bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear Factor-κB Decoy Oligodeoxynucleotide Attenuates Cartilage Resorption In Vitro
Authors: Nemoto Hitoshi , Sakai Daisuke , Watson Deborah , Masuda Koichi
Published: January 2024

Background: Cartilage harvest and transplantation is a common surgery using costal, auricular, and septal cartilage for craniofacial reconstruction. However, absorption and warping of the cartilage grafts can occur due to inflammatory factors associated with wound healing. Transcription factor nuclear factor-κB (NF-κB) is activated by the various stimulation such as interleukin-1 (IL-1), and plays a central role in the transactivation of this inflammatory cytokine gene. Inhibition of NF-κB may have anti-inflammatory effects. The aim of this study was to explore the potential of an NF-κB decoy oligodeoxynucleotide (Decoy) as a chondroprotective agent. Materials and Methods: Safe and efficacious concentrations of Decoy were assessed using rabbit nasal septal chondrocytes (rNSChs) and assays for cytotoxicity, proteoglycan (PG) synthesis, and PG turnover were carried out. The efficacious concentration of Decoy determined from the rNSChs was then applied to human nasal septal cartilage (hNSC) in vitro and analyzed for PG turnover, the levels of inflammatory markers, and catabolic enzymes in explant-conditioned culture medium. Results: Over the range of Decoy conditions and concentrations, no inhibition of PG synthesis or cytotoxicity was observed. Decoy at 10 μM effectively inhibited PG degradation in the hNSC explant, prolonging PG half-life by 63% and decreasing matrix metalloprotease 3 (MMP-3) by 70.7% (p = 0.027). Conclusions: Decoy may be considered a novel chondroprotective therapeutic agent in cartilage transplantation due to its ability to inhibit cartilage degradation due to inflammation cytokines.
Casein Kinase 1 Phosphomimetic Mutations Negatively Impact Connexin-43 Gap Junctions in Human Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Al-attar Rasha , Jargstorf Joseph , Romagnuolo Rocco , Jouni Mariam , Alibhai Faisal J. , Lampe Paul D. , Solan Joell L. , Laflamme Michael A.
Published: January 2024

The transplantation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) has shown promise in preclinical models of myocardial infarction, but graft myocardium exhibits incomplete host–graft electromechanical integration and a propensity for pro-arrhythmic behavior. Perhaps contributing to this situation, hPSC-CM grafts show low expression of connexin 43 (Cx43), the major gap junction (GJ) protein, in ventricular myocardia. We hypothesized that Cx43 expression and function could be rescued by engineering Cx43 in hPSC-CMs with a series of phosphatase-resistant mutations at three casein kinase 1 phosphorylation sites (Cx43-S3E) that have been previously reported to stabilize Cx43 GJs and reduce arrhythmias in transgenic mice. However, contrary to our predictions, transgenic Cx43-S3E hPSC-CMs exhibited reduced Cx43 expression relative to wild-type cells, both at baseline and following ischemic challenge. Cx43-S3E hPSC-CMs showed correspondingly slower conduction velocities, increased automaticity, and differential expression of other connexin isoforms and various genes involved in cardiac excitation–contraction coupling. Cx43-S3E hPSC-CMs also had phosphorylation marks associated with Cx43 GJ internalization, a finding that may account for their impaired GJ localization. Taken collectively, our data indicate that the Cx43-S3E mutation behaves differently in hPSC-CMs than in adult mouse ventricular myocytes and that multiple biological factors likely need to be addressed synchronously to ensure proper Cx43 expression, localization, and function.
Role of Natural Compounds Modulating Heme Catabolic Pathway in Gut, Liver, Cardiovascular, and Brain Diseases
Authors: Jayanti Sri , Vitek Libor , Verde Camilla Dalla , Llido John Paul , Sukowati Caecilia , Tiribelli Claudio , Gazzin Silvia
Published: January 2024

