bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of High-Q Lithium Niobate-Based Double Ring Resonator Used in RF Signal Modulation
Authors: Wu Zhenlin , Zhang Lin , Han Shaoshuai , Lian Di , Wu Tongfei , Chu Wenjie , Li Haoyu , Guo Lei , Zhao Mingshan , Yang Xin
Published: April 2023

In recent years, millimeter-wave communication has played a crucial role in satellite communication, 5G, and even 6G applications. The millimeter-wave electro-optic modulator is capable of receiving and processing millimeter-wave signals effectively. However, the large attenuation of millimeter waves in the air remains a primary limiting factor for their future applications. Therefore, finding a waveguide structure with a high quality factor (Q-factor) is critical for millimeter-wave electro-optic modulators. This manuscript presents the demonstration of a double ring modulator made of lithium niobate with the specific goal of modulating an RF signal at approximately 35 GHz. By optimizing the microring structure, the double ring resonator with high Q-factor is studied to obtain high sensitivity modulation of the RF signal. This manuscript employs the transfer matrix method to investigate the operational principles of the double ring structure and conducts simulations to explore the influence of structural parameters on its performance. Through a comparison with the traditional single ring structure, it is observed that the Q-factor of the double ring modulator can reach 7.05 × 108, which is two orders of magnitude greater than that of the single ring structure. Meanwhile, the electro-optical tunability of the double ring modulator is 6 pm/V with a bandwidth of 2.4 pm, which only needs 0.4 V driving voltage. The high Q double ring structure proposed in this study has potential applications not only in the field of communication but also as a promising candidate for a variety of chemical and biomedical sensing applications.
Detecting Phishing Domains Using Machine Learning
Authors: Alnemari Shouq , Alshammari Majid
Published: April 2023

Phishing is an online threat where an attacker impersonates an authentic and trustworthy organization to obtain sensitive information from a victim. One example of such is trolling, which has long been considered a problem. However, recent advances in phishing detection, such as machine learning-based methods, have assisted in combatting these attacks. Therefore, this paper develops and compares four models for investigating the efficiency of using machine learning to detect phishing domains. It also compares the most accurate model of the four with existing solutions in the literature. These models were developed using artificial neural networks (ANNs), support vector machines (SVMs), decision trees (DTs), and random forest (RF) techniques. Moreover, the uniform resource locator’s (URL’s) UCI phishing domains dataset is used as a benchmark to evaluate the models. Our findings show that the model based on the random forest technique is the most accurate of the other four techniques and outperforms other solutions in the literature.
Identification of Impact Frequency for Down-the-Hole Drills Using Motor Current Signature Analysis
Authors: Brito Diego , Gómez René , Carvajal Gonzalo , Reyes-Chamorro Lorenzo , Ramírez Guillermo
Published: April 2023

In rotary-percussion drilling, the impact frequency is a crucial variable that is closely linked to operational factors that determine the efficacy of the drilling process, such as the rate of penetration, bit wear, and rock mass characteristics. Typical identification methods rely on complex simulation models or the analysis of different sensor signals installed on specially adapted setups, which are difficult to be implemented in the field. This paper presents a novel study where the impact frequency is identified by motor current signature analysis (MCSA) applied to an induction motor driving a DTH drilling setup. The analysis of the case study begins with the definition of characteristic drilling stages where the pressure and sound signals allow the detection of an impact frequency of 14.10 Hz, which is then used as a reference to validate three MCSA identification approaches. As a result of the analysis, the envelope approach is the most robust for nearly real-time implementations considering its simplicity and range of coverage. Experimental results provide evidence about the feasibility of the proposed MCSA methods to be integrated into Measurement-While-Drilling (MWD) systems to improve drilling condition monitoring and rock mass characterization.
Towards a Digital Twin Warehouse through the Optimization of Internal Transport
Authors: Félix-Cigalat Joaquín S. , Domingo Rosario
Published: April 2023

Through the construction of parametric simulation models in which possible storage space distributions and positioning logics are also considered as variables, it is possible to build scenarios that allow analyzing the changing reality of storage needs in order to minimize material movements in each case, optimize internal transportation, and increase the efficiency of production processes. This article shows a particular analysis of a restricted storage space in height, typical to when it comes to logistics associated with raw material in a “big bag” format made of recycled and easily deteriorated material. In conjunction, a location management solution based on passive RFID (radio-frequency identification) tags has been chosen. The process is carried out through simulations with object-oriented discrete event software, where the optimization of the internal transport associated with the layout is carried out considering network theory to define the shortest path between warehouse nodes. The combination of both approaches allows, on the one hand, the evaluation of alternatives in terms of distribution and positioning logics, while the implemented system enables the possibility of making agile changes in the physical configuration of this type of storage space.
Roles of Marine Shellfish Proteins with High Contents of Angiotensin-Converting Enzyme (ACE)-Binding Peptides in Nutrition Support for Hypertension
Authors: Yang Li , Shu Tianyu , Wang Kai , Yuan Zhen , Zhang Xuewu
Published: April 2023

