bluuebunny/crossref_metadata_2025 huggingface dataset:
Candidate Set Expansion for Entity and Relation Linking Based on Mutual Entity–Relation Interaction
Authors: Zhang Botao , Feng Yong , Fu Lin , Gu Jinguang , Xu Fangfang
Published: March 2023

Entity and relation linking are the core tasks in knowledge base question answering (KBQA). They connect natural language questions with triples in the knowledge base. In most studies, researchers perform these two tasks independently, which ignores the interplay between the entity and relation linking. To address the above problems, some researchers have proposed a framework for joint entity and relation linking based on feature joint and multi-attention. In this paper, based on their method, we offer a candidate set generation expansion model to improve the coverage of correct candidate words and to ensure that the correct disambiguation objects exist in the candidate list as much as possible. Our framework first uses the initial relation candidate set to obtain the entity nodes in the knowledge graph related to this relation. Second, the filtering rule filters out the less-relevant entity candidates to obtain the expanded entity candidate set. Third, the relation nodes directly connected to the nodes in the expanded entity candidate set are added to the initial relation candidate set. Finally, a ranking algorithm filters out the less-relevant relation candidates to obtain the expanded relation candidate set. An empirical study shows that this model improves the recall and correctness of the entity and relation linking for KBQA. The candidate set expansion method based on entity–relation interaction proposed in this paper is highly portable and scalable. The method in this paper considers the connections between question subgraphs in knowledge graphs and provides new ideas for the candidate set expansion.
Electroencephalography-Based Brain–Machine Interfaces in Older Adults: A Literature Review
Authors: Mesin Luca , Cipriani Giuseppina Elena , Amanzio Martina
Published: March 2023

The aging process is a multifaceted phenomenon that affects cognitive-affective and physical functioning as well as interactions with the environment. Although subjective cognitive decline may be part of normal aging, negative changes objectified as cognitive impairment are present in neurocognitive disorders and functional abilities are most impaired in patients with dementia. Electroencephalography-based brain–machine interfaces (BMI) are being used to assist older people in their daily activities and to improve their quality of life with neuro-rehabilitative applications. This paper provides an overview of BMI used to assist older adults. Both technical issues (detection of signals, extraction of features, classification) and application-related aspects with respect to the users’ needs are considered.
Sodium Hexametaphosphate Serves as an Inducer of Calcium Signaling
Authors: Katano Daiki , Kang Woojin , Harada Yuichirou , Kawano Natsuko , Miyado Mami , Saito Takako , Fukuoka Mio , Yamada Mitsutoshi , Miyado Kenji
Published: March 2023

In bacteria, polymers of inorganic phosphates, particularly linear polyphosphate, are used as alternative phosphate donors for adenosine triphosphate production. A six-chain form of sodium metaphosphate, sodium hexametaphosphate (SHMP), is believed to have no physiological functions in mammalian cells. In this study, we explored the possible effects of SHMP on mammalian cells, using mouse oocytes, which are useful for observing various spatiotemporal intracellular changes. Fertilization-competent oocytes were isolated from the oviducts of superovulated mice and cultured in an SHMP-containing medium. In the absence of co-incubation with sperm, SHMP-treated oocytes frequently formed pronuclei and developed into two-cell embryos owing to the increase in calcium concentration in the cytoplasm. We discovered an intriguing role for SHMP as an initiator of calcium rise in mouse oocytes, presumably in a wide variety of mammalian cells.
Regulation of Epithelial Sodium Transport by SARS-CoV-2 Is Closely Related with Fibrinolytic System-Associated Proteins
Authors: Wang Tingyu , Zhai Yiman , Xue Hao , Zhou Wei , Ding Yan , Nie Hongguang
Published: March 2023

Dyspnea and progressive hypoxemia are the main clinical features of patients with coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pulmonary pathology shows diffuse alveolar damage with edema, hemorrhage, and the deposition of fibrinogens in the alveolar space, which are consistent with the Berlin Acute Respiratory Distress Syndrome Criteria. The epithelial sodium channel (ENaC) is a key channel protein in alveolar ion transport and the rate-limiting step for pulmonary edema fluid clearance, the dysregulation of which is associated with acute lung injury/acute respiratory distress syndrome. The main protein of the fibrinolysis system, plasmin, can bind to the furin site of γ-ENaC and induce it to an activation state, facilitating pulmonary fluid reabsorption. Intriguingly, the unique feature of SARS-CoV-2 from other β-coronaviruses is that the spike protein of the former has the same furin site (RRAR) with ENaC, suggesting that a potential competition exists between SARS-CoV-2 and ENaC for the cleavage by plasmin. Extensive pulmonary microthrombosis caused by disorders of the coagulation and fibrinolysis system has also been seen in COVID-19 patients. To some extent, high plasmin (ogen) is a common risk factor for SARS-CoV-2 infection since an increased cleavage by plasmin accelerates virus invasion. This review elaborates on the closely related relationship between SARS-CoV-2 and ENaC for fibrinolysis system-related proteins, aiming to clarify the regulation of ENaC under SARS-CoV-2 infection and provide a novel reference for the treatment of COVID-19 from the view of sodium transport regulation in the lung epithelium.
Bacillary Layer Detachment in Neovascular Age-Related Macular Degeneration: Case Series
Authors: Palmieri Filomena , Younis Saad , Raslan Walid , Fabozzi Lorenzo
Published: March 2023

