bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing Data-Conscious Deep Learning Models for Product Classification
Authors: Kim Yijin , Lee Hong Joo , Shim Junho
Published: June 2021

In online commerce systems that trade in many products, it is important to classify the products accurately according to the product description. As may be expected, the recent advances in deep learning technologies have been applied to automatic product classification. The efficiency of a deep learning model depends on the training data and the appropriateness of the learning model for the data domain. This is also applicable to deep learning models for automatic product classification. In this study, we propose deep learning models that are conscious of input data comprising text-based product information. Our approaches exploit two well-known deep learning models and integrate them with the processes of input data selection, transformation, and filtering. We demonstrate the practicality of these models through experiments using actual product information data. The experimental results show that the models that systematically consider the input data may differ in accuracy by approximately 30% from those that do not. This study indicates that input data should be sufficiently considered in the development of deep learning models for product classification.
Fourier Singular Values-Based False Data Injection Attack Detection in AC Smart-Grids
Authors: Dehghani Moslem , Niknam Taher , Ghiasi Mohammad , Siano Pierluigi , Haes Alhelou Hassan , Al-Hinai Amer
Published: June 2021

Cyber-physical threats as false data injection attacks (FDIAs) in islanded smart microgrids (ISMGs) are typical accretion attacks, which need urgent consideration. In this regard, this paper proposes a novel cyber-attack detection model to detect FDIAs based on singular value decomposition (SVD) and fast Fourier transform (FFT). Since new research are mostly focusing on FDIAs detection in DC systems, paying attention to AC systems attack detection is also necessary; hence, AC state estimation (SE) have been used in SI analysis and in considering renewable energy sources effect. Whenever malicious data are added into the system state vectors, vectors’ temporal and spatial datum relations might drift from usual operating conditions. In this approach, switching surface based on sliding mode controllers is dialyzed to regulate detailed FFT’s coefficients to calculate singular values. Indexes are determined according to the composition of FFT and SVD in voltage/current switching surface to distinguish the potential cyber-attack. This protection layout is presented for cyber-attack detection and is studied in various types of FDIA forms like amplitude and vector derivation of signals, which exchanged between agents such as smart sensor, control units, smart loads, etc. The prominent advantage of the proposed detection layout is to reduce the time (less than 10 milliseconds from the attack outset) in several kinds of case studies. The proposed method can detect more than 96% accuracy from 2967 sample tests. The performances of the method are carried out on AC-ISMG in MATLAB/Simulink environment.
Internet of Things Botnet Detection Approaches: Analysis and Recommendations for Future Research
Authors: Wazzan Majda , Algazzawi Daniyal , Bamasaq Omaima , Albeshri Aiiad , Cheng Li
Published: June 2021

Internet of Things (IoT) is promising technology that brings tremendous benefits if used optimally. At the same time, it has resulted in an increase in cybersecurity risks due to the lack of security for IoT devices. IoT botnets, for instance, have become a critical threat; however, systematic and comprehensive studies analyzing the importance of botnet detection methods are limited in the IoT environment. Thus, this study aimed to identify, assess and provide a thoroughly review of experimental works on the research relevant to the detection of IoT botnets. To accomplish this goal, a systematic literature review (SLR), an effective method, was applied for gathering and critically reviewing research papers. This work employed three research questions on the detection methods used to detect IoT botnets, the botnet phases and the different malicious activity scenarios. The authors analyzed the nominated research and the key methods related to them. The detection methods have been classified based on the techniques used, and the authors investigated the botnet phases during which detection is accomplished. This research procedure was used to create a source of foundational knowledge of IoT botnet detection methods. As a result of this study, the authors analyzed the current research gaps and suggest future research directions.
Influences of the Pretreatments of Residual Biomass on Gasification Processes: Experimental Devolatilizations Study in a Fluidized Bed
Authors: Lucantonio Stefania , Di Giuliano Andrea , Gallucci Katia
Published: June 2021

The European research project CLARA (chemical looping gasification for sustainable production of biofuels, G.A. 817841) investigated chemical looping gasification of wheat straw pellets. This work focuses on pretreatments for this residual biomass, i.e., torrefaction and torrefaction-washing. Devolatilizations of individual pellets were performed in a laboratory-scale fluidized bed made of sand, at 700, 800, and 900 °C, to quantify and analyze the syngas released from differently pretreated biomasses; experimental data were assessed by integral-average parameters: gas yield, H2/CO molar ratio, and carbon conversion. A new analysis of devolatilization data was performed, based on information from instantaneous peaks of released syngas, by simple regressions with straight lines. For all biomasses, the increase of devolatilization temperature between 700 and 900 °C enhanced the thermochemical conversion in terms of gas yield, carbon conversion, and H2/CO ratio in the syngas. Regarding pretreatments, the main evidence is the general improvement of syngas quality (i.e., composition) and quantity, compared to those of untreated pellets; only slighter differentiations were observed concerning different pretreatments, mainly thanks to peak quantities, which highlighted an improvement of the H2/CO molar ratio in correlation with increased torrefaction temperature from 250 to 270 °C. The proposed methods emerged as suitable straightforward tools to investigate the behavior of biomasses and the effects of process parameters and biomass nature.
Prediction of Oleic Acid Content of Rapeseed Using Hyperspectral Technique
Authors: Liu Fan , Wang Fang , Liao Guiping , Lu Xin , Yang Jiayi
Published: June 2021

