bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Tech Training for Birds of Prey
Authors: Granati Giovanni , Cichella Francesca , Lucidi Pia
Published: February 2021

Raptors are some of the most at-risk groups of birds in the world and saving these top predators is essential for maintaining the health of many ecosystems. After hospitalization, raptors are often released when muscular recovery is still unfitting when they are unable to hunt efficiently and are at risk of dying from starvation within a few days. On the other hand, if a convalescent bird is trained with the only use of classic falconry techniques, it is likely to remain dependent on the caretaker/falconer even long after the release, so unable to hunt independently. To overcome these problems, a new training method was conceived, which could improve raptors’ muscular strength while limiting habituation to humans. This has been possible due to the combination of classic falconry techniques and modern technologies, such as the introduction of specific workouts with drones. Three falconry raptors and one wild Eurasian hobby were trained through high-tech falconry to develop the ability to catch, grasp, and airlift their prey at a different speed, altitude, and resistance. The main findings of this study were: (i) The rapid increase of the raptors’ speed; (ii) the muscular growth and endurance, and (iii) successful reintroduction of a wild bird.
Appropriate Data Quality Checks Improve the Reliability of Values Predicted from Milk Mid-Infrared Spectra
Authors: Zhang Lei , Li Chunfang , Dehareng Frédéric , Grelet Clément , Colinet Frédéric , Gengler Nicolas , Brostaux Yves , Soyeurt Hélène
Published: February 2021

The use of abnormal milk mid-infrared (MIR) spectrum strongly affects prediction quality, even if the prediction equations used are accurate. So, this record must be detected after or before the prediction process to avoid erroneous spectral extrapolation or the use of poor-quality spectral data by dairy herd improvement (DHI) organizations. For financial or practical reasons, adapting the quality protocol currently used to improve the accuracy of fat and protein contents is unfeasible. This study proposed three different statistical methods that would be easy to implement by DHI organizations to solve this issue: the deletion of 1% of the extreme high and low predictive values (M1), the deletion of records based on the Global-H (GH) distance (M2), and the deletion of records based on the absolute fat residual value (M3). Additionally, the combinations of these three methods were investigated. A total of 346,818 milk samples were analyzed by MIR spectrometry to predict the contents of fat, protein, and fatty acids. Then, the same traits were also predicted externally using their corresponded standardized MIR spectra. The interest in cleaning procedures was assessed by estimating the root mean square differences (RMSDs) between those internal and external predicted phenotypes. All methods allowed for a decrease in the RMSD, with a gain ranging from 0.32% to 41.39%. Based on the obtained results, the “M1 and M2” combination should be preferred to be more parsimonious in the data loss, as it had the higher ratio of RMSD gain to data loss. This method deleted the records based on the 2% extreme predictions and a GH threshold set at 5. However, to ensure the lowest RMSD, the “M2 or M3” combination, considering a GH threshold of 5 and an absolute fat residual difference set at 0.30 g/dL of milk, was the most relevant. Both combinations involved M2 confirming the high interest of calculating the GH distance for all samples to predict. However, if it is impossible to estimate the GH distance due to a lack of relevant information to compute this statistical parameter, the obtained results recommended the use of M1 combined with M3. The limitation used in M3 must be adapted by the DHI, as this will depend on the spectral data and the equation used. The methodology proposed in this study can be generalized for other MIR-based phenotypes.
Why Can’t I Resist Those “Puppy Dog” (or “Kitty Cat”) Eyes? A Study of Owner Attachment and Factors Associated with Pet Obesity
Authors: Coy Anthony E. , Green Jeffrey D , Behler Anna Maria C.
Published: February 2021

Attachment theory posits that patterns of interaction derived from the attachment system provide a starting point for understanding how people both receive and provide care. Extending this theory to human-animal interactions provides insights into how human psychology affects pets, such as pet obesity. The goal of this study was to determine how attachment anxiety and avoidance might contribute to pet obesity. We assessed 563 pet owners’ attachment-related anxiety and avoidance, as well as additional attachment-related constructs (emotional rejection, evaluation concern, caregiving, and attentiveness to a pet). We also assessed various factors associated with pet obesity, including weight, body condition, daily treats, and daily interaction. The results indicate that dog owners high in attachment anxiety are concerned about how their pet may evaluate them, leading to more caregiving and attentiveness that results in more treats given per day, and a larger body condition (but not weight). In addition, owners high in attachment avoidance may seek to downplay the possibility of the dog negatively evaluating them, thus providing more negligent care. These findings suggest that attachment plays a unique role in shaping the pet-caregiver relationship and influences various elements that contribute to pet obesity, particularly in dogs. As such, the findings may lend a novel perspective to strategies for reducing pet obesity and provide a framework for future research into pet health.
LOXL2 Inhibitors and Breast Cancer Progression
Authors: Ferreira Sandra , Saraiva Nuno , Rijo Patrícia , Fernandes Ana S.
Published: February 2021