The crucial physiological process of heme breakdown yields biliverdin (BV) and bilirubin (BR) as byproducts. BV, BR, and the enzymes involved in their production (the “yellow players—YP”) are increasingly documented as endogenous modulators of human health. Mildly elevated serum bilirubin concentration has been correlated with a reduced risk of multiple chronic pro-oxidant and pro-inflammatory diseases, especially in the elderly. BR and BV per se have been demonstrated to protect against neurodegenerative diseases, in which heme oxygenase (HMOX), the main enzyme in the production of pigments, is almost always altered. HMOX upregulation has been interpreted as a tentative defense against the ongoing pathologic mechanisms. With the demonstration that multiple cells possess YP, their propensity to be modulated, and their broad spectrum of activity on multiple signaling pathways, the YP have assumed the role of an adjustable system that can promote health in adults. Based on that, there is an ongoing effort to induce their activity as a therapeutic option, and natural compounds are an attractive alternative to the goal, possibly requiring only minimal changes in the life style. We review the most recent evidence of the potential of natural compounds in targeting the YP in the context of the most common pathologic condition of adult and elderly life.
Aedes aegypti Beta-1,3-Glucan-Binding Protein Inhibits Dengue and ZIKA Virus Replication
Authors: Xie Xiaoxue , Wang Di , Li Bo , Liang Guorui , Chen Xiaoli , Xing Dan , Zhao Teng , Zhou Xinyu , Li Chunxiao
Published: January 2024

GNBPB6, a beta-1,3-glucan-binding protein, was identified in the transcriptome of Aedes aegypti (A. aegypti) with dengue (DENV), Zika (ZIKV), and chikungunya viruses (CHIKV). In this study, we not only clarified that DENV2 and ZIKV regulate the changes in GNBPB6 expression but also identified the relationship of this gene with viral infections. The changes in GNBPB6 expression were quantified and showed a decrease in A. aegypti cells (Aag2 cells) at 2 dpi and 3 dpi and an increase at 4 dpi and 5 dpi (p < 0.05). A significant increase was observed only at 5 dpi after DENV2 infection. Subsequently, a GNBPB6 knockout (KO) cell line was constructed using the CRISPR/Cas9 system, and the DENV2 and ZIKV RNA copies, along with cell densities, were quantified and compared between the KO and wild type (WT) cells at different dpi. The result showed that DENV2 and ZIKV RNA copies were significantly increased in the KO cell line with no significant change in cell growth. Finally, DENV2 copies decreased after GNBPB6 was complemented in the KO. In conclusion, GNBPB6 knockout and complementation in Aag2 cells revealed that GNBPB6 can inhibit the replication of both DENV2 and ZIKV. These results contribute to subsequent research on mosquito–virus interactions.
Implications of siRNA Therapy in Bone Health: Silencing Communicates
Authors: Singh Puneetpal , Singh Monica , Singh Baani , Sharma Kirti , Kumar Nitin , Singh Deepinder , Klair Harpal Singh , Mastana Sarabjit
Published: January 2024

The global statistics of bone disorders, skeletal defects, and fractures are frightening. Several therapeutic strategies are being used to fix them; however, RNAi-based siRNA therapy is starting to prove to be a promising approach for the prevention of bone disorders because of its advanced capabilities to deliver siRNA or siRNA drug conjugate to the target tissue. Despite its ‘bench-to-bedside’ usefulness and approval by food and drug administration for five siRNA-based therapeutic medicines: Patisiran, Vutrisiran, Inclisiran, Lumasiran, and Givosiran, its use for the other diseases still remains to be resolved. By correcting the complications and complexities involved in siRNA delivery for its sustained release, better absorption, and toxicity-free activity, siRNA therapy can be harnessed as an experimental tool for the prevention of complex and undruggable diseases with a personalized medicine approach. The present review summarizes the findings of notable research to address the implications of siRNA in bone health for the restoration of bone mass, recovery of bone loss, and recuperation of bone fractures.
Identification of MDK as a Hypoxia- and Epithelial–Mesenchymal Transition-Related Gene Biomarker of Glioblastoma Based on a Novel Risk Model and In Vitro Experiments
Authors: Xia Minqi , Tong Shiao , Gao Ling
Published: January 2024

