bluuebunny/crossref_metadata_2025 huggingface dataset:
Vibration Suppression for Flexible Plate with Tunable Magnetically Controlled Joint Stiffness/Damping
Authors: Hu Wei , Wu Jianming , Zhu Qinghua , Shen Jie , Zheng Xunjiang
Published: November 2022

Large flexible solar panels have the properties of light weight, low stiffness, and weak damping, which leads to low-frequency and large-amplitude vibrations. The existing vibration control methods of solar panels mainly adopt intelligent piezoelectric structures. However, the disadvantage is that the large stroke drive and control are limited. In the present study, a semi-active vibration control approach is proposed for flexible space solar panels based on magnetically controlled joints. The magnetic stiffness comes from the linear relationship between the joint output torque and rotation angle. The magnetic damping stems from the eddy current damping resulting from the relative motion between the permanent magnet rotor and the stator core of the joint. Firstly, the coupling dynamic modeling of a flexible plate and magnetic joints is established by adopting the Lagrange equation and the assumed mode approach. Secondly, semi-active vibration control simulations of the coupled system are performed. Meanwhile, the influence of the variable joint stiffness on the system frequency-shift effect is studied. Finally, the experimental platform is built, and simultaneously, non-contact permanent magnets and airflow are used to simulate single- and multi- frequency excitations, respectively. The experimental results indicate that, in the range of 0.06–0.343 Hz, magnetic damping is the leading factor with magnetic stiffness being the auxiliary. Additionally, it is also experimentally verified that the dual joint actuation has good synchronization. This study provides a new solution for the low-frequency vibration control of large flexible space structures.
Long-Term Deformations and Mechanical Properties of Fine Recycled Aggregate Earth Concrete
Authors: Fardoun Hassan , Saliba Jacqueline , Coureau Jean-Luc , Cointe Alain , Saiyouri Nadia
Published: November 2022

Earth-based materials are currently receiving high attention, as they are considered as sustainable. In addition, the reuse of waste materials and more particularly recycled aggregates can boost circular economy while reducing landfilling and mineral resource depletion. Incorporating recycled aggregates in earth concrete can be an innovative way to valorize them. However, investigations are required concerning their long-term behavior. Such an aspect is more important when fine recycled aggregates are considered. In this paper, the vulnerability to long term deformations of natural sand (NS) and recycled sand (RS) earth concrete mixtures is examined under real exposure conditions. Autogenous shrinkage, drying shrinkage, basic creep and drying creep of the different mixtures were monitored for a period of two months. Specimens were then subjected to compressive tests in order to evaluate their residual strength. Furthermore, the destructive tests were monitored in parallel with the acoustic emission (AE) technique. The results show an increase in the rate of drying creep and shrinkage for RS earth concrete mixtures. In addition, NS and RS earth concrete mixtures subjected to drying, with and without loading, reported a strength development in comparison to the reference mixtures. However, the Young’s modulus reported its lowest value for drying shrinkage of both mixtures. Regarding the AE technique, the distribution of its activity reflected the higher rate of damage of dried specimens in the pre-peak region.
Identity-Based and Leakage-Resilient Broadcast Encryption Scheme for Cloud Storage Service
Authors: Yu Qihong , Li Jiguo , Ji Sai
Published: November 2022

Cloud storage services are an important application of cloud computing. An increasing number of data owners store their data on cloud platforms. Since cloud platforms are far away from users, data security and privacy protection are very important issues that need to be addressed. Identity-based broadcast encryption (IBBE) is an important method to provide security and privacy protection for cloud storage services. Because the side channel attacks may lead to the disclosure of the key information of the cryptographic system, which will damage the security of the system, this paper provides an identity-based broadcast encryption with leakage resilience by state partition (LR-SP-IBBE). By using a binary extractor to compensate for the loss in entropy of the symmetric key caused by side-channel attacks, the proposed scheme randomizes the encapsulated symmetric key. Furthermore, using a state partition technique, we split the private key into two parts, and the corresponding decryption was divided into two stages. Through the double-system encryption skill, the security and leakage-resilience were proved in the composite order group model.
Time Series Recovery Using Adjacent Channel Data Based on LSTM: A Case Study of Subway Vibrations
Authors: Xin Tao , Yang Yi , Zheng Xiaoli , Lin Jing , Wang Sen , Wang Pengsong
Published: November 2022

Multi-sensor technology has been widely applied in the condition monitoring of rail transit. In practice, the data of some channels in the high channel counts are often abnormal or lost due to the abnormality and damage of the sensors, thus resulting in a large amount of data waste. A method for the data recovery of lost channels by using adjacent channel data is proposed to solve this problem. Based on the LSTM network algorithm, a data recovery model is established based on the “sequence-to-sequence” regression analysis of adjacent channel data. Taking the measured vibration data of a subway as an example, the network is trained with multi-channel measured data to recover the lost channel data of time-series characteristics. The results show that this multi-channel data recovery model is feasible, and the accuracy is up to 98%. This method can also further reduce the number of channels that need to be collected.
The Evaluation of Creditworthiness of Trade and Enterprises of Service Using the Method Based on Fuzzy Logic
Authors: Makhazhanova Ulzhan , Kerimkhulle Seyit , Mukhanova Ayagoz , Bayegizova Aigulim , Aitkozha Zhankeldi , Mukhiyadin Ainur , Tassuov Bolat , Saliyeva Ainur , Taberkhan Roman , Azieva Gulmira
Published: November 2022