LOX (lysyl oxidase) and lysyl oxidase like-1–4 (LOXL 1–4) are amine oxidases, which catalyze cross-linking reactions of elastin and collagen in the connective tissue. These amine oxidases also allow the cross-link of collagen and elastin in the extracellular matrix of tumors, facilitating the process of cell migration and the formation of metastases. LOXL2 is of particular interest in cancer biology as it is highly expressed in some tumors. This protein also promotes oncogenic transformation and affects the proliferation of breast cancer cells. LOX and LOXL2 inhibition have thus been suggested as a promising strategy to prevent metastasis and invasion of breast cancer. BAPN (β-aminopropionitrile) was the first compound described as a LOX inhibitor and was obtained from a natural source. However, novel synthetic compounds that act as LOX/LOXL2 selective inhibitors or as dual LOX/LOX-L inhibitors have been recently developed. In this review, we describe LOX enzymes and their role in promoting cancer development and metastases, with a special focus on LOXL2 and breast cancer progression. Moreover, the recent advances in the development of LOXL2 inhibitors are also addressed. Overall, this work contextualizes and explores the importance of LOXL2 inhibition as a promising novel complementary and effective therapeutic approach for breast cancer treatment.
Compact Fuzzy Systems Based on Boolean Relations
Authors: Espitia Helbert , Soriano José , Machón Iván , López Hilario
Published: February 2021

This document presents some considerations and procedures to design a compact fuzzy system based on Boolean relations. In the design process, a Boolean codification of two elements is extended to a Kleene’s of three elements to perform simplifications for obtaining a compact fuzzy system. The design methodology employed a set of considerations producing equivalent expressions when using Boole and Kleene algebras establishing cases where simplification can be carried out, thus obtaining compact forms. In addition, the development of two compact fuzzy systems based on Boolean relations is shown, presenting its application for the identification of a nonlinear plant and the control of a hydraulic system where it can be seen that compact structures describes satisfactory performance for both identification and control when using algorithms for optimizing the parameters of the compact fuzzy systems. Finally, the applications where compact fuzzy systems are based on Boolean relationships are discussed allowing the observation of other scenarios where these structures can be used.
A Modelling and Validation Approach for Predicting Particle Concentrations of Airborne Dust during the Filling Process of Cylindrical Silos
Authors: Stone Luke , Zigan Stefan , Waduge Lahiru L. Lulbadda , Hastie David B.
Published: February 2021

Traditionally, when undertaking feasibility studies for designing new storage facilities such as storage silos, engineers will extract design information from experiments and evaluate potential risks associated with health and safety, suitability design for reliable material flow, and quality of products. The simulation approach applied incorporates Computational Fluid Dynamics (CFD), and Discrete Element Modelling (DEM) approaches and experimental tests will be used for validating these simulation results. One important aspect related to handling fine and dusty materials (particles smaller than 100 microns) is the associated risk of dust explosions, which needs to be evaluated before the commissioning of storage silos; to evaluate the accumulation of fines during the silo filling process, simulations and experiments were conducted. Alumina and salt were used here as reference materials for calibration and the validation purposes. The validation efforts are significant due to the fact that the data that is accessible in simulations is vastly different to the accessible data in experiments, which is restricted by measurement techniques and equipment. Such restrictions are observed in the evaluation of particle concentrations in a large confined volume. A new methodology has been developed to evaluate concentrations in both simulations and experiments by employing a non-dimensional factor [k], here called “Concentration Rank Factor” (CRF). A significant finding of this research is that experiments and simulations can be compared using CRF. It has been found to be within 2% of the experiment averaged value of 0.64.
Simulation of Scalability in Cloud-Based IoT Reactive Systems Leveraged on a WSAN Simulator and Cloud Computing Technologies
Authors: Jurado Pérez Luis , Salvachúa Joaquín
Published: February 2021

Implementing a wireless sensor and actuator network (WSAN) in Internet of Things (IoT) applications is a complex task. The need to establish the number of nodes, sensors, and actuators, and their location and characteristics, requires a tool that allows the preliminary determination of this information. Additionally, in IoT scenarios where a large number of sensors and actuators are present, such as in a smart city, it is necessary to analyze the scalability of these systems. Modeling and simulation can help to conduct an early study and reduce development and deployment times in environments such as a smart city. The design-time verification of the system through a network simulation tool is useful for the most complex and expensive part of the system formed by a WSAN. However, the use of real components for other parts of the IoT system is feasible by using cloud computing infrastructure. Although there are cloud computing simulators, the cloud layer is poorly developed for the requirements of IoT applications. Technologies around cloud computing can be used for the rapid deployment of some parts of the IoT application and software services using containers. With this framework, it is possible to accelerate the development of the real system, facilitate the rapid deployment of a prototype, and provide more realistic simulations. This article proposes an approach for the modeling and simulation of IoT systems and services in a smart city leveraged in a WSAN simulator and technologies of cloud computing. Our approach was verified through experiments with two use cases. (1) A model of sensor and actuator networks as an integral part of an IoT application to monitor and control parks in a city. Through this use case, we analyze the scalability of a system whose sensors constantly emit data. (2) A model for cloud-based IoT reactive parking lot systems for a city. Through our approach, we have created an IoT parking system simulation model. The model contains an M/M/c/N queuing system to simulate service requests from users. In this use case, the model replication through hierarchical modeling and scalability of a distributed parking reservation service were evaluated. This last use case showed how the simulation model could provide information to size the system through probability distribution variables related to the queuing system. The experimental results show that the use of simulation techniques for this type of application makes it possible to analyze scalability in a more realistic way.
Augmented CWT Features for Deep Learning-Based Indoor Localization Using WiFi RSSI Data
Authors: Ssekidde Paul , Steven Eyobu Odongo , Han Dong Seog , Oyana Tonny J.
Published: February 2021

