bluuebunny/crossref_metadata_2025 huggingface dataset:
Herbal Preparation (Bromelain, Papain, Curcuma, Black Pepper) Enhances Mineralization and Reduces Glucocorticoid-Induced Osteoporosis in Zebrafish
Authors: Carnovali Marta , Ramoni Gina , Banfi Giuseppe , Mariotti Massimo
Published: December 2021

Natural foods with antioxidant properties, such as curcuma, papain, bromelain and black pepper, have been indicated as a potential natural therapeutic approach against osteoporosis. Zebrafish are an excellent animal model to study the effects of herbal preparations on osteogenesis and bone metabolism, both in physiological and in pathological conditions. Our study was aimed at evaluating whether curcuma-bromelain-papain-pepper herbal preparation (CHP) administered in embryos and adult fish is capable of promoting bone wellness in physiological and osteoporotic conditions. The effect of CHP has been studied in embryonic osteogenesis and glucocorticoid-induced osteoporosis (GIOP) in an adult fish model in which drug treatment induces a bone-loss phenotype in adult scales very similar to that which characterizes the bones of human patients. CHP prevented the onset of the osteoporotic phenotype in the scales of GIOP in adult zebrafish, with the osteoblastic and osteoclastic metabolic activity maintaining unaltered. CHP is also able to attenuate an already established GIOP phenotype, even if the alteration is in an advanced phase, partially restoring the normal balance of the bone markers alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) and stimulating anabolic reparative processes. The results obtained indicated CHP as a potential integrative antioxidant therapy in human bone-loss diseases.
Potential Anti-Mycobacterium tuberculosis Activity of Plant Secondary Metabolites: Insight with Molecular Docking Interactions
Authors: Kumar Manu , Singh Sandeep Kumar , Singh Prem Pratap , Singh Vipin Kumar , Rai Avinash Chandra , Srivastava Akhileshwar Kumar , Shukla Livleen , Kesawat Mahipal Singh , Kumar Jaiswal Atul , Chung Sang-Min , Kumar Ajay
Published: December 2021

Tuberculosis (TB) is a recurrent and progressive disease, with high mortality rates worldwide. The drug-resistance phenomenon of Mycobacterium tuberculosis is a major obstruction of allelopathy treatment. An adverse side effect of allelopathic treatment is that it causes serious health complications. The search for suitable alternatives of conventional regimens is needed, i.e., by considering medicinal plant secondary metabolites to explore anti-TB drugs, targeting the action site of M. tuberculosis. Nowadays, plant-derived secondary metabolites are widely known for their beneficial uses, i.e., as antioxidants, antimicrobial agents, and in the treatment of a wide range of chronic human diseases (e.g., tuberculosis), and are known to “thwart” disease virulence. In this regard, in silico studies can reveal the inhibitory potential of plant-derived secondary metabolites against Mycobacterium at the very early stage of infection. Computational approaches based on different algorithms could play a significant role in screening plant metabolites against disease virulence of tuberculosis for drug designing.
Evaluation of Picker Discomfort and Its Impact on Maintaining Strawberry Picking Quality
Authors: Komarnicki Piotr , Kuta Łukasz
Published: December 2021

In this paper, the authors present the relationship between the assumptions of ergonomics in the work of a strawberry picker and quality of picked fruit. The body posture that a person adopts while working has a significant impact on their health, working comfort, and productivity, but also on the quality of the fruit that is harvested. This paper identifies three characteristic picker positions during strawberry harvesting. A synchronized surface electromyography (sEMG) instrument together with the Tekscan® surface pressure measurement system allowed for the determination of the influence of working position on changes in the load of the picker’s musculoskeletal system and the surface pressure exerted on the fruit during manual strawberry picking, which are decisive factors for maintaining fruit quality. In addition, compression tests on whole strawberry fruit were carried out as a benchmark to evaluate and compare the maximum forces as well as the destructive pressures on the fruit. From the tests, we found that the most comfortable position of the worker’s body was determined along with the harvesting technique (position during work) that has the least negative effect on the quality of the harvested fruit. Consequently, the level of dynamic load on the worker was determined.
Comparative Study of Potato (Solanum tuberosum L.) and Sweet Potato (Ipomoea batatas L.): Evaluation of Proximate Composition, Polyphenol Content, Mineral and Antioxidant Activities
Authors: Arshad Ammara , Iqbal Hira , Siddiqa Ayesha , Zulfiqar Taha , Tareen Muhammad B. K. , Amna Dua , Shakir Muhammad , Hazafa Abu , Naeem Muhammad , Lorenzo José M. , Domínguez Rubén
Published: December 2021

The objective of the present study was to differentiate and compare the proximate composition, minerals, flesh colour, phenolic composition, and antioxidant activities of varieties of white-fleshed sweet potato (WFSP) and potato (WFP) locally grown in Pakistan. The results showed that WFP presented higher moisture and crude fat content, while WFSP offered better ash, crude protein, and crude fibre contents. Colour analysis revealed that WFSP and WFP showed the highest L* (lightness) values and exhibited the maximum total phenolic content and total flavonoids content of 9.27 ± 0.88 mg GAE/g and 19.01 ± 0.66 mg QE/g. In vitro, results demonstrated that WFSP possessed better antioxidant activity with the highest ferric reducing antioxidant power of 58.67 ± 0.22 mM Fe2+/g and DPPH scavenging activity of 39.12 ± 0.33% compared to WFP. It is concluded that WFSP possesses a better proximate and mineral profile followed by higher antioxidant activity.
A Compact Accelerator-Based Light Source for High-Power, Full-Bandwidth Tunable Coherent THz Generation
Authors: Zhang Kaiqing , Kang Yin , Liu Tao , Wang Zhen , Feng Chao , Fang Wencheng , Zhao Zhentang
Published: December 2021