This article considered the problem of determining the creditworthiness of an enterprise operating in the field of trade and services. The assessment of the creditworthiness of borrowers, particularly small businesses, needs to be more careful: the level of development of small enterprises and their specific activities must be considered, as well as the uncertainty in obtaining any financial result. A method for assessing the creditworthiness of enterprises (trade and services) is proposed, based on the use of the mathematical apparatus of the theory of fuzzy sets. This article analyzes the indicators of industry and regional specifics, indicators of the activity of a small enterprise, and financial and economic indicators typical for the service sector and trade. The rules on the basis of which decisions are made are formed in the form of logical formulas containing parameters. In its most general form, one parameter is predicted, called the creditworthiness index, which varies from 0 to 1 and has a natural interpretation. On the basis of the proposed method, examples of calculating the assessment of the creditworthiness of enterprises operating in the field of trade and services are given. The proposed scientific approach can be used as a basis for creating expert decision support systems for lending to small businesses.
Mandibular Second Molar Impaction-Part II: Etiology and Role of the Third Molar
Authors: Shapira Yehoshua , Lai Yon , Schonberger Shirley , Shpack Nir , Finkelstein Tamar
Published: November 2022

(1) Introduction: Mandibular second molar (MM2) impaction is a relatively rare dental anomaly, but its early detection is imperative for orthodontic diagnosis and treatment. This study evaluates early radiographic characteristics of MM2 in the process of its impaction and the role of the third molar (MM3) in this process. (2) Materials and Methods: Panoramic radiographs of orthodontic patients of Chinese-American origin (n = 5575), age 9–15 years (mean 13.13) were examined for MM2 impactions and the presence of MM3. (3) Results: A total of 151 patients with 212 impacted MM2s were detected in the Chinese-American study group. Unilateral impactions were found more than bilateral and were distributed equally between the left and right sides. Mesial angulation of the impacted teeth was present in 92.7% of the cases, and MM3s were found adjacent to the impacted MM2s in 97.4% of the cases. (4) Conclusions: MM2 differential root developments with deficient mesial root lengths appeared to be the primary cause for MM2 impaction. Posterior crowding and arch length deficiency were contributing factors causing MM2 impaction. This impaction occurred early, before the third molar bud was developed. It sometimes occurred even when the third molar was congenitally missing. Nevertheless, the possible involvement of the third molar in MM2 impaction needs further investigation.
RoadNet: Efficient Model to Detect and Classify Road Damages
Authors: Alqethami Sara , Alghamdi Shaimaa , Alsubait Tahani , Alhakami Hosam
Published: November 2022

Poorly maintained roads can cause lethal automobile accidents in various ways. Thus, detecting and reporting damaged parts of roads is one of the most crucial road maintenance tasks, and it is vital to identify the type and severity of the damage to help fix it as soon as possible. Several researchers have used computer vision and detection algorithms to detect and classify road damages, including cracking, distortion, and disintegration. Providing automatic road damage detection methods can help municipalities save time and effort and speed up maintenance operations. This study proposes a method to classify road damage and its severity based on CNN and trained on a newly curated dataset collected from Saudi roads. Hence, this study also presents a dataset with labeled classes, which are cracks, potholes, depressions, and shoving. The dataset was collected in collaboration with maintenance employees in the municipality of Rabigh Governorate using a smartphone device and reviewed by experts. In addition, several deep learning algorithms were implemented and evaluated using the proposed dataset. The study found that the proposed custom CNN (RoadNet) has higher accuracy than pre-trained models.
The Impact of Eggshell Thickness on the Qualitative Characteristics of Stored Eggs Produced by Three Breeds of Laying Hens of the Cage and Cage-Free Housed Systems
Authors: Kocetkovs Vjaceslavs , Radenkovs Vitalijs , Juhnevica-Radenkova Karina , Jakovlevs Dmitrijs , Muizniece-Brasava Sandra
Published: November 2022

The study aimed to compare the physical-chemical attributes of table eggs from three laying hen breeds housed in the cage and cage-free conditions and to characterize the morphological characteristics of the eggshell interior. A morphological and elemental analysis performed by scanning electron microscope coupled with energy dispersive X-ray spectroscopy revealed no abnormalities in the structural integrity of eggshells. The thickness of the eggshell varied in the range from 356.2 to 366.4 µm, with no statistically significant differences between the values. Eggshell membrane thickness was between 20.0 and 59.9 µm, with eggs derived from cage-housed hens, i.e., H/LS/CCE and H/HN/CCE having thinner membrane layers. The results revealed no direct relationships between eggshell and membrane thickness and physical-chemical parameters’ change. However, the presence of thick and long spider-like microcracks on the eggshell surface of eggs from cage-free housed hens H/D/BWE was the main factor that presumably contributed to substantial weight loss during 36 days of egg storage. A noticeable decline in eggshell-breaking strength along with the enlargement of air cells was observed in eggs produced under an enriched cage system H/LS/CCE after 28 days. In contrast, the minor changes in air cell size occurred in eggs from cage-free housed laying hens H/D/BWE. Protein quality indicators such as albumen height and Haugh units were well correlated with each other, and the intensity of their changes during egg storage, to a greater extent, was found to be storage time-dependent. No significant depletion of egg albumen was revealed during the first 15 days of egg storage. According to the United States Department of Agriculture, the quality corresponded to grade A (reasonably firm). However, after 18 days of storage, Haugh unit values were lower than 60, corresponding to grade B (weak and watery). The most apparent reduction in the Haugh unit was observed in eggs produced by enriched cage H/HN/CCE and cage-free H/D/BWE hens. The egg quality was storage time-dependent, and their deterioration rate was primarily associated with the genetic background of laying hens and housing conditions.
Globally Disseminated Multidrug Resistance Plasmids Revealed by Complete Assembly of Multidrug Resistant Escherichia coli and Klebsiella pneumoniae Genomes from Diarrheal Disease in Botswana
Authors: Rahube Teddie O. , Cameron Andrew D. S. , Lerminiaux Nicole A. , Bhat Supriya V. , Alexander Kathleen A.
Published: November 2022

