bluuebunny/crossref_metadata_2025 huggingface dataset:
Op-Trans: An Optimization Framework for Negative Sampling and Triplet-Mapping Properties in Knowledge Graph Embedding
Authors: Han Huixia , Li Xinyue , Wu Kaijun
Published: February 2023

Knowledge graphs are a popular research field in artificial intelligence, and store large amounts of real-world data. Since data are enriched over time, the knowledge graph is often incomplete. Therefore, knowledge graph completion is particularly important as it predicts missing links based on existing facts. Currently, the family of translation models delivers a better performance in knowledge graph completion. However, most of these models randomly generate negative triplets during the training process, resulting in the low quality of negative triplets. In addition, such models ignore the important characteristics of triplet-mapping properties during model learning. Therefore, we propose an optimization framework based on the translation models (Op-Trans). It enhances the knowledge-graph completion effect from both negative sampling and triplet-mapping properties. First, we propose a clustering cache to generate negative triplets, which generate negative triplets based on entity similarity. This sampling method can directly use the cache to track the negative triplets with large scores. In addition, we focus on the different contributions of the triplets to the optimization goal. We calculate the distinct weight for each triplet according to its mapping properties. In this way, the scoring function deals with each triplet depending on its own weight. The experimental results show that Op-Trans can help the state-of-the-art baselines to obtain a better performance in a link prediction task.
Optimized Isolation Procedure for the Extraction of Bioactive Compounds from Spent Coffee Grounds
Authors: Chatzimitakos Theodoros , Athanasiadis Vassilis , Kotsou Konstantina , Palaiogiannis Dimitrios , Bozinou Eleni , Lalas Stavros I.
Published: February 2023

Due to the worldwide consumption of coffee, many tons of spent coffee grounds (SCGs) are discarded each year, as a by-product of coffee preparation. Not only their disposal is costly, but also it may cause the release of compounds that can endanger the environment. However, there are valuable chemical compounds that can be extracted from SCGs and used in the food industry. The aim of this study was to investigate the main parameters affecting the extraction of caffeine and polyphenols (i.e., chlorogenic acid, neochlorogenic acid, and caffeic acid) and to evaluate the antioxidant properties of the extracts. To this end, extraction solvent, temperature, time, and liquid-to-solid ratio were studied. A response surface methodology was used to optimize the extraction process. According to the results, the caffeine content of the optimum extract was found to be 6.14 mg/g in dry SCGs, the total polyphenol content was 19.85 mg gallic acid equivalents/g, while the ferric reducing antioxidant power and DPPH scavenging values were 136.69 μmoL ascorbic acid equivalents/g and 230.41 μmoL DPPH/g, respectively. The experimental values were in close agreement with the predicted ones, highlighting the potential of SCGs to be used for the isolation of bioactive compounds with the proposed extraction procedure.
A Novel and Practicable Approach for Determining the Beam Parameters of Soft Pneumatic Multi-Chamber Bending Actuators
Authors: Lamping Frederik , de Payrebrune Kristin M.
Published: February 2023

The design of many pneumatic soft actuators is based on multiple chambers in parallel alignment. The Cosserat beam theory is an established technique for modeling this kind of actuator, where existing approaches mainly differ in the parameters being required for simulation. The modeling approach presented in this study particularly aims at finding the beam parameters necessary for a simulation even with limited experimental methods. Importantly, it provides a straightforward relationship between the bending stiffness, the extensional stiffness and the axial stretch of the actuator. If the actuator to be modeled has an elementary design, axial measurements are sufficient to identify the parameters to perform three-dimensional simulations, which is of interest to adopters with limited testing equipment. The experimentally parameterized model of such an actuator of elementary design shows high accuracy. Both without load and with a weight of 1N applied to the tip, the mean error of the tip position in vertical orientation is less than 3.4% for a constant extensional stiffness and less than 2.7% for a pressure-dependent extensional stiffness. Further reduction of the error could be achieved by more refined identification techniques that decompose the complex interrelationship of pressurization, forces and material stiffness.
Development of New Spectral Amplitude Coding OCDMA Code by Using Polarization Encoding Technique
Authors: Ammar Syed Mohammad , Ali Norshamsuri , Saad Mohamad Naufal , Aljunid Syed Alwee , Endut Rosdisham , Alhassan Ahmed M. , Edet Collins Okon
Published: February 2023

OCDMA is an optical access technology that has a lot of potential because it can be asynchronously accessed and provides a higher level of security. The authors presented a new DW family code, a flexible double weight (FDW) code, and a novel polarization encoding approach in this paper. The new code is applicable to both odd- and even-weighted codes. The novel polarization encoding approach may be used for numerous wavelengths that overlap. Based on analytic principles, a comparison of two widely used spectrum amplitude-coding SAC-based OCDMA codes, notably modified frequency hopping (MFH), Hadamard, and the double weight (DW) code family. The comparison was based on observing the bit error rate (BER) in each situation. The DW code has a fixed weight of two. The FDW code was introduced to reduce phase-induced intensity noise and multiple access interference (MAI) in transmission networks. FDW codes are versions of the DW code family with weights larger than two. The FDW code outperforms the Hadamard, MFH, DW, modified double weight (MDW), and enhanced double weight (EDW) algorithms. FDW has the capacity to support up to 220 concurrent users. With the new polarization encoding technology, the FDW code can travel up to 60 km at a bit rate of 2.5 Gb/s and 40 km for a 10 Gb/s bit rate.
Binaural Auralization of Room Acoustics with a Highly Scalable Wave-Based Acoustics Simulation
Authors: Yoshida Takumi , Okuzono Takeshi , Sakagami Kimihiro
Published: February 2023