Purpose: This study seeks to report the clinical and multimodal imaging findings of eight eyes of seven patients with neovascular age-related macular degeneration (nAMD) who developed bacillary layer detachment (BALAD). Setting/Venue: The patients were analysed at the Western Eye Hospital in London, UK. Methods: The approaches of this research include clinical examinations and multimodal imaging-based description of cases of nAMD with BALAD. Results: We report multimodal imaging findings of bacillary layer detachment (BALAD) in patients with nAMD. Conclusions: A bacillary layer detachment was detected in patients with neovascular age-related macular degeneration. This multimodal imaging finding is not commonly described in the literature for this disease.
Exploration and Clinical Verification of the Blood Co-Expression Genes of Type 2 Diabetes Mellitus and Mild Cognitive Dysfunction in the Elderly
Authors: Zhang Yu , Deng Shengfeng , Zhong Hongfei , Liu Miao , Ding Jingwen , Geng Rulin , Tu Qiuyun
Published: March 2023

With the development of society, the incidence of dementia and type 2 diabetes (T2DM) in the elderly has been increasing. Although the correlation between T2DM and mild cognitive impairment (MCI) has been confirmed in the previous literature, the interaction mechanism remains to be clarified. To explore the co-pathogenic genes in the blood of MCI and T2DM patients, clarify the correlation between T2DM and MCI, achieve the purpose of early disease prediction, and provide new ideas for the prevention and treatment of dementia. We downloaded T2DM and MCI microarray data from GEO databases and identified the differentially expressed genes associated with MCI and T2DM. We obtained co-expressed genes by intersecting differentially expressed genes. Then, we performed GO and KEGG enrichment analysis of co-DEGs. Next, we constructed the PPI network and found the hub genes in the network. By constructing the ROC curve of hub genes, the most valuable genes for diagnosis were obtained. Finally, the correlation between MCI and T2DM was clinically verified by means of a current situation investigation, and the hub gene was verified by qRT-PCR. A total of 214 co-DEGs were selected, 28 co-DEGs were up-regulated, and 90 co-DEGs were down-regulated. Functional enrichment analysis showed that co-DEGs were mainly enriched in metabolic diseases and some signaling pathways. The construction of the PPI network identified the hub genes in MCI and T2DM co-expression genes. We identified nine hub genes of co-DEGs, namely LNX2, BIRC6, ANKRD46, IRS1, TGFB1, APOA1, PSEN1, NPY, and ALDH2. Logistic regression analysis and person correlation analysis showed that T2DM was correlated with MCI, and T2DM increased the risk of cognitive impairment. The qRT-PCR results showed that the expressions of LNX2, BIRC6, ANKRD46, TGFB1, PSEN1, and ALDH2 were consistent with the results of bioinformatic analysis. This study screened the co-expressed genes of MCI and T2DM, which may provide new therapeutic targets for the diagnosis and treatment of diseases.
Modeling and Analysis of a Reconfigurable Rover for Improved Traversing over Soft Sloped Terrains
Authors: Lyu Shipeng , Zhang Wenyao , Yao Chen , Zhu Zheng , Jia Zhenzhong
Published: March 2023

Adjusting the roll angle of a rover’s body is a commonly used strategy to improve its traversability over sloped terrains. However, its range of adjustment is often limited, due to constraints imposed by the rover design and geometry factors such as suspension, chassis, size, and suspension travel. In order to improve the rover’s traversability under these constraints, this paper proposes a reconfigurable rover design with a two-level (sliding and rolling) mechanism to adjust the body’s roll angle. Specifically, the rolling mechanism is a bionic structure, akin to the human ankle joint which can change the contact pose between the wheel and the terrain. This novel adjustment mechanism can modulate the wheel–terrain contact pose, center-of-mass projection over the supporting polygon, wheel load, and the rover driving mode. Combining the wheel–load model and terramechanics-based wheel–terrain interaction model, we develop an integrated model to describe the system dynamics, especially the relationship between rover pose and wheel slippage parameters. Using this model, we develop an associated attitude control strategy to calculate the desired rover pose using particle swarm algorithm while considering the slip rate and angle constraints. We then adjust the sliding and rolling servo angles accordingly for slope traversing operations. To evaluate the proposed design and control strategies, we conduct extensive simulation and experimental studies. The results indicate that our proposed rover design and associated control strategy can double the maximum slope angles that the rover can negotiate, resulting in significantly improved traversability over soft sloped terrains.
A Short Review on Miniaturized Biosensors for the Detection of Nucleic Acid Biomarkers
Authors: Kulkarni Madhusudan B. , Ayachit Narasimha H. , Aminabhavi Tejraj M.
Published: March 2023

Even today, most biomarker testing is executed in centralized, dedicated laboratories using bulky instruments, automated analyzers, and increased analysis time and expenses. The development of miniaturized, faster, low-cost microdevices is immensely anticipated for substituting for these conventional laboratory-oriented assays and transferring diagnostic results directly onto the patient’s smartphone using a cloud server. Pioneering biosensor-based approaches might make it possible to test biomarkers with reliability in a decentralized setting, but there are still a number of issues and restrictions that must be resolved before the development and use of several biosensors for the proper understanding of the measured biomarkers of numerous bioanalytes such as DNA, RNA, urine, and blood. One of the most promising processes to address some of the issues relating to the growing demand for susceptible, quick, and affordable analysis techniques in medical diagnostics is the creation of biosensors. This article critically discusses a short review of biosensors used for detecting nucleic acid biomarkers, and their use in biomedical prognostics will be addressed while considering several essential characteristics.
The Relationship between Happiness and Mental Health among Saudi Women
Authors: Almadani Noura Abdulla , Alwesmi Mai B.
Published: March 2023