In order to detect the oleic acid content of rapeseed quickly and accurately, we propose, in this paper, an artificial BP neural networks based model for predicting oleic acid content by using rapeseed’s hyperspectral information. Four types of spectral features are selected for our investigation, namely multifractal index, sensitive band, trilateral parameters, and spectral index. Both univariate variable and multiple variables are considered as our model input. The result shows that the combined feature has higher precision and better stability than when using a single parameter. An interesting finding shows that the combined feature involving multifractal parameters can significantly improve the model performance. Taking the combined feature {MF-h(0), SB-DR574, SPI-NDSI(R575, R576)} as the model input, the constructed BP (back propagation) neural networks model has the highest precision, with the coefficient of determination (R2) 0.8753, root mean square error (RMSE) 1.0301, and relative error (RE) 1.047%. This result provides some experience for the rapid detection of rapeseed’s oleic acid content.
Selection of Vertiports Using K-Means Algorithm and Noise Analyses for Urban Air Mobility (UAM) in the Seoul Metropolitan Area
Authors: Jeong Junyoung , So Minjun , Hwang Ho-Yon
Published: June 2021

In this study, a combination of well-established algorithms and real-world data was implemented for the forward-looking problem of future vertiport network design in a large metropolitan city. The locations of vertiports were selected to operate urban air mobility (UAM) in the Seoul metropolitan area based on the population of commuters, and a noise priority route was created to minimize the number of people affected by noise using Aviation Environmental Design Tool (AEDT) software. Demand data were analyzed using survey data from the commuting population and were marked on a map using MATLAB. To cluster the data, the K-means algorithm function built in MATLAB was used to select the center of the cluster as the location of the vertiports, and the accuracy and reliability of the clustering were evaluated using silhouette techniques. The locations of the selected vertiports were also identified using satellite image maps to ensure that the location of the selected vertiports were suitable for the actual vertiport location, and if the location was not appropriate, final vertiports were selected through the repositioning process. A helicopter model was then used to analyze the amount of noise reduction achieved by the noise priority route, which is the route between the selected K-UAM vertiports compared to the shortest distance route. As a result, it was shown that the noise priority route that minimized the amount of noise exposure was more efficient than the business priority routes.
Quality-Aware Resource Model Discovery
Authors: Cho Minsu , Park Gyunam , Song Minseok , Lee Jinyoun , Kum Euiseok
Published: June 2021

Context-aware process mining aims at extending a contemporary approach with process contexts for realistic process modeling. Regarding this discipline, there have been several attempts to combine process discovery and predictive process modeling and context information, e.g., time and cost. The focus of this paper is to develop a new method for deriving a quality-aware resource model. It first generates a resource-oriented transition system and identifies the quality-based superior and inferior cases. The quality-aware resource model is constructed by integrating these two results, and we also propose a model simplification method based on statistical analyses for better resource model visualization. This paper includes tooling support for our method, and one of the case studies on a semiconductor manufacturing process is presented to validate the usefulness of the proposed approach. We expect our work is practically applicable to a range of fields, including manufacturing and healthcare systems.
Complementary Metaresonator Sensor with Dual Notch Resonance for Evaluation of Vegetable Oils in C and X Bands
Authors: Armghan Ammar
Published: June 2021

This paper investigates the effect of complementary metaresonator for evaluation of vegetable oils in C and X bands. Tremendously increasing technology demands the exploration of complementary metaresonators for high performance in the related bands. This research probes the complementary mirror-symmetric S resonator (CMSSR) that can operate in two bands with compact size and high sensitivity features. The prime motivation behind the proposed technique is to utilize the dual notch resonance to estimate the dielectric constant of the oil under test (OUT). The proposed sensor is designed on a compact 30×25 mm2 and 1.6 mm thick FR-4 substrate. A 50 Ω microstrip transmission line is printed on one side, while a unit cell of CMSSR is etched on the other side of the substrate to achieve dual notch resonance. A Teflon container is attached to CMSSR in the ground plane to act as a pool for the OUT. According to the simulated transmission spectrum, the proposed design manifested dual notch resonance precisely at 7.21 GHz (C band) and 8.97 GHz (X band). A prototype of complementary metaresonator sensor is fabricated and tested using CEYEAR AV3672D vector network analyzer. The comparison of measured and simulated data shows that the difference between the first resonance frequency is 0.01 GHz and the second is 0.04 GHz. Furthermore, a mathematical model is developed for the complementary metaresonator sensor to evaluate dielectric constant of the OUT in terms of the relevant, resonant frequency.
Complex Systems, Emergence, and Multiscale Analysis: A Tutorial and Brief Survey
Authors: Gao Jianbo , Xu Bo
Published: June 2021