Terahertz (THz) radiation sources are increasingly significant for many scientific frontiers, while the generation of THz radiation with high-power at wide-tunable frequencies is still a limitation for most existing methods. In this paper, a compact accelerator-based light source is proposed to produce coherent THz radiation with high pulse energy and tunable frequency from 0.1 THz to 60 THz. By using a frequency beating laser-modulated electron beam and undulator taper, intense coherent THz radiation can be generated through undulators. Theoretical analysis and numerical simulations demonstrate that the proposed technique can generate narrow-bandwidth THz radiation with a pulse energy up to 6.3 millijoule (mJ) and the three-dimensional effects of beam has limited influence on its performance. The proposed technique will open up new opportunities for THz spectroscopic and time-resolved experiments.
Tracking of Stiffness Variation in Structural Members Using Input Error Function Observers
Authors: Dharap Prasad , Nagarajaiah Satish
Published: December 2021

This study evaluates input error function observers for tracking of stiffness variation in real-time. The input error function is an Analytical Redundancy (AR)-based diagnosis method and necessitates a mathematical model of the system and system identification techniques. In practice, mathematical models used during numerical simulations differ from the actual status of the structure, and thus, accurate mathematical models are rarely available for reference. Noise is an unwanted signal in the input–output measurements but unavoidable in real-world applications (as in long span bridge trusses) and hard to imitate during numerical simulations. Simulation data from the truss system clearly indicates the effectiveness of the proposed structural damage detection method for estimating the severity of the damage. Optimization of the input error function can further automate the stiffness estimation in structural members and address critical aspects such as system uncertainties and the presence of noise in input–output measurements. Stiffness tracking in one of the planar truss members indicates the potential of optimization of the input error function for online structural health monitoring and implementing condition-based maintenance.
Special Issue on Multi-Robot Systems: Challenges, Trends, and Applications
Authors: Roldán-Gómez Juan Jesús , Barrientos Antonio
Published: December 2021

Multi-Robot Systems (MRSs) have emerged as a suitable alternative to single robots to improve current and enable new missions [...]
Applying Infinite Petri Nets to the Cybersecurity of Intelligent Networks, Grids and Clouds
Authors: Zaitsev Dmitry A. , Shmeleva Tatiana R. , Probert David E.
Published: December 2021

Correctness of networking protocols represents the principal requirement of cybersecurity. Correctness of protocols is established via the procedures of their verification. A classical communication system includes a pair of interacting systems. Recent developments of computing and communication grids for radio broadcasting, cellular networks, communication subsystems of supercomputers, specialized grids for numerical methods and networks on chips require verification of protocols for any number of devices. For analysis of computing and communication grid structures, a new class of infinite Petri nets has been introduced and studied for more than 10 years. Infinite Petri nets were also applied for simulating cellular automata. Rectangular, triangular and hexagonal grids on plane, hyper cube and hyper torus in multidimensional space have been considered. Composing and solving in parametric form infinite Diophantine systems of linear equations allowed us to prove the protocol properties for any grid size and any number of dimensions. Software generators of infinite Petri net models have been developed. Special classes of graphs, such as a graph of packet transmission directions and a graph of blockings, have been introduced and studied. Complex deadlocks have been revealed and classified. In the present paper, infinite Petri nets are divided into two following kinds: a single infinite construct and an infinite set of constructs of specified size (and number of dimensions). Finally, the paper discusses possible future work directions.
Modelling and Study of the Effect of Geometrical Parameters of Piezoelectric Plate and Stack
Authors: Degefa Tolera G. , Wróbel Andrzej , Płaczek Marek
Published: December 2021

The piezoelectric stack is employed as an actuator and a sensor in a variety of technical applications. The dynamic modelling of piezoelectric plates and stack is used to investigate and search for new applications in mechatronics systems that are based on various loading frequencies. Stacks are composed of series of the same size and whose plates feature the same material properties and are layered by dielectric sheets. This enables increased displacements to be achieved while freeing up more space. The major aim of this study was to investigate the feasibility of using differently modulated piezoelectric plates in a single stack. Mathematical modelling and the study of the characteristics of piezoelectric plates, as well as the stack, with respect to various geometrical parameters, enhances the utilization of the plate in mechatronics systems. The work focuses on the ability of piezoelectric stacks to generate complex vibration spectra comprising numerous frequencies. This is accomplished by utilizing different piezoelectric plates in the stack or by stimulating each plate with a distinct carrier frequency. The plate responses at a wide frequency of piezoelectric plates were investigated using several modeling environments and, finally, experimental findings were obtained. In addition to generating the hypothesis of triggering the plate in a single stack with a varied frequency spectrum, the experiment performed was employed for parameter identification. The experiment demonstrated that it is possible to increase the flexibility of systems by employing piezoelectric stacks as a mode of actuation and that piezo stacks can be used in systems that require precise actuation over a wide frequency range.
Thermally Constrained Conceptual Deep Geological Repository Design under Spacing and Placing Uncertainties
Authors: Leong Jeremy , Ponnambalam Kumaraswamy , Binns Jeff , Elkamel Ali
Published: December 2021