In this study, experimental tests, together with computer analyses, were carried out to identify the essential nutritional markers that can offer protein supplementation-based nutrition support for hypertension. In particular, 16 marine shellfish proteins were firstly screened for in silico hydrolysis by gastrointestinal enzymes and then the binding abilities of the obtained oligopeptides to angiotensin-converting enzyme (ACE) were examined. In addition, the ACE inhibition activities of selected oligopeptides were assayed in vitro. It was discovered that mussel-derived NADH dehydrogenase and AMP-activated protein kinase and razor-clam-derived cytochrome b, NADH dehydrogenase, and ATP synthase were excellent sources of protein that are able to release a high amount of ACE-binding peptides. Meanwhile, four oligopeptides (SCCGY, SSGAW, PICQF, and IQPEW) were detected as strong ACE binders, with IC50 values of 0.09, 0.25, 0.41, and 0.60 mM, respectively. Therefore, our findings demonstrate that shellfish proteins can serve as nutritional support for hypertension when patients are supplemented with these markers. In particular, oligopeptides are identified as the most promising compounds.
Fault Prediction of Mechanical Equipment Based on Hilbert–Full-Vector Spectrum and TCDAN
Authors: Chen Lei , Wei Lijun , Li Wenlong , Wang Junhui , Han Dongyang
Published: April 2023

To solve the problem of “under-maintenance” and “over-maintenance” in the daily maintenance of equipment, the predictive maintenance method based on the running state of equipment has shown great advantages, and fault prediction is an important part of predictive maintenance. First, the spectrum information of the equipment is extracted by the Hilbert–full-vector spectrum as the input of fault prediction. Compared with the traditional spectrum, this spectrum information fuses the signals of two sensors in the same section of the device, which can reflect the actual operational state of the device more comprehensively. Then, the temporal convolutional network is used to predict the amplitudes of different feature frequencies, and the double-layer attention mechanism is introduced to mine the correlation between the corresponding amplitudes of different feature frequencies and between the data at different historical moments, to highlight the more important influencing factors. In this way, the prediction accuracy of the model for the amplitude corresponding to the feature frequency of concern is improved. Finally, experimental verification is carried out on the XJTU-SY dataset. The results show that the TCDAN model proposed in this paper is significantly superior to TCN, GRU, BiLSTM, and LSTM, which can provide a more effective decision-making basis for the predictive maintenance of equipment.
A Comprehensive Study of Machine Learning Application to Transmission Quality Assessment in Optical Networks
Authors: Kozdrowski Stanisław , Paziewski Piotr , Cichosz Paweł , Sujecki Sławomir
Published: April 2023

This paper examines applying machine learning to the assessment of the quality of the transmission in optical networks. The motivation for research into this problem derives from the fact that the accurate assessment of transmission quality is key to an effective management of an optical network by a network operator. In order to facilitate a potential implementation of the proposed solution by a network operator, the training data for the machine learning algorithms are directly extracted from an operating network via a control plane. Particularly, this work focuses on the application of single class and binary classification machine learning algorithms to optical network transmission quality assessment. The results obtained show that the best performance can be achieved using gradient boosting and random forest algorithms.
A Calculation Model for Determining the Bearing Capacity of Strengthened Reinforced Concrete Beams on the Shear
Authors: Kos Zeljko , Blikharskyi Zinovii , Vegera Pavlo , Grynyova Iryna
Published: April 2023

This article presents research on the bearing capacity and methods of calculating reinforced concrete beams on the shear without internal shear reinforcement, which are strengthened with a composite FRCM system. The test samples were divided into two series: the first series—control, in which the variable parameter was the shear span (a/d = 2, a/d = 1.5, and a/d = 1); and the second series—reinforced by the FRCM system, without load, and strengthened at different load levels. The method of calculating experimental beams was tested according to the current code and data from the fib report. In this article, recommendations for determining the angle of inclined struts θ, the coefficient of the concrete shear strength CRd,c, and the coefficient of the load level at which strengthening is performed are proposed. The calculation with the these recommendations showed a good convergence of experimental and theoretical data in the 16–29% range, which is a much higher convergence than the calculation without these recommendations.
A Versatile Resilience Packet Ring Protocol Model for Homogeneous Networks
Authors: Minhas Tayyeba , Khan Shawal , Arslan Farrukh , Ali Anum , Hussain Aamir , Ali Jehad
Published: April 2023

Optimizing routes and paths improves network performance. Due to the encapsulation and tunneling of the packets, mobile IP-based communication contributes to packet drops or significant delays between the sender and receiver. Packet loss during handoff reduces TCP throughput as well. One solution is to use the IEEE 802.11 Medium Access Control (MAC) protocol and TCP or UDP models to increase routing protocol performance. In the linkage of homogeneous networks, it is challenging to determine route failure. In addition, the 802.11 MAC also uses a link connection. As a result, re-covering the entire route path takes a longer time. Thus, improving wired and wireless mobile node communication and handover is both challenging and critical. To overcome this challenge, we propose to use the Versatile Resilience Packet Ring protocol (VRPR)-based model. In this paper, we propose a novel VRPR-based network model that allows uninterrupted communication in both wired and wireless media. VRPR is used in the network layer to avoid buffer overflow and client mobility. Our new model also identifies the cause of the route failure, whether it is due to client mobility (handover), due to link breakage (channel degradation), or due to buffer overflow. We evaluate our network model based on three performance factors, namely, the delay, packet, and packet loss, and compared it between wired and wireless media. Our Enhanced-VRPR-based network model outperforms the current VRPR wired and wireless network models. We validate our model through OMNet++ simulations.
Continuity: Sharing Space in teamLab’s Digital Ecosystems
Authors: Lawhead Emily
Published: April 2023