Antimicrobial resistance is a disseminated global health challenge because many of the genes that cause resistance can transfer horizontally between bacteria. Despite the central role of extrachromosomal DNA elements called plasmids in driving the spread of resistance, the detection and surveillance of plasmids remains a significant barrier in molecular epidemiology. We assessed two DNA sequencing platforms alone and in combination for laboratory diagnostics in Botswana by annotating antibiotic resistance genes and plasmids in extensively drug resistant bacteria from diarrhea in Botswana. Long-read Nanopore DNA sequencing and high accuracy basecalling effectively estimated the architecture and gene content of three plasmids in Escherichia coli HUM3355 and two plasmids in Klebsiella pneumoniae HUM7199. Polishing the assemblies with Illumina reads increased base calling precision with small improvements to gene prediction. All five plasmids encoded one or more antibiotic resistance genes, usually within gene islands containing multiple antibiotic and metal resistance genes, and four plasmids encoded genes associated with conjugative transfer. Two plasmids were almost identical to antibiotic resistance plasmids sequenced in Europe and North America from human infection and a pig farm. These One Health connections demonstrate how low-, middle-, and high-income countries collectively benefit from increased whole genome sequencing capacity for surveillance and tracking of infectious diseases and antibiotic resistance genes that can transfer between animal hosts and move across continents.
Radiative Properties of Rb-Isoelectronic Technetium (Tc VII), Ruthenium (Ru VIII) and Rhodium (Rh IX) Ions for Astrophysical Applications
Authors: Jyoti  , Kaur Mandeep , Arora Bindiya
Published: November 2022

In this work, we present high-accuracy spectroscopic properties, such as line strengths, transition probabilities and oscillator strengths for allowed transitions among nD3/2,5/2,n′S1/2 and n′P1/2,3/2(n=4,n′=5,6) states of Rb-isoelectronic Tc (Tc VII), Ru (Ru VIII) and Rh (Rh IX) ions for their applications in the analysis of astrophysical phenomena occurring inside celestial bodies containing Tc, Ru and Rh ions. Due to the scarcity of computational data of atomic properties of these transitions, as well as considerable discrepancies within the literature about these ions, the precise determination of these properties is necessary. For this purpose, we have implemented relativistic many-body perturbation theory (RMBPT) for evaluation of the wave functions of the considered states. For better accuracy, we have accounted for electron interactions through random phase approximation, Brückner orbitals and structural radiations of wave functions in our RMBPT method for further precise evaluation of electric dipole amplitudes. Combining these values of the observed wavelengths, the above transition properties and radiative lifetimes, a number of excited states of Tc VII, Ru VIII and Rh IX ions have been calculated. For further validation of our work, we have compared our results with the data already available in the literature.
A Flashback on Control Logic Injection Attacks against Programmable Logic Controllers
Authors: Alsabbagh Wael , Langendörfer Peter
Published: November 2022

Programmable logic controllers (PLCs) make up a substantial part of critical infrastructures (CIs) and industrial control systems (ICSs). They are programmed with a control logic that defines how to drive and operate critical processes such as nuclear power plants, petrochemical factories, water treatment systems, and other facilities. Unfortunately, these devices are not fully secure and are prone to malicious threats, especially those exploiting vulnerabilities in the control logic of PLCs. Such threats are known as control logic injection attacks. They mainly aim at sabotaging physical processes controlled by exposed PLCs, causing catastrophic damage to target systems as shown by Stuxnet. Looking back over the last decade, many research endeavors exploring and discussing these threats have been published. In this article, we present a flashback on the recent works related to control logic injection attacks against PLCs. To this end, we provide the security research community with a new systematization based on the attacker techniques under three main attack scenarios. For each study presented in this work, we overview the attack strategies, tools, security goals, infected devices, and underlying vulnerabilities. Based on our analysis, we highlight the current security challenges in protecting PLCs from such severe attacks and suggest security recommendations for future research directions.
Enhancing Electrocardiogram Classification with Multiple Datasets and Distant Transfer Learning
Authors: Chui Kwok Tai , Gupta Brij B. , Zhao Mingbo , Malibari Areej , Arya Varsha , Alhalabi Wadee , Ruiz Miguel Torres
Published: November 2022