This paper presents a proposal of an efficient binaural room-acoustics auralization method, an essential goal of room-acoustics modeling. The method uses a massively parallel wave-based room-acoustics solver based on a dispersion-optimized explicit time-domain finite element method (TD-FEM). The binaural room-acoustics auralization uses a hybrid technique of first-order Ambisonics (FOA) and head-related transfer functions. Ambisonics encoding uses room impulse responses computed by a parallel wave-based room-acoustics solver that can model sound absorbers with complex-valued surface impedance. Details are given of the novel procedure for computing expansion coefficients of spherical harmonics composing the FOA signal. This report is the first presenting a parallel wave-based solver able to simulate room impulse responses with practical computational times using an HPC cloud environment. A meeting room problem and a classroom problem are used, respectively, having 35 million degrees of freedom (DOF) and 100 million DOF, to test the parallel performance of up to 6144 CPU cores. Then, the potential of the proposed binaural room-acoustics auralization method is demonstrated via an auditorium acoustics simulation of up to 5 kHz having 750,000,000 DOFs. Room-acoustics auralization is performed with two acoustics treatment scenarios and room-acoustics evaluations that use an FOA signal, binaural room impulse response, and four room acoustical parameters. The auditorium acoustics simulation showed that the proposed method enables binaural room-acoustics auralization within 13,000 s using 6144 cores.
Multi-Microgrid Energy Management Strategy Based on Multi-Agent Deep Reinforcement Learning with Prioritized Experience Replay
Authors: Guo Guodong , Gong Yanfeng
Published: February 2023

The multi-microgrid (MMG) system has attracted more and more attention due to its low carbon emissions and flexibility. This paper proposes a multi-agent reinforcement learning algorithm for real-time energy management of an MMG. In this problem, the MMG is connected to a distribution network (DN). The distribution network operator (DSO) and each microgrid (MG) are modeled as autonomous agents. Each agent makes decisions to suit its interests based on local information. The decision-making problem of multiple agents is modeled as a Markov game and solved by the prioritized multi-agent deep deterministic policy gradient (PMADDPG), where only local observation is required for each agent to make decisions, the centralized training mechanism is applied to learn coordination strategy, and a prioritized experience replay (PER) strategy is adopted to improve learning efficiency. The proposed method can deal with the non-stationary problems in the process of a multi-agent game with partial observable information. In the execution stage, all trained agents are deployed in a distributed manner and make decisions in real time. Simulation results show that according to the proposed method, the training process of a multi-agent game is accelerated, and multiple agents can make optimal decisions only by local information.
Primed Seeds of NERICA 4 Stored for Long Periods under High Temperature and Humidity Conditions Maintain Germination Rates
Authors: Bore Emmanuel Kiprono , Ishikawa Eri , Libron Julie Ann Mher Alcances , Goto Keita , Odama Emmanuel , Nakao Yoshihiro , Yabuta Shin , Sakagami Jun-Ichi
Published: February 2023

Agriculture depends on the ability of seeds to survive until the next planting season under ambient conditions that may be averse to seed quality even when the seed is in a quiescent state. Seed priming invigorates seeds, but the impact on the longevity of seeds has limited its adoption. This study investigated the effect of the storage of primed rice seed on seed viability, vigor, and longevity. Three seed priming methods were employed on the rice cultivar New Rice for Africa (NERICA 4) seeds. Subsequently, the seeds were stored for 120 days at 25 °C and 65% relative humidity, simulating the ambient seed storage conditions of the tropics and sub-tropics. The primed seed recorded increased vigor compared to the non-primed seed until 90 days of storage. However, seed storage for 120 days reduced seed vigor and viability for all the seeds. The results indicated a significant reduction in seed vigor, increased solute leakage, generation of hydrogen peroxide, and accumulation of malondialdehyde after storage. Priming enhances cell membrane integrity and maintains seed vigor in storage at near ambient conditions long enough before reversal of its performance by the storage conditions. This assures that primed seed can either be stored until the following planting season or remain viable in the soil during delayed germination.
Stability of Heterogeneous Beams with Three Supports—Solutions Using Integral Equations
Authors: Kiss László , Messaoudi Abderrazek , Szeidl György
Published: February 2023

It is our main objective to find the critical load for three beams with cross sectional heterogeneity. Each beam has three supports, of which the intermediate one is a spring support. Determination of the critical load for these beams leads to three point boundary value problems (BVPs) associated with homogeneous boundary conditions—the mentioned BVPs constitute three eigenvalue problems. They are solved by using a novel solution strategy based on the Green functions that belong to these BVPs: the eigenvalue problems established for the critical load are transformed into eigenvalue problems governed by homogeneous Fredholm integral equations with kernels that can be given in closed forms provided that the Green function of each BVP is known. Then the eigenvalue problems governed by the Fredholm integral equations can be manipulated into algebraic eigenvalue problems solved numerically by using effective algorithms. It is an advantage of the way we attack these problems that the formalism established and the results obtained remain valid for homogeneous beams as well. The numerical results for the critical forces can be applied to solve some stability problems in the engineering practice.
Representation and Identity in Contemporary Women Artists’ Video
Authors: Leuzzi Laura
Published: February 2023