In 2021, the Asian Art Museum of San Francisco inaugurated the opening of its new contemporary wing with teamLab: Continuity. The immersive exhibition spanned six galleries and was fully interactive via sensors and digital projection mapping technology; flowers bloom and grow, flying crows burst into colorful chrysanthemums, and butterflies are born or killed at a moment’s touch. The digital objects dynamically interact with one another and with humans, blurring boundaries between art, participant, and technology. This article examines Continuity as a “collective interactive experience” situated within a digital ecosystem. It explores teamLab’s approach to the natural environment and its digital replication, with a focus on the relationship between humans and machines in shared exhibition spaces.
Data Verification in the Agent, Combining Blockchain and Quantum Keys by Means of Multiple-Valued Logic
Authors: Bykovsky Alexey Yu. , Vasiliev Nikolay A.
Published: April 2023

Network control of autonomous robotic devices involves a vast number of secured data coding, verification, and identification procedures to provide reliable work of distant agents. Blockchain scheme provides here the model of the extended linked list for the verification of critical data, approved by quasi-random hash values assigned by external network nodes. And quantum lines are the source of high-quality quasi-random keys used as hash values. Discrete multiple-valued logic in such procedures is a simple and flexible tool to form the logic linked list, combining critical internal parameters of agents with data taken from external nodes. Such combination enlarges the set of possible schemes for data protection from illegal modifications and for data restoration.
Assessing Indoor Climate Control in a Water-Pad System for Small-Scale Agriculture in Taiwan: A CFD Study on Fan Modes
Authors: Chen Jia-Kun , Sun Yung-Ling , Hsu Chia-Chi , Tseng Tzu-I , Liang Yu-Chuan
Published: April 2023

Heat stress poses a significant challenge to egg production in layer hens. High temperatures can disrupt the physiological functions of these birds, leading to reduced egg production and lower egg quality. This study evaluated the microclimate of laying hen houses using different management systems to determine the impact of heat stress on productivity and hen health. The results showed that the ALPS system, which manages the hen feeding environment, effectively improved productivity and decreased the daily death rate. In the traditional layer house, the daily death rate decreased by 0.045%, ranging from 0.086% to 0.041%, while the daily production rate increased by 3.51%, ranging from 69.73% to 73.24%. On the other hand, in a water-pad layer house, the daily death rate decreased by 0.033%, ranging from 0.082% to 0.049%, while the daily production rate increased by 21.3%, ranging from 70.8% to 92.1%. The simplified hen model helped design the indoor microclimate of commercial layer houses. The average difference in the model was about 4.4%. The study also demonstrated that fan models lowered the house’s average temperature and reduced the impact of heat stress on hen health and egg production. Findings indicate the need to control the humidity of inlet air to regulate temperature and humidity, and suggest that Model 3 is an energy-saving and intelligent solution for small-scale agriculture. The humidity of the inlet air affects the temperature experienced by the hens. The THI drops to the alert zone (70–75) when humidity is below 70%. In subtropical regions, we consider it necessary to control the humidity of the inlet air.
Piperitone (p-Menth-1-En-3-One): A New Repellent for Tea Shot Hole Borer (Coleoptera: Curculionidae) in Florida Avocado Groves
Authors: Kendra Paul E. , Montgomery Wayne S. , Tabanca Nurhayat , Schnell Elena Q. , Vázquez Aimé , Menocal Octavio , Carrillo Daniel , Cloonan Kevin R.
Published: April 2023

The tea shot hole borer, Euwallacea perbrevis, has been recently established in Florida, USA, where it vectors fungal pathogens that cause Fusarium dieback in avocado. Pest monitoring uses a two-component lure containing quercivorol and α-copaene. Incorporation of a repellent into IPM programs may reduce the incidence of dieback in avocado groves, particularly if combined with lures in a push–pull system. This study evaluated piperitone and α-farnesene as potential repellents for E. perbrevis, comparing their efficacy to that of verbenone. Replicate 12-week field tests were conducted in commercial avocado groves. Each test compared beetle captures in traps baited with two-component lures versus captures in traps containing lures plus repellent. To complement field trials, Super-Q collections followed by GC analyses were performed to quantify emissions from repellent dispensers field-aged for 12 weeks. Electroantennography (EAG) was also used to measure beetle olfactory response to each repellent. Results indicated that α-farnesene was ineffective; however, piperitone and verbenone were comparable in repellency, achieving 50–70% reduction in captures, with longevity of 10–12 weeks. EAG responses to piperitone and verbenone were equivalent, and significantly greater than response to α-farnesene. Since piperitone is less expensive than verbenone, this study identifies a potential new E. perbrevis repellent.
Spermiogenesis in Caenorhabditis elegans: An Excellent Model to Explore the Molecular Basis for Sperm Activation
Authors: Shimada Yoshihiro , Kanazawa-Takino Nana , Nishimura Hitoshi
Published: April 2023