Electrocardiogram classification is crucial for various applications such as the medical diagnosis of cardiovascular diseases, the level of heart damage, and stress. One of the typical challenges of electrocardiogram classification problems is the small size of the datasets, which may lead to limitation in the performance of the classification models, particularly for models based on deep-learning algorithms. Transfer learning has demonstrated effectiveness in transferring knowledge from a source model with a similar domain and can enhance the performance of the target model. Nevertheless, the consideration of datasets with similar domains restricts the selection of source domains. In this paper, electrocardiogram classification was enhanced by distant transfer learning where a generative-adversarial-network-based auxiliary domain with a domain-feature-classifier negative-transfer-avoidance (GANAD-DFCNTA) algorithm was proposed to bridge the knowledge transfer from distant sources to target domains. To evaluate the performance of the proposed algorithm, eight benchmark datasets were chosen, with four from electrocardiogram datasets and four from the following distant domains: ImageNet, COCO, WordNet, and Sentiment140. The results showed an average accuracy improvement of 3.67 to 4.89%. The proposed algorithm was also compared with existing works using traditional transfer learning, revealing an average accuracy improvement of 0.303–5.19%. Ablation studies confirmed the effectiveness of the components of GANAD-DFCNTA.
A Rapid and Sensitive Aptamer-Based Biosensor for Amnesic Shellfish Toxin Domoic Acid
Authors: Zhao Luming , Guo Han , Chen Han , Zou Bin , Yang Chengfang , Zhang Xiaojuan , Gao Yun , Sun Mingjuan , Wang Lianghua
Published: November 2022

With the incidence of harmful algal blooms (HABs) increasing in recent years, the urgent demand for the detection of domoic acid (DA), an amnesic shellfish toxin mainly produced by red tide algae Pseudonitzschia, has aroused increasing attention. Aptamers, a new molecular recognition element, provide clarity in the monitoring of DA. In this study, aptamers of DA were successfully screened by Capture-SELEX. Through identification and truncation optimization, aptamer C1-d with a high affinity (KD value, 109 nM) and high specificity for DA was obtained. The binding mechanism between DA and the aptamer was explored by molecular docking and molecular dynamics (MD) simulation, revealing the critical sites for DA–aptamer interaction. Meanwhile, a BLI-based aptasensor was constructed by C1-d, which displayed a linear range from 0.625 to 10 μM and a LOD of 13.7 nM. This aptasensor exhibited high specificity, good precision and repeatability, and high recovery rates for real samples; the process of detection could be completed in 7 min. This study is the first to identify and investigate the binding mechanism of DA–aptamer interaction and constructed a BLI-based aptasensor for DA, which lays a theoretical foundation for the detection and prevention of DA.
Organ-On-A-Chip Database Revealed—Achieving the Human Avatar in Silicon
Authors: Jiang Lincao , Li Qiwei , Liang Weicheng , Du Xuan , Yang Yi , Zhang Zilin , Xu Lili , Zhang Jing , Li Jian , Chen Zaozao , Gu Zhongze
Published: November 2022

Organ-on-a-chip (OOC) provides microphysiological conditions on a microfluidic chip, which makes up for the shortcomings of traditional in vitro cellular culture models and animal models. It has broad application prospects in drug development and screening, toxicological mechanism research, and precision medicine. A large amount of data could be generated through its applications, including image data, measurement data from sensors, ~omics data, etc. A database with proper architecture is required to help scholars in this field design experiments, organize inputted data, perform analysis, and promote the future development of novel OOC systems. In this review, we overview existing OOC databases that have been developed, including the BioSystics Analytics Platform (BAP) developed by the University of Pittsburgh, which supports study design as well as data uploading, storage, visualization, analysis, etc., and the organ-on-a-chip database (Ocdb) developed by Southeast University, which has collected a large amount of literature and patents as well as relevant toxicological and pharmaceutical data and provides other major functions. We used examples to overview how the BAP database has contributed to the development and applications of OOC technology in the United States for the MPS consortium and how the Ocdb has supported researchers in the Chinese Organoid and Organs-On-A-Chip society. Lastly, the characteristics, advantages, and limitations of these two databases were discussed.
A Surrogate Model Based on a Finite Element Model of Abdomen for Real-Time Visualisation of Tissue Stress during Physical Examination Training
Authors: Leong Florence , Lai Chow Yin , Khosroshahi Siamak Farajzadeh , He Liang , de Lusignan Simon , Nanayakkara Thrishantha , Ghajari Mazdak
Published: November 2022

Robotic patients show great potential for helping to improve medical palpation training, as they can provide feedback that cannot be obtained in a real patient. They provide information about internal organ deformation that can significantly enhance palpation training by giving medical trainees visual insight based on the pressure they apply for palpation. This can be achieved by using computational models of abdomen mechanics. However, such models are computationally expensive, and thus unable to provide real-time predictions. In this work, we proposed an innovative surrogate model of abdomen mechanics by using machine learning (ML) and finite element (FE) modelling to virtually render internal tissue deformation in real time. We first developed a new high-fidelity FE model of the abdomen mechanics from computerized tomography (CT) images. We performed palpation simulations to produce a large database of stress distribution on the liver edge, an area of interest in most examinations. We then used artificial neural networks (ANNs) to develop the surrogate model and demonstrated its application in an experimental palpation platform. Our FE simulations took 1.5 h to predict stress distribution for each palpation while this only took a fraction of a second for the surrogate model. Our results show that our artificial neural network (ANN) surrogate has an accuracy of 92.6%. We also showed that the surrogate model is able to use the experimental input of palpation location and force to provide real-time projections onto the robotics platform. This enhanced robotics platform has the potential to be used as a training simulator for trainees to hone their palpation skills.
SRF Rearrangements in Soft Tissue Tumors with Muscle Differentiation
Authors: Costa Alice , Gozzellino Livia , Urbini Milena , Indio Valentina , Nannini Margherita , Pantaleo Maria Abbondanza , Stacchiotti Silvia , Astolfi Annalisa , Pasquinelli Gianandrea
Published: November 2022