The happiness and mental health of individuals are crucial for national developments. In Saudi Arabia, wellbeing occupies a central position in Vision 2030, along with women’s empowerment. Rapidly changing rights and responsibilities might result in more sources of stress. The aim of this study was to explore happiness and mental health among Saudi women during their contributions to a fast-growing nation in all fields. We assessed happiness and mental health (somatic symptoms, depression, anxiety, insomnia, and social dysfunction) in 308 Saudi women aged 15–50 years using a self-administered online survey comprising the short Oxford Happiness Questionnaire (OHQ-8) and the General Health Questionnaire (GHQ-28). The participants demonstrated general satisfaction yet showed rising psychological distress. Married women reported better mental health compared to single women, particularly with regards to anxiety, insomnia, and depression. Depression was highest among younger women. Employed women demonstrated lower social functioning compared to unemployed women. Women with a higher educational level showed lower social functioning. Happiness scores were significantly and inversely related with overall mental health scores as well as mental health subscales (somatic, anxiety, and depression), except for social dysfunction, which showed a positive correlation to happiness scores. This study contributes to the body of literature on women’s mental health and happiness by providing recommendations for improving both as well as directions for future research.
Structural Assessment and Strengthening of a Historic Masonry Orthodox Church
Authors: Spiridon Ionuț Alexandru , Ungureanu Dragoș , Țăranu Nicolae , Onuțu Cătălin , Isopescu Dorina Nicolina , Șerbănoiu Adrian Alexandru
Published: March 2023

This study provides insight into the structural assessment, diagnosis, and strengthening of the medieval church of Tazlău Monastery in Piatra Neamț, Romania. The first part of the paper briefly presents the wider context of strengthening and preserving heritage churches and monastic buildings and describes the architectural setting and the structural features of the traditional Romanian Orthodox churches. The second part of the paper is a case study related to the rehabilitation of a medieval heritage church, which is the paramount building of a larger monastic complex. Erected in 1496, the church of the Nativity of the Blessed Virgin Mary closely follows the medieval traditional Orthodox patterns from both architectural and structural points of view. Structural assessment and diagnosis revealed that degradations were induced and developed throughout the life of the structure due to approximately 24 earthquakes (estimated at over 6.0 magnitude) having endangered the structural safety of the building and the mural iconography. After the structural diagnosis, a combined and complex method of strengthening consisting of both grouting and introducing steel rods in vertically drilled galleries along the entire height of the walls was selected. The main advantage of applying this combined strengthening strategy was a remarkable enhancement of the structural seismic performance of the church building.
The Mediators of the Relationship between Digitalisation and Construction Productivity: A Systematic Literature Review
Authors: Zulu Sambo Lyson , Saad Ali M. , Omotayo Temitope
Published: March 2023

The construction industry has long been perceived as reluctant to embrace change, and digital transformation is not an exception. The slow adoption rate has been linked to the perceptions of the effectiveness of construction innovations. An implied link exists between digitalisation and productivity improvements. However, such a link is yet associated with ambiguities, suggesting that the influence is not linear. Despite the very low productivity rates achieved in the construction industry, studies on the association between technology adoption and productivity-related benefits and advantages are rare, and this may be a contributing factor to the indecision of construction firms to embrace digitalisation. A systematic literature review enables scholars to disseminate past research efforts in one scholarly resource, in pursuit of new knowledge. Through systematically reviewing the literature, this study identifies, classifies, and critically analyses research efforts, aiming to shed light on the mediators of the relationship between digitalisation and productivity. Overall, sixty articles have been identified, screened, and included in this study. Productivity, in this context, is positively related to digitalization, by promoting more safety and well-being, planning enhancements, collaboration, waste reduction, employee upskilling, design enhancements, communication and knowledge transfer, and accuracy in information management. The findings also reflect the popular use of qualitative methods when studying digitalisation in the construction context, a stance that may be a reflection of a less diverse use of methodological approaches, and presents a call for more quantitative studies, to explore the relationship between digitalisation and productivity. Future research is encouraged to use this extensive review as a foundation for comparable empirical investigations, considering areas of similar interest, to accelerate the adoption of digitalisation.
Study on the Air Inlet Velocity and Temperature Distribution in an Inclined Tunnel with Single Shaft under Natural Ventilation
Authors: Yi Liang , Lan Shihan , Wang Xiaofei , Bu Rongwei , Zhao Jiaming , Zhou Yang
Published: March 2023

The emergence of inclined tunnels under natural ventilation has brought many new fire safety issues. The smoke movement in the tunnel is affected by the chimney effect induced by the shaft and the downstream tunnel. The characteristics of temperature distribution in inclined tunnels are different from horizontal tunnels, which is worthy of further study. A series of conditions were carried out in an inclined model tunnel with a single shaft to investigate the temperature distribution characteristics. In this study, the longitudinal air inlet velocity is used to replace the longitudinal ventilation wind velocity. Results showed that the variation of fire source location Lf,, shaft height Ls, and the tunnel slope φ have obvious effect on the air inlet velocity. Based on the previous theories and the non-dimension analysis, the formulas of the dimensionless longitudinal inlet air velocity and the distribution of the maximum smoke temperature under the ceiling are proposed, which show good consistency with the simulation results. The reduced-scale experiments were conducted to validate the results of numerical simulation. The error range between the theoretical results and the simulation results is less than 20%.
Quantitative MRI to Characterize Hypoxic Tumors in Comparison to FMISO PET/CT for Radiotherapy in Oropharynx Cancers
Authors: Gouel Pierrick , Callonnec Françoise , Obongo-Anga Franchel-Raïs , Bohn Pierre , Lévêque Emilie , Gensanne David , Hapdey Sébastien , Modzelewski Romain , Vera Pierre , Thureau Sébastien
Published: March 2023