Mankind has long been fascinated by emergence in complex systems. With the rapidly accumulating big data in almost every branch of science, engineering, and society, a golden age for the study of complex systems and emergence has arisen. Among the many values of big data are to detect changes in system dynamics and to help science to extend its reach, and most desirably, to possibly uncover new fundamental laws. Unfortunately, these goals are hard to achieve using black-box machine-learning based approaches for big data analysis. Especially, when systems are not functioning properly, their dynamics must be highly nonlinear, and as long as abnormal behaviors occur rarely, relevant data for abnormal behaviors cannot be expected to be abundant enough to be adequately tackled by machine-learning based approaches. To better cope with these situations, we advocate to synergistically use mainstream machine learning based approaches and multiscale approaches from complexity science. The latter are very useful for finding key parameters characterizing the evolution of a dynamical system, including malfunctioning of the system. One of the many uses of such parameters is to design simpler but more accurate unsupervised machine learning schemes. To illustrate the ideas, we will first provide a tutorial introduction to complex systems and emergence, then we present two multiscale approaches. One is based on adaptive filtering, which is excellent at trend analysis, noise reduction, and (multi)fractal analysis. The other originates from chaos theory and can unify the major complexity measures that have been developed in recent decades. To make the ideas and methods better accessed by a wider audience, the paper is designed as a tutorial survey, emphasizing the connections among the different concepts from complexity science. Many original discussions, arguments, and results pertinent to real-world applications are also presented so that readers can be best stimulated to apply and further develop the ideas and methods covered in the article to solve their own problems. This article is purported both as a tutorial and a survey. It can be used as course material, including summer extensive training courses. When the material is used for teaching purposes, it will be beneficial to motivate students to have hands-on experiences with the many methods discussed in the paper. Instructors as well as readers interested in the computer analysis programs are welcome to contact the corresponding author.
Human–Robot Collaborative Assembly Based on Eye-Hand and a Finite State Machine in a Virtual Environment
Authors: Zhao Xue , He Ye , Chen Xiaoan , Liu Zhi
Published: June 2021

With the development of the global economy, the demand for manufacturing is increasing. Accordingly, human–robot collaborative assembly has become a research hotspot. This paper aims to solve the efficiency problems inherent in traditional human-machine collaboration. Based on eye–hand and finite state machines, a collaborative assembly method is proposed. The method determines the human’s intention by collecting posture and eye data, which can control a robot to grasp an object, move it, and perform co-assembly. The robot’s automatic path planning is based on a probabilistic roadmap planner. Virtual reality tests show that the proposed method is more efficient than traditional methods.
Combined Effect of Hot Weather and Outdoor Air Pollution on Respiratory Health: Literature Review
Authors: Grigorieva Elena , Lukyanets Artem
Published: June 2021

Association between short-term exposure to ambient air pollution and respiratory health is well documented. At the same time, it is widely known that extreme weather events intrinsically exacerbate air pollution impact. Particularly, hot weather and extreme temperatures during heat waves (HW) significantly affect human health, increasing risks of respiratory mortality and morbidity. Concurrently, a synergistic effect of air pollution and high temperatures can be combined with weather–air pollution interaction during wildfires. The purpose of the current review is to summarize literature on interplay of hot weather, air pollution, and respiratory health consequences worldwide, with the ultimate goal of identifying the most dangerous pollution agents and vulnerable population groups. A literature search was conducted using electronic databases Web of Science, Pubmed, Science Direct, and Scopus, focusing only on peer-reviewed journal articles published in English from 2000 to 2021. The main findings demonstrate that the increased level of PM10 and O3 results in significantly higher rates of respiratory and cardiopulmonary mortality. Increments in PM2.5 and PM10, O3, CO, and NO2 concentrations during high temperature episodes are dramatically associated with higher admissions to hospital in patients with chronic obstructive pulmonary disease, daily hospital emergency transports for asthma, acute and chronic bronchitis, and premature mortality caused by respiratory disease. Excessive respiratory health risk is more pronounced in elderly cohorts and small children. Both heat waves and outdoor air pollution are synergistically linked and are expected to be more serious in the future due to greater climate instability, being a crucial threat to global public health that requires the responsible involvement of researchers at all levels. Sustainable urban planning and smart city design could significantly reduce both urban heat islands effect and air pollution.
Impacts of Climate Change on the Hydrometeorological Characteristics of the Soan River Basin, Pakistan
Authors: Usman Muhammad , Ndehedehe Christopher E. , Manzanas Rodrigo , Ahmad Burhan , Adeyeri Oluwafemi E.
Published: June 2021

The global hydrological cycle is vulnerable to changing climatic conditions, especially in developing regions, which lack abundant resources and management of freshwater resources. This study evaluates the impacts of climate change on the hydrological regime of the Chirah and Dhoke Pathan sub catchments of the Soan River Basin (SRB), in Pakistan, by using the climate models included in the NEX-GDDP dataset and the hydrological model HBV-light. After proper calibration and validation, the latter is forced with NEX-GDDP inputs to simulate a historic and a future (under the RCP 4.5 and RCP 8.5 emission scenarios) streamflow. Multiple evaluation criteria were employed to find the best performing NEX-GDDP models. A different ensemble was produced for each sub catchment by including the five best performing NEX-GDDP GCMs (ACCESS1-0, CCSM4, CESM1-BGC, MIROC5, and MRI-CGCM3 for Chirah and BNU-ESM, CCSM4, GFDL-CM3. IPSL-CM5A-LR and NorESM1-M for Dhoke Pathan). Our results show that the streamflow is projected to decrease significantly for the two sub catchments, highlighting the vulnerability of the SRB to climate change.
Spatial and Temporal Analysis of Dry and Wet Spells in the Wadi Cheliff Basin, Algeria
Authors: Achite Mohammed , Krakauer Nir Y. , Wałęga Andrzej , Caloiero Tommaso
Published: June 2021

