients may not be adequately informed about multiple effects of LUTS and OAB.
Bimodal Data Fusion of Simultaneous Measurements of EEG and fNIRS during Lower Limb Movements
Authors: AL-Quraishi Maged S. , Elamvazuthi Irraivan , Tang Tong Boon , Al-Qurishi Muhammad , Adil Syed Hasan , Ebrahim Mansoor
Published: May 2021

Electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) have temporal and spatial characteristics that may complement each other and, therefore, pose an intriguing approach for brain-computer interaction (BCI). In this work, the relationship between the hemodynamic response and brain oscillation activity was investigated using the concurrent recording of fNIRS and EEG during ankle joint movements. Twenty subjects participated in this experiment. The EEG was recorded using 20 electrodes and hemodynamic responses were recorded using 32 optodes positioned over the motor cortex areas. The event-related desynchronization (ERD) feature was extracted from the EEG signal in the alpha band (8–11) Hz, and the concentration change of the oxy-hemoglobin (oxyHb) was evaluated from the hemodynamics response. During the motor execution of the ankle joint movements, a decrease in the alpha (8–11) Hz amplitude (desynchronization) was found to be correlated with an increase of the oxyHb (r = −0.64061, p < 0.00001) observed on the Cz electrode and the average of the fNIRS channels (ch28, ch25, ch32, ch35) close to the foot area representation. Then, the correlated channels in both modalities were used for ankle joint movement classification. The result demonstrates that the integrated modality based on the correlated channels provides a substantial enhancement in ankle joint classification accuracy of 93.01 ± 5.60% (p < 0.01) compared with single modality. These results highlight the potential of the bimodal fNIR–EEG approach for the development of future BCI for lower limb rehabilitation.
Hybrid Krill Herd-ANN Model for Prediction Strength and Stiffness of Bolted Connections
Authors: Faridmehr Iman , Nikoo Mehdi , Baghban Mohammad Hajmohammadian , Pucinotti Raffaele
Published: May 2021

The behavior of beam-to-column connections significantly influences the stability, strength, and stiffness of steel structures. This is particularly important in extreme non-elastic responses, i.e., earthquakes, and sudden column removal, as the fluctuation in strength and stiffness affects both supply and demand. Accordingly, it is essential to accurately estimate the strength and stiffness of connections in the analysis of and design procedures for steel structures. Beginning with the state-of-the-art, the capacity of three available component-based mechanical models to estimate the complex mechanical properties of top- and seat-angle connections with double-web angles (TSACWs), with variable parameters, were investigated. Subsequently, a novel hybrid krill herd algorithm-artificial neural network (KHA-ANN) model was proposed to acquire an informational model from the available experimental dataset. Using several statistical metrics, including the corresponding coefficient of variation (CoV), correlation coefficient (R), and the correlation coefficient provided by the Taylor diagram, this study revealed that the krill herd-ANN model achieved the most reliable predictive accuracy for the strength and stiffness of top- and seat-angle connections with double web angles.
Altered Expression of Secreted Mediator Genes That Mediate Aggressive Breast Cancer Metastasis to Distant Organs
Authors: Maiti Aparna , Okano Ichiro , Oshi Masanori , Okano Maiko , Tian Wanqing , Kawaguchi Tsutomu , Katsuta Eriko , Takabe Kazuaki , Yan Li , Patnaik Santosh K. , Hait Nitai C.
Published: May 2021