This essay is an initial study that examines selected contemporary video artworks addressing identity and representation by contemporary Italian women artists. The author shows how these women artists seek to avoid the objectification and sanitisation of the traditional iconographies involving women in patriarchal Catholic systems. Selected works by Elisabetta Di Sopra, Francesca Fini, and Mariateresa Sartori are discussed by comparing elements from works by earlier generations of feminist video artists, such as Pipilotti Rist, Elaine Shemilt, and Catherine Elwes. Drawing on theories of both video and feminist art, this article examines how the development of a new aesthetic in early women’s video art practice in the 1970s and 1980s is still relevant to the task of critically examining and assessing aesthetics in video today, and how video remains a key tool used to experiment with the remediation of women’s representation and identity.
A Distinctive Explainable Machine Learning Framework for Detection of Polycystic Ovary Syndrome
Authors: Khanna Varada Vivek , Chadaga Krishnaraj , Sampathila Niranajana , Prabhu Srikanth , Bhandage Venkatesh , Hegde Govardhan K.
Published: February 2023

Polycystic Ovary Syndrome (PCOS) is a complex disorder predominantly defined by biochemical hyperandrogenism, oligomenorrhea, anovulation, and in some cases, the presence of ovarian microcysts. This endocrinopathy inhibits ovarian follicle development causing symptoms like obesity, acne, infertility, and hirsutism. Artificial Intelligence (AI) has revolutionized healthcare, contributing remarkably to science and engineering domains. Therefore, we have demonstrated an AI approach using heterogeneous Machine Learning (ML) and Deep Learning (DL) classifiers to predict PCOS among fertile patients. We used an Open-source dataset of 541 patients from Kerala, India. Among all the classifiers, the final multi-stack of ML models performed best with accuracy, precision, recall, and F1-score of 98%, 97%, 98%, and 98%. Explainable AI (XAI) techniques make model predictions understandable, interpretable, and trustworthy. Hence, we have utilized XAI techniques such as SHAP (SHapley Additive Values), LIME (Local Interpretable Model Explainer), ELI5, Qlattice, and feature importance with Random Forest for explaining tree-based classifiers. The motivation of this study is to accurately detect PCOS in patients while simultaneously proposing an automated screening architecture with explainable machine learning tools to assist medical professionals in decision-making.
A Case Study of the Wavenumber Transition between Westward Quasi-2 Day Wave s = 3 and s = 4 Modes in the Mesosphere
Authors: Gu Sheng-Yang , Wei Yafei , Sha Xiaoming , Tang Liang , Li Na
Published: February 2023

We report observations of the wave number transition between two types of westward-propagating quasi-2 day wave (QTDW) with zonal wave number s = 3 and s = 4 in the mesosphere. The Aura/MLS temperature datasets from January and February 2011 are utilized in the analysis. A strong W4 was observed in the Southern Hemisphere in early February, following the fading away of a strong W3 in late January. The W3 and W4 were maximized on days 23 and 36 with maximum amplitudes of ~15 K and ~8 K, respectively. Both the amplitudes and periods were nearly equal on day 30, which coincided with the peak of the Sudden Stratospheric Warming (SSW) on day 31 in the polar region of the Northern Hemisphere. Our analysis shows that the equatorial barotropic/baroclinic and inertial instabilities, which are related with the winter planetary wave activities that lead to the SSW, may have triggered this wavenumber transition event and contributed significantly to the growth of the QTDW. Meanwhile, the relatively strong summer easterly jet at middle and high latitude regions in early February also provided favorable conditions for the amplification of W4 during 2011, and thus facilitated the wavenumber transition.
Neural Field Continuum Limits and the Structure–Function Partitioning of Cognitive–Emotional Brain Networks
Authors: Clark Kevin B.
Published: February 2023

In The cognitive-emotional brain, Pessoa overlooks continuum effects on nonlinear brain network connectivity by eschewing neural field theories and physiologically derived constructs representative of neuronal plasticity. The absence of this content, which is so very important for understanding the dynamic structure-function embedding and partitioning of brains, diminishes the rich competitive and cooperative nature of neural networks and trivializes Pessoa’s arguments, and similar arguments by other authors, on the phylogenetic and operational significance of an optimally integrated brain filled with variable-strength neural connections. Riemannian neuromanifolds, containing limit-imposing metaplastic Hebbian- and antiHebbian-type control variables, simulate scalable network behavior that is difficult to capture from the simpler graph-theoretic analysis preferred by Pessoa and other neuroscientists. Field theories suggest the partitioning and performance benefits of embedded cognitive-emotional networks that optimally evolve between exotic classical and quantum computational phases, where matrix singularities and condensations produce degenerate structure-function homogeneities unrealistic of healthy brains. Some network partitioning, as opposed to unconstrained embeddedness, is thus required for effective execution of cognitive-emotional network functions and, in our new era of neuroscience, should be considered a critical aspect of proper brain organization and operation.
Morphological Abnormalities in Early-Onset Schizophrenia Revealed by Structural Magnetic Resonance Imaging
Authors: Levman Jacob , Kabaria Priya , Nangaku Masahito , Takahashi Emi
Published: February 2023