The Mediterranean Basin, located in a transition zone between the temperate and rainy climate of central Europe and the arid climate of North Africa, is considered a major hotspot of climate change, subject to water scarcity and drought. In this work, dry and wet spells have been analyzed in the Wadi Cheliff basin (Algeria) by means of annual precipitation observed at 150 rain gauges in the period 1970–2018. In particular, the characteristics of dry and wet spells (frequency, duration, severity, and intensity) have been evaluated by means of the run theory applied to the 12-month standardized precipitation index (SPI) values. Moreover, in order to detect possible tendencies in the SPI values, a trend analysis has been performed by means of two non-parametric tests, the Theil–Sen and Mann–Kendall test. The results indicated similar values of frequency, severity, duration, and intensity between the dry and the wet spells, although wet events showed higher values in the extreme. Moreover, the results of the trend analysis evidenced a different behavior between the northern side of the basin, characterized by a negative trend in the 12-month SPI values, and the southern side, in which positive trends were detected.
Autophagy a Close Relative of AML Biology
Authors: Joffre Carine , Ducau Charlotte , Poillet-Perez Laura , Courdy Charly , Mansat-De Mas Véronique
Published: June 2021

Autophagy, which literally means “eat yourself”, is more than just a lysosomal degradation pathway. It is a well-known regulator of cellular metabolism and a mechanism implicated in tumor initiation/progression and therapeutic resistance in many cancers. However, whether autophagy acts as a tumor suppressor or promoter is still a matter of debate. In acute myeloid leukemia (AML), it is now proven that autophagy supports cell proliferation in vitro and leukemic progression in vivo. Mitophagy, the specific degradation of mitochondria through autophagy, was recently shown to be required for leukemic stem cell functions and survival, highlighting the prominent role of this selective autophagy in leukemia initiation and progression. Moreover, autophagy in AML sustains fatty acid oxidation through lipophagy to support mitochondrial oxidative phosphorylation (OxPHOS), a hallmark of chemotherapy-resistant cells. Nevertheless, in the context of therapy, in AML, as well as in other cancers, autophagy could be either cytoprotective or cytotoxic, depending on the drugs used. This review summarizes the recent findings that mechanistically show how autophagy favors leukemic transformation of normal hematopoietic stem cells, as well as AML progression and also recapitulates its ambivalent role in resistance to chemotherapies and targeted therapies.
Genome-Wide Atlas of Promoter Expression Reveals Contribution of Transcribed Regulatory Elements to Genetic Control of Disuse-Mediated Atrophy of Skeletal Muscle
Authors: Pintus Sergey S. , Akberdin Ilya R. , Yevshin Ivan , Makhnovskii Pavel , Tyapkina Oksana , Nigmetzyanov Islam , Nurullin Leniz , Devyatiyarov Ruslan , Shagimardanova Elena , Popov Daniil , Kolpakov Fedor A. , Gusev Oleg , Gazizova Guzel R.
Published: June 2021

The prevention of muscle atrophy carries with it clinical significance for the control of increased morbidity and mortality following physical inactivity. While major transcriptional events associated with muscle atrophy-recovery processes are the subject of active research on the gene level, the contribution of non-coding regulatory elements and alternative promoter usage is a major source for both the production of alternative protein products and new insights into the activity of transcription factors. We used the cap-analysis of gene expression (CAGE) to create a genome-wide atlas of promoter-level transcription in fast (m. EDL) and slow (m. soleus) muscles in rats that were subjected to hindlimb unloading and subsequent recovery. We found that the genetic regulation of the atrophy-recovery cycle in two types of muscle is mediated by different pathways, including a unique set of non-coding transcribed regulatory elements. We showed that the activation of “shadow” enhancers is tightly linked to specific stages of atrophy and recovery dynamics, with the largest number of specific regulatory elements being transcriptionally active in the muscles on the first day of recovery after a week of disuse. The developed comprehensive database of transcription of regulatory elements will further stimulate research on the gene regulation of muscle homeostasis in mammals.
Lab-on-a-Chip Platforms as Tools for Drug Screening in Neuropathologies Associated with Blood–Brain Barrier Alterations
Authors: Staicu Cristina Elena , Jipa Florin , Axente Emanuel , Radu Mihai , Radu Beatrice Mihaela , Sima Felix
Published: June 2021

Lab-on-a-chip (LOC) and organ-on-a-chip (OOC) devices are highly versatile platforms that enable miniaturization and advanced controlled laboratory functions (i.e., microfluidics, advanced optical or electrical recordings, high-throughput screening). The manufacturing advancements of LOCs/OOCs for biomedical applications and their current limitations are briefly discussed. Multiple studies have exploited the advantages of mimicking organs or tissues on a chip. Among these, we focused our attention on the brain-on-a-chip, blood–brain barrier (BBB)-on-a-chip, and neurovascular unit (NVU)-on-a-chip applications. Mainly, we review the latest developments of brain-on-a-chip, BBB-on-a-chip, and NVU-on-a-chip devices and their use as testing platforms for high-throughput pharmacological screening. In particular, we analyze the most important contributions of these studies in the field of neurodegenerative diseases and their relevance in translational personalized medicine.
Polystyrene Microsphere-Based Immunochromatographic Assay for Detection of Aflatoxin B1 in Maize
Authors: Wang Jin , Li Xiangmei , Shen Xing , Zhang Ang , Liu Jinxiu , Lei Hongtao
Published: June 2021