The Serum Response Factor (SRF) is a transcription factor that regulates the expression of a wide set of genes involved in cell proliferation, migration, cytoskeletal organization and myogenesis. Accumulating evidence suggests that SRF may play a role in carcinogenesis and tumor progression in various neoplasms, where it is often involved in different fusion events. Here we investigated SRF rearrangements in soft tissue tumors, along with a gene expression profile analysis to gain insight into the oncogenic mechanism driven by SRF fusion. Whole transcriptome analysis of cell lines transiently overexpressing the SRF::E2F1 chimeric transcript uncovered the specific gene expression profile driven by the aberrant gene fusion, including overexpression of SRF-dependent target genes and of signatures related to myogenic commitment, inflammation and immune activation. This result was confirmed by the analysis of two cases of myoepitheliomas harboring SRF::E2F1 fusion with respect to EWSR1-fusion positive tumors. The recognition of the specific gene signature driven by SRF rearrangement in soft tissue tumors could aid the molecular classification of this rare tumor entity and support therapeutic decisions.
Changes in the Fecal Metabolome Accompany an Increase in Aberrant Crypt Foci in the Colon of C57BL/6 Mice Fed with a High-Fat Diet
Authors: Zeng Huawei , Safratowich Bryan D. , Cheng Wen-Hsing , Magnuson Andrew D. , Picklo Matthew J.
Published: November 2022

High-fat diet (HFD)-induced obesity is a risk factor for colon cancer. Our previous data show that compared to an AIN-93 diet (AIN), a HFD promotes azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) formation and microbial dysbiosis in C57BL/6 mice. To explore the underlying metabolic basis, we hypothesize that AOM treatment triggers a different fecal metabolomic profile in C57BL/6 mice fed the HFD or the AIN. We found that 65 of 196 identified metabolites were significantly different among the four groups of mice (AIN, AIN + AOM, HFD, and HFD + AOM). A sparse partial least squares discriminant analysis (sPLSDA) showed that concentrations of nine fecal lipid metabolites were increased in the HFD + AOM compared to the HFD, which played a key role in overall metabolome group separation. These nine fecal lipid metabolite concentrations were positively associated with the number of colonic ACF, the cell proliferation of Ki67 proteins, and the abundance of dysbiotic bacteria. These data suggest that the process of AOM-induced ACF formation may increase selective fecal lipid concentrations in mice fed with a HFD but not an AIN. Collectively, the accumulation of these critical fecal lipid species may alter the overall metabolome during tumorigenesis in the colon.
Paralytic Impact of Centrifugation on Human Neutrophils
Authors: Hundhammer Tobias , Gruber Michael , Wittmann Sigrid
Published: November 2022

Centrifugation is a common step in most of the popular protocols for the isolation of neutrophils from whole blood. Inconsistent results from previous studies on neutrophils may originate from an underestimation of the centrifugation effect, as in consequence impaired, not native cells, being investigated. We hypothesize, that centrifugation significantly impairs major neutrophil functions. However, there is no data yet whether the application of g-force itself or the product of g-force and duration of centrifugation (=“g-time”) defines the impact on neutrophils. Neutrophils were isolated from whole blood via centrifugation with different g-times and subsequently analyzed via live cell imaging for migration, as well as via flow cytometry for oxidative burst and surface antigen expression. Chemotactic migration was significantly reduced with increasing g-time. Oxidative burst decreased likewise the higher the g-time applied. Expression of CD11b was no longer upregulated in response to an n-formylmethionine-leucyl-phenylalanine (fMLP) stimulus in neutrophils having experienced high g-time during the isolation process. We conclude that centrifugation “paralyzes” neutrophils in the form of a significant decrease in functionality. Future investigations on neutrophil granulocytes should reduce the g-time load as far as possible.
PLGA/Gelatin/Hyaluronic Acid Fibrous Membrane Scaffold for Therapeutic Delivery of Adipose-Derived Stem Cells to Promote Wound Healing
Authors: Hsieh Chia-Fen , Chen Chih-Hao , Kao Hao-Hsi , Govindaraju Darshan Tagadur , Dash Banendu Sunder , Chen Jyh-Ping
Published: November 2022