Intratumoral hypoxia is associated with a poor prognosis and poor response to treatment in head and neck cancers. Its identification would allow for increasing the radiation dose to hypoxic tumor subvolumes. 18F-FMISO PET imaging is the gold standard; however, quantitative multiparametric MRI could show the presence of intratumoral hypoxia. Thus, 16 patients were prospectively included and underwent 18F-FDG PET/CT, 18F-FMISO PET/CT, and multiparametric quantitative MRI (DCE, diffusion and relaxometry T1 and T2 techniques) in the same position before treatment. PET and MRI sub-volumes were segmented and classified as hypoxic or non-hypoxic volumes to compare quantitative MRI parameters between normoxic and hypoxic volumes. In total, 13 patients had hypoxic lesions. The Dice, Jaccard, and overlap fraction similarity indices were 0.43, 0.28, and 0.71, respectively, between the FDG PET and MRI-measured lesion volumes, showing that the FDG PET tumor volume is partially contained within the MRI tumor volume. The results showed significant differences in the parameters of SUV in FDG and FMISO PET between patients with and without measurable hypoxic lesions. The quantitative MRI parameters of ADC, T1 max mapping and T2 max mapping were different between hypoxic and normoxic subvolumes. Quantitative MRI, based on free water diffusion and T1 and T2 mapping, seems to be able to identify intra-tumoral hypoxic sub-volumes for additional radiotherapy doses.
Mismatch between Bioluminescence Imaging (BLI) and MRI When Evaluating Glioblastoma Growth: Lessons from a Study Where BLI Suggested “Regression” while MRI Showed “Progression”
Authors: Bausart Mathilde , Bozzato Elia , Joudiou Nicolas , Koutsoumpou Xanthippi , Manshian Bella , Préat Véronique , Gallez Bernard
Published: March 2023

Orthotopic glioblastoma xenografts are paramount for evaluating the effect of innovative anti-cancer treatments. In longitudinal studies, tumor growth (or regression) of glioblastoma can only be monitored by noninvasive imaging. For this purpose, bioluminescence imaging (BLI) has gained popularity because of its low cost and easy access. In the context of the development of new nanomedicines for treating glioblastoma, we were using luciferase-expressing GL261 cell lines. Incidentally, using BLI in a specific GL261 glioblastoma model with cells expressing both luciferase and the green fluorescent protein (GL261-luc-GFP), we observed an apparent spontaneous regression. By contrast, the magnetic resonance imaging (MRI) analysis revealed that the tumors were actually growing over time. For other models (GL261 expressing only luciferase and U87 expressing both luciferase and GFP), data from BLI and MRI correlated well. We found that the divergence in results coming from different imaging modalities was not due to the tumor localization nor the penetration depth of light but was rather linked to the instability in luciferase expression in the viral construct used for the GL261-luc-GFP model. In conclusion, the use of multi-modality imaging prevents possible errors in tumor growth evaluation, and checking the stability of luciferase expression is mandatory when using BLI as the sole imaging modality.
Prevention of Inflammation-Driven Colon Carcinogenesis in Human MUC1 Transgenic Mice by Vaccination with MUC1 DNA and Dendritic Cells
Authors: Murwanti Retno , Denda-Nagai Kaori , Sugiura Daisuke , Mogushi Kaoru , Gendler Sandra J. , Irimura Tatsuro
Published: March 2023

The preventive efficacy of MUC1-specific DNA immunization on inflammation-driven colon carcinogenesis in human MUC1 transgenic (MUC1.Tg) mice was investigated. Mice were vaccinated with MUC1 DNA mixed with autologous bone-marrow-derived dendritic cells (BMDCs), and then colonic tumors were induced by azoxymethane (AOM) injection and oral administration of dextran sulfate sodium (DSS). Two types of tumors, squamous metaplasia and tubular adenoma, were observed. Both expressed high levels of MUC1 as indicated by the binding of anti-MUC1 antibodies with different specificities, whereas MUC1 expression was not detected in normal colonic mucosa. When mice were immunized with MUC1 DNA + BMDCs, tumor incidence, tumor number, and tumor size were significantly reduced. In contrast, vaccination with MUC1 DNA alone or BMDCs alone was ineffective in reducing tumor burden. Inflammation caused by DSS was not suppressed by the MUC1 DNA + BMDCs vaccination. Furthermore, MUC1 protein expression levels, as judged by anti-MUC1 antibody binding in tumors grown after vaccination, did not significantly differ from the control. In conclusion, an inflammation-driven carcinogenesis model was established in MUC1.Tg mice, closely resembling human colon carcinogenesis. In this model, vaccination with MUC1 DNA + BMDCs was effective in overriding MUC1 tolerance and reducing the tumor burden by a mechanism not affecting the level of colonic inflammation.
Predicting Breast Cancer Events in Ductal Carcinoma In Situ (DCIS) Using Generative Adversarial Network Augmented Deep Learning Model
Authors: Ghose Soumya , Cho Sanghee , Ginty Fiona , McDonough Elizabeth , Davis Cynthia , Zhang Zhanpan , Mitra Jhimli , Harris Adrian L. , Thike Aye Aye , Tan Puay Hoon , Gökmen-Polar Yesim , Badve Sunil S.
Published: March 2023