Schizophrenia is a pathological condition characterized by delusions, hallucinations, and a lack of motivation. In this study, we performed a morphological analysis of regional biomarkers in early-onset schizophrenia, including cortical thicknesses, surface areas, surface curvature, and volumes extracted from T1-weighted structural magnetic resonance imaging (MRI) and compared these findings with a large cohort of neurotypical controls. Results demonstrate statistically significant abnormal presentation of the curvature of select brain regions in early-onset schizophrenia with large effect sizes, inclusive of the pars orbitalis, pars triangularis, posterior cingulate cortex, frontal pole, orbital gyrus, lateral orbitofrontal gyrus, inferior occipital gyrus, as well as in medial occipito-temporal, lingual, and insular sulci. We also observed reduced regional volumes, surface areas, and variability of cortical thicknesses in early-onset schizophrenia relative to neurotypical controls in the lingual, transverse temporal, cuneus, and parahippocampal cortices that did not reach our stringent standard for statistical significance and should be confirmed in future studies with higher statistical power. These results imply that abnormal neurodevelopment associated with early-onset schizophrenia can be characterized with structural MRI and may reflect abnormal and possibly accelerated pruning of the cortex in schizophrenia.
Predicting Response to Radical Chemoradiotherapy with Circulating HPV DNA (cHPV-DNA) in Locally Advanced Uterine Cervix Cancer
Authors: Lalondrelle Susan , Lee Jen , Cutts Rosalind J. , Garcia Murillas Isaac , Matthews Nik , Turner Nicholas , Harrington Kevin , Vroobel Katherine , Moretti Emily , Bhide Shreerang A.
Published: February 2023

Background: The majority of locally advanced cervical cancers (LaCC) are causally related to HPV. We sought to investigate the utility of an ultra-sensitive HPV-DNA next generation sequencing (NGS) assay—panHPV-detect—in LaCC treated with chemoradiotherapy, as a marker of treatment response and persistent disease. Method: Serial blood samples were collected from 22 patients with LaCC before, during and after chemoradiation. The presence of circulating HPV-DNA was correlated with clinical and radiological outcomes. Results: The panHPV-detect test demonstrated a sensitivity and specificity of 88% (95% CI-70–99%) and 100% (95% CI-30–100%), respectively, and correctly identified the HPV-subtype (16, 18, 45, 58). After a median follow up of 16 months, and three relapses all had detectable cHPV-DNA at 3 months post-CRT despite complete response on imaging. Another four patients with radiological partial or equivocal response and undetectable cHPV-DNA at the 3-month time point did not go on to develop relapse. All patients with radiological CR and undetectable cHPV-DNA at 3-months remained disease free. Conclusions: These results demonstrate that the panHPV-detect test shows high sensitivity and specificity for detecting cHPV-DNA in plasma. The test has potential applications in assessment of the response to CRT and in monitoring for relapse, and these initial findings warrant validation in a larger cohort.
PD-1+CD8+ T Cells Proximal to PD-L1+CD68+ Macrophages Are Associated with Poor Prognosis in Pancreatic Ductal Adenocarcinoma Patients
Authors: Yang Xiaobao , Wang Guanzheng , Song Yue , Zhuang Tongtao , Li Yifei , Xie Yujie , Fei Xuefeng , Zhao Yanan , Xu Dakang , Hu Yiqun
Published: February 2023

Immune complexity status in the TME has been linked to clinical outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. TME assessments with current cell marker and cell density-based analyses do not identify the original phenotypes of single cells with multilineage selectivity, the functional status of the cells, or cellular spatial information in the tissues. Here, we describe a method that circumvents these problems. The combined strategy of multiplexed IHC with computational image cytometry and multiparameter cytometric quantification allows us to assess multiple lineage-selective and functional phenotypic biomarkers in the TME. Our study revealed that the percentage of CD8+ T lymphoid cells expressing the T cell exhaustion marker PD-1 and the high expression of the checkpoint PD-L1 in CD68+ cells are associated with a poor prognosis. The prognostic value of this combined approach is more significant than that of lymphoid and myeloid cell density analyses. In addition, a spatial analysis revealed a correlation between the abundance of PD-L1+CD68+ tumor-associated macrophages and PD-1+CD8+T cell infiltration, indicating pro-tumor immunity associated with a poor prognosis. These data highlight the implications of practical monitoring for understanding the complexity of immune cells in situ. Digital imaging and multiparameter cytometric processing of cell phenotypes in the TME and tissue architecture can reveal biomarkers and assessment parameters for patient stratification.
The Atypical MAP Kinase MAPK15 Is Required for Lung Adenocarcinoma Metastasis via Its Interaction with NF-κB p50 Subunit and Transcriptional Regulation of Prostaglandin E2 Receptor EP3 Subtype
Authors: Yu Fei-Yuan , Xu Qian , Zhao Xiao-Yun , Mo Hai-Ying , Zhong Qiu-Hua , Luo Li , Lau Andy T. Y. , Xu Yan-Ming
Published: February 2023

Studying the relatively underexplored atypical MAP Kinase MAPK15 on cancer progression/patient outcomes and its potential transcriptional regulation of downstream genes would be highly valuable for the diagnosis, prognosis, and potential oncotherapy of malignant tumors such as lung adenocarcinoma (LUAD). Here, the expression of MAPK15 in LUAD was detected by immunohistochemistry and its correlation with clinical parameters such as lymph node metastasis and clinical stage was analyzed. The correlation between the prostaglandin E2 receptor EP3 subtype (EP3) and MAPK15 expression in LUAD tissues was examined, and the transcriptional regulation of EP3 and cell migration by MAPK15 in LUAD cell lines were studied using the luciferase reporter assay, immunoblot analysis, qRT-PCR, and transwell assay. We found that MAPK15 is highly expressed in LUAD with lymph node metastasis. In addition, EP3 is positively correlated with the expression of MAPK15 in LUAD tissues, and we confirmed that MAPK15 transcriptionally regulates the expression of EP3. Upon the knockdown of MAPK15, the expression of EP3 was down-regulated and the cell migration ability was decreased in vitro; similarly, the mesenteric metastasis ability of the MAPK15 knockdown cells was inhibited in in vivo animal experiments. Mechanistically, we demonstrate for the first time that MAPK15 interacts with NF-κB p50 and enters the nucleus, and NF-κB p50 binds to the EP3 promoter and transcriptionally regulates the expression of EP3. Taken together, we show that a novel atypical MAPK and NF-κB subunit interaction promotes LUAD cell migration through transcriptional regulation of EP3, and higher MAPK15 level is associated with lymph node metastasis in patients with LUAD.
Correction: Zhu et al. A Feedback Loop Formed by ATG7/Autophagy, FOXO3a/miR-145 and PD-L1 Regulates Stem-like Properties and Invasion in Human Bladder Cancer. Cancers 2019, 11, 349
Authors: Zhu Junlan , Li Yang , Luo Yisi , Xu Jiheng , Liufu Huating , Tian Zhongxian , Huang Chao , Li Jingxia , Huang Chuanshu
Published: February 2023