C. elegans spermiogenesis converts non-motile spermatids into motile, fertilization-competent spermatozoa. Two major events include the building of a pseudopod required for motility and fusion of membranous organelles (MOs)—intracellular secretory vesicles—with the spermatid plasma membrane required for the proper distribution of sperm molecules in mature spermatozoa. The mouse sperm acrosome reaction—a sperm activation event occurring during capacitation—is similar to MO fusion in terms of cytological features and biological significance. Moreover, C. elegans fer-1 and mouse Fer1l5, both encoding members of the ferlin family, are indispensable for MO fusion and acrosome reaction, respectively. Genetics-based studies have identified many C. elegans genes involved in spermiogenesis pathways; however, it is unclear whether mouse orthologs of these genes are involved in the acrosome reaction. One significant advantage of using C. elegans for studying sperm activation is the availability of in vitro spermiogenesis, which enables combining pharmacology and genetics for the assay. If certain drugs can activate both C. elegans and mouse spermatozoa, these drugs would be useful probes to explore the mechanism underlying sperm activation in these two species. By analyzing C. elegans mutants whose spermatids are insensitive to the drugs, genes functionally relevant to the drugs’ effects can be identified.
Oral Cavity Squamous Cell Carcinoma: An Update of the Pharmacological Treatment
Authors: Imbesi Bellantoni Martina , Picciolo Giacomo , Pirrotta Igor , Irrera Natasha , Vaccaro Mario , Vaccaro Federico , Squadrito Francesco , Pallio Giovanni
Published: April 2023

Oral cavity squamous cell carcinoma (OCSCC) represents a serious health and socio-economic problem in different geographical areas of the world. It is characterized by a high rate of mortality, recurrence and metastasis. Despite the therapeutic strategies implemented for its management and resolution, currently the survival estimate for locally advanced disease is about 50%. The available therapeutic options comprise surgery and pharmacological treatment. Recently, an increased emphasis has been placed on the drugs that might be of benefit in this life-threatening disease. Therefore, the aim of this present review was to offer a general survey of the current available pharmacological treatment for OCSCC. The PubMed database was used to retrieve the papers using “OCSCC” as the search terms. We limited our search to the last 5 years to give a more updated and recent picture of the state of the art, including preclinical and clinical investigations. We found that 77 out of 201 papers were on the surgical treatment of OCSCC, 43 out of 201 focused on the radiotherapy and 81 out of 201 underwent evaluation for the aim of our review. We excluded the case reports, editorial letters, observational studies and papers written in languages other than English. A total of 12 articles were included in the final review. Our results showed that nanotechnologies use to enhance the efficacy of anticancer drugs such as: cisplatin, paclitaxel, cetuximab, EGFR antagonists, MEK1/2 and immune check inhibitors combination could have promising anti-cancer activity. However, the paucity of available data on drugs suggests the urgent need to improve the pharmacological armamentarium for OCSCC treatment.
Cubosomes in Drug Delivery—A Comprehensive Review on Its Structural Components, Preparation Techniques and Therapeutic Applications
Authors: Sivadasan Durgaramani , Sultan Muhammad H. , Alqahtani Saad S. , Javed Shamama
Published: April 2023

Cubosomes are lipid vesicles that are comparable to vesicular systems like liposomes. Cubosomes are created with certain amphiphilic lipids in the presence of a suitable stabiliser. Since its discovery and designation, self-assembled cubosomes as active drug delivery vehicles have drawn much attention and interest. Oral, ocular, transdermal, and chemotherapeutic are just a few of the drug delivery methods in which they are used. Cubosomes show tremendous potential in drug nanoformulations for cancer therapeutics because of their prospective advantages, which include high drug dispersal due to the structure of the cubic, large surface area, a relatively simple manufacturing process, biodegradability, ability to encapsulate hydrophobic, hydrophilic, and amphiphilic compounds, targeted and controlled release of bioactive agents, and biodegradability of lipids. The most typical technique of preparation is the simple emulsification of a monoglyceride with a polymer, followed by sonication and homogenisation. Top-down and bottom-up are two different sorts of preparation techniques. This review will critically analyse the composition, preparation techniques, drug encapsulation approaches, drug loading, release mechanism and applications relevant to cubosomes. Furthermore, the challenges faced in optimising various parameters to enhance the loading capacities and future potentialities are also addressed.
The Potassium Channel Blocker β-Bungarotoxin from the Krait Bungarus multicinctus Venom Manifests Antiprotozoal Activity
Authors: Osipov Alexey V. , Cheremnykh Elena G. , Ziganshin Rustam H. , Starkov Vladislav G. , Nguyen Trang Thuy Thi , Nguyen Khoa Cuu , Le Dung Tien , Hoang Anh Ngoc , Tsetlin Victor I. , Utkin Yuri N.
Published: April 2023

Protozoal infections are a world-wide problem. The toxicity and somewhat low effectiveness of the existing drugs require the search for new ways of protozoa suppression. Snake venom contains structurally diverse components manifesting antiprotozoal activity; for example, those in cobra venom are cytotoxins. In this work, we aimed to characterize a novel antiprotozoal component(s) in the Bungarus multicinctus krait venom using the ciliate Tetrahymena pyriformis as a model organism. To determine the toxicity of the substances under study, surviving ciliates were registered automatically by an original BioLaT-3.2 instrument. The krait venom was separated by three-step liquid chromatography and the toxicity of the obtained fractions against T. pyriformis was analyzed. As a result, 21 kDa protein toxic to Tetrahymena was isolated and its amino acid sequence was determined by MALDI TOF MS and high-resolution mass spectrometry. It was found that antiprotozoal activity was manifested by β-bungarotoxin (β-Bgt) differing from the known toxins by two amino acid residues. Inactivation of β-Bgt phospholipolytic activity with p-bromophenacyl bromide did not change its antiprotozoal activity. Thus, this is the first demonstration of the antiprotozoal activity of β-Bgt, which is shown to be independent of its phospholipolytic activity.
Altered Resting-State Functional Networks in Nondialysis Patients with Stage 5 Chronic Kidney Disease: A Graph–Theoretical Analysis
Authors: Song Lijun , Liu Xu , Yang Wenbo , Chen Qian , Lv Han , Yang Zhenghan , Liu Wenhu , Wang Hao , Wang Zhenchang
Published: April 2023