Hyaluronic acid (HA) has been suggested to be a preferential material for the delivery of adipose-derived stem cells (ASCs) in wound healing. By incorporating HA in electrospun poly (lactide-co-glycolide) (PLGA)/gelatin (PG) fibrous membrane scaffolds (FMS), we aim to fabricate PLGA/gelatin/HA (PGH) FMS to provide a milieu for 3D culture and delivery of ASCs. The prepared FMS shows adequate cytocompatibility and is suitable for attachment and growth of ASCs. Compared with PG, the PGH offers an enhanced proliferation rate of ASCs, shows higher cell viability, and better maintains an ASC-like phenotype during in vitro cell culture. The ASCs in PGH also show upregulated expression of genes associated with angiogenesis and wound healing. From a rat full-thickness wound healing model, a wound treated with PGH/ASCs can accelerate the wound closure rate compared with wounds treated with PGH, alginate wound dressing, and gauze. From H&E and Masson’s trichrome staining, the PGH/ASC treatment can promote wound healing by increasing the epithelialization rate and forming well-organized dermis. This is supported by immunohistochemical staining of macrophages and α-smooth muscle actin, where early recruitment of macrophages, macrophage polarization, and angiogenesis was found due to the delivered ASCs. The content of type III collagen is also higher than type I collagen within the newly formed skin tissue, implying scarless wound healing. Taken together, using PGH FMS as a topical wound dressing material for the therapeutic delivery of ASCs, a wound treated with PGH/ASCs was shown to accelerate wound healing significantly in rats, through modulating immunoreaction, promoting angiogenesis, and reducing scar formation at the wound sites.
Effect of a Novel E3 Probiotics Formula on the Gut Microbiome in Atopic Dermatitis Patients: A Pilot Study
Authors: Wang Yiwei , Choy Chi Tung , Lin Yufeng , Wang Lin , Hou Jinpao , Tsui Joseph Chi Ching , Zhou Junwei , Wong Chi Ho , Yim Tai Ki , Tsui Wai Kai , Chan Un Kei , Siu Pui Ling Kella , Loo Steven King Fan , Tsui Stephen Kwok Wing
Published: November 2022

Atopic dermatitis (AD) has been shown to be closely related to gut dysbiosis mediated through the gut–skin axis, and thus the gut microbiome has recently been explored as a potential therapeutic target for the treatment of AD. Contrasting and varying efficacy have been reported since then. In order to investigate the determining factor of probiotics responsiveness in individuals with AD, we initiated the analysis of 41 AD patients with varying disease severity in Hong Kong, whereas the severity was assessed by Eczema Area and Severity Index (EASI) by board certified dermatologist. 16S rRNA sequencing on the fecal samples from AD patients were performed to obtain the metagenomics profile at baseline and after 8 weeks of oral administration of a novel E3 probiotics formula (including prebiotics, probiotics and postbiotics). While EASI of the participants were significantly lower after the probiotics treatment (p < 0.001, paired Wilcoxon signed rank), subjects with mild AD were found to be more likely to respond to the probiotics treatment. Species richness among responders regardless of disease severity were significantly increased (p < 0.001, paired Wilcoxon signed rank). Responders exhibited (1) elevated relative abundance of Clostridium, Fecalibacterium, Lactobacillus, Romboutsia, and Streptococcus, (2) reduced relative abundance of Collinsella, Bifidobacterium, Fusicatenibacter, and Escherichia-Shigella amid orally-intake probiotics identified using the machine learning algorithm and (3) gut microbiome composition and structure resembling healthy subjects after probiotics treatment. Here, we presented the gut microbiome dynamics in AD patients after the administration of the E3 probiotics formula and delineated the unique gut microbiome signatures in individuals with AD who were responding to the probiotics. These findings could guide the future development of probiotics use for AD management.
Macrophage-Targeted Sodium Chlorite (NP001) Slows Progression of Amyotrophic Lateral Sclerosis (ALS) through Regulation of Microbial Translocation
Authors: Zhang Rongzhen , Bracci Paige M. , Azhir Ari , Forrest Bruce D. , McGrath Michael S.
Published: November 2022

Amyotrophic lateral sclerosis (ALS) is a heterogeneous, progressive, and universally fatal neurodegenerative disease. A subset of ALS patients has measurable plasma levels of lipopolysaccharide (LPS) and C-reactive protein (CRP) consistent with low-grade microbial translocation (MT). Unless interrupted, MT sets up a self-perpetuating loop of inflammation associated with systemic macrophage activation. To test whether MT contributed to ALS progression, blood specimens from a phase 2 study of NP001 in ALS patients were evaluated for changes in activity in treated patients as compared to controls over the 6-month study. In this post hoc analysis, plasma specimens from baseline and six-month timepoints were analyzed. Compared with baseline values, biomarkers related to MT were significantly decreased (LPS, LPS binding protein (LBP), IL-18, Hepatocyte growth factor (HGF), soluble CD163 (sCD163)) in NP001-treated patients as compared to controls, whereas wound healing and immunoregulatory factors were increased (IL-10, Epidermal growth factor (EGF), neopterin) by the end of study. These biomarker results linked to the positive clinical trial outcome confirm that regulation of macrophage activation may be an effective approach for the treatment of ALS and, potentially, other neuroinflammatory diseases related to MT.
Characterization of microRNA Levels in Synovial Fluid from Knee Osteoarthritis and Anterior Cruciate Ligament Tears
Authors: Rizzi Laura , Turati Marco , Bresciani Elena , Anghilieri Filippo Maria , Meanti Ramona , Molteni Laura , Piatti Massimiliano , Zanchi Nicolò , Coco Silvia , Buonanotte Francesco , Rigamonti Luca , Zatti Giovanni , Locatelli Vittorio , Omeljaniuk Robert J. , Bigoni Marco , Torsello Antonio
Published: November 2022