Background: Tumor cells are commonly exposed to a hypoxic environment, which can easily induce the epithelial–mesenchymal transition (EMT) of tumor cells, further affecting tumor proliferation, invasion, metastasis, and drug resistance. However, the predictive role of hypoxia and EMT-related genes in glioblastoma (GBM) has not been investigated. Methods: Intersection genes were identified by weighted correlation network analysis (WGCNA) and differential expression analyses, and a risk model was further constructed by LASSO and Cox analyses. Clinical, immune infiltration, tumor mutation, drug treatment, and enrichment profiles were analyzed based on the risk model. The expression level of the MDK gene was tested using RT-PCR, immunohistochemistry, and immunofluorescence. CCK8 and EdU were employed to determine the GBM cells’ capacity for proliferation while the migration and invasion ability were detected by a wound healing assay and transwell assay, respectively. Results: Based on the GBM data of the TCGA and GTEx databases, 58 intersection genes were identified, and a risk model was constructed. The model was verified in the CGGA cohort, and its accuracy was confirmed by the ROC curve (AUC = 0.807). After combining clinical subgroups, univariate and multivariate Cox regression analyses showed that risk score and age were independent risk factors for GBM patients. Furthermore, our subsequent analysis of immune infiltration, tumor mutation, and drug treatment showed that risk score and high- and low-risk groups were associated with multiple immune cells, mutated genes, and drugs. Enrichment analysis indicated that the differences between high- and low-risk groups were manifested in tumor-related pathways, including the PI3K-AKT and JAK-STAT pathways. Finally, in vivo experiments proved that the hypoxia environment promoted the expression of MDK, and MDK knockdown reduced the proliferation, migration, and EMT of GBM cells induced by hypoxia. Conclusions: Our novel prognostic correlation model provided more potential treatment strategies for GBM patients.
Chemokine Receptor Antagonists Prevent and Reverse Cofilin-Actin Rod Pathology and Protect Synapses in Cultured Rodent and Human iPSC-Derived Neurons
Authors: Kuhn Thomas B. , Minamide Laurie S. , Tahtamouni Lubna H. , Alderfer Sydney A. , Walsh Keifer P. , Shaw Alisa E. , Yanouri Omar , Haigler Henry J. , Ruff Michael R. , Bamburg James R.
Published: January 2024

Synapse loss is the principal cause of cognitive decline in Alzheimer’s disease (AD) and related disorders (ADRD). Synapse development depends on the intricate dynamics of the neuronal cytoskeleton. Cofilin, the major protein regulating actin dynamics, can be sequestered into cofilactin rods, intra-neurite bundles of cofilin-saturated actin filaments that can disrupt vesicular trafficking and cause synaptic loss. Rods are a brain pathology in human AD and mouse models of AD and ADRD. Eliminating rods is the focus of this paper. One pathway for rod formation is triggered in ~20% of rodent hippocampal neurons by disease-related factors (e.g., soluble oligomers of Amyloid-β (Aβ)) and requires cellular prion protein (PrPC), active NADPH oxidase (NOX), and cytokine/chemokine receptors (CCRs). FDA-approved antagonists of CXCR4 and CCR5 inhibit Aβ-induced rods in both rodent and human neurons with effective concentrations for 50% rod reduction (EC50) of 1–10 nM. Remarkably, two D-amino acid receptor-active peptides (RAP-103 and RAP-310) inhibit Aβ-induced rods with an EC50 of ~1 pM in mouse neurons and ~0.1 pM in human neurons. These peptides are analogs of D-Ala-Peptide T-Amide (DAPTA) and share a pentapeptide sequence (TTNYT) antagonistic to several CCR-dependent responses. RAP-103 does not inhibit neuritogenesis or outgrowth even at 1 µM, >106-fold above its EC50. N-terminal methylation, or D-Thr to D-Ser substitution, decreases the rod-inhibiting potency of RAP-103 by 103-fold, suggesting high target specificity. Neither RAP peptide inhibits neuronal rod formation induced by excitotoxic glutamate, but both inhibit rods induced in human neurons by several PrPC/NOX pathway activators (Aβ, HIV-gp120 protein, and IL-6). Significantly, RAP-103 completely protects against Aβ-induced loss of mature and developing synapses and, at 0.1 nM, reverses rods in both rodent and human neurons (T½ ~ 3 h) even in the continuous presence of Aβ. Thus, this orally available, brain-permeable peptide should be highly effective in reducing rod pathology in multifactorial neurological diseases with mixed proteinopathies acting through PrPC/NOX.
The Expression of Kisspeptins and Matrix Metalloproteinases in Extragenital Endometriosis
Authors: Kleimenova Tatiana , Polyakova Victoria , Linkova Natalia , Drobintseva Anna , Medvedev Dmitriy , Krasichkov Alexander
Published: January 2024