In the original article [...]
Adh Promotes Actinobacillus pleuropneumoniae Survival in Porcine Alveolar Macrophages by Inhibiting CHAC2-Mediated Respiratory Burst and Inflammatory Cytokine Expression
Authors: Zhu Junhui , Zhu Rining , Jiang Hexiang , Li Ziheng , Jiang Xuan , Li Fengyang , Zhang Fuxian , Feng Xin , Gu Jingmin , Li Na , Lei Liancheng
Published: February 2023

Actinobacillus pleuropneumoniae (A. pleuropneumoniae) causes porcine pleuropneumonia that seriously endangers pig’s health. Adh, located in the head region of trimeric autotransporter adhesion of A. pleuropneumoniae, affects bacterial adhesion and pathogenicity. However, how Adh mediates A. pleuropneumoniae immune invasion is still unclear. Here, we established the A. pleuropneumoniae strain L20 or L20 ΔAdh-infected porcine alveolar macrophages (PAM) model, and applied protein overexpression, RNA interference, qRT-PCR, Western blot and immunoflourescence techniques to dissect the effects of Adh on PAM during A. pleuropneumoniae infection. We found that Adh could increase the A. pleuropneumoniae adhesion and intracellular survival in PAM. Gene chip analysis of piglet lungs further showed that Adh significantly induced cation transport regulatory-like protein 2 (CHAC2) expression, whose overexpression suppressed the phagocytic capacity of PAM. Furthermore, CHAC2 overexpression dramatically increased glutathione (GSH) expression, decreased reactive oxygen species (ROS), and promoted A. pleuropneumoniae survival in PAM, while the knockdown of CHAC2 reversed these phenomena. Meanwhile, CHAC2 silence activated the NOD1/NF-κB pathway, resulting in an increase in IL-1β, IL-6, and TNF-α expression, whereas this effect was weakened by CHAC2 overexpression and addition of NOD1/NF-κB inhibitor ML130. Moreover, Adh enhanced the secretion of LPS of A. pleuropneumoniae, which regulated the expression of CHAC2 via TLR4. In conclusion, through a LPS-TLR4-CHAC2 pathway, Adh inhibits respiratory burst and inflammatory cytokines expression to promote A. pleuropneumoniae survival in PAM. This finding may provide a novel target for the prevention and treatment of A. pleuropneumoniae.
Oligonucleotide Enhancing Compound Increases Tricyclo-DNA Mediated Exon-Skipping Efficacy in the Mdx Mouse Model
Authors: Bizot Flavien , Fayssoil Abdallah , Gastaldi Cécile , Irawan Tabitha , Phongsavanh Xaysongkhame , Mansart Arnaud , Tensorer Thomas , Brisebard Elise , Garcia Luis , Juliano Rudolph L , Goyenvalle Aurélie
Published: February 2023

Nucleic acid-based therapeutics hold great promise for the treatment of numerous diseases, including neuromuscular disorders, such as Duchenne muscular dystrophy (DMD). Some antisense oligonucleotide (ASO) drugs have already been approved by the US FDA for DMD, but the potential of this therapy is still limited by several challenges, including the poor distribution of ASOs to target tissues, but also the entrapment of ASO in the endosomal compartment. Endosomal escape is a well recognized limitation that prevents ASO from reaching their target pre-mRNA in the nucleus. Small molecules named oligonucleotide-enhancing compounds (OEC) have been shown to release ASO from endosomal entrapment, thus increasing ASO nuclear concentration and ultimately correcting more pre-mRNA targets. In this study, we evaluated the impact of a therapy combining ASO and OEC on dystrophin restoration in mdx mice. Analysis of exon-skipping levels at different time points after the co-treatment revealed improved efficacy, particularly at early time points, reaching up to 4.4-fold increase at 72 h post treatment in the heart compared to treatment with ASO alone. Significantly higher levels of dystrophin restoration were detected two weeks after the end of the combined therapy, reaching up to 2.7-fold increase in the heart compared to mice treated with ASO alone. Moreover, we demonstrated a normalization of cardiac function in mdx mice after a 12-week-long treatment with the combined ASO + OEC therapy. Altogether, these findings indicate that compounds facilitating endosomal escape can significantly improve the therapeutic potential of exon-skipping approaches offering promising perspectives for the treatment of DMD.
IL-33 via PKCμ/PRKD1 Mediated α-Catenin Phosphorylation Regulates Endothelial Cell-Barrier Integrity and Ischemia-Induced Vascular Leakage
Authors: Sharma Deepti , Kaur Geetika , Bisen Shivantika , Sharma Anamika , Ibrahim Ahmed S. , Singh Nikhlesh K.
Published: February 2023