Standard clinicopathological parameters (age, growth pattern, tumor size, margin status, and grade) have been shown to have limited value in predicting recurrence in ductal carcinoma in situ (DCIS) patients. Early and accurate recurrence prediction would facilitate a more aggressive treatment policy for high-risk patients (mastectomy or adjuvant radiation therapy), and simultaneously reduce over-treatment of low-risk patients. Generative adversarial networks (GAN) are a class of DL models in which two adversarial neural networks, generator and discriminator, compete with each other to generate high quality images. In this work, we have developed a deep learning (DL) classification network that predicts breast cancer events (BCEs) in DCIS patients using hematoxylin and eosin (H & E) images. The DL classification model was trained on 67 patients using image patches from the actual DCIS cores and GAN generated image patches to predict breast cancer events (BCEs). The hold-out validation dataset (n = 66) had an AUC of 0.82. Bayesian analysis further confirmed the independence of the model from classical clinicopathological parameters. DL models of H & E images may be used as a risk stratification strategy for DCIS patients to personalize therapy.
Comparison of Four Albumin-Based Liver Reserve Models (ALBI/EZ-ALBI/PALBI/PAL) against MELD for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization
Authors: Ho Shu-Yein , Liu Po-Hong , Hsu Chia-Yang , Huang Yi-Hsiang , Liao Jia-I , Su Chien-Wei , Hou Ming-Chih , Huo Teh-Ia
Published: March 2023

(1) Background: The severity of liver functional reserve plays an important role in the management of hepatocellular carcinoma (HCC). Noninvasive models such as the model for end-stage liver disease (MELD), albumin-bilirubin (ALBI) grade and easy (EZ)-ALBI grade, platelet-albumin-bilirubin (PALBI) and platelet-albumin (PAL) are used to evaluate liver dysfunction. We aimed to compare the prognostic performance of these four albumin-based models against MELD in HCC patients undergoing transarterial chemoembolization (TACE). (2) Methods: A total of 1038 treatment naïve HCC patients who received TACE as the primary treatment were enrolled. A multivariate Cox model was used to determine independent survival predictors. (3) Results: Multivariate analysis revealed that higher serum creatinine and α-fetoprotein level, vascular invasion, large tumor size, ALBI grades 2–3, EZ-ALBI grades 2–3, PALBI grades 2–3, PAL grades 2–3, but not the MELD score, were independent predictors associated with decreased survival in different Cox models. Among these models, the PALBI grade had the highest homogeneity and lowest corrected Akaike information criteria value, followed by EZ-ALBI, PAL, ALBI and, lastly, MELD. (4) Conclusions: All four albumin-based liver reserve models are better prognostic tools than MELD score in HCC patients undergoing TACE. Of these, the PALBI score is the best model to evaluate the liver reserve and should be considered a surrogate marker in these patients.
Senescent Stromal Cells in the Tumor Microenvironment: Victims or Accomplices?
Authors: Ye Minghan , Huang Xinyi , Wu Qianju , Liu Fei
Published: March 2023

Cellular senescence is a unique cellular state. Senescent cells enter a non-proliferative phase, and the cell cycle is arrested. However, senescence is essentially an active cellular phenotype, with senescent cells affecting themselves and neighboring cells via autocrine and paracrine patterns. A growing body of research suggests that the dysregulation of senescent stromal cells in the microenvironment is tightly associated with the development of a variety of complex cancers. The role of senescent stromal cells in impacting the cancer cell and tumor microenvironment has also attracted the attention of researchers. In this review, we summarize the generation of senescent stromal cells in the tumor microenvironment and their specific biological functions. By concluding the signaling pathways and regulatory mechanisms by which senescent stromal cells promote tumor progression, distant metastasis, immune infiltration, and therapy resistance, this paper suggests that senescent stromal cells may serve as potential targets for drug therapy, thus providing new clues for future related research.
Identification of YWHAH as a Novel Brain-Derived Extracellular Vesicle Marker Post Long-Term Midazolam Exposure during Early Development
Authors: Nguyen Nghi M. , Meyer Daniel , Meyer Luke , Chand Subhash , Jagadesan Sankarasubramanian , Miravite Maireen , Guda Chittibabu , Yelamanchili Sowmya V. , Pendyala Gurudutt
Published: March 2023