The temperature evolution within a deep geological repository (DGR) is a key design consideration for the safe and permanent storage of the high-level radioactive waste contained inside used nuclear fuel containers (UFCs). Due to the material limitations of engineered components with respect to high temperature tolerance, the Nuclear Waste Management Organization of Canada requires the maximum temperature within a future Canadian DGR to be less than 100 °C. Densely placing UFCs within a DGR is economically ideal, but greater UFC placement density will increase the maximum temperature reached in the repository. This paper was aimed to optimize (i) the separation between UFCs, (ii) the distance between container placement rooms, and (iii) the locations of the age-dependent UFCs in the placement rooms for a conceptual DGR constructed in crystalline rock. Surrogate-based optimization reduced the amount of computationally expensive evaluations of a COMSOL Multiphysics model used to study the temperature evolution within the conceptual DGR and determined optimal repository design points. Via yield optimization, nominal design points that considered uncertainties in the design process were observed. As more information becomes available during the design process for the Canadian DGR, the methods employed in this paper can be revisited to aid in selecting a UFC placement plan and to mitigate risks that may cause repository failure.
Design and Implementation of a Tether-Powered Hexacopter for Long Endurance Missions
Authors: Chang Kai-Hung , Hung Shao-Kang
Published: December 2021

A tether-powered unmanned aerial vehicle is presented in this article to demonstrate the highest altitude and the longest flight time among surveyed literature. The grid-powered ground station transmits high voltage electrical energy through a well-managed conductive tether to a 2-kg hexacopter hovering in the air. Designs, implementations, and theoretical models are discussed in this research work. Experimental results show that the proposed system can operate over 50 m for 4 h continuously. Compared with battery-powered multicopters, tether-powered ones have great advantages on specific-area long-endurance applications, such as precision agriculture, intelligent surveillance, and vehicle-deployed cellular sites.
Superposition of 2ω and Electrostatic Field Induced Terahertz Waveforms in DC-Biased Two-Color Filament
Authors: Ushakov Aleksandr , Chizhov Pavel , Nikolaeva Irina , Shipilo Daniil , Panov Nikolay , Bukin Vladimir , Mamaeva Kseniia , Kosareva Olga , Garnov Sergey
Published: December 2021

Increase in conversion efficiency from a femtosecond optical pump into broadband terahertz (THz) radiation is currently an essential issue since it boosts THz source performance for medicine and security applications. An air-plasma based THz radiation from a two-color femtosecond filament is the most efficient gas-based THz emitter, with a dipole local source having a maximum on the beam propagation axis. In this work, we show the novel advancement to THz yield increase with preservation of the forwardly directed dipole radiation. The two-color THz source can be enhanced if the filament plasma channel is placed into an external electrostatic field (DC bias), which is parallel to the second harmonic polarization direction. In the experiment, we produce a plasma channel from 800-nm, ∼50-fs, 2-mJ pulse with 200 μJ of 400-nm, ∼50-fs mixed with the pump, and allocate it between the electrodes carrying 7-kV/cm static field. Time-domain measurements and 3D+time simulations of THz waveforms from the two-color DC-biased filament show that the THz emission is the superposition of the THz waveforms generated in the 800+400-nm filament without a DC-bias and in the 800-nm (without 400-nm) plasma channel biased by 7-kV/cm static field. The additivity of the two local dipole THz sources is possible if the majority of free electrons are produced by the pump pulse.
Features of Acoustic Emission in Tensile Testing of Dissimilar Welded Joints of Pearlitic and Austenitic Steels
Authors: Barat Vera , Marchenkov Artem , Bardakov Vladimir , Karpova Marina , Zhgut Daria , Elizarov Sergey
Published: December 2021

This paper presents a study of acoustic emission (AE) during the deformation of dissimilar welded joints of austenitic steel to pearlitic steel. One of the specific problems in these welded joints is the presence of decarburized and carbide diffusion interlayers, which intensively increase in width during long-term high-temperature operation. The presence of wide interlayers negatively affects the mechanical properties of welded joints. Moreover, welded defects are difficult to diagnose in welded joints containing interlayers: due to the high structural heterogeneity, interlayers create structural noises that can hinder the detection of defects such as cracks, pores, or a lack of penetration. The AE method may become a complex decision for diagnosing dissimilar welded joints due to applicability to the testing of heterogenic materials with a complex microstructure. Specimens cut from dissimilar welded joints of austenitic steel to pearlitic steel were tested by tension to rupture, with parallel AE data registration. According to the research results, the characteristic features of the AE were revealed for specimens containing defects in the form of lack of penetration as well as for specimens with diffusion interlayers. The results obtained show that the AE method can be used to test both typical welding defects and diffusion interlayers in welded joints of steels of different structural classes.
Mango Leaf Disease Recognition and Classification Using Novel Segmentation and Vein Pattern Technique
Authors: Saleem Rabia , Shah Jamal Hussain , Sharif Muhammad , Yasmin Mussarat , Yong Hwan-Seung , Cha Jaehyuk
Published: December 2021