Aflatoxin B1 (AFB1), a mycotoxin, is hepatotoxic, carcinogenic, and nephrotoxic in humans and animals, and contaminate a wide range of maize. In this study, an immunochromatographic assay (ICA) based on polystyrene microspheres (PMs) was developed for sensitive and quantitative detection of AFB1 in maize. The amounts of PMs, the condition for activating carboxyl groups of PMs, the amount of monoclonal antibody (mAb), and the volume of the immune probe were optimized to enhance the performance PMs-ICA for point-of-care testing of AFB1 in maize. The PMs-ICA showed the cut-off value of 1 ng/mL in phosphate buffer (PB) and 6 µg/kg in maize samples, respectively. The quantitative limit of detection (qLOD) was 0.27 and 1.43 µg/kg in PB and maize samples, respectively. The accuracy and precision of the PMs-ICA were evaluated by analysis of spiked maize samples with recoveries of 96.0% to 107.6% with coefficients of variation below 10%. In addition, the reliability of PMs-ICA was confirmed by the liquid chromatography-tandem mass spectrometry method. The results indicated that the PMs-ICA could be used as a sensitive, simple, rapid point-of-care testing of AFB1 in maize.
Electrochemical Immunosensing of ST2: A Checkpoint Target in Cancer Diseases
Authors: Torrente-Rodríguez Rebeca M. , Martín Cristina Muñoz-San , Gamella Maria , Pedrero María , Martínez-Bosch Neus , Navarro Pilar , García de Frutos Pablo , Pingarrón José M. , Campuzano Susana
Published: June 2021

A magnetic beads (MB)-involved amperometric immunosensor for the determination of ST2, a member of the IL1 receptor family, is reported in this work. The method utilizes a sandwich immunoassay and disposable screen-printed carbon electrodes (SPCEs). Magnetic immunoconjugates built on the surface of carboxylic acid-microsized magnetic particles (HOOC-MBs) were used to selectively capture ST2. A biotinylated secondary antibody further conjugated with a streptavidin peroxidase conjugate (Strep-HRP) was used to accomplish the sandwiching of the target protein. The immune platform exhibits great selectivity and a low limit of detection (39.6 pg mL−1) for ST2, allowing the determination of soluble ST2 (sST2) in plasma samples from healthy individuals and patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) in only 45 min once the immunoconjugates have been prepared. The good correlation of the obtained results with those provided by an ELISA kit performed using the same immunoreagents demonstrates the potential of the developed strategy for early diagnosis and/or prognosis of the fatal PDAC disease.
The Influence of Stimuli Valence and Arousal on Spatio-Temporal Representation of a Route
Authors: Ruotolo Francesco , Sbordone Filomena L. , van der Ham Ineke J. M.
Published: June 2021

This study assesses the influence of valence and arousal of element/landmarks along a route on the spatio-temporal representation of the route itself. Participants watched a movie of a virtual route containing landmarks with high arousal and positive (HP) or negative valence (HN), or landmarks with low arousal and positive (LP) or negative valence (LN). Afterwards, they had to (a) imagine walking distances between landmarks, (b) indicate the position of the landmarks along the route, (c) judge the spatial and temporal length of the route, and (d) draw the route. Results showed that the tasks were differentially influenced by the valence and arousal levels. Specifically, participants were more accurate in representing distances between positive, rather than negative, landmarks and in localizing positive high arousing landmarks. Moreover, the high arousing landmarks improved performance at the route drawing task. Finally, participants in the negative and low arousing conditions judged the route as being metrically and temporally longer than participants in positive and high arousing conditions. These results are interpreted in the light of theories about the effects of emotions on memory processes and the “feelings-as-information” theory. In brief, the results support the idea that representations of a route reflect a combination of cognitive and emotional processes.
Self-Boundary Dissolution in Meditation: A Phenomenological Investigation
Authors: Nave Ohad , Trautwein Fynn-Mathis , Ataria Yochai , Dor-Ziderman Yair , Schweitzer Yoav , Fulder Stephen , Berkovich-Ohana Aviva
Published: June 2021