Endometriosis is characterized by a condition where endometrial tissue grows outside the uterine cavity. The mechanisms of endometrium growth during endometriosis might be similar to the development of a tumor. The kisspeptin (KISS1) gene was initially discovered as a suppressor of metastasis. Matrix metalloproteinases (MMPs) and their inhibitors are described as factors in the early stages of endometriosis and tumor growth progression. We applied the quantitative polymerase chain reaction and the immunofluorescence method to investigate KISS1, its receptor (KISS1R), MMP-2, and MMP-9 in the eutopic and ectopic endometrium in women with and without endometriosis. We presume that the dysregulation of KISS1 and MMPs might contribute to endometriosis pathogenesis. Samples for the immunofluorescence study were collected from patients with a confirmed diagnosis of endometriosis in stages I–IV, aged 23 to 38 years old (n = 40). The cell line was derived from the endometrium of patients with extragenital endometriosis (n = 7). KISS1 and KISS1R expression are present in the ectopic endometrium of patients with extragenital endometriosis, as opposed to the control group where these proteins were not expressed. There is a decrease in KISS1 and KISS1R values at all stages of endometriosis. MMP-2 and MMP-9 genes express statistically significant increases in stages II, III, and IV of extragenital endometriosis. MMP synthesis increased in the last stages of endometriosis. We suppose that the KISS1/KISS1R system can be used in the future as a suppressive complex to reduce MMP-2 and MMP-9 expression and prevent endometrial cells from invading.
Assessment of Pedestrians’ Head and Lower Limb Injuries in Tram–Pedestrian Collisions
Authors: Peng Yong , Hu Zhengsheng , Liu Zhixiang , Che Quanwei , Deng Gongxun
Published: January 2024

Analysis of pedestrians’ head and lower limb injuries at the tissue level is lacking in studies of tram–pedestrian collisions. The purpose of this paper therefore to investigate the impact response process and severity of pedestrians’ injuries in tram–pedestrian collisions, using the Total Human Model for Safety (THUMS) pedestrian human body model together with the tram FE model. Two full-scale tram–pedestrian dummy crash tests were performed to validate the FE model, and the total correlation and analysis (CORA) score of head acceleration yielded values of 0.840 and 0.734, confirming a strong agreement between the FE-simulated head responses and the experimental head kinematics. The effects of different tram speeds and impact angles on pedestrians’ impact response injuries and the differences were further analyzed. The results indicate that direct impact of the lower limb with the tram’s obstacle deflector leads to lower limb bone shaft fractures and knee tissue damage. Neck fling contributed to worsened head injury. Coup contusions were the predominant type of brain contusion, surpassing contrecoup contusions, while diffuse axonal injury was mainly concentrated in the collision-side region of the brain. Pedestrians’ injuries are influenced by tram velocity and impact angle: higher tram velocities increase the risk of lower limb and head injuries. The risk of head injury for pedestrians is higher when the impact angle is negative, while lower limb injuries are more significant when the impact angle is 0°. This study provides practical guidance for enhancing tram safety and protecting pedestrians.
Detection of Micrometer-Sized Virus Aerosols by Using a Real-Time Bioaerosol Monitoring System
Authors: Seo Hyunsoo , Jeong Young-Su , Bae Jaekyung , Choi Kibong , Seo Moon-Hyeong
Published: January 2024