This study investigated modifications of microRNA expression profiles in knee synovial fluid of patients with osteoarthritis (OA) and rupture of the anterior cruciate ligament (ACL). Twelve microRNAs (26a-5p, 27a-3p, let7a-5p, 140-5p, 146-5p, 155-5p, 16-5p,186-5p, 199a-3p, 210-3p, 205-5p, and 30b-5p) were measured by real-time quantitative polymerase chain reaction (RT-qPCR) in synovial fluids obtained from 30 patients with ACL tear and 18 patients with knee OA. These 12 miRNAs were chosen on the basis of their involvement in pathological processes of bone and cartilage. Our results show that miR-26a-5p, miR-186-5p, and miR-30b-5p were expressed in the majority of OA and ACL tear samples, whereas miR-199a-3p, miR-210-3p, and miR-205-5p were detectable only in a few samples. Interestingly, miR-140-5p was expressed in only one sample of thirty in the ACL tear group. miR-140-5p has been proposed to modulate two genes (BGN and COL5A1100) that are involved in ligamentous homeostasis; their altered expression could be linked with ACL rupture susceptibility. The expression of miR-30b-5p was higher in OA and chronic ACL groups compared to acute ACL samples. We provide evidence that specific miRNAs could be detected not only in synovial fluid of patients with OA, but also in post-traumatic ACL tears.
Neutrophils Play an Important Role in the Recurrence of Chronic Rhinosinusitis with Nasal Polyps
Authors: Yu Hyunjae , Kim Dong-Kyu
Published: November 2022

Despite the heterogeneity of chronic rhinosinusitis (CRS), a clear link exists between type 2 immunity and the severity of CRS with nasal polyps (CRSwNP). However, recent studies have demonstrated that patients with severe type 2 CRSwNP also display abundant neutrophilic inflammation. Therefore, we investigated the factors associated with the recurrence of CRSwNP following sinus surgery using a machine-learning algorithm. We collected the demographics, clinical variables, and inflammatory profiles of 210 patients with CRSwNP who underwent sinus surgery. After one year, we evaluated whether each patient showed recurrence. Machine-learning methods, such as decision trees, random forests, and support vector machine models, have been used to predict the recurrence of CRSwNP. The results indicated that neutrophil inflammation, such as tissue and serum neutrophils, is an important factor affecting the recurrence of surgical CRSwNP. Specifically, the random forest model showed the highest accuracy in detecting recurrence among the three machine-learning methods, which revealed tissue neutrophilia to be the most important variable in determining surgical outcomes. Therefore, our machine-learning approach suggests that neutrophilic inflammation is increased in patients with difficult-to-treat CRSwNP, and the increased presence of neutrophils in subepithelial regions is closely related to poor surgical outcomes in patients with CRSwNP.
Current and Future Perspectives for Chimeric Antigen Receptor T Cells Development in Poland
Authors: Ślebioda Tomasz , Stanisławowski Marcin , Kaszubowska Lucyna , Zaucha Jan , Żmijewski Michał
Published: November 2022

Chimeric antigen receptor T (CAR-T) cells are genetically modified autologous T cells that have revolutionized the treatment of relapsing and refractory haematological malignancies. In this review we present molecular pathways involved in the activation of CAR-T cells, describe in details the structures of receptors and the biological activity of CAR-T cells currently approved for clinical practice in the European Union, and explain the functional differences between them. Finally, we present the potential for the development of CAR-T cells in Poland, as well as indicate the possible directions of future research in this area, including novel modifications and applications of CAR-T cells and CAR-natural killer (NK) cells.
Necroptosis Blockade Potentiates the Neuroprotective Effect of Hypothermia in Neonatal Hypoxic-Ischemic Encephalopathy
Authors: Chevin Mathilde , Chabrier Stéphane , Allard Marie-Julie , Sébire Guillaume
Published: November 2022

Neonatal encephalopathy (NE) caused by hypoxia-ischemia (HI) affects around 1 per 1000 term newborns and is the leading cause of acquired brain injury and neurodisability. Despite the use of hypothermia (HT) as a standard of care, the incidence of NE and its devastating outcomes remains a major issue. Ongoing research surrounding add-on neuroprotective strategies against NE is important as HT effects are limited, leaving 50% of treated patients with neurological sequelae. Little is known about the interaction between necroptotic blockade and HT in neonatal HI. Using a preclinical Lewis rat model of term human NE induced by HI, we showed a neuroprotective effect of Necrostatin-1 (Nec-1: a compound blocking necroptosis) in combination with HT. The beneficial effect of Nec-1 added to HT against NE injuries was observed at the mechanistic level on both pMLKL and TNF-α, and at the anatomical level on brain volume loss visualized by magnetic resonance imaging (MRI). HT alone showed no effect on activated necroptotic effectors and did not preserve the brain MRI volume. This study opens new avenues of research to understand better the specific cell death mechanisms of brain injuries as well as the potential use of new therapeutics targeting the necroptosis pathway.
Application of Two-Dimensional Entropy Measures to Detect the Radiographic Signs of Tooth Resorption and Hypercementosis in an Equine Model
Authors: Górski Kamil , Borowska Marta , Stefanik Elżbieta , Polkowska Izabela , Turek Bernard , Bereznowski Andrzej , Domino Małgorzata
Published: November 2022