Mango fruit is in high demand. So, the timely control of mango plant diseases is necessary to gain high returns. Automated recognition of mango plant leaf diseases is still a challenge as manual disease detection is not a feasible choice in this computerized era due to its high cost and the non-availability of mango experts and the variations in the symptoms. Amongst all the challenges, the segmentation of diseased parts is a big issue, being the pre-requisite for correct recognition and identification. For this purpose, a novel segmentation approach is proposed in this study to segment the diseased part by considering the vein pattern of the leaf. This leaf vein-seg approach segments the vein pattern of the leaf. Afterward, features are extracted and fused using canonical correlation analysis (CCA)-based fusion. As a final identification step, a cubic support vector machine (SVM) is implemented to validate the results. The highest accuracy achieved by this proposed model is 95.5%, which proves that the proposed model is very helpful to mango plant growers for the timely recognition and identification of diseases.
Nelson Goodman’s Aesthetics—A Critique
Authors: Guczalski Krzysztof
Published: December 2021

Nelson Goodman (1906–1998) is one of the leading American philosophers of the twentieth century. His well-known book Languages of Art is considered a major contribution to analytical aesthetics. While his views on particular issues have often been criticized, on the whole, he is considered to be a leading figure in twentieth-century aesthetics. Contrary to such a stance, I intend to argue that Goodman’s overall contribution to aesthetics is not as outstanding and valuable as is often maintained. Rather, I will try to show that his aesthetic views are grounded on a distorted representation of the earlier aesthetic tradition, without which they lose the novelty and originality ascribed to them. Once that representation is corrected, some of Goodman’s proposals turn out to be derivative and redundant. Additionally, where they do actually diverge from the earlier tradition and might stake a claim to originality, they turn out to be simply erroneous and misconceived, and sometimes even logically flawed. To conclude, Goodman’s lofty reputation as an aesthetician certainly requires major revision.
Automatic Diagnosis of Epileptic Seizures in EEG Signals Using Fractal Dimension Features and Convolutional Autoencoder Method
Authors: Malekzadeh Anis , Zare Assef , Yaghoobi Mahdi , Alizadehsani Roohallah
Published: December 2021

This paper proposes a new method for epileptic seizure detection in electroencephalography (EEG) signals using nonlinear features based on fractal dimension (FD) and a deep learning (DL) model. Firstly, Bonn and Freiburg datasets were used to perform experiments. The Bonn dataset consists of binary and multi-class classification problems, and the Freiburg dataset consists of two-class EEG classification problems. In the preprocessing step, all datasets were prepossessed using a Butterworth band pass filter with 0.5–60 Hz cut-off frequency. Then, the EEG signals of the datasets were segmented into different time windows. In this section, dual-tree complex wavelet transform (DT-CWT) was used to decompose the EEG signals into the different sub-bands. In the following section, in order to feature extraction, various FD techniques were used, including Higuchi (HFD), Katz (KFD), Petrosian (PFD), Hurst exponent (HE), detrended fluctuation analysis (DFA), Sevcik, box counting (BC), multiresolution box-counting (MBC), Margaos-Sun (MSFD), multifractal DFA (MF-DFA), and recurrence quantification analysis (RQA). In the next step, the minimum redundancy maximum relevance (mRMR) technique was used for feature selection. Finally, the k-nearest neighbors (KNN), support vector machine (SVM), and convolutional autoencoder (CNN-AE) were used for the classification step. In the classification step, the K-fold cross-validation with k = 10 was employed to demonstrate the effectiveness of the classifier methods. The experiment results show that the proposed CNN-AE method achieved an accuracy of 99.736% and 99.176% for the Bonn and Freiburg datasets, respectively.
Nitrosative Stress Molecules in Multiple Sclerosis: A Meta-Analysis
Authors: Förster Moritz , Nelke Christopher , Räuber Saskia , Lassmann Hans , Ruck Tobias , Sormani Maria Pia , Signori Alessio , Hartung Hans-Peter , Küry Patrick , Meuth Sven G. , Kremer David
Published: December 2021

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system of unknown etiology. As it is still a diagnosis of exclusion, there is an urgent need for biomarkers supporting its diagnosis. Increasing evidence suggests that nitrosative stress may play a pivotal role in the pathogenesis of MS. However, previous reports supporting the role of nitrosative stress molecules as disease biomarkers are inconsistent overall. We therefore systematically analyzed the existing literature to compare the serum and cerebrospinal fluid (CSF) levels of nitrite/nitrate in MS patients with those in patients with noninflammatory other neurological diseases (NIOND) and healthy controls (HC), respectively. We searched the PubMed database and included original articles investigating nitrite/nitrate levels in MS patients and NIOND patients or HC based on predefined selection criteria. Effect sizes were estimated by the standardized mean difference using a random effects model. Our results suggest that MS is associated with higher nitrite/nitrate levels within the CSF compared with patients with NIOND (SMD of 1.51; 95% CI: 0.72, 2.30; p = 0.0008). Likewise, nitrite/nitrate in the CSF of MS patients trends towards increased levels compared with those of HC but does not reach statistical significance (SMD of 3.35; 95% CI: −0.48, 7.19; p = 0.07). Measurement of nitrite/nitrate in the CSF might be a valuable tool facilitating the differentiation of MS and NIOND. Further studies with more homogeneous study criteria are needed to corroborate this hypothesis.
Current Understanding of the Physiopathology, Diagnosis and Therapeutic Approach to Alzheimer’s Disease
Authors: García-Morales Victoria , González-Acedo Anabel , Melguizo-Rodríguez Lucía , Pardo-Moreno Teresa , Costela-Ruiz Víctor Javier , Montiel-Troya María , Ramos-Rodríguez Juan José
Published: December 2021