A fundamental aspect of the sense of self is its pre-reflective dimension specifying the self as a bounded and embodied knower and agent. Being a constant and tacit feature structuring consciousness, it eludes robust empirical exploration. Recently, deep meditative states involving global dissolution of the sense of self have been suggested as a promising path for advancing such an investigation. To that end, we conducted a comprehensive phenomenological inquiry into meditative self-boundary alteration. The induced states were systematically characterized by changes in six experiential features including the sense of location, agency, first-person perspective, attention, body sensations, and affective valence, as well as their interaction with meditative technique and overall degree of dissolution. Quantitative analyses of the relationships between these phenomenological categories highlighted a unitary dimension of boundary dissolution. Notably, passive meditative gestures of “letting go”, which reduce attentional engagement and sense of agency, emerged as driving the depth of dissolution. These findings are aligned with an enactive approach to the pre-reflective sense of self, linking its generation to sensorimotor activity and attention-demanding processes. Moreover, they set the stage for future phenomenologically informed analyses of neurophysiological data and highlight the utility of combining phenomenology and intense contemplative training for a scientific characterization of processes giving rise to the basic sense of being a bounded self.
Relationship Satisfaction in People with Parkinson’s Disease and Their Caregivers: A Cross-Sectional Observational Study
Authors: Heine Johanne , von Eichel Hannah , Staege Selma , Höglinger Günter U. , Wegner Florian , Klietz Martin
Published: June 2021

Parkinson’s disease (PD) is a neurodegenerative disorder, which leads to reduced health-related quality of life (HR-QoL) and autonomy in advanced stages of the disease. Hence, people with PD (PwPD) are in need of help, which is often provided by informal caregivers, especially spouses. This might influence the relationship satisfaction in patients and their spousal caregivers. Additionally, previous studies have shown that a reduced relationship satisfaction may result in mental disorders and reduced physical health. The aim of this study is to identify factors influencing PwPD and their caregivers’ relationship satisfaction in a cross-sectional observational study. Analyses revealed an overall satisfying relationship, measured by the Quality of Marriage Index, in PwPD (n = 84) and their caregivers (n = 79). Relationship satisfaction in PwPD mildly decreased with reduced HR-QoL and more severe depressive symptoms. Reduced relationship satisfaction in caregivers was significantly associated with decreased HR-QoL, higher caregiver burden, more severe depressive symptoms and increased neuropsychiatric symptoms in PwPD. Further studies are needed to investigate the influence of the identified factors over time and if relationship satisfaction has a reciprocal impact on caregiver burden, HR-QoL as well as mental and physical health.
Hacking Trust: The Presence of Faces on Automated Teller Machines (ATMs) Affects Trustworthiness
Authors: Gabrieli Giulio , Ng Sarah , Esposito Gianluca
Published: June 2021

Trustworthiness is a core concept that drives individuals’ interaction with others, as well with objects and digital interfaces. The perceived trustworthiness of strangers from the evaluation of their faces has been widely studies in social psychology; however, little is known about the possibility of transferring trustworthiness from human faces to other individuals, objects or interfaces. In this study, we explore how the perceived trustworthiness of automated teller machines (ATMs) is influenced by the presence of faces on the machines, and how the trustworthiness of the faces themselves is transferred to the machine. In our study, participants (N = 57) rated the trustworthiness of ATMs on which faces of different age, gender, and ethnicity are placed. Subsequently, the trustworthiness of the ATMs is compared to the trustworthiness ratings of faces presented on their own. Results of our works support the idea that faces’ trustworthiness can be transferred to objects on which faces are presented. Moreover, the trustworthiness of ATMs seems to be influenced by the age of presented faces, with ATMs on which children faces are presented are trusted more than the same machines when adults’ or elders’ faces are presented, but not by the ethnicity (Asian or Caucasian) or gender (male or female) of presented faces.
Structural Chromosome Instability: Types, Origins, Consequences, and Therapeutic Opportunities
Authors: Siri Sebastián Omar , Martino Julieta , Gottifredi Vanesa
Published: June 2021

Chromosomal instability (CIN) refers to an increased rate of acquisition of numerical and structural changes in chromosomes and is considered an enabling characteristic of tumors. Given its role as a facilitator of genomic changes, CIN is increasingly being considered as a possible therapeutic target, raising the question of which variables may convert CIN into an ally instead of an enemy during cancer treatment. This review discusses the origins of structural chromosome abnormalities and the cellular mechanisms that prevent and resolve them, as well as how different CIN phenotypes relate to each other. We discuss the possible fates of cells containing structural CIN, focusing on how a few cell duplication cycles suffice to induce profound CIN-mediated genome alterations. Because such alterations can promote tumor adaptation to treatment, we discuss currently proposed strategies to either avoid CIN or enhance CIN to a level that is no longer compatible with cell survival.
Nectin-1 Expression Correlates with the Susceptibility of Malignant Melanoma to Oncolytic Herpes Simplex Virus In Vitro and In Vivo
Authors: Schwertner Barbara , Lindner Georg , Toledo Stauner Camila Toledo , Klapproth Elisa , Magnus Clara , Rohrhofer Anette , Gross Stefanie , Schuler-Thurner Beatrice , Öttl Veronika , Feichtgruber Nicole , Drexler Konstantin , Evert Katja , Krahn Michael P. , Berneburg Mark , Schmidt Barbara , Schuster Philipp , Haferkamp Sebastian
Published: June 2021