Dental disorders are a serious health problem in equine medicine, their early recognition benefits the long-term general health of the horse. Most of the initial signs of Equine Odontoclastic Tooth Resorption and Hypercementosis (EOTRH) syndrome concern the alveolar aspect of the teeth, thus, the need for early recognition radiographic imaging. This study is aimed to evaluate the applicability of entropy measures to quantify the radiological signs of tooth resorption and hypercementosis as well as to enhance radiographic image quality in order to facilitate the identification of the signs of EOTRH syndrome. A detailed examination of the oral cavity was performed in eighty horses. Each evaluated incisor tooth was assigned to one of four grade–related EOTRH groups (0–3). Radiographs of the incisor teeth were taken and digitally processed. For each radiograph, two–dimensional sample (SampEn2D), fuzzy (FuzzEn2D), permutation (PermEn2D), dispersion (DispEn2D), and distribution (DistEn2D) entropies were measured after image filtering was performed using Normalize, Median, and LaplacianSharpening filters. Moreover, the similarities between entropy measures and selected Gray–Level Co–occurrence Matrix (GLCM) texture features were investigated. Among the 15 returned measures, DistEn2D was EOTRH grade–related. Moreover, DistEn2D extracted after Normalize filtering was the most informative. The EOTRH grade–related similarity between DistEn2D and Difference Entropy (GLCM) confirms the higher irregularity and complexity of incisor teeth radiographs in advanced EOTRH syndrome, demonstrating the greatest sensitivity (0.50) and specificity (0.95) of EOTRH 3 group detection. An application of DistEn2D to Normalize filtered incisor teeth radiographs enables the identification of the radiological signs of advanced EOTRH with higher accuracy than the previously used entropy–related GLCM texture features.
Blinatumomab Prior to CAR-T Cell Therapy—A Treatment Option Worth Consideration for High Disease Burden
Authors: Marschollek Paweł , Liszka Karolina , Mielcarek-Siedziuk Monika , Rybka Blanka , Ryczan-Krawczyk Renata , Panasiuk Anna , Olejnik Igor , Frączkiewicz Jowita , Dachowska-Kałwak Iwona , Mizia-Malarz Agnieszka , Szczepański Tomasz , Młynarski Wojciech , Styczyński Jan , Drabko Katarzyna , Karolczyk Grażyna , Gorczyńska Ewa , Maciej Zaucha Jan , Kałwak Krzysztof
Published: November 2022

The optimal bridging therapy before CAR-T cell infusion in pediatric relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r BCP-ALL) still remains an open question. The administration of blinatumomab prior to CAR-T therapy is controversial since a potential loss of CD19+ target cells may negatively impact the activation, persistence, and, as a consequence, the efficacy of subsequently used CAR-T cells. Here, we report a single-center experience in seven children with chemorefractory BCP-ALL treated with blinatumomab before CAR-T cell therapy either to reduce disease burden before apheresis (six patients) or as a bridging therapy (two patients). All patients responded to blinatumomab except one. At the time of CAR-T cell infusion, all patients were in cytological complete remission (CR). Four patients had low positive PCR-MRD, and the remaining three were MRD-negative. All patients remained in CR at day +28 after CAR-T infusion, and six out of seven patients were MRD-negative. With a median follow-up of 497 days, four patients remain in CR and MRD-negative. Three children relapsed with CD19 negative disease: two of them died, and one, who previously did not respond to blinatumomab, was successfully rescued by stem cell transplant. To conclude, blinatumomab can effectively lower disease burden with fewer side effects than standard chemotherapeutics. Therefore, it may be a valid option for patients with high-disease burden prior to CAR-T cell therapy without clear evidence of compromising efficacy; however, further investigations are necessary.
Altered Immunomodulatory Responses in the CX3CL1/CX3CR1 Axis Mediated by hMSCs in an Early In Vitro SOD1G93A Model of ALS
Authors: Sarikidi Anastasia , Kefalakes Ekaterini , Falk Christine S. , Esser Ruth , Ganser Arnold , Thau-Habermann Nadine , Petri Susanne
Published: November 2022

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron (MN) disease characterized by progressive MN loss and muscular atrophy resulting in rapidly progressive paralysis and respiratory failure. Human mesenchymal stem/stromal cell (hMSC)-based therapy has been suggested to prolong MN survival via secretion of growth factors and modulation of cytokines/chemokines. We investigated the effects of hMSCs and a hMSC-conditioned medium (CM) on Cu/Zn superoxidase dismutase 1G93A (SOD1G93A) transgenic primary MNs. We found that co-culture of hMSCs and MNs resulted in slightly higher MN numbers, but did not protect against staurosporine (STS)-induced toxicity, implying marginal direct trophic effects of hMSCs. Aiming to elucidate the crosstalk between hMSCs and MNs in vitro, we found high levels of vascular endothelial growth factor (VEGF) and C-X3-C motif chemokine 1 (CX3CL1) in the hMSC secretome. Co-culture of hMSCs and MNs resulted in altered gene expression of growth factors and cytokines/chemokines in both MNs and hMSCs. hMSCs showed upregulation of CX3CL1 and its receptor CX3CR1 and downregulation of interleukin-1 β (IL1β) and interleukin-8 (IL8) when co-cultured with SOD1G93A MNs. MNs, on the other hand, showed upregulation of growth factors as well as CX3CR1 upon hMSC co-culture. Our results indicate that hMSCs only provide moderate trophic support to MNs by growth factor gene regulation and may mediate anti-inflammatory responses through the CX3CL1/CX3CR1 axis, but also increase expression of pro-inflammatory cytokines, which limits their therapeutic potential.