Localization is one of the current challenges in indoor navigation research. The conventional global positioning system (GPS) is affected by weak signal strengths due to high levels of signal interference and fading in indoor environments. Therefore, new positioning solutions tailored for indoor environments need to be developed. In this paper, we propose a deep learning approach for indoor localization. However, the performance of a deep learning system depends on the quality of the feature representation. This paper introduces two novel feature set extractions based on the continuous wavelet transforms (CWT) of the received signal strength indicators’ (RSSI) data. The two novel CWT feature sets were augmented with additive white Gaussian noise. The first feature set is CWT image-based, and the second is composed of the CWT PSD numerical data that were dimensionally equalized using principal component analysis (PCA). These proposed image and numerical data feature sets were both evaluated using CNN and ANN models with the goal of identifying the room that the human subject was in and estimating the precise location of the human subject in that particular room. Extensive experiments were conducted to generate the proposed augmented CWT feature set and numerical CWT PSD feature set using two analyzing functions, namely, Morlet and Morse. For validation purposes, the performance of the two proposed feature sets were compared with each other and other existing feature set formulations. The accuracy, precision and recall results show that the proposed feature sets performed better than the conventional feature sets used to validate the study. Similarly, the mean localization error generated by the proposed feature set predictions was less than those of the conventional feature sets used in indoor localization. More particularly, the proposed augmented CWT-image feature set outperformed the augmented CWT-PSD numerical feature set. The results also show that the Morse-based feature sets trained with CNN produced the best indoor positioning results compared to all Morlet and ANN-based feature set formulations.
Cyber Ranges and TestBeds for Education, Training, and Research
Authors: Chouliaras Nestoras , Kittes George , Kantzavelou Ioanna , Maglaras Leandros , Pantziou Grammati , Ferrag Mohamed Amine
Published: February 2021

In recent years, there has been a growing demand for cybersecurity experts, and, according to predictions, this demand will continue to increase. Cyber Ranges can fill this gap by combining hands-on experience with educational courses, and conducting cybersecurity competitions. In this paper, we conduct a systematic survey of ten Cyber Ranges that were developed in the last decade, with a structured interview. The purpose of the interview is to find details about essential components, and especially the tools used to design, create, implement and operate a Cyber Range platform, and to present the findings.
The Archaeometallurgical Evaluation of Three Bronze Socketed Axes, Discovered in Eastern Romania
Authors: Vasilache Viorica , Diaconu Vasile , Mircea Otilia , Drob Ana , Sandu Ion
Published: February 2021

This paper presents the study of three bronze socketed axes discovered in Neamţ County, Romania. The surface structures and those from the interface of the corrosion layer with the metal core of the basic alloy were analyzed, in order to elucidate the nature of the materials used and the manufacturing processes. The analyzes by optical microscopy (OM) and electron microscopy (SEM), coupled with X-ray spectrometry (EDX), revealed the type of their degradation during the depositional period, as a result of the processes of chemical alteration and physical damage. A series of metallurgical techniques used were also established, as well as the identification of some finishing and decoration processes that led to the establishment of the objects’ functionality.
Predictive Validity of the Single Leg Hamstring Bridge Test in Military Settings
Authors: Pori Primož , Kovčan Bogdan , Vodičar Janez , Dervišević Edvin , Karpljuk Damir , Hadžić Vedran , Šimenko Jožef
Published: February 2021

The hamstrings are biarticular muscle group that plays an important role in the occupational performance of military personnel. The single leg hamstring bridge test (SLHBT) could be a good test to screen military personnel performance. The aims of our study were to assess the reproducibility of the SLHBT in the military population and to use receiver operating curve (ROC) analysis to examine the ability of the SLHBT to discriminate between soldiers with poor and good baseline fitness. A cross-sectional study was performed on 201 male members of the Slovenian Armed Forces (SAF). They undertook army physical fitness testing (APFT) and functional physical fitness testing (FPFT), which included the SLHBT. The SLHBT showed acceptable reproducibility in a military setting and had moderate predictive validity to discriminate between soldiers with poor and good overall physical fitness performance using a cut-off value of 20 repetitions. In conclusion, the SLHBT could be a good candidate test for the military population as the ROC analysis showed the ability of the SLHBT to discriminate between soldiers with poor and good baseline fitness. The SLHBT represents a simple and affordable test that can be used to evaluate performance and form preventive guidelines for military personnel.
Detection and Classification of Bearing Surface Defects Based on Machine Vision
Authors: Lu Manhuai , Chen Chin-Ling
Published: February 2021