Recently, the long-term use of sedative agents in the neonatal intensive care unit (NICU) has raised concerns about neurodevelopmental outcomes in exposed neonates. Midazolam (MDZ), a common neonatal sedative in the NICU, has been suggested to increase learning disturbances and cognitive impairment in children. However, molecular mechanisms contributing to such outcomes with long-term MDZ use during the early stages of life remain unclear. In this study, we for the first time elucidate the role of brain-derived extracellular vesicles (BDEVs), including mining the BDEV proteome post long-term MDZ exposure during early development. Employing our previously established rodent model system that mimics the exposure of MDZ in the NICU using an increasing dosage regimen, we isolated BDEVs from postnatal 21-days-old control and MDZ groups using a differential sucrose density gradient. BDEVs from the control and MDZ groups were then characterized using a ZetaView nanoparticle tracking analyzer and transmission electron microscopy analysis. Next, using RT-qPCR, we examined the expression of key ESCRT-related genes involved in EV biogenesis. Lastly, using quantitative mass spectrometry-based proteomics, we mined the BDEV protein cargo that revealed key differentially expressed proteins and associated molecular pathways to be altered post long-term MDZ exposure. Our study characterized the proteome in BDEV cargo from long-term MDZ exposure at early development. Importantly, we identified and validated the expression of YWHAH as a potential target for further characterization of its downstream mechanism and a potential biomarker for the early onset of neurodevelopment and neurodegenerative diseases. Overall, the present study demonstrated long-term exposure to MDZ at early development stages could influence BDEV protein cargo, which potentially impact neural functions and behavior at later stages of development.
Effects of Sex on the Susceptibility for Atrial Fibrillation in Pigs with Ischemic Heart Failure
Authors: Pauly Valerie , Vlcek Julia , Zhang Zhihao , Hesse Nora , Xia Ruibing , Bauer Julia , Loy Simone , Schneider Sarah , Renner Simone , Wolf Eckhard , Kääb Stefan , Schüttler Dominik , Tomsits Philipp , Clauss Sebastian
Published: March 2023

Atrial fibrillation (AF) is the most prevalent arrhythmia, often caused by myocardial ischemia/infarction (MI). Men have a 1.5× higher prevalence of AF, whereas women show a higher risk for new onset AF after MI. However, the underlying mechanisms of how sex affects AF pathophysiology are largely unknown. In 72 pigs with/without ischemic heart failure (IHF) we investigated the impact of sex on ischemia-induced proarrhythmic atrial remodeling and the susceptibility for AF. Electrocardiogram (ECG) and electrophysiological studies were conducted to assess electrical remodeling; histological analyses were performed to assess atrial fibrosis in male and female pigs. IHF pigs of both sexes showed a significantly increased vulnerability for AF, but in male pigs more and longer episodes were observed. Unchanged conduction properties but enhanced left atrial fibrosis indicated structural rather than electrical remodeling underlying AF susceptibility. Sex differences were only observed in controls with female pigs showing an increased intrinsic heart rate, a prolonged QRS interval and a prolonged sinus node recovery time. In sum, susceptibility for AF is significantly increased both in male and female pigs with ischemic heart failure. Differences between males and females are moderate, including more and longer AF episodes in male pigs and sinus node dysfunction in female pigs.
STAT3 Drives GFAP Accumulation and Astrocyte Pathology in a Mouse Model of Alexander Disease
Authors: Hagemann Tracy L. , Coyne Sierra , Levin Alder , Wang Liqun , Feany Mel B. , Messing Albee
Published: March 2023

Alexander disease (AxD) is caused by mutations in the gene for glial fibrillary acidic protein (GFAP), an intermediate filament expressed by astrocytes in the central nervous system. AxD-associated mutations cause GFAP aggregation and astrogliosis, and GFAP is elevated with the astrocyte stress response, exacerbating mutant protein toxicity. Studies in mouse models suggest disease severity is tied to Gfap expression levels, and signal transducer and activator of transcription (STAT)-3 regulates Gfap during astrocyte development and in response to injury and is activated in astrocytes in rodent models of AxD. In this report, we show that STAT3 is also activated in the human disease. To determine whether STAT3 contributes to GFAP elevation, we used a combination of genetic approaches to knockout or reduce STAT3 activation in AxD mouse models. Conditional knockout of Stat3 in cells expressing Gfap reduced Gfap transactivation and prevented protein accumulation. Astrocyte-specific Stat3 knockout in adult mice with existing pathology reversed GFAP accumulation and aggregation. Preventing STAT3 activation reduced markers of reactive astrocytes, stress-related transcripts, and microglial activation, regardless of disease stage or genetic knockout approach. These results suggest that pharmacological inhibition of STAT3 could potentially reduce GFAP toxicity and provide a therapeutic benefit in patients with AxD.
The Glymphatic System May Play a Vital Role in the Pathogenesis of Hepatic Encephalopathy: A Narrative Review
Authors: Sepehrinezhad Ali , Stolze Larsen Fin , Ashayeri Ahmadabad Rezan , Shahbazi Ali , Sahab Negah Sajad
Published: March 2023

Hepatic encephalopathy (HE) is a neurological complication of liver disease resulting in cognitive, psychiatric, and motor symptoms. Although hyperammonemia is a key factor in the pathogenesis of HE, several other factors have recently been discovered. Among these, the impairment of a highly organized perivascular network known as the glymphatic pathway seems to be involved in the progression of some neurological complications due to the accumulation of misfolded proteins and waste substances in the brain interstitial fluids (ISF). The glymphatic system plays an important role in the clearance of brain metabolic derivatives and prevents aggregation of neurotoxic agents in the brain ISF. Impairment of it will result in aggravated accumulation of neurotoxic agents in the brain ISF. This could also be the case in patients with liver failure complicated by HE. Indeed, accumulation of some metabolic by-products and agents such as ammonia, glutamine, glutamate, and aromatic amino acids has been reported in the human brain ISF using microdialysis technique is attributed to worsening of HE and correlates with brain edema. Furthermore, it has been reported that the glymphatic system is impaired in the olfactory bulb, prefrontal cortex, and hippocampus in an experimental model of HE. In this review, we discuss different factors that may affect the function of the glymphatic pathways and how these changes may be involved in HE.
Study of the Phase Formation Processes and Their Influence on the Change in the Optical and Shielding Characteristics of 0.25ZnO–0.25Al2O3–0.25WO3–0.25Bi2O3 Ceramics
Authors: Seitbayev Aibek S. , Kozlovskiy Artem L. , Borgekov Daryn B. , Zdorovets Maxim V.
Published: March 2023