Angiogenesis, neovascularization, and vascular remodeling are highly dynamic processes, where endothelial cell–cell adhesion within the vessel wall controls a range of physiological processes, such as growth, integrity, and barrier function. The cadherin–catenin adhesion complex is a key contributor to inner blood–retinal barrier (iBRB) integrity and dynamic cell movements. However, the pre-eminent role of cadherins and their associated catenins in iBRB structure and function is not fully understood. Using a murine model of oxygen-induced retinopathy (OIR) and human retinal microvascular endothelial cells (HRMVECs), we try to understand the significance of IL-33 on retinal endothelial barrier disruption, leading to abnormal angiogenesis and enhanced vascular permeability. Using electric cell-substrate impedance sensing (ECIS) analysis and FITC-dextran permeability assay, we observed that IL-33 at a 20 ng/mL concentration induced endothelial-barrier disruption in HRMVECs. The adherens junction (AJs) proteins play a prominent role in the selective diffusion of molecules from the blood to the retina and in maintaining retinal homeostasis. Therefore, we looked for the involvement of adherens junction proteins in IL-33-mediated endothelial dysfunction. We observed that IL-33 induces α-catenin phosphorylation at serine/threonine (Ser/Thr) residues in HRMVECs. Furthermore, mass-spectroscopy (MS) analysis revealed that IL-33 induces the phosphorylation of α-catenin at Thr654 residue in HRMVECs. We also observed that PKCμ/PRKD1-p38 MAPK signaling regulates IL-33-induced α-catenin phosphorylation and retinal endothelial cell-barrier integrity. Our OIR studies revealed that genetic deletion of IL-33 resulted in reduced vascular leakage in the hypoxic retina. We also observed that the genetic deletion of IL-33 reduced OIR-induced PKCμ/PRKD1-p38 MAPK-α-catenin signaling in the hypoxic retina. Therefore, we conclude that IL-33-induced PKCμ/PRKD1-p38 MAPK-α-catenin signaling plays a significant role in endothelial permeability and iBRB integrity.
Tuning between Nuclear Organization and Functionality in Health and Disease
Authors: Manda Naresh Kumar , Golla Upendarrao , Sesham Kishore , Desai Parth , Joshi Shrushti , Patel Satyam , Nalla Sharada , Kondam Susmitha , Singh Lakhwinder , Dewansh Deepak , Manda Hemalatha , Rokana Namita
Published: February 2023

The organization of eukaryotic genome in the nucleus, a double-membraned organelle separated from the cytoplasm, is highly complex and dynamic. The functional architecture of the nucleus is confined by the layers of internal and cytoplasmic elements, including chromatin organization, nuclear envelope associated proteome and transport, nuclear–cytoskeletal contacts, and the mechano-regulatory signaling cascades. The size and morphology of the nucleus could impose a significant impact on nuclear mechanics, chromatin organization, gene expression, cell functionality and disease development. The maintenance of nuclear organization during genetic or physical perturbation is crucial for the viability and lifespan of the cell. Abnormal nuclear envelope morphologies, such as invagination and blebbing, have functional implications in several human disorders, including cancer, accelerated aging, thyroid disorders, and different types of neuro-muscular diseases. Despite the evident interplay between nuclear structure and nuclear function, our knowledge about the underlying molecular mechanisms for regulation of nuclear morphology and cell functionality during health and illness is rather poor. This review highlights the essential nuclear, cellular, and extracellular components that govern the organization of nuclei and functional consequences associated with nuclear morphometric aberrations. Finally, we discuss the recent developments with diagnostic and therapeutic implications targeting nuclear morphology in health and disease.
Hypotheses on Atherogenesis Triggering: Does the Infectious Nature of Atherosclerosis Development Have a Substruction?
Authors: Lusta Konstantin A. , Poznyak Anastasia V. , Sukhorukov Vasily N. , Eremin Ilya I. , Nadelyaeva Irina I. , Orekhov Alexander N.
Published: February 2023

Since the end of the 20th century, it has been clear that atherosclerosis is an inflammatory disease. However, the main triggering mechanism of the inflammatory process in the vascular walls is still unclear. To date, many different hypotheses have been put forward to explain the causes of atherogenesis, and all of them are supported by strong evidence. Among the main causes of atherosclerosis, which underlies these hypotheses, the following can be mentioned: lipoprotein modification, oxidative transformation, shear stress, endothelial dysfunction, free radicals’ action, homocysteinemia, diabetes mellitus, and decreased nitric oxide level. One of the latest hypotheses concerns the infectious nature of atherogenesis. The currently available data indicate that pathogen-associated molecular patterns from bacteria or viruses may be an etiological factor in atherosclerosis. This paper is devoted to the analysis of existing hypotheses for atherogenesis triggering, and special attention is paid to the contribution of bacterial and viral infections to the pathogenesis of atherosclerosis and cardiovascular disease.
Powders Synthesized from Solutions of Calcium Chloride, Sodium Hydrogen Phosphate, and Sodium Sulfate for Bioceramics Production
Authors: Safronova Tatiana V. , Khantimirov Alexander S. , Shatalova Tatiana B. , Filippov Yaroslav Y. , Kolesnik Irina V. , Knotko Alexander V.
Published: February 2023