Surface defects on bearings can directly affect the service life and reduce the performance of equipment. At present, the detection of bearing surface defects is mostly done manually, which is labor-intensive and results in poor stability. To improve the inspection speed and the defect recognition rate, we proposed a bearing surface defect detection and classification method using machine vision technology. The method makes two main contributions. It proposes a local multi-neural network (Lc-MNN) image segmentation algorithm with the wavelet transform as the classification feature. The precision segmentation of the defect image is accomplished in three steps: wavelet feature extraction, Lc-MNN region division, and Lc-MNN classification. It also proposes a feature selection algorithm (SCV) that makes comprehensive use of scalar feature selection, correlation analysis, and vector feature selection to first remove similar features through correlation analysis, further screen the results with a scalar feature selection algorithm, and finally select the classification features using a feature vector selection algorithm. Using 600 test samples with three types of defect in the experiment, an identification rate of 99.5% was achieved without the need for large-scale calculation. The comparison tests indicated that the proposed method can achieve efficient feature selection and defect classification.
Baltic Sea Spray Emissions: In Situ Eddy Covariance Fluxes vs. Simulated Tank Sea Spray
Authors: Nilsson Ernst Douglas , Hultin Kim A. H. , Mårtensson Eva Monica , Markuszewski Piotr , Rosman Kai , Krejci Radovan
Published: February 2021

We present the first ever evaluation of sea spray aerosol eddy covariance (EC) fluxes at near coastal conditions and with limited fetch, and the first over water with brackish water (on average 7 ppt). The measurements were made on the island of Garpen in the Baltic Sea (56°23′ N, 16°06′ E) in September 2005. We found that wind speed is a major factor that is driving an exponential increase in sea spray sea salt emissions, comparable to previous studies over waters with higher salinity. We were able to show that the inclusion of a thermodenuder in the EC system allowed for the parallel measurements of the dry unheated aerosol flux (representing both organic and sea salt sea spray emissions) and the heated (300 °C) non-volatile sea salt emissions. This study’s experimental approach also included measurements of the artificial sea spray formed in a tank in locally sampled water at the same location as the EC fluxes. We attempted to use the EC aerosol flux measurements to scale the tank measurements to aerosol emissions in order to derive a complete size distribution for the sea spray emission fluxes below the size range (0.3–2 µm dry diameter) of the optical particle counters (OPCs) in the EC system, covering in total 0.01 µm to 2 µm diameter. In the wind directions with long fetches (corresponding to conditions similar to open sea), we were able to distinguish between the aerosol emission fluxes of dry aerosol and heated non-volatile (sea salt only) in the smallest size bins of the OPC, and could therefore indirectly estimate the organic sea spray fraction. In agreement with several previous ambient and tank experiments deriving the size resolved chemical mass concentration of sea salt and water-insoluble organic sea spray, our EC fluxes showed that sea sprays were dominated by sea salt at sizes ≥1 µm diameter, and by organics at the smallest OPC sizes. Since we used direct measures of the sea spray emission fluxes, we confirmed previous suggestions that this size distribution of sea salt and organics is a signature of sea spray aerosols. We were able to show that two sea salt source parameterizations (Mårtensson et al. (2003) and Salter et al. (2015)) agreed fairly well with our observed heated EC aerosol emission fluxes, as long as their predicted emissions were modified for the actual salinity by shifting the particle diameters proportionally to the cubic rote of the salinity. If, in addition, we added organics to the parameterized sea spray following the mono-layer model by Ellison et al. (1999), the combined sea spray parameterizations for sea salt and organics fell reasonably close to the observed fluxes for diameters > 0.15 µm, while one of them overpredicted the sea spray emissions below this size. The organic mono-layer model by Ellison et al. appeared to be able to explain most of the differences we observed between the aerosol emission fluxes with and without the thermodenuder.
Epigenetics and Communication Mechanisms in Microglia Activation with a View on Technological Approaches
Authors: Petralla Sabrina , De Chirico Francesca , Miti Andrea , Tartagni Ottavia , Massenzio Francesca , Poeta Eleonora , Virgili Marco , Zuccheri Giampaolo , Monti Barbara
Published: February 2021

Microglial cells, the immune cells of the central nervous system (CNS), play a crucial role for the proper brain development and function and in CNS homeostasis. While in physiological conditions, microglia continuously check the state of brain parenchyma, in pathological conditions, microglia can show different activated phenotypes: In the early phases, microglia acquire the M2 phenotype, increasing phagocytosis and releasing neurotrophic and neuroprotective factors. In advanced phases, they acquire the M1 phenotype, becoming neurotoxic and contributing to neurodegeneration. Underlying this phenotypic change, there is a switch in the expression of specific microglial genes, in turn modulated by epigenetic changes, such as DNA methylation, histones post-translational modifications and activity of miRNAs. New roles are attributed to microglial cells, including specific communication with neurons, both through direct cell–cell contact and by release of many different molecules, either directly or indirectly, through extracellular vesicles. In this review, recent findings on the bidirectional interaction between neurons and microglia, in both physiological and pathological conditions, are highlighted, with a focus on the complex field of microglia immunomodulation through epigenetic mechanisms and/or released factors. In addition, advanced technologies used to study these mechanisms, such as microfluidic, 3D culture and in vivo imaging, are presented.
Comparison of SYK Signaling Networks Reveals the Potential Molecular Determinants of Its Tumor-Promoting and Suppressing Functions
Authors: Buffard Marion , Naldi Aurélien , Freiss Gilles , Deckert Marcel , Radulescu Ovidiu , Coopman Peter J. , Larive Romain M.
Published: February 2021