The phase formation processes in 0.25ZnO–0.25Al2O3–0.25WO3–0.25Bi2O3 ceramics with variation in the thermal annealing temperature were evaluated in this study. According to the obtained data on the phase composition dependent on the annealing temperature, the phase transformation dynamics, which can be written in the form of ZnO/Bi2O3/WO3/Al2O3 → ZnBi38O60/ZnO/Bi2WO6/WO3 → Bi2Al4O9/ZnBi38O60/Bi2WO6/ZnO/WO3 → ZnWO4/Bi2WO6/ZnAl2O4/ZnO → ZnWO4/Bi2WO6/ZnAl2O4 → Bi2WO6/ZnWO4/ZnAl2O4 → ZnAl2O4/Bi2WO6/Bi2W2O9, were established. It has been found that the formation of phases of complex oxides of the ZnWO4, Bi2WO6 and Bi2W2O9 types in the composition of ceramics leads to an increase in the density of ceramics up to 8.05–8.10 g/cm3, which positively affects the shielding efficiency and strength characteristics. According to the data on the change in strength characteristics, it was found that a change in the density of ceramics from 6.3 to 8.05–8.10 g/cm3 leads to strengthening and an increase in the crack resistance of ceramics by 75–80%, which indicates a high strength of ceramics and their increased resistance to external influences. As shown by the evaluation of the shielding characteristics, an increase in the density of ceramics due to a phase composition change leads to an increase in the shielding efficiency and a decrease in gamma intensity by a factor of 3–3.5. At the same time, on the base of the data presented, it can be concluded that ceramics obtained in the range of 900–1100 °C have both high shielding characteristics and high strength and resistance to external influences.
Orthodontic Approaches in the Management of Mandibular Fractures: A Scoping Review
Authors: Polizzi Alessandro , Ronsivalle Vincenzo , Lo Giudice Antonino , Isola Gaetano , Bianchi Alberto , Santonocito Simona , Leonardi Rosalia , Mummolo Stefano
Published: March 2023

Non-surgical approaches have been proposed in the management of mandibular fractures, especially in children, but there is a lack of clear guidelines on the clinical indications of conservative approaches. The aim of this scoping review is to provide the available evidence of the role of the orthodontist in the management of mandibular fractures. The PRISMA-ScR guidelines were followed to select eligible articles from the PubMed, Scopus, and Web of Science databases according to precise inclusion criteria. The research questions were formulated as follows: “what is the scientific evidence concerning the rule of orthodontists in the management of mandibular fractures” and “the preferential use of the direct bonding technique with orthodontic brackets rather than rigid arch bars”? Seventeen articles were included. Five articles presented the use of removable acrylic splints or functional appliances, six articles concerned the employment of cemented acrylic or rigid splints, and six articles described the management of mandibular fractures in adults and children using orthodontic brackets or mini-screws. Most of these techniques have been employed in children and growing subjects, while fewer data were available regarding conservative treatments in adults. Preliminary evidence suggests that condylar and some minor parasymphyseal fractures in children may be managed with conservative approaches. In adults, minor condylar and stable body mandibular fractures with minimal displacement have been reduced similarly. However, there are no sufficient elements that could suggest the preferential use of orthodontic brackets over rigid arch bars in adults. Further randomized and non-randomized clinical trials with long follow-ups will be needed to better define the clinical indications of the orthodontic approaches in the management of mandibular fractures based on severity, location, and age.
Strabismus and Pediatric Psychiatric Illness: A Literature Review
Authors: Huang Tiffany L. , Pineles Stacy L.
Published: March 2023

Purpose: This literature review aims to investigate the potential association between strabismus and mental illness among children. Materials: The search was conducted in the PubMed and Google Scholar databases using a wide range of search terms related to strabismus, mental disorders, psychiatric illness, childhood, and adolescence. Results: Eleven published studies were included in this review. The findings from this review suggest an association between strabismus and mental illness. Negative attitudes and social bias against children with strabismus were also noted. Conclusions: These findings should alert healthcare providers to counsel children and their caregivers regarding the risk for mood disorders in children with strabismus and to consider mental health screening and referral as needed.
Sucrose Transporter StSUT2 Affects Potato Plants Growth, Flowering Time, and Tuber Yield
Authors: Gong Hui-Ling , Liu Jin-Bao , Igiraneza Clement , Dusengemungu Leonce
Published: March 2023