Fine powders of brushite CaHPO4·2H2O, ardealite Ca(HPO4)x(SO4)1−x·2H2O (Ca(HPO4)0.5(SO4)0.5·2H2O), and calcium sulfate dihydrate CaSO4·2H2O—all containing sodium chloride NaCl as a reaction by-product—were synthesized from 0.5 M aqueous solution of calcium chloride CaCl2, sodium hydrophosphate Na2HPO4 and/or sodium sulfate Na2SO4. Powder of ardealite Ca(HPO4)x(SO4)1−x·2H2O (Ca(HPO4)0.5(SO4)0.5·2H2O) was synthesized by precipitation from aqueous solution of calcium chloride CaCl2 and mixed-anionic solution simultaneously containing the hydrogen phosphate anion HPO42− (Na2HPO4) and sulfate anion SO42− (Na2SO4). Sodium chloride NaCl, presenting in compacts based on synthesized powders of brushite CaHPO4·2H2O, ardealite Ca(HPO4)x(SO4)1−x·2H2O (Ca(HPO4)0.5(SO4)0.5·2H2O) and calcium sulfate dihydrate CaSO4·2H2O, was responsible for both low-temperature melt formation and the creation of phase composition of ceramics. Heterophase interaction of components led to the resulting phase composition of the ceramic samples during heating, including the formation of chlorapatite Ca5(PO4)3Cl in powders of brushite and ardealite. The phase composition of the ceramics based on the powder of brushite CaHPO4·2H2O containing NaCl as a by-product after firing at 800–1000 °C included β-Ca2P2O7, and Ca5(PO4)3Cl. The phase composition of ceramics based on the powder of ardealite Ca(HPO4)x(SO4)1−x·2H2O (Ca(HPO4)0.5(SO4)0.5·2H2O) containing NaCl as a by-product after firing at 800 and 900 °C included β-Ca2P2O7, CaSO4, and Ca5(PO4)3Cl; after firing at 1000 °C, it includedCaSO4, Ca5(PO4)3Cl and Ca3(PO4)2/Ca10Na(PO4)7, and after firing at 1100 °C, it included CaSO4 and Ca5(PO4)3Cl. The phase composition of ceramics based on powder of calcium sulfate dihydrate CaSO4·2H2O containing NaCl as a by-product after firing at 800–1100 °C included CaSO4 as the predominant phase. The phase composition of all ceramic samples under investigation consisted of biocompatible crystalline phases with different abilities to biodegrade. For this reason, the created ceramics can be recommended for testing as materials for treatment of bone defects using regenerative medicine methods.
Novel Phthalic-Based Anticancer Tyrosine Kinase Inhibitors: Design, Synthesis and Biological Activity
Authors: Kalinichenko Elena , Faryna Aliaksandr , Bozhok Tatyana , Golyakovich Anna , Panibrat Alesya
Published: February 2023

In this work, fragments of isophthalic and terephthalic acids are proposed as a structural scaffold to develop potential inhibitors of protein kinases. Novel isophthalic and terephthalic acid derivatives were designed as type-2 protein kinase inhibitors, synthesized and subjected to physicochemical characterization. The screening of their cytotoxic actions against a panel of cell lines derived from different types of tumors (liver, renal, breast and lung carcinomas, as well as chronic myelogenous and promyelocytic leukemia) and normal human B lymphocyte, for the sake of comparison, was performed. Compound 5 showed the highest inhibitory activity against four cancer cell lines, K562, HL-60, MCF-7 and HepG2 (IC50 = 3.42, 7.04, 4.91 and 8.84 µM, respectively). Isophthalic derivative 9 revealed a high potency against EGFR and HER2, at the levels of 90% and 64%, respectively, being comparable to lapatinib at 10 µM. In general, tumor cell cultures were more sensitive to isophthalic acid derivatives than to terephthalic acid ones. In cell cycle studies, isophthalic analogue 5 showed a pronounced dose-dependent effect, and with the increase in its concentration up to 10.0 µM, the number of living cells decreased to 38.66%, while necrosis reached 16.38%. The considered isophthalic compounds had a similar docking performance to that of sorafenib against the VEGFR-2 (PDB id: 4asd, 3wze). The correct binding of compounds 11 and 14 with VEGFR-2 was validated using MD simulations and MM-GPSA calculations.
Understanding Quality of Products from Customers’ Attitude Using Advanced Machine Learning Methods
Authors: Ullah Aman , Khan Khairullah , Khan Aurangzeb , Ullah Shoukat
Published: February 2023

The trend of E-commerce and online shopping is increasing rapidly. However, it is difficult to know about the quality of items from pictures and videos available on the online stores. Therefore, online stores and independent products reviews sites share user reviews about the products for the ease of buyers to find out the best quality products. The proposed work is about measuring and detecting product quality based on consumers’ attitude in product reviews. Predicting the quality of a product from customers’ reviews is a challenging and novel research area. Natural Language Processing and machine learning methods are popularly employed to identify product quality from customer reviews. Most of the existing research for the product review system has been done using traditional sentiment analysis and opinion mining. Going beyond the constraints of opinion and sentiment, such as a deeper description of the input text, is made possible by utilizing appraisal categories. The main focus of this study is exploiting the quality subcategory of the appraisal framework in order to predict the quality of the product. This paper presents a quality of product-based classification model (named QLeBERT) by combining quality of product-related lexicon, N-grams, Bidirectional Encoder Representations from Transformers (BERT), and Bidirectional Long Short Term Memory (BiLSTM). In the proposed model, the quality of the product-related lexicon, N-grams, and BERT are employed to generate vectors of words from part of the customers’ reviews. The main contribution of this work is the preparation of the quality of product-related lexicon dictionary based on an appraisal framework and automatically labelling the data accordingly before using them as the training data in the BiLSTM model. The proposed model is evaluated on an Amazon product reviews dataset. The proposed QLeBERT outperforms the existing state-of-the-art models by achieving an F1macro score of 0.91 in binary classification.
The Impact of Ammonium Fluoride on Structural, Absorbance Edge, and the Dielectric Properties of Polyvinyl Alcohol Films: Towards a Novel Analysis of the Optical Refractive Index, and CUT-OFF Laser Filters
Authors: Zyoud Samer H. , Jilani Wissal , Bouzidi Abdelfatteh , AlAbdulaal Thekrayat H. , Harraz Farid A. , Al-Assiri Mohammad S. , Yahia Ibrahim S. , Zahran Heba Y. , Ibrahim Medhat A. , Abdel-wahab Mohamed Sh.
Published: February 2023