Alzheimer’s disease (AD) is the most common cause of dementia. It is characterized by cognitive decline and progressive memory loss. The aim of this review was to update the state of knowledge on the pathophysiological mechanisms, diagnostic methods and therapeutic approach to AD. Currently, the amyloid cascade hypothesis remains the leading theory in the pathophysiology of AD. This hypothesis states that amyloid-β (Aβ) deposition triggers a chemical cascade of events leading to the development of AD dementia. The antemortem diagnosis of AD is still based on clinical parameters. Diagnostic procedures in AD include fluid-based biomarkers such as those present in cerebrospinal fluid and plasma or diagnostic imaging methods. Currently, the therapeutic armory available focuses on symptom control and is based on four pillars: pharmacological treatment where acetylcholinesterase inhibitors stand out; pharmacological treatment under investigation which includes drugs focused on the control of Aβ pathology and tau hyperphosphorylation; treatment focusing on risk factors such as diabetes; or nonpharmacological treatments aimed at preventing development of the disease or treating symptoms through occupational therapy or psychological help. AD remains a largely unknown disease. Further research is needed to identify new biomarkers and therapies that can prevent progression of the pathology.
One-Step Fabrication of Stimuli-Responsive Chitosan-Platinum Brushes for Listeria monocytogenes Detection
Authors: Oliveira Daniela A. , Althawab Suleiman , McLamore Eric S. , Gomes Carmen L.
Published: December 2021

Bacterial contamination in food-processing facilities is a critical issue that leads to outbreaks compromising the integrity of the food supply and public health. We developed a label-free and rapid electrochemical biosensor for Listeria monocytogenes detection using a new one-step simultaneous sonoelectrodeposition of platinum and chitosan (CHI/Pt) to create a biomimetic nanostructure that actuates under pH changes. The XPS analysis shows the effective co-deposition of chitosan and platinum on the electrode surface. This deposition was optimized to enhance the electroactive surface area by 11 times compared with a bare platinum–iridium electrode (p < 0.05). Electrochemical behavior during chitosan actuation (pH-stimulated osmotic swelling) was characterized with three different redox probes (positive, neutral, and negative charge) above and below the isoelectric point of chitosan. These results showed that using a negatively charged redox probe led to the highest electroactive surface area, corroborating previous studies of stimulus–response polymers on metal electrodes. Following this material characterization, CHI/Pt brushes were functionalized with aptamers selective for L. monocytogenes capture. These aptasensors were functional at concentrations up to 106 CFU/mL with no preconcentration nor extraneous reagent addition. Selectivity was assessed in the presence of other Gram-positive bacteria (Staphylococcus aureus) and with a food product (chicken broth). Actuation led to improved L. monocytogenes detection with a low limit of detection (33 CFU/10 mL in chicken broth). The aptasensor developed herein offers a simple fabrication procedure with only one-step deposition followed by functionalization and rapid L. monocytogenes detection, with 15 min bacteria capture and 2 min sensing.
Mandatory Vaccination during the Period of a Pandemic: Legal and Ethical Considerations in Europe
Authors: Panagopoulou Fereniki
Published: December 2021

The present study explores the pressing matter of mandatory vaccination in Europe from an ethical–constitutional perspective. To start with, it considers the bases of the concerns that have been raised to date, as well as those of the documented opposition. This is followed by an analysis of the applicable European legal framework and a discussion on mandatory vaccination in the workplace, education and the leisure industry, before outlining the conclusions reached. The position taken by this paper is that as long as certain conditions are met, mandatory vaccination does not violate fundamental rights. On the contrary, provided that the principle of proportionality is satisfied, mandatory vaccination as a form of medical intervention constitutes a manifestation of the obligation on the part of the state to protect the fundamental rights to life and health.
An Analysis of Characteristics of Post-Stroke Fatigue in Patients without Depression: A Retrospective Chart Review
Authors: Lee Yu Jin , Jung Woo-Sang , Kwon Seungwon , Jin Chul , Cho Seung-Yeon , Park Seong-Uk , Moon Sang-Kwan , Park Jung-Mi , Ko Chang-Nam , Cho Ki-Ho
Published: December 2021

Post-stroke fatigue (PSF) is among the most common stroke sequelae and affects rehabilitation, resulting in poor recovery. A main influencing factor may be depression, which has been investigated with fatigue in several clinical trials. We aimed to evaluate the characteristics of fatigue in post-stroke patients without depression through a retrospective chart review. The medical records of stroke patients hospitalized in the Stroke and Brain Disease Center, Kyung Hee University Korean Medicine Hospital were reviewed. Stroke patients without depression were divided into a PSF group and control group (without fatigue). The demographic characteristics, type of stroke, medical history, laboratory examinations, clinical features, and pattern identification of each patient were recorded and compared between the study groups. The medical records of 216 patients were reviewed; 85 and 131 patients were assigned to the PSF and control group, respectively. Apolipoprotein A1 levels were significantly lower in the PSF than in the control group (105.6 ± 16.5 vs. 116.2 ± 21.8). We found a significantly higher occurrence of reversal cold of the extremities and a lower probability of fire-heat pattern in the PSF group than in the control group. This study suggests that apolipoprotein A1 levels are lower and cold manifestations are more common in PSF patients without depression than in those without fatigue.
A Novel and Effective Method for Human Primary Skin Melanocytes and Metastatic Melanoma Cell Isolation
Authors: Ścieżyńska Aneta , Sobiepanek Anna , Kowalska Patrycja D. , Soszyńska Marta , Łuszczyński Krzysztof , Grzywa Tomasz M. , Krześniak Natalia , Góźdź Agata , Włodarski Paweł K. , Galus Ryszard , Kobiela Tomasz , Malejczyk Jacek
Published: December 2021