Due to the heterogeneous nature of breast cancer, metastasis organotropism has been poorly understood. This study assessed the specific cancer-related gene expression changes occurring with metastatic breast cancer recurrence to distant organs compared with non-metastatic breast cancer. We found that several secreted mediators encoding genes notably, LCN2 and S100A8 overexpressed at the distant metastatic site spine (LCN2, 5-fold; S100A8, 6-fold) and bone (LCN2, 5-fold; S100A8, 3-fold) vs. primary tumors in the syngeneic implantation/tumor-resection metastasis mouse model. In contrast, the ESM-1 encoding gene is overexpressed in the primary tumors and markedly downregulated at distant metastatic sites. Further digging into TCAGA-BRCA, SCAN-B, and METABRIC cohorts data analysis revealed that LCN2, S100A8, and ESM-1 mediators encoding individual gene expression scores were strongly associated with disease-specific survival (DSS) in the METABRIC cohort (hazard ratio (HR) > 1, p < 0.0004). The gene expression scores predicted worse clinically aggressive tumors, such as high Nottingham histological grade and advanced cancer staging. Higher gene expression score of ESM-1 gene was strongly associated with worse overall survival (OS) in the triple-negative breast cancer (TNBC) and hormonal receptor (HR)-positive/HER2-negative subtype in METABRIC cohort, HER2+ subtype in TCGA-BRCA and SCAN-B breast cancer cohorts. Our data suggested that mediators encoding genes with prognostic and predictive values may be clinically useful for breast cancer spine, bone, and lung metastasis, particularly in more aggressive subtypes such as TNBC and HER2+ breast cancer.
Targeting Natural Killer T Cells in Solid Malignancies
Authors: Ingram Zewde , Madan Shriya , Merchant Jenoy , Carter Zakiya , Gordon Zen , Carey Gregory , Webb Tonya J.
Published: May 2021

Natural killer T (NKT) cells are a unique subset of lymphocytes that recognize lipid antigens in the context of the non-classical class I MHC molecule, CD1d, and serve as a link between the innate and adaptive immune system through their expeditious release of cytokines. Whereas NKT have well-established roles in mitigating a number of human diseases, herein, we focus on their role in cancer. NKT cells have been shown to directly and indirectly mediate anti-tumor immunity and manipulating their effector functions can have therapeutic significances in treatment of cancer. In this review, we highlight several therapeutic strategies that have been used to harness the effector functions of NKT cells to target different types of solid tumors. We also discuss several barriers to the successful utilization of NKT cells and summarize effective strategies being developed to harness the unique strengths of this potent population of T cells. Collectively, studies investigating the therapeutic potential of NKT cells serve not only to advance our understanding of this powerful immune cell subset, but also pave the way for future treatments focused on the modulation of NKT cell responses to enhance cancer immunotherapy.
Renal Cell Carcinoma-Infiltrating CD3low Vγ9Vδ1 T Cells Represent Potentially Novel Anti-Tumor Immune Players
Authors: Lee Hye Won , Park Chanho , Joung Je-Gun , Kang Minyong , Chung Yun Shin , Oh Won Joon , Yeom Seon-Yong , Park Woong-Yang , Kim Tae Jin , Seo Seong Il
Published: May 2021

Due to the highly immunogenic nature of renal cell carcinoma (RCC), the tumor microenvironment (TME) is enriched with various innate and adaptive immune subsets. In particular, gamma-delta (γδ) T cells can act as potent attractive mediators of adoptive cell transfer immunotherapy because of their unique properties such as non-reliance on major histocompatibility complex expression, their ability to infiltrate human tumors and recognize tumor antigens, relative insensitivity to immune checkpoint molecules, and broad tumor cytotoxicity. Therefore, it is now critical to better characterize human γδ T-cell subsets and their mechanisms in RCCs, especially the stage of differentiation. In this study, we aimed to identify γδ T cells that might have adaptive responses against RCC progression. We characterized γδ T cells in peripheral blood and tumor-infiltrating lymphocytes (TILs) in freshly resected tumor specimens from 20 RCC patients. Furthermore, we performed a gene set enrichment analysis on RNA-sequencing data from The Cancer Genome Atlas (TCGA) derived from normal kidneys and RCC tumors to ascertain the association between γδ T-cell infiltration and anti-cancer immune activity. Notably, RCC-infiltrating CD3low Vγ9Vδ1 T cells with a terminally differentiated effector memory phenotype with up-regulated activation/exhaustion molecules were newly detected as predominant TILs, and the cytotoxic activity of these cells against RCC was confirmed in vitro. In an additional analysis of the TCGA RCC dataset, γδ T-cell enrichment scores correlated strongly with those for CTLs, Th1 cells, “exhausted” T cells, and M1 macrophages, suggesting active involvement of γδ T cells in anti-tumor rather than pro-tumor activity, and Vδ1 cells were more abundant than Vδ2 or Vδ3 cells in RCC tumor samples. Thus, we posit that Vγ9Vδ1 T cells may represent an excellent candidate for adoptive immunotherapy in RCC patients with a high risk of relapse after surgery.