Spleen tyrosine kinase (SYK) can behave as an oncogene or a tumor suppressor, depending on the cell and tissue type. As pharmacological SYK inhibitors are currently evaluated in clinical trials, it is important to gain more information on the molecular mechanisms underpinning these opposite roles. To this aim, we reconstructed and compared its signaling networks using phosphoproteomic data from breast cancer and Burkitt lymphoma cell lines where SYK behaves as a tumor suppressor and promoter. Bioinformatic analyses allowed for unveiling the main differences in signaling pathways, network topology and signal propagation from SYK to its potential effectors. In breast cancer cells, the SYK target-enriched signaling pathways included intercellular adhesion and Hippo signaling components that are often linked to tumor suppression. In Burkitt lymphoma cells, the SYK target-enriched signaling pathways included molecules that could play a role in SYK pro-oncogenic function in B-cell lymphomas. Several protein interactions were profoundly rewired in the breast cancer network compared with the Burkitt lymphoma network. These data demonstrate that proteomic profiling combined with mathematical network modeling allows untangling complex pathway interplays and revealing difficult to discern interactions among the SYK pathways that positively and negatively affect tumor formation and progression.
Unique Benefits of Tumor-Specific Nanobodies for Fluorescence Guided Surgery
Authors: Lwin Thinzar M. , Hoffman Robert M. , Bouvet Michael
Published: February 2021

Tumor-specific fluorescence labeling is promising for real-time visualization of solid malignancies during surgery. There are a number of technologies to confer tumor-specific fluorescence. Antibodies have traditionally been used due to their versatility in modifications; however, their large size hampers efficient fluorophore delivery. Nanobodies are a novel class of molecules, derived from camelid heavy-chain only antibodies, that have shown promise for tumor-specific fluorescence labeling. Nanobodies are ten times smaller than standard antibodies, while maintaining antigen-binding capacity and have advantageous features, including rapidity of tumor labeling, that are reviewed in the present report. The present report reviews special considerations needed in developing nanobody probes, the status of current literature on the use of nanobody probes in fluorescence guided surgery, and potential challenges to be addressed for clinical translation.
Interpersonal Motor Interactions Shape Multisensory Representations of the Peripersonal Space
Authors: Fanghella Martina , Era Vanessa , Candidi Matteo
Published: February 2021

This perspective review focuses on the proposal that predictive multisensory integration occurring in one’s peripersonal space (PPS) supports individuals’ ability to efficiently interact with others, and that integrating sensorimotor signals from the interacting partners leads to the emergence of a shared representation of the PPS. To support this proposal, we first introduce the features of body and PPS representations that are relevant for interpersonal motor interactions. Then, we highlight the role of action planning and execution on the dynamic expansion of the PPS. We continue by presenting evidence of PPS modulations after tool use and review studies suggesting that PPS expansions may be accounted for by Bayesian sensory filtering through predictive coding. In the central section, we describe how this conceptual framework can be used to explain the mechanisms through which the PPS may be modulated by the actions of our interaction partner, in order to facilitate interpersonal coordination. Last, we discuss how this proposal may support recent evidence concerning PPS rigidity in Autism Spectrum Disorder (ASD) and its possible relationship with ASD individuals’ difficulties during interpersonal coordination. Future studies will need to clarify the mechanisms and neural underpinning of these dynamic, interpersonal modulations of the PPS.
Network Analysis Identifies Drug Targets and Small Molecules to Modulate Apoptosis Resistant Cancers
Authors: Fathima Samreen , Sinha Swati , Donakonda Sainitin
Published: February 2021

Programed cell death or apoptosis fails to induce cell death in many recalcitrant cancers. Thus, there is an emerging need to activate the alternate cell death pathways in such cancers. In this study, we analyzed the apoptosis-resistant colon adenocarcinoma, glioblastoma multiforme, and small cell lung cancers transcriptome profiles. We extracted clusters of non-apoptotic cell death genes from each cancer to understand functional networks affected by these genes and their role in the induction of cell death when apoptosis fails. We identified transcription factors regulating cell death genes and protein–protein interaction networks to understand their role in regulating cell death mechanisms. Topological analysis of networks yielded FANCD2 (ferroptosis, negative regulator, down), NCOA4 (ferroptosis, up), IKBKB (alkaliptosis, down), and RHOA (entotic cell death, down) as potential drug targets in colon adenocarcinoma, glioblastoma multiforme, small cell lung cancer phenotypes respectively. We also assessed the miRNA association with the drug targets. We identified tumor growth-related interacting partners based on the pathway information of drug-target interaction networks. The protein–protein interaction binding site between the drug targets and their interacting proteins provided an opportunity to identify small molecules that can modulate the activity of functional cell death interactions in each cancer. Overall, our systematic screening of non-apoptotic cell death-related genes uncovered targets helpful for cancer therapy.
The Radiation-Induced Regenerative Response of Adult Tissue-Specific Stem Cells: Models and Signaling Pathways
Authors: Serrano Martinez Paola , Giuranno Lorena , Vooijs Marc , Coppes Robert P.
Published: February 2021