The development of an effective method of melanocyte isolation and culture is necessary for basic and clinical studies concerning skin diseases, including skin pigmentation disorders and melanoma. In this paper, we describe a novel, non-enzymatic and effective method of skin melanocyte and metastatic melanoma cell isolation and culture (along with the spontaneous spheroid creation) from skin or lymph node explants. The method is based on the selective harvesting of melanocytes and melanoma cells emigrating from the cultured explants. Thereby, isolated cells retain their natural phenotypical features, such as expression of tyrosinase and Melan-A as well as melanin production and are not contaminated by keratinocytes and fibroblasts. Such melanocyte and melanoma cell cultures may be very useful for medical and cosmetology studies, including studies of antitumor therapies.
Immunotherapy as a Turning Point in the Treatment of Acute Myeloid Leukemia
Authors: Aureli Anna , Marziani Beatrice , Sconocchia Tommaso , Del Principe Maria Ilaria , Buzzatti Elisa , Pasqualone Gianmario , Venditti Adriano , Sconocchia Giuseppe
Published: December 2021

Acute myeloid leukemia (AML) is a malignant disease of hematopoietic precursors at the earliest stage of maturation, resulting in a clonalproliferation of myoblasts replacing normal hematopoiesis. AML represents one of the most common types of leukemia, mostly affecting elderly patients. To date, standard chemotherapy protocols are only effective in patients at low risk of relapse and therapy-related mortality. The average 5-year overall survival (OS) is approximately 28%. Allogeneic hematopoietic stem cell transplantation (HSCT) improves prognosis but is limited by donor availability, a relatively young age of patients, and absence of significant comorbidities. Moreover, it is associated with significant morbidity and mortality. However, increasing understanding of AML immunobiology is leading to the development of innovative therapeutic strategies. Immunotherapy is considered an attractive strategy for controlling and eliminating the disease. It can be a real breakthrough in the treatment of leukemia, especially in patients who are not eligible forintensive chemotherapy. In this review, we focused on the progress of immunotherapy in the field of AML by discussing monoclonal antibodies (mAbs), immune checkpoint inhibitors, chimeric antigen receptor T cells (CAR-T cells), and vaccine therapeutic choices.
RKIP Pleiotropic Activities in Cancer and Inflammatory Diseases: Role in Immunity
Authors: Touboul Roni , Baritaki Stavroula , Zaravinos Apostolos , Bonavida Benjamin
Published: December 2021

Several gene products play pivotal roles in the induction of inflammation and the progression of cancer. The Raf kinase inhibitory protein (RKIP) is a cytosolic protein that exerts pleiotropic activities in such conditions, and thus regulates oncogenesis and immune-mediated diseases through its deregulation. Herein, we review the general properties of RKIP, including its: (i) molecular structure; (ii) involvement in various cell signaling pathways (i.e., inhibition of the Raf/MEK/ERK pathway; the NF-kB pathway; GRK-2 or the STAT-3 pathway; as well as regulation of the GSK3Beta signaling; and the spindle checkpoints); (iii) regulation of RKIP expression; (iv) expression’s effects on oncogenesis; (v) role in the regulation of the immune system to diseases (i.e., RKIP regulation of T cell functions; the secretion of cytokines and immune mediators, apoptosis, immune check point inhibitors and RKIP involvement in inflammatory diseases); and (vi) bioinformatic analysis between normal and malignant tissues, as well as across various immune-related cells. Overall, the regulation of RKIP in different cancers and inflammatory diseases suggest that it can be used as a potential therapeutic target in the treatment of these diseases.
Anthocyanidins Inhibit Growth and Chemosensitize Triple-Negative Breast Cancer via the NF-κB Signaling Pathway
Authors: Aqil Farrukh , Munagala Radha , Agrawal Ashish K. , Jeyabalan Jeyaprakash , Tyagi Neha , Rai Shesh N. , Gupta Ramesh C.
Published: December 2021

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Due to the lack of drug-targetable receptors, chemotherapy is the only systemic treatment option. Although chemotherapeutic drugs respond initially in TNBC, many patients relapse and have a poor prognosis. Poor survival after metastatic relapse is largely attributed to the development of resistance to chemotherapeutic drugs. In this study, we show that bilberry-derived anthocyanidins (Anthos) can inhibit the growth and metastasis of TNBC and chemosensitize paclitaxel (PAC)-resistant TNBC cells by modulating the NF-κB signaling pathway, as well as metastatic and angiogenic mediators. Anthos administered orally significantly decreased MDA-MB-231 orthoxenograft tumor volume and led to lower rates of lymph node and lung metastasis, compared to control. Treatment of PAC-resistant MDA-MB-231Tx cells with Anthos and PAC in combination lowered the IC50 of PAC by nearly 20-fold. The combination treatment also significantly (p < 0.01) decreased the tumor volume in MDA-MB-231Tx orthoxenografts, compared to control. In contrast, Anthos and PAC alone were ineffective against MDA-MB-231Tx tumors. Our approach of using Anthos to inhibit the growth and metastasis of breast cancers, as well as to chemosensitize PAC-resistant TNBC, provides a highly promising and effective strategy for the management of TNBC.
Immune Milieu and Genomic Alterations Set the Triple-Negative Breast Cancer Immunomodulatory Subtype Tumor Behavior
Authors: Rodríguez-Bautista Rubén , Caro-Sánchez Claudia H. , Cabrera-Galeana Paula , Alanis-Funes Gerardo J. , Gutierrez-Millán Everardo , Ávila-Ríos Santiago , Matías-Florentino Margarita , Reyes-Terán Gustavo , Díaz-Chávez José , Villarreal-Garza Cynthia , Hernández-Pedro Norma Y. , Ortega-Gómez Alette , Lara-Mejía Luis , Rangel-Escareño Claudia , Arrieta Oscar
Published: December 2021

Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous disease. Seven subtypes have been described based on gene expression patterns. Herein, we characterized the tumor biology and clinical behavior of the immunomodulatory (IM) subtype. Methods: Formalin-fixed paraffin-embedded tumor samples from 68 high-risk (stage III-IV) TNBC patients were analyzed through microarrays, immunohistochemistry, and DNA sequencing. Results: The IM subtype was identified in 24% of TNBC tumor samples and characterized by a higher intratumoral (intT) and stromal (strml) infiltration of FOXP3+ TILs (Treg) compared with non-IM subtypes. Further, PD-L1+ (>1%) expression was significantly higher, as well as CTLA-4+ intT and strml expression in the IM subtype. Differential expression and gene set enrichment analysis identified biological processes associated with the immune system. Pathway analysis revealed enrichment of the β-catenin signaling pathway. The non-coding analysis led to seven Long Intergenic Non-Protein Coding RNAs (lincRNAs) (6 up-regulated and 1 down-regulated) that were associated with a favorable prognosis in the TNBC-IM subtype. The DNA sequencing highlighted two genes relevant to immune system responses: CTNNB1 (Catenin β-1) and IDH1. Conclusion: the IM subtype showed a distinct immune microenvironment, as well as subtype-specific genomic alterations. Characterizing TNBC at a molecular and transcriptomic level might guide immune-based therapy in this subgroup of patients.
Harnessing Macrophages through the Blockage of CD47: Implications for Acute Myeloid Leukemia
Authors: Melo Garcia Luciana , Barabé Frédéric
Published: December 2021

CD47 is a surface membrane protein expressed by all normal tissues. It is the so-called “don’t eat me signal” because it protects the cells against phagocytosis. The CD47 interacts with the signal regulatory protein alpha (SIRPα) on the surface of macrophages, leading to downstream inhibitory signaling that dampens phagocytic capacity. Since macrophages exert immune surveillance against cancers, cancer cells overexpress CD47 to defend themselves against phagocytosis. Acute myeloid leukemia (AML) is a cancer of hematopoietic stem/progenitor cells (HSPC), and similar to other types of cancers, leukemic blasts show enhanced levels of CD47. In patients with AML, CD47 has been associated with a higher disease burden and poor overall survival. Blockage of CD47-SIRPα signaling leads to improved phagocytosis of AML cells and better overall survival in xenograft models. However, the introduction of a pro-phagocytic signal is needed to induce greater phagocytic capacity. These pro-phagocytic signals can be either Fc receptor stimulants (such as monoclonal antibodies) or natural pro-phagocytic molecules (such as calreticulin). Based on these pre-clinical findings, various clinical trials investigating the blockade of CD47-SIRPα interaction have been designed as monotherapy and in combination with other anti-leukemic agents. In this review, we will discuss CD47 biology, highlight its implications for AML pathophysiology, and explore the potential clinical translation of disrupting CD47-SIRPα to treat patients with AML.
YB1 Is a Major Contributor to Health Disparities in Triple Negative Breast Cancer
Authors: Rana Priyanka Shailendra , Wang Wei , Alkrekshi Akram , Markovic Vesna , Khiyami Amer , Chan Ricky , Perzynski Adam , Joseph Natalie , Sossey-Alaoui Khalid
Published: December 2021

Triple negative breast cancer (TNBC) is the most aggressive amongst all breast cancer (BC) subtypes. While TNBC tumors represent less than 20% of all BC subtypes, they are responsible for the most BC-related deaths. More significantly, when considering TNBC incidence across all racial/ethnic groups, TNBC accounts for less than 20% of all BCs. However, in non-Hispanic black women, the incidence rate of TNBC is more than 40%, which may be a contributing factor to the higher BC-related death rate in this population. These disparities remain strong even after accounting for differences in socioeconomic status, healthcare access, and lifestyle factors. Increased evidence now points to biological mechanisms that are intrinsic to the tumor that contribute to disparate TNBC disease burdens. Here, we show that YB1, a multifunction gene, plays a major role in the TNBC disparities between African American (AA) and Caucasian American (CA) women. We show in three independent TNBC tumors cohorts, that YB1 is significantly highly expressed in AA TNBC tumors when compared to CAs, and that increased levels of YB1 correlate with poor survival of AA patients with TNBC. We used a combination of genetic manipulation of YB1 and chemotherapy treatment, both in vitro and in animal models of TNBC to show that YB1 oncogenic activity is more enhanced in TNBC cell lines of AA origin, by increasing their tumorigenic and aggressive behaviors, trough the activation of cancer stem cell phenotype and resistance to chemotherapeutic treatments.
Pre-Treatment Neutrophil-to-Lymphocyte Ratio (NLR) as a Predictive Marker of Pazopanib Treatment for Soft-Tissue Sarcoma
Authors: Sato Yasuyoshi , Nakano Kenji , Wang Xiaofei , Fukuda Naoki , Urasaki Tetsuya , Ohmoto Akihiro , Hayashi Naomi , Yunokawa Mayu , Ono Makiko , Tomomatsu Junichi , Saito Masanori , Minami Yusuke , Hayakawa Keiko , Funauchi Yuki , Tanizawa Taisuke , Ae Keisuke , Matsumoto Seiichi , Takahashi Shunji
Published: December 2021