The new proton-conducting composite electrolyte films (PCCEFs) consisting of polyvinyl alcohol (PVA) with varying ammonium fluoride salt concentrations were created using an expanded liquid casting process. The X-ray diffraction (XRD) study confirms the composite electrolyte films (CEFs) formation. The improvement in AMF02 salt doping compared to the PVA matrix film approach resulted in decreased variation in the crystalline size values, thus explaining how [NH4+] and polymer PVA matrix films interact. The band gaps decrease when the AMF02 salt filler concentration increases due to increased crystallite size. The suggested composites evaluated successful CUT-OFF laser filters and attenuation, as well as limiting laser power systems. For the 11.11 wt% AMF02 doping salt, the highest DC conductivity was 73.205 × 10−9 (siemens/m) at ambient temperature. Our dielectric results demonstrate that the CEFs are usually suitable for optoelectronic systems. There is a huge need to develop low dielectric permittivity composite electrolyte films (CEFs) for microelectronic devices and the high-frequency region.
Study on Texture Formation of Sb2Te Thin Films for Phase Change Memory Applications
Authors: Kang Lei , Chen Leng
Published: February 2023

We investigated the texture formation of Sb2Te thin films for phase change memory applications. The Sb2Te thin films with different thicknesses were deposited on Si (100) wafers by the magnetron sputtering method. As-deposited Sb2Te thin films were annealed at various temperatures and times. The texture characterization was performed by using X-ray diffraction (XRD) and electron backscatter diffraction (EBSD). Experimental results show that the annealed Sb2Te thin films exhibit the 112¯0 and 101¯0 prismatic texture. The formation of prismatic texture is induced by the lattice strain, surface energy, and coarse grains, in which the lattice strain is the essential origin of prismatic preference. Electronic transport properties of Sb2Te thin films were monitored by a physical property measurement system (PPMS). It was found that the formation of prismatic texture promotes the increase of carrier mobility. The stability of the film–substrate interface was also assessed by calculating mismatch. The prismatic-preferred Sb2Te thin films exhibit higher mismatch with a silicon wafer, reducing the interface stability.
Artificial Intelligence in Brain Tumor Imaging: A Step toward Personalized Medicine
Authors: Cè Maurizio , Irmici Giovanni , Foschini Chiara , Danesini Giulia Maria , Falsitta Lydia Viviana , Serio Maria Lina , Fontana Andrea , Martinenghi Carlo , Oliva Giancarlo , Cellina Michaela
Published: February 2023

The application of artificial intelligence (AI) is accelerating the paradigm shift towards patient-tailored brain tumor management, achieving optimal onco-functional balance for each individual. AI-based models can positively impact different stages of the diagnostic and therapeutic process. Although the histological investigation will remain difficult to replace, in the near future the radiomic approach will allow a complementary, repeatable and non-invasive characterization of the lesion, assisting oncologists and neurosurgeons in selecting the best therapeutic option and the correct molecular target in chemotherapy. AI-driven tools are already playing an important role in surgical planning, delimiting the extent of the lesion (segmentation) and its relationships with the brain structures, thus allowing precision brain surgery as radical as reasonably acceptable to preserve the quality of life. Finally, AI-assisted models allow the prediction of complications, recurrences and therapeutic response, suggesting the most appropriate follow-up. Looking to the future, AI-powered models promise to integrate biochemical and clinical data to stratify risk and direct patients to personalized screening protocols.
Investigating the Potential Utility of Environmental DNA to Provide a Relative Abundance Index for the Depleted Teleost, Mulloway, Argyrosomus japonicus
Authors: Rourke Meaghan L. , Broadhurst Matt K. , Fowler Ashley M. , Wilkes Walburn Jackson , Hughes Julian M. , Fielder Donald Stewart , DiBattista Joseph D. , Furlan Elise M.
Published: February 2023

Non-invasive, low-cost methods for censusing depleted fish populations are being prioritised among many jurisdictions worldwide. Collecting environmental DNA (eDNA) could offer one such option for augmenting fish population assessments. However, candidate species need to be carefully selected because species-specific DNA shedding and decay rates are affected by many biotic and abiotic factors that may influence relative abundance estimates. In this study, we sought to ascertain if the eDNA of a depleted Australian teleost, mulloway, Argyrosomus japonicus, reflects its weight under controlled aquaria conditions. With four experiments, we investigated the relationships between mulloway eDNA concentrations and their weight tank−1 as a function of: (1) time post-tank establishment; (2) water temperatures (within the species’ tolerance range); (3) stocking densities; and (4) among individual, similar-sized fish. The concentrations of eDNA in tanks stabilised after six days, and a positive relationship was found between fish weight and eDNA concentration, despite some variability in shedding rates by similar-sized fish. There was also a positive effect of water temperature on eDNA concentrations, which reinforces the need to control for such abiotic factors. We conclude that there is strong utility in applying eDNA concentrations as an index of relative abundance for mulloway under controlled conditions, which justifies future field-based investigations.