This study aimed to investigate the topological characteristics of the resting-state functional network and the underlying pathological mechanism in nondialysis patients with stage 5 chronic kidney disease (CKD5 ND). Eighty-five subjects (21 patients with CKD5 ND, 32 patients with CKD on maintenance hemodialysis (HD), and 32 healthy controls (HCs)) underwent laboratory examinations, neuropsychological tests, and brain magnetic resonance imaging. The topological characteristics of networks were compared with a graph–theoretical approach, and correlations between neuropsychological scores and network properties were analyzed. All participants exhibited networks with small-world attributes, and global topological attributes were impaired in both groups of patients with CKD 5 (ND and HD) compared with HCs (p < 0.05); these impairments were more severe in the CKD5 ND group than in the HD group (p < 0.05). Compared with the HC group, the degree centrality of the CKD5 ND group decreased mainly in the basal ganglia and increased in the bilateral orbitofrontal gyrus, bilateral precuneus, and right cuneus. Correlation analysis showed that the degree of small-worldness, normalized clustering coefficients, and Montreal Cognitive Assessment (MoCA) scores were positively correlated and that characteristic path length was negatively correlated with these variables in patients with CKD5 ND. The nodal efficiency of the bilateral putamen (r = 0.53, p < 0.001 and r = 0.47, p < 0.001), left thalamus (r = 0.37, p < 0.001), and right caudate nucleus (r = 0.28, p = 0.01) was positively correlated with MoCA scores. In conclusion, all CKD5 ND patients exhibited changes in functional network topological properties and were closely associated with mild cognitive impairment. More interestingly, the topological property changes in CKD5 ND patients were dominated by basal ganglia areas, which may be more helpful to understand and possibly reveal the underlying pathological mechanisms of cognitive impairment in CKD5 ND.
Cerebral Neural Changes in Venous–Arterial Extracorporeal Membrane Oxygenation Survivors
Authors: Yan Jueyue , Xu Zhipeng , Fang Xing , You Jingyu , Niu Jianhua , Xu Mi , Zhang Jingchen , Hu Jia , He Xujian , Li Tong
Published: April 2023

Background: Extracorporeal membrane oxygenation (ECMO) is used as temporary cardiorespiratory support in patients with critical ailments, but very little is known about the functional cerebral changes in ECMO survivors. Degree centrality (DC), a graph-based assessment of network organization, was performed to explore the neural connectivity changes in ECMO survivors compared to controls and their correlation with cognitive and neurological measures. Methods: This exploratory observational study was conducted from August 2020 to May 2022. ECMO survivors and controls underwent functional magnetic resonance imaging (fMRI) of the brain. We performed DC analysis to identify voxels that showed changes in whole-brain functional connectivity with other voxels. DC was measured by the fMRI graph method and comparisons between the two groups were performed. All participants underwent neuropsychological assessment (Montreal Cognitive Assessment, MoCA). Blood serum neuron-specific enolase and the Glasgow Coma Scale (GCS) were assessed in ECMO survivors. Results: DC values in the right insula and right precuneus gyrus were lower in ECMO survivors and higher in the right medial superior frontal gyrus compared to controls (all p < 0.001). Decreased connectivity in the right insular and right precuneus gyrus correlated with total MoCA scores, delayed recollection, and calculation (all p < 0.05). Increased serum NSE levels, GCS score, and GCS–motor response correlated with decreased connectivity in the right insular and right precuneus gyrus and increased connectivity in the right medial superior frontal gyrus (all p < 0.05). Conclusions: We showed that both functional impairment and adaptation were observed in survivors of ECMO, suggesting that neural connectivity changes may provide insights into the mechanisms that may potentially link ECMO survivors to neurological and cognitive disorders.
Detection and Molecular Characterization of Circulating Tumour Cells: Challenges for the Clinical Setting
Authors: Strati Areti , Markou Athina , Kyriakopoulou Evgenia , Lianidou Evi
Published: April 2023

Over the last decade, liquid biopsy has gained much attention as a powerful tool in personalized medicine since it enables monitoring cancer evolution and follow-up of cancer patients in real time. Through minimally invasive procedures, liquid biopsy provides important information through the analysis of circulating tumour cells (CTCs) and circulating tumour-derived material, such as circulating tumour DNA (ctDNA), circulating miRNAs (cfmiRNAs) and extracellular vehicles (EVs). CTC analysis has already had an important impact on the prognosis, detection of minimal residual disease (MRD), treatment selection and monitoring of cancer patients. Numerous clinical trials nowadays include a liquid biopsy arm. CTC analysis is now an exponentially expanding field in almost all types of solid cancers. Functional studies, mainly based on CTC-derived cell-lines and CTC-derived explants (CDx), provide important insights into the metastatic process. The purpose of this review is to summarize the latest findings on the clinical significance of CTCs for the management of cancer patients, covering the last four years. This review focuses on providing a comprehensive overview of CTC analysis in breast, prostate and non-small-cell lung cancer. The unique potential of CTC single-cell analysis for understanding metastasis biology, and the importance of quality control and standardization of methodologies used in this field, is also discussed.
THY1 (CD90) Maintains the Adherens Junctions in Nasopharyngeal Carcinoma via Inhibition of SRC Activation
Authors: Chen Luo , Chau Wai Yin , Yuen Hei Tung , Liu Xiao Han , Qi Robert Zhong , Lung Maria Li , Lung Hong Lok
Published: April 2023