Pazopanib with trabectedin and eribulin is widely used to treat soft-tissue sarcoma (STS). We have shown that baseline neutrophil-to-lymphocyte ratio (NLR) may predict the efficacy and patient prognosis of eribulin. Changes in NLR, but not baseline NLR, can predict patient prognosis of trabectedin. However, prognostic factors of pazopanib for STS have not been identified. We present a retrospective analysis of 141 patients treated with pazopanib for recurrent or metastatic non-round cell STS. Univariate and multivariate analyses were performed to determine the predictive factors of durable clinical benefit (DCB), overall survival (OS), and progression-free survival. L-sarcoma histology (odds ratio [OR] = 0.31, 95% CI = 0.12–0.79; p = 0.014) and pre-treatment NLR < 3.0 (OR = 2.03, 95% CI = 1.02–6.67; p = 0.045) were independent predictive factors of DCB. Pre-treatment NLR < 3.0 (hazard ratio [HR] = 0.55, 95% CI = 0.36–0.84; p = 0.0057), liposarcoma histology (HR = 1.78, 95% CI = 1.09–2.91; p = 0.022), primary extremity site (HR = 0.48, 95% CI = 0.31–0.75; p = 0.0010), ECOG PS ≥ 1 (HR = 1.62, 95% CI = 1.08–2.42; p = 0.019), and CRP < 0.3 (HR = 0.52, 95% CI = 0.33–0.82; p = 0.0050) were independent predictive factors of OS. These findings indicate that baseline NLR predicts the efficacy and patient prognosis of pazopanib for STS.
Augmented Reality and Image-Guided Robotic Liver Surgery
Authors: Giannone Fabio , Felli Emanuele , Cherkaoui Zineb , Mascagni Pietro , Pessaux Patrick
Published: December 2021

Artificial intelligence makes surgical resection easier and safer, and, at the same time, can improve oncological results. The robotic system fits perfectly with these more or less diffused technologies, and it seems that this benefit is mutual. In liver surgery, robotic systems help surgeons to localize tumors and improve surgical results with well-defined preoperative planning or increased intraoperative detection. Furthermore, they can balance the absence of tactile feedback and help recognize intrahepatic biliary or vascular structures during parenchymal transection. Some of these systems are well known and are already widely diffused in open and laparoscopic hepatectomies, such as indocyanine green fluorescence or ultrasound-guided resections, whereas other tools, such as Augmented Reality, are far from being standardized because of the high complexity and elevated costs. In this paper, we review all the experiences in the literature on the use of artificial intelligence systems in robotic liver resections, describing all their practical applications and their weaknesses.
Using a Prime-Boost Vaccination Strategy That Proved Effective for High Resolution Epitope Mapping to Characterize the Elusive Immunogenicity of Survivin
Authors: Mould Robert C. , van Vloten Jacob P. , AuYeung Amanda W. K. , Walsh Scott R. , de Jong Jondavid , Susta Leonardo , Mutsaers Anthony J. , Petrik James J. , Wood Geoffrey A. , Wootton Sarah K. , Karimi Khalil , Bridle Byram W.
Published: December 2021

Survivin is a member of the inhibitor of apoptosis family of proteins and has been reported to be highly expressed in a variety of cancer types, making it a high priority target for cancer vaccination. We previously described a heterologous prime-boost strategy using a replication-deficient adenovirus, followed by an oncolytic rhabdovirus that generates unprecedented antigen-specific T cell responses. We engineered each vector to express a mutated version of full-length murine survivin. We first sought to uncover the complete epitope map for survivin-specific T cell responses in C57BL/6 and BALB/c mice by flow cytometry. However, no T cell responses were detected by intracellular cytokine staining after re-stimulation of T cells. Survivin has been found to be expressed by activated T cells, which could theoretically cause T cell-mediated killing of activated T cells, known as fratricide. We were unable to recapitulate this phenomenon in experiments. Interestingly, the inactivated survivin construct has been previously shown to directly kill tumor cells in vitro. However, there was no evidence in our models of induction of death in antigen-presenting cells due to treatment with a survivin-expressing vector. Using the same recombinant virus-vectored prime-boost strategy targeting the poorly immunogenic enhanced green fluorescent protein proved to be a highly sensitive method for mapping T cell epitopes, particularly in the context of identifying novel epitopes recognized by CD4+ T cells. Overall, these results suggested there may be unusually robust tolerance to survivin in commonly used mouse strains that cannot be broken, even when using a particularly potent vaccination platform. However, the vaccination method shows great promise as a strategy for identifying novel and subdominant T cell epitopes.