This study investigates a real-time handheld bioaerosol monitoring system for the detection of biological particles using UV-LED and light-induced fluorescence technology. Biological particles produce both scattering and fluorescence signals simultaneously, which can help distinguish them from general particles. The detected scattering, fluorescence, and simultaneous signals are then converted into photon signals and categorized based on predetermined criteria. A reliable biological particle generator was required to validate the performance of the system. This study explores the use of an M13 bacteriophage as a virus simulant of biological agents and employs a customized inkjet aerosol generator to produce M13 bacteriophage aerosols of a specific size by controlling the concentration of M13. We confirmed that micro-sized, narrowly dispersed M13 aerosols were efficiently generated. Additionally, we confirmed the performance of this real-time handheld bioaerosol monitoring system by detecting viruses.
The Relationship between Occupational Fatigue and Well-Being: The Moderating Effect of Unhealthy Eating Behaviour
Authors: Wu Tingyu , Tan Xiaotong , Li Yuying , Liang Yongqi , Fan Jialin
Published: January 2024

Tech giants are large, well-known internet and technology companies. Employees of such companies are generally expected to work fast and for long periods of time, causing them to experience high occupational fatigue. The relationship between occupational fatigue and well-being is complex. Furthermore, in the context of the workplace, unhealthy eating behaviour may be used as a mechanism to cope with fatigue and stress. This study explored the relationship between occupational fatigue, well-being and unhealthy eating behaviour within this specific professional population. Study 1 used qualitative research methods, in which in-depth interviews were conducted with staff working at 13 tech giants in Shenzhen, China (N = 50). The findings revealed that work-related stress and occupational fatigue are common among employees working for tech giants. Additionally, factors such as unhealthy eating behaviour, workload, working hours and workplace interpersonal relationships were found to influence occupational well-being. Study 2 involved a cross-sessional survey of 237 employees of tech giants. The results indicated that occupational fatigue negatively impacts occupational well-being and that unhealthy eating behaviours play a moderating role between occupational fatigue and occupational well-being. These findings highlight the significance of adopting appropriate measures to improve the situation and cope with the effects of occupational fatigue by managing unhealthy eating behaviours.
Development and Validation of an Explainable Radiomics Model to Predict High-Aggressive Prostate Cancer: A Multicenter Radiomics Study Based on Biparametric MRI
Authors: Nicoletti Giulia , Mazzetti Simone , Maimone Giovanni , Cignini Valentina , Cuocolo Renato , Faletti Riccardo , Gatti Marco , Imbriaco Massimo , Longo Nicola , Ponsiglione Andrea , Russo Filippo , Serafini Alessandro , Stanzione Arnaldo , Regge Daniele , Giannini Valentina
Published: January 2024

In the last years, several studies demonstrated that low-aggressive (Grade Group (GG) ≤ 2) and high-aggressive (GG ≥ 3) prostate cancers (PCas) have different prognoses and mortality. Therefore, the aim of this study was to develop and externally validate a radiomic model to noninvasively classify low-aggressive and high-aggressive PCas based on biparametric magnetic resonance imaging (bpMRI). To this end, 283 patients were retrospectively enrolled from four centers. Features were extracted from apparent diffusion coefficient (ADC) maps and T2-weighted (T2w) sequences. A cross-validation (CV) strategy was adopted to assess the robustness of several classifiers using two out of the four centers. Then, the best classifier was externally validated using the other two centers. An explanation for the final radiomics signature was provided through Shapley additive explanation (SHAP) values and partial dependence plots (PDP). The best combination was a naïve Bayes classifier trained with ten features that reached promising results, i.e., an area under the receiver operating characteristic (ROC) curve (AUC) of 0.75 and 0.73 in the construction and external validation set, respectively. The findings of our work suggest that our radiomics model could help distinguish between low- and high-aggressive PCa. This noninvasive approach, if further validated and integrated into a clinical decision support system able to automatically detect PCa, could help clinicians managing men with suspicion of PCa.
Pancreatic Cyst Size Measurement on Magnetic Resonance Imaging Compared to Pathology
Authors: Jeong Daniel , Morse Brian , Polk Stuart Lane , Chen Dung-Tsa , Li Jiannong , Hodul Pamela , Centeno Barbara A. , Costello James , Jiang Kun , Machado Sebastian , El Naqa Issam , Farah Paola T. , Huynh Tri , Raghunand Natarajan , Mok Shaffer , Dam Aamir , Malafa Mokenge , Qayyum