Radiotherapy is involved in the treatment of many cancers, but damage induced to the surrounding normal tissue is often inevitable. Evidence suggests that the maintenance of homeostasis and regeneration of the normal tissue is driven by specific adult tissue stem/progenitor cells. These tasks involve the input from several signaling pathways. Irradiation also targets these stem/progenitor cells, triggering a cellular response aimed at achieving tissue regeneration. Here we discuss the currently used in vitro and in vivo models and the involved specific tissue stem/progenitor cell signaling pathways to study the response to irradiation. The combination of the use of complex in vitro models that offer high in vivo resemblance and lineage tracing models, which address organ complexity constitute potential tools for the study of the stem/progenitor cellular response post-irradiation. The Notch, Wnt, Hippo, Hedgehog, and autophagy signaling pathways have been found as crucial for driving stem/progenitor radiation-induced tissue regeneration. We review how these signaling pathways drive the response of solid tissue-specific stem/progenitor cells to radiotherapy and the used models to address this.
p62-Induced Cancer-Associated Fibroblast Activation via the Nrf2-ATF6 Pathway Promotes Lung Tumorigenesis
Authors: Kang Ji In , Kim Dong Hyun , Sung Ki Woon , Shim Sang Mi , Cha-Molstad Hyunjoo , Soung Nak Kyun , Lee Kyung Ho , Hwang Joonsung , Lee Hee Gu , Kwon Yong Tae , Kim Bo Yeon
Published: February 2021

Cancer-associated fibroblasts (CAFs) are important in tumor progression. The autophagy adaptor protein, p62/SQSTM1/Sequestosome-1, is up-regulated in tumors, but down-regulated in CAFs in the early stages of lung adenocarcinoma. We investigated whether p62-induced autophagy might control CAF activation. Under CAF-inducing conditions, like hypoxia or cancer cell co-cultures, p62 ablation or autophagy inhibition with hydroxychloroquine (HCQ) impaired CAF activation and reduced transforming growth factor beta (TGFβ) production, which impeded tumor growth. During CAF activation, p62-induced autophagy up-regulated the expression of the anti-oxidant signaling protein, nuclear factor erythroid 2-related factor 2 (Nrf2), and the ER-stress response regulator, activating transcription factor 6 (ATF6). Genetically or pharmacologically inhibiting the Nrf2-ATF6 pathway totally blocked CAF activation and tumor progression. These results demonstrate that p62 is a key modulator of primary lung adenocarcinoma progression. Thus, targeting the p62-Nrf2 autophagy signaling pathway might be a novel, stroma-focused, cancer prevention and/or treatment strategy.
Targeting CAR to the Peptide-MHC Complex Reveals Distinct Signaling Compared to That of TCR in a Jurkat T Cell Model
Authors: Wu Ling , Brzostek Joanna , Sankaran Shvetha , Wei Qianru , Yap Jiawei , Tan Triscilla Y.Y. , Lai Junyun , MacAry Paul A. , Gascoigne Nicholas R. J.
Published: February 2021

Chimeric antigen receptor T cells (CAR-T) utilize T cell receptor (TCR) signaling cascades and the recognition functions of antibodies. This allows T cells, normally restricted by the major histocompatibility complex (MHC), to be redirected to target cells by their surface antigens, such as tumor associated antigens (TAAs). CAR-T technology has achieved significant successes in treatment of certain cancers, primarily liquid cancers. Nonetheless, many challenges hinder development of this therapy, such as cytokine release syndrome (CRS) and the efficacy of CAR-T treatments for solid tumors. These challenges show our inadequate understanding of this technology, particularly regarding CAR signaling, which has been less studied. To dissect CAR signaling, we designed a CAR that targets an epitope from latent membrane protein 2 A (LMP2 A) of the Epstein–Barr virus (EBV) presented on HLA*A02:01. Because of this, CAR and TCR signaling can be compared directly, allowing us to study the involvement of other signaling molecules, such as coreceptors. This comparison revealed that CAR was sufficient to bind monomeric antigens due to its high affinity but required oligomeric antigens for its activation. CAR sustained the transduced signal significantly longer, but at a lower magnitude, than did TCR. CD8 coreceptor was recruited to the CAR synapse but played a negligible role in signaling, unlike for TCR signaling. The distinct CAR signaling processes could provide explanations for clinical behavior of CAR-T therapy and suggest ways to improve the technology.
Organoid and Spheroid Tumor Models: Techniques and Applications
Authors: Gunti Sreenivasulu , Hoke Austin T.K. , Vu Kenny P. , London Nyall R.
Published: February 2021