Talimogene laherparepvec (T-VEC), an oncolytic herpes simplex virus, is approved for intralesional injection of unresectable stage IIIB/IVM1a melanoma. However, it is still unclear which parameter(s) predict treatment response or failure. Our study aimed at characterizing surface receptors Nectin-1 and the herpes virus entry mediator (HVEM) in addition to intracellular molecules cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) as potential bio-markers for oncolytic virus treatment. In 20 melanoma cell lines, oncolytic activity of T-VEC was correlated with the expression of Nectin-1 but not HVEM, as evaluated via flow cytometry and immunohistochemistry. Knockout using CRISPR/Cas9 technology confirmed the superior role of Nectin-1 over HVEM for entry and oncolytic activity of T-VEC. Neither cGAS nor STING as evaluated by Western Blot and immunohistochemistry correlated with T-VEC induced oncolysis. The role of these biomarkers was retrospectively analyzed for the response of 35 cutaneous melanoma metastases of 21 patients to intralesional T-VEC injection, with 21 (60.0%) of these lesions responding with complete (n = 16) or partial regression (n = 5). Nectin-1 expression in pretreatment biopsies significantly predicted treatment outcome, while the expression of HVEM, cGAS, and STING was not prognostic. Altogether, Nectin-1 served as biomarker for T-VEC-induced melanoma regression in vitro and in vivo.
Perspectives on Hypoxia Signaling in Tumor Stroma
Authors: Zhang Yuqing , Coleman Morgan , Brekken Rolf A.
Published: June 2021

Hypoxia is a well-known characteristic of solid tumors that contributes to tumor progression and metastasis. Oxygen deprivation due to high demand of proliferating cancer cells and standard of care therapies induce hypoxia. Hypoxia signaling, mainly mediated by the hypoxia-inducible transcription factor (HIF) family, results in tumor cell migration, proliferation, metabolic changes, and resistance to therapy. Additionally, the hypoxic tumor microenvironment impacts multiple cellular and non-cellular compartments in the tumor stroma, including disordered tumor vasculature, homeostasis of ECM. Hypoxia also has a multifaceted and often contradictory influence on immune cell function, which contributes to an immunosuppressive environment. Here, we review the important function of HIF in tumor stromal components and summarize current clinical trials targeting hypoxia. We provide an overview of hypoxia signaling in tumor stroma that might help address some of the challenges associated with hypoxia-targeted therapies.
Global Alternative Splicing Defects in Human Breast Cancer Cells
Authors: Oh Jagyeong , Pradella Davide , Kim Yoonseong , Shao Changwei , Li Hairi , Choi Namjeong , Ha Jiyeon , Di Matteo Anna , Fu Xiang-Dong , Zheng Xuexiu , Ghigna Claudia , Shen Haihong
Published: June 2021

Breast cancer is the most frequently occurred cancer type and the second cause of death in women worldwide. Alternative splicing (AS) is the process that generates more than one mRNA isoform from a single gene, and it plays a major role in expanding the human protein diversity. Aberrant AS contributes to breast cancer metastasis and resistance to chemotherapeutic interventions. Therefore, identifying cancer-specific isoforms is the prerequisite for therapeutic interventions intended to correct aberrantly expressed AS events. Here, we performed RNA-mediated oligonucleotide annealing, selection, and ligation coupled with next-generation sequencing (RASL-seq) in breast cancer cells, to identify global breast cancer-specific AS defects. By RT-PCR validation, we demonstrate the high accuracy of RASL-seq results. In addition, we analyzed identified AS events using the Cancer Genome Atlas (TCGA) database in a large number of non-pathological and breast tumor specimens and validated them in normal and breast cancer samples. Interestingly, aberrantly regulated AS cassette exons in cancer tissues do not encode for known functional domains but instead encode for amino acids constituting regions of intrinsically disordered protein portions characterized by high flexibility and prone to be subjected to post-translational modifications. Collectively, our results reveal novel AS errors occurring in human breast cancer, potentially affecting breast cancer-related biological processes.
Balancing the CD38 Expression on Effector and Target Cells in Daratumumab-Mediated NK Cell ADCC against Multiple Myeloma
Authors: Lejeune Margaux , Duray Elodie , Peipp Matthias , Clémenceau Béatrice , Baron Frédéric , Beguin Yves , Caers Jo
Published: June 2021

Multiple myeloma (MM) is an incurable cancer characterized by the proliferation and accumulation of monoclonal plasma cells in the bone marrow. The monoclonal anti-CD38 daratumumab has taken a central place in the different treatment regimens for newly diagnosed and relapsed, refractory myeloma. In this study, we correlated the NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and potential fratricide induced by daratumumab with CD38-expression levels on both effector and target cells. We show that CD38 expression can be modulated by adding all-trans retinoic acid (ATRA) or interferon-α to MM cells to further fine-tune these effects. In addition, we observed that ADCC becomes inefficient when fratricide occurs and both ADCC and fratricide depend on the balance between CD38 expression on effector and target cells. However, the addition of adjuvants (retinoic acid or interferon-α) to myeloma cells or the inhibition of fratricide using a CD38-blocking nanobody on NK-cells can reverse this balance towards ADCC and thus promote lysis of target cells by ADCC. ATRA and interferon-α increased the CD38 expression at the surface of MM cells about three-fold and two-fold, respectively. This increase was of interest for MM cells with low CD38 expression, that became susceptible to daratumumab-mediated ADCC after preincubation. A CD38-blocking nanobody prevented the binding of daratumumab to these NK-cells and blunted the fratricidal effect on effector NK cells. In conclusion, our study highlights the importance of a balanced CD38 expression on target and effector cells and attempts to alter this balance will affect the susceptibility of MM cells towards daratumumab-mediated ADCC.
Immunotherapy Discontinuation in Metastatic Melanoma: Lessons from Real-Life Clinical Experience
Authors: Asher Nethanel , Israeli-Weller Noa , Shapira-Frommer Ronnie , Ben-Betzalel Guy , Schachter Jacob , Meirson Tomer , Markel Gal
Published: June 2021