Background: Sucrose transporters (SUTs) mediate sucrose phloem loading in source tissue and sucrose unloading into sink tissue in potatoes and higher plants, thus playing a crucial role in plant growth and development. In potatoes, the physiological function of the sucrose transporters StSUT1 and StSUT4 has been clarified, whereas the physiological role of StSUT2 is not yet fully understood. Methods and Results: This study analyzed the relative expression of StSUT2 compared to that of StSUT1 and StSUT4 in different tissues from potatoes and its impact on different physiological characteristics by using StSUT2-RNA interference lines. Here, we report a negative effect of StSUT2-RNA interference on plant height, fresh weight, internodes number, leaf area, flowering time, and tuber yield. However, our data indicate that StSUT2 is not involved in carbohydrate accumulation in potato leaves and tubers. In addition, the data of the RNA-seq between the StSUT2-RNA interference line and WT showed that 152 genes were differentially expressed, of which 128 genes were upregulated and 24 genes were downregulated, and the GO and KEGG analyses revealed that differentially expressed genes were mainly related to cell wall composition metabolism. Conclusions: Thus, StSUT2 functions in potato plant growth, flowering time, and tuber yield without affecting carbohydrate accumulation in the leaves and tubers but may be involved in cell wall composition metabolism.
Corrosion Resistance and Biological Properties of Pure Magnesium Modified by PEO in Alkaline Phosphate Solutions
Authors: Echeverry-Rendón Mónica , Berrio Luisa F. , Robledo Sara M. , Calderón Jorge A. , Castaño Juan G. , Echeverría Felix
Published: March 2023

Magnesium (Mg) has been explored during the last few decades in the biomedical industry as a biodegradable implant. However, mechanical properties and corrosion resistance are still big concerns for clinical use. Therefore, this study proposes a suitable surface modification of the Mg by plasma electrolytic oxidation (PEO) to improve its corrosion resistance and biological performance. Mg samples were processed in a galvanostatic mode using an electrolytic solution of a phosphate compound supplemented with either potassium pyrophosphate or sodium-potassium tartrate. The obtained coatings were physiochemically characterized by SEM, XRD, EDS, and micro-Raman spectroscopy. The corrosion resistance of the coatings was studied using a hydrogen evolution setup and electrochemical tests. Finally, the biological performance of the material was evaluated by using an indirect test with osteoblasts. Obtained coatings showed a porous morphology with thicknesses ranging from 2 to 3 µm, which was closely dependent on the PEO solution. The corrosion resistance tests improved the degradation rate compared to the raw material. Additionally, an unreported active–passive corrosion behavior was evidence of a protective layer of corrosion products underneath the anodic coating. Indirect in vitro cytotoxicity assays indicated that the coatings improved the biocompatibility of the material. In conclusion, it was found that the produced coatings from this study not only lead to material protection but also improve the biological performance of the material and ensure cell survival, indicating that this could be a potential material used for bone implants.
First Approach to ZrB2 Thin Films Alloyed with Silver Prepared by Magnetron Co-Sputtering
Authors: Fiantok Tomáš , Truchlý Martin , Šroba Viktor , Roch Tomáš , Izai Vitalii , Vidiš Marek , Haršáni Marián , Satrapinskyy Leonid , Mikula Marián
Published: March 2023

Hexagonal ZrB2 belongs to the group of ultra-high temperature ceramics representing an important class of materials with the potential to meet the high demands of today’s industry. However, this potential is limited by inherent brittleness and poor tribological properties. Here, the combination of density functional theory and experiment is used to investigate the effect of silver alloying on the mechanical and tribological properties of hexagonal ZrB2 thin films. Calculations indicate strong insolubility of Ag atoms in the ZrB2 metal sublattice and a significant effect on the mechanical properties, pointing out an improvement in ductility and tribological properties but at the cost of reduced hardness. The experiments confirmed the theoretical predictions of the strong insolubility of silver, where the magnetron-sputtered Zr1−xAgxB2+Δ films form a segregated nanostructure consisting of separated hexagonal ZrB2 and cubic Ag phases. With increased Ag content, values of Young’s modulus decrease from EZrB2.31 = 375 GPa to EZr0.26Ag0.74B0.89 = 154 GPa, followed by a decrease in hardness from HZrB2.31 = 30 GPa to a value of HZr0.26Ag0.74B0.89 = 4 GPa. The suppression of crack formation is also shown with the material flow around cube corner indents, indicating enhanced ductility. The improvement of tribological properties was also confirmed when the coefficient of friction (COF) was reduced from COFZrB2.31 ~0.9 to a value of COFZr0.26Ag0.74B0.89 ~0.25 for all counterpart materials—steel (100Cr6), Si3N4, and WC/Co.
Mechanical Strengths of Alkali-Activated Blast Furnace Slag Powder with Different Alkali Activators and Plant Fibers
Authors: Zhu Jing , Song Lizhuo , Qu Zijian , Wang Xiaopeng , Wen Zijie , Liu Xiaodong , Wang Hui
Published: March 2023

In this paper, the influence of water glass types, the modulus of water glass, the alkali content, the water consumption, and plant fibers on the mechanical strengths of alkali-activated blast furnace slag powder (BFS) is investigated. Moreover, the fiber types and pretreatment on the plant fibers and the measuring temperature on the performance of alkali-activated BFS are further considered. Results indicate that BFS activated by potassium silicate shows higher mechanical strengths than that activated by sodium silicate. The alkali-activated BFS with alkali treatment on fibers is the most advantageous. The modulus of alkali leads to decreasing the compressive strength. A total of 35% water consumption is the most beneficial to the specimens’ flexural and compressive strengths. Samples with 14% potassium silicate show the maximum mechanical strength. Alkali-activated BFS with 1% wheat straw fibers in addition by total volume represents the maximum mechanical strength. The alkali-activated BFS with alkali treatment on fibers is the most advantageous. The addition of potassium silicate can improve the flexural and compressive strengths by the maximum values of 30.4% and 16.8% compared to specimens with sodium silicate. A total of 35% water consumption can increase the flexural and compressive strengths by 33.8% and 32.7%.