Techniques to develop three-dimensional cell culture models are rapidly expanding to bridge the gap between conventional cell culture and animal models. Organoid and spheroid cultures have distinct and overlapping purposes and differ in cellular sources and protocol for establishment. Spheroids are of lower complexity structurally but are simple and popular models for drug screening. Organoids histologically and genetically resemble the original tumor from which they were derived. Ease of generation, ability for long-term culture and cryopreservation make organoids suitable for a wide range of applications. Organoids-on-chip models combine organoid methods with powerful designing and fabrication of micro-chip technology. Organoid-chip models can emulate the dynamic microenvironment of tumor pathophysiology as well as tissue–tissue interactions. In this review, we outline different tumor spheroid and organoid models and techniques to establish them. We also discuss the recent advances and applications of tumor organoids with an emphasis on tumor modeling, drug screening, personalized medicine and immunotherapy.
The Value of Real-World Data in Understanding Prostate Cancer Risk and Improving Clinical Care: Examples from Swedish Registries
Authors: Beckmann Kerri , Garmo Hans , Franck Lissbrant Ingela , Stattin Pär
Published: February 2021

Real-world data (RWD), that is, data from sources other than controlled clinical trials, play an increasingly important role in medical research. The development of quality clinical registers, increasing access to administrative data sources, growing computing power and data linkage capacities have contributed to greater availability of RWD. Evidence derived from RWD increases our understanding of prostate cancer (PCa) aetiology, natural history and effective management. While randomised controlled trials offer the best level of evidence for establishing the efficacy of medical interventions and making causal inferences, studies using RWD offer complementary evidence about the effectiveness, long-term outcomes and safety of interventions in real-world settings. RWD provide the only means of addressing questions about risk factors and exposures that cannot be “controlled”, or when assessing rare outcomes. This review provides examples of the value of RWD for generating evidence about PCa, focusing on studies using data from a quality clinical register, namely the National Prostate Cancer Register (NPCR) Sweden, with longitudinal data on advanced PCa in Patient-overview Prostate Cancer (PPC) and data linkages to other sources in Prostate Cancer data Base Sweden (PCBaSe).
Advances in Homogeneous Photocatalytic Organic Synthesis with Colloidal Quantum Dots
Authors: Wang Dan-Yan , Yin Yu-Yun , Feng Chuan-Wei , Rukhsana  , Shen Yong-Miao
Published: February 2021

Colloidal semiconductor quantum dots (QDs) have been proven to be excellent photocatalysts due to their high photostability, large extinction coefficients, and tunable optoelectrical properties, and have attracted extensive attention by synthetic chemists. These excellent properties demonstrate its promise in the field of photocatalysis. In this review, we summarize the recent application of QDs as homogeneous catalysts in various photocatalytic organic reactions. These meaningful works in organic transformations show the unique catalytic activity of quantum dots, which are different from other semiconductors.
Therapeutic Potential of Mesenchymal Stromal Cells and Extracellular Vesicles in the Treatment of Radiation Lesions—A Review
Authors: Rezvani Mohi
Published: February 2021

Ionising radiation-induced normal tissue damage is a major concern in clinic and public health. It is the most limiting factor in radiotherapy treatment of malignant diseases. It can also cause a serious harm to populations exposed to accidental radiation exposure or nuclear warfare. With regard to the clinical use of radiation, there has been a number of modalities used in the field of radiotherapy. These includes physical modalities such modified collimators or fractionation schedules in radiotherapy. In addition, there are a number of pharmacological agents such as essential fatty acids, vasoactive drugs, enzyme inhibitors, antioxidants, and growth factors for the prevention or treatment of radiation lesions in general. However, at present, there is no standard procedure for the treatment of radiation-induced normal tissue lesions. Stem cells and their role in tissue regeneration have been known to biologists, in particular to radiobiologists, for many years. It was only recently that the potential of stem cells was studied in the treatment of radiation lesions. Stem cells, immediately after their successful isolation from a variety of animal and human tissues, demonstrated their likely application in the treatment of various diseases. This paper describes the types and origin of stem cells, their characteristics, current research, and reviews their potential in the treatment and regeneration of radiation induced normal tissue lesions. Adult stem cells, among those mesenchymal stem cells (MSCs), are the most extensively studied of stem cells. This review focuses on the effects of MSCs in the treatment of radiation lesions.
MiRNAs in Canine and Human Osteosarcoma: A Highlight Review on Comparative Biomolecular Aspects
Authors: Leonardi Leonardo , Scotlandi Katia , Pettinari Ilaria , Benassi Maria Serena , Porcellato Ilaria , Pazzaglia Laura
Published: February 2021

Osteosarcoma (OS) is the most frequent primary malignant tumor of bone in humans and animals. Comparative oncology is a field of study that examines the cancer risk and tumor progression across the species. The canine model is ideally suited for translational cancer research. The biological and clinical characteristics of human and canine OS are common to hypothesize as that several living and environmental common conditions shared between the two species can influence some etiopathogenetic mechanisms, for which the canine species represents an important model of comparison with the human species. In the canine and human species, osteosarcoma is the tumor of bone with the highest frequency, with a value of about 80–85% (in respect to all other bone tumors), a high degree of invasiveness, and a high rate of metastasis and malignancy. Humans and dogs have many genetic and biomolecular similarities such as alterations in the expression of p53 and in some types of microRNAs that our working group has already described previously in several separate works. In this paper, we report and collect new comparative biomolecular features of osteosarcoma in dogs and humans, which may represent an innovative update on the biomolecular profile of this tumor.
Ablation of Aquaporin-9 Ameliorates the Systemic Inflammatory Response of LPS-Induced Endotoxic Shock in Mouse
Authors: Tesse Angela , Gena Patrizia , Rützler Michael , Calamita Giuseppe
Published: February 2021