Background: Immunotherapy has revolutionized outcomes for melanoma patients, by significantly prolonging survival and probably even curing a fraction of metastatic patients. In daily practice, treatment for responding patients is often discontinued due to treatment-limiting toxicity, or electively, following a major tumor response. To date, the criteria for a safe stop and the optimal duration of treatment remain unclear. Patients and methods: This is a real-world single-site cohort of 106 advanced melanoma patients who were treated with immunotherapy and who discontinued treatments in the absence of disease progression. Here, we describe their long-term outcomes, and analyze the differential characteristics between patients who ultimately experienced progression and those who remained in unmaintained durable response. Results: Patients were treated with anti-PD-1 monotherapy (81%) or in combination with ipilimumab (19%) for a median of 15.2 m (range, 0.7–42.3 m). Upon discontinuation, 75.5% had achieved a complete response (CR). After a median follow-up of 20.8 m (range, 6–58) from discontinuation, 32% experienced disease progression. Median time to progression was 8.5 m (range, 1.5–37). Response to re-induction with anti-PD-1 was observed in 47%. On multivariate analysis, achieving a non-CR response, immunotherapy given in advanced line, and shorter treatment duration were significantly associated with lesser progression-free survival. Conclusions: This is one of the few reports on real-world melanoma patients who discontinued immunotherapy while responding to treatment. This study reveals the key factors to bear in mind when considering an elective treatment cessation. Specifically, patients with non-CR as best response and patients treated in an advanced-line setting should be treated for longer periods, and elective discontinuation should not take place prior to 18 m.
Ca2+ Signaling and Its Potential Targeting in Pancreatic Ductal Carcinoma
Authors: Bettaieb Louay , Brulé Maxime , Chomy Axel , Diedro Mel , Fruit Malory , Happernegg Eloise , Heni Leila , Horochowska Anaïs , Housseini Mahya , Klouyovo Kekely , Laratte Agathe , Leroy Alice , Lewandowski Paul , Louvieaux Joséphine , Moitié Amélie , Tellier Rémi , Titah Sofia , Vanauberg Dimitri , Woesteland Flavie , Prevarskaya Natalia , Lehen’kyi V’yacheslav
Published: June 2021

Pancreatic cancer (PC) is a major cause of cancer-associated mortality in Western countries (and estimated to be the second cause of cancer deaths by 2030). The main form of PC is pancreatic adenocarcinoma, which is the fourth most common cause of cancer-related death, and this situation has remained virtually unchanged for several decades. Pancreatic ductal adenocarcinoma (PDAC) is inherently linked to the unique physiology and microenvironment of the exocrine pancreas, such as pH, mechanical stress, and hypoxia. Of them, calcium (Ca2+) signals, being pivotal molecular devices in sensing and integrating signals from the microenvironment, are emerging to be particularly relevant in cancer. Mutations or aberrant expression of key proteins that control Ca2+ levels can cause deregulation of Ca2+-dependent effectors that control signaling pathways determining the cells’ behavior in a way that promotes pathophysiological cancer hallmarks, such as enhanced proliferation, survival and invasion. So far, it is essentially unknown how the cancer-associated Ca2+ signaling is regulated within the characteristic landscape of PDAC. This work provides a complete overview of the Ca2+ signaling and its main players in PDAC. Special consideration is given to the Ca2+ signaling as a potential target in PDAC treatment and its role in drug resistance.
Transforming Growth Factor-β and Oxidative Stress in Cancer: A Crosstalk in Driving Tumor Transformation
Authors: Ramundo Valeria , Giribaldi Giuliana , Aldieri Elisabetta
Published: June 2021

Cancer metabolism involves different changes at a cellular level, and altered metabolic pathways have been demonstrated to be heavily involved in tumorigenesis and invasiveness. A crucial role for oxidative stress in cancer initiation and progression has been demonstrated; redox imbalance, due to aberrant reactive oxygen species (ROS) production or deregulated efficacy of antioxidant systems (superoxide dismutase, catalase, GSH), contributes to tumor initiation and progression of several types of cancer. ROS may modulate cancer cell metabolism by acting as secondary messengers in the signaling pathways (NF-kB, HIF-1α) involved in cellular proliferation and metastasis. It is known that ROS mediate many of the effects of transforming growth factor β (TGF-β), a key cytokine central in tumorigenesis and cancer progression, which in turn can modulate ROS production and the related antioxidant system activity. Thus, ROS synergize with TGF-β in cancer cell metabolism by increasing the redox imbalance in cancer cells and by inducing the epithelial mesenchymal transition (EMT), a crucial event associated with tumor invasiveness and metastases. Taken as a whole, this review is addressed to better understanding this crosstalk between TGF-β and oxidative stress in cancer cell metabolism, in the attempt to improve the pharmacological and therapeutic approach against cancer.