We had previously shown that THY1 (CD90) is a tumor suppressor in nasopharyngeal carcinoma (NPC) and that its down-regulation and loss of expression are associated with tumor metastasis, yet the mechanism leading to such effects remains unknown. In this study we show that tumor invasion could be suppressed by THY1 via adherens junction formation in a few NPC cell lines, and knockdown of THY1 would disrupt this cell-cell adhesion phenotype. Mechanistically, the activity of the SRC family kinase (SFK) member, SRC, and canonical Wnt signaling were dramatically reduced when THY1 was constitutively expressed. Previous studies by others have found that high levels of SRC activity in NPCs are associated with EMT and a poor prognosis. We hypothesized that THY1 can suppress tumor invasion in NPC via inhibition of SRC. By gene silencing of SRC, we found that the in vitro NPC cell invasion was significantly reduced and adherens junctions were restored. Through proteomic analysis, we identified that platelet-derived growth factor receptor β (PDGF-Rβ) and protein tyrosine phosphatase nonreceptor type 22 (PTPN22) are novel and potential binding partners of THY1, which were subsequently verified by co-immunoprecipitation (co-IP) analysis. The ligand of PDGF-Rβ (PDGF-BB) could highly induce SRC activation and NPC cell invasion, which could be almost completely suppressed by THY1 expression. On the other hand, the PTPN22 siRNA could enhance both the SRC activities and the cell invasion and could also disrupt the adherens junctions in the THY1-expressing NPC cells; the original THY1-induced phenotypes were reverted when the PTPN22 expression was reduced. Together, our results identified that PTPN22 is essential for THY1 to suppress cell invasion and SRC activity, maintain tight adherens junctions, and prevent NPC metastasis. These results suggested that PDGF-Rβ and SRC can be used as drug targets for suppressing NPC metastasis. Indeed, our in vivo assay using the SRC inhibitor KX2-391, clearly showed that inhibition of SRC signaling can prevent the metastasis of NPC, indicating that targeting SRC can be a promising approach to control the NPC progression.
PATZ1 in Non-Small Cell Lung Cancer: A New Biomarker That Negatively Correlates with PD-L1 Expression and Suppresses the Malignant Phenotype
Authors: Lucà Stefano , Franco Renato , Napolitano Antonella , Soria Valeria , Ronchi Andrea , Zito Marino Federica , Della Corte Carminia Maria , Morgillo Floriana , Fiorelli Alfonso , Luciano Antonio , Palma Giuseppe , Arra Claudio , Battista Sabrina , Cerchia Laura , Fedele Monica
Published: April 2023

Non-small cell lung cancer (NSCLC), the leading cause of cancer death worldwide, is still an unmet medical problem due to the lack of both effective therapies against advanced stages and markers to allow a diagnosis of the disease at early stages before its progression. Immunotherapy targeting the PD-1/PD-L1 checkpoint is promising for many cancers, including NSCLC, but its success depends on the tumor expression of PD-L1. PATZ1 is an emerging cancer-related transcriptional regulator and diagnostic/prognostic biomarker in different malignant tumors, but its role in lung cancer is still obscure. Here we investigated expression and role of PATZ1 in NSCLC, in correlation with NSCLC subtypes and PD-L1 expression. A cohort of 104 NSCLCs, including lung squamous cell carcinomas (LUSCs) and adenocarcinomas (LUADs), was retrospectively analyzed by immunohistochemistry for the expression of PATZ1 and PD-L1. The results were correlated with each other and with the clinical characteristics, showing on the one hand a positive correlation between the high expression of PATZ1 and the LUSC subtype and, on the other hand, a negative correlation between PATZ1 and PD-L1, validated at the mRNA level in independent NSCLC datasets. Consistently, two NSCLC cell lines transfected with a PATZ1-overexpressing plasmid showed PD-L1 downregulation, suggesting a role for PATZ1 in the negative regulation of PD-L1. We also showed that PATZ1 overexpression inhibits NSCLC cell proliferation, migration, and invasion, and that Patz1-knockout mice develop LUAD. Overall, this suggests that PATZ1 may act as a tumor suppressor in NSCLC.
Precancerous Lesions of the Head and Neck Region and Their Stromal Aberrations: Piecemeal Data
Authors: Harris Ashlee , Andl Thomas
Published: April 2023

Head and neck squamous cell carcinomas (HNSCCs) develop through a series of precancerous stages from a pool of potentially malignant disorders (PMDs). Although we understand the genetic changes that lead to HNSCC, our understanding of the role of the stroma in the progression from precancer to cancer is limited. The stroma is the primary battleground between the forces that prevent and promote cancer growth. Targeting the stroma has yielded promising cancer therapies. However, the stroma at the precancerous stage of HNSCCs is poorly defined, and we may miss opportunities for chemopreventive interventions. PMDs already exhibit many features of the HNSCC stroma, such as inflammation, neovascularization, and immune suppression. Still, they do not induce cancer-associated fibroblasts or destroy the basal lamina, the stroma’s initial structure. Our review aims to summarize the current understanding of the transition from precancer to cancer stroma and how this knowledge can reveal opportunities and limitations for diagnostic, prognostic, and therapeutic decisions to benefit patients. We will discuss what may be needed to fulfill the promise of the precancerous stroma as a target to prevent progression to cancer.
Description of Copy Number Variations in a Series of Children and Adolescents with FASD in Reunion Island
Authors: Sennsfelder Laëtitia , Guilly Susie , Leruste Sébastien , Hoareau Ludovic , Léocadie Willy , Beuvain Pauline , Nekaa Meïssa , Bagard Maïté , Robin Stéphanie , Lanneaux Justine , Etchebarren Léa , Tallot Marilyn , Spodenkiewicz Michel , Alessandri Jean-Luc , Morel Godelieve , Blanluet Maud , Gueguen Paul , Roy-Doray Bérénice
Published: April 2023

Background: Fetal Alcohol Spectrum Disorders (FASD) are the most common cause of neurocognitive impairment and social inadaptation, affecting 1 birth in 100. Despite the existence of precise diagnostic criteria, the diagnosis remains difficult, often confounded with other genetic syndromes or neurodevelopmental disorders. Since 2016, Reunion Island has been a pilot region for the identification, diagnosis, and care of FASD in France. Objective: To evaluate the prevalence and the types of Copy Number Variations (CNV) in FASD patients. Methods: A retrospective chart review of 101 patients diagnosed with FASD in the Reference Center for developmental anomalies and in the FASD Diagnostic Center of the University Hospital was performed. Records of all patients were reviewed to obtain their medical history, family history, clinical phenotype, and investigations, including genetic testing (CGH- or SNP-array). Results: A rate of 20.8% (n = 21) of CNVs was found including 57% (12/21) of pathogenic variants and 29% (6/21) of variants of uncertain signification (VUS). Conclusion: A particularly high number of CNVs was found in children and adolescents with FASD. It reinforces the plea for a multidisciplinary approach for developmental disorders to explore both environmental factors, such as avoidable teratogens and intrinsic vulnerabilities, especially genetic determinants.
A Novel MSH6 Gene Variant in a Lynch Syndrome Patient with Lipomas
Authors: Giannoni Ana Paula , Sevic Ina , Parenti Fernanda , Alaniz Laura
Published: April 2023

Colorectal cancer is one of the most frequently occurring cancers today, with a large percentage of cases having a hereditary basis. Lynch syndrome is the most common cause of hereditary colorectal cancer. The genetic defect characteristics of this syndrome involve mutations in mismatch repair (MMR) genes, which result in microsatellite instability. Early detection of the mutation can help evaluate the cancer risk and, consequently, a proper course of clinical management for the person harboring the mutation. Herein, we describe the first report of a c.1458dup (p.Glu487*) new mutation in a 53-year-old colorectal cancer patient with diagnosed Lynch syndrome. Additionally, the existence of lipomas in this patient and his family could be related to this syndrome. Further investigation may provide a possible visual clue that can indicate a need for genetic screening.
First Stranding Event of a Common Minke Whale (Balaenoptera acutorostrata Lacépède, 1804) Reported in the Gulf of Thailand
Authors: Chantra Rachawadee , Nganvongpanit Korakot , Yaowasooth Patcharaporn , Thongsukdee Surasak , Kitiwatthanawong Kongkiat , Thongcharoenchaikit Cholawit , Brown Janine L. , Piboon Promporn
Published: April 2023

On 5 September 2022, a dead baleen whale was found stranded at Laem Phak Bia, Phetchaburi, the Gulf of Thailand, Thailand but could not be identified because it was in an advanced stage of decomposition. It was first suspected to be Omura’s whale (Balaenoptera Omurai), as that is a common species in the Gulf of Thailand. However, the cranium morphology was different from B. omurai and more similar to the common minke whale (Balaenoptera acutorostrata) from the North Pacific Ocean, which has never been reported in Thai territorial waters. The mitochondrial DNA control region (D-loop) was then used to identify the species through the Basic Local Alignment Search Tool (BLAST) available at the National Center for Biotechnology Information (NCBI) GenBank, which resulted in a high percent identity, 96.49 to 98.84, with B. acutorostrata. A Bayesian phylogenetic tree was further used to confirm the species, which grouped with B. acutorostrata from the North Pacific Ocean. This study provides evidence of the first stranding event of B. acutorostrata in the Gulf of Thailand. It is new information that extends previous knowledge on the distribution of the common minke whale and raises the need for more active surveys of cetaceans in the South China Sea going forward.
Learn the Past and Present to Teach the Future—Role of Active Surveillance of Exposure to Endemic and Emerging Viruses in the Approach of European Bison Health Protection
Authors: Larska Magdalena , Tomana Jarosław , Socha Wojciech , Rola Jerzy , Kubiś Piotr , Olech Wanda , Krzysiak Michał K.
Published: April 2023

As the population size of free-living European bison in Poland has increased significantly over the last few years, conservation and management should be reconsidered to face new challenges, which aim to protect the whole population, not just individuals. The aim of our study was to analyse prevalence and identify risk factors for infections with viruses affecting reproduction (BVDV, BoHV-1, and BoHV-4), causing respiratory diseases (BRV3, BAdV-3, and BRSV), and emerging vector-borne viruses (BTV and SBV). Over 600 serum samples used in serology and 270 lung tissue samples, and 284 nasal swabs used in virological tests were collected from 24 free-living and captive European bison herds between 2016 and 2023. The seroprevalences varied between low (0.3–6.1% for BVDV, BoHV-1, and BoHV-4), medium (15.9% for BRSV and 22.1% for BTV) and high (43.3% for BRV3, 59.5% for BAdV-3, and 69.5% for SBV). Interspecies’ and intraspecies’ risk of endemic viral infections was observed to be density-dependent, while the effect of anthropogenic factors on the spread of infections in free-living European bison has not been demonstrated. BTV is no longer circulating, while SBV has become endemic. The higher exposure to viruses in the European bison eliminated on the basis of a veterinary decision indicates the importance of an expert supervision for disease control and prevention.
Hybridization of Deep Learning Pre-Trained Models with Machine Learning Classifiers and Fuzzy Min–Max Neural Network for Cervical Cancer Diagnosis
Authors: Kalbhor Madhura , Shinde Swati , Popescu Daniela Elena , Hemanth D. Jude
Published: April 2023

Medical image analysis and classification is an important application of computer vision wherein disease prediction based on an input image is provided to assist healthcare professionals. There are many deep learning architectures that accept the different medical image modalities and provide the decisions about the diagnosis of various cancers, including breast cancer, cervical cancer, etc. The Pap-smear test is the commonly used diagnostic procedure for early identification of cervical cancer, but it has a high rate of false-positive results due to human error. Therefore, computer-aided diagnostic systems based on deep learning need to be further researched to classify the pap-smear images accurately. A fuzzy min–max neural network is a neuro fuzzy architecture that has many advantages, such as training with a minimum number of passes, handling overlapping class classification, supporting online training and adaptation, etc. This paper has proposed a novel hybrid technique that combines the deep learning architectures with machine learning classifiers and fuzzy min–max neural network for feature extraction and Pap-smear image classification, respectively. The deep learning pretrained models used are Alexnet, ResNet-18, ResNet-50, and GoogleNet. Benchmark datasets used for the experimentation are Herlev and Sipakmed. The highest classification accuracy of 95.33% is obtained using Resnet-50 fine-tuned architecture followed by Alexnet on Sipakmed dataset. In addition to the improved accuracies, the proposed model has utilized the advantages of fuzzy min–max neural network classifiers mentioned in the literature.
Multiplex RT Real-Time PCR Based on Target Failure to Detect and Identify Different Variants of SARS-CoV-2: A Feasible Method That Can Be Applied in Clinical Laboratories
Authors: Pham Van Hung , Pham Huong Thien , Balzanelli Mario G. , Distratis Pietro , Lazzaro Rita , Nguyen Quoc Viet , Tran Viet Quoc , Tran Duy Khanh , Phan Luan Duy , Pham Sang Minh , Pham Binh Thai , Duc Chien Vo , Nguyen Ha Minh , Nguyen Dung Ngoc Thi , Tran Ngoc Van , Pham Son Truong , Queck Camelia , Nguyen Kieu Diem Cao , Inchingolo Francesco , Del Prete Raffaele , Nguyen Nam Hai Dinh , Santacroce Luigi , Gargiulo Isacco Ciro
Published: April 2023

Shortly after its emergence, Omicron and its sub-variants have quickly replaced the Delta variant during the current COVID-19 outbreaks in Vietnam and around the world. To enable the rapid and timely detection of existing and future variants for epidemiological surveillance and diagnostic applications, a robust, economical real-time PCR method that can specifically and sensitively detect and identify multiple different circulating variants is needed. The principle of target- failure (TF) real-time PCR is simple. If a target contains a deletion mutation, then there is a mismatch with the primer or probe, and the real-time PCR will fail to amplify the target. In this study, we designed and evaluated a novel multiplex RT real-time PCR (MPL RT-rPCR) based on the principle of target failure to detect and identify different variants of SARS-CoV-2 directly from the nasopharyngeal swabs collected from COVID-19 suspected cases. The primers and probes were designed based on the specific deletion mutations of current circulating variants. To evaluate the results from the MPL RT-rPCR, this study also designed nine pairs of primers for amplifying and sequencing of nine fragments from the S gene containing mutations of known variants. We demonstrated that (i) our MPL RT-rPCR was able to accurately detect multiple variants that existed in a single sample; (ii) the limit of detection of the MPL RT-rPCR in the detection of the variants ranged from 1 to 10 copies for Omicron BA.2 and BA.5, and from 10 to 100 copies for Delta, Omicron BA.1, recombination of BA.1 and BA.2, and BA.4; (iii) between January and September 2022, Omicron BA.1 emerged and co-existed with the Delta variant during the early period, both of which were rapidly replaced by Omicron BA.2, and this was followed by Omicron BA.5 as the dominant variant toward the later period. Our results showed that SARS-CoV-2 variants rapidly evolved within a short period of time, proving the importance of a robust, economical, and easy-to-access method not just for epidemiological surveillance but also for diagnoses around the world where SARS-CoV-2 variants remain the WHO’s highest health concern. Our highly sensitive and specific MPL RT-rPCR is considered suitable for further implementation in many laboratories, especially in developing countries.