Septic shock is the most severe complication of sepsis, being characterized by a systemic inflammatory response following bacterial infection, leading to multiple organ failure and dramatically high mortality. Aquaporin-9 (AQP9), a membrane channel protein mainly expressed in hepatocytes and leukocytes, has been recently associated with inflammatory and infectious responses, thus triggering strong interest as a potential target for reducing septic shock-dependent mortality. Here, we evaluated whether AQP9 contributes to murine systemic inflammation during endotoxic shock. Wild type (Aqp9+/+; WT) and Aqp9 gene knockout (Aqp9−/−; KO) male mice were submitted to endotoxic shock by i.p. injection of lipopolysaccharide (LPS; 40 mg/kg) and the related survival times were followed during 72 h. The electronic paramagnetic resonance and confocal microscopy were employed to analyze the nitric oxide (NO) and superoxide anion (O2−) production, and the expression of inducible NO-synthase (iNOS) and cyclooxigenase-2 (COX-2), respectively, in the liver, kidney, aorta, heart and lung of the mouse specimens. LPS-treated KO mice survived significantly longer than corresponding WT mice, and 25% of the KO mice fully recovered from the endotoxin treatment. The LPS-injected KO mice showed lower inflammatory NO and O2− productions and reduced iNOS and COX-2 levels through impaired NF-κB p65 activation in the liver, kidney, aorta, and heart as compared to the LPS-treated WT mice. Consistent with these results, the treatment of FaO cells, a rodent hepatoma cell line, with the AQP9 blocker HTS13268 prevented the LPS-induced increase of inflammatory NO and O2−. A role for AQP9 is suggested in the early acute phase of LPS-induced endotoxic shock involving NF-κB signaling. The modulation of AQP9 expression/function may reveal to be useful in developing novel endotoxemia therapeutics.
Promising Anti-Mitochondrial Agents for Overcoming Acquired Drug Resistance in Multiple Myeloma
Authors: Innao Vanessa , Rizzo Vincenzo , Allegra Andrea Gaetano , Musolino Caterina , Allegra Alessandro
Published: February 2021

Multiple myeloma (MM) remains an incurable tumor due to the high rate of relapse that still occurs. Acquired drug resistance represents the most challenging obstacle to the extension of survival and several studies have been conducted to understand the mechanisms of this phenomenon. Mitochondrial pathways have been extensively investigated, demonstrating that cancer cells become resistant to drugs by reprogramming their metabolic assessment. MM cells acquire resistance to proteasome inhibitors (PIs), activating protection programs, such as a reduction in oxidative stress, down-regulating pro-apoptotic, and up-regulating anti-apoptotic signals. Knowledge of the mechanisms through which tumor cells escape control of the immune system and acquire resistance to drugs has led to the creation of new compounds that can restore the response by leading to cell death. In this scenario, based on all literature data available, our review represents the first collection of anti-mitochondrial compounds able to overcome drug resistance in MM. Caspase-independent mechanisms, mainly based on increased oxidative stress, result from 2-methoxyestradiol, Artesunate, ascorbic acid, Dihydroartemisinin, Evodiamine, b-AP15, VLX1570, Erw-ASNase, and TAK-242. Other agents restore PIs’ efficacy through caspase-dependent tools, such as CDDO-Im, NOXA-inhibitors, FTY720, GCS-100, LBH589, a derivative of ellipticine, AT-101, KD5170, SMAC-mimetics, glutaminase-1 (GLS1)-inhibitors, and thenoyltrifluoroacetone. Each of these substances improved the efficacy rates when employed in combination with the most frequently used antimyeloma drugs.
Respiratory Distress in the Newborn with Primary Ciliary Dyskinesia
Authors: Machogu Evans , Gaston Benjamin
Published: February 2021

Primary ciliary dyskinesia (PCD) is inherited in a predominantly autosomal recessive manner with over 45 currently identified causative genes. It is a clinically heterogeneous disorder that results in a chronic wet cough and drainage from the paranasal sinuses, chronic otitis media with hearing impairment as well as male infertility. Approximately 50% of patients have situs inversus totalis. Prior to the development of chronic oto-sino-pulmonary symptoms, neonatal respiratory distress occurs in more than 80% of patients as a result of impaired mucociliary clearance and mucus impaction causing atelectasis and lobar collapse. Diagnosis is often delayed due to overlapping symptoms with other causes of neonatal respiratory distress. A work up for PCD should be initiated in the newborn with compatible clinical features, especially those with respiratory distress, consistent radiographic findings or persistent oxygen requirement and/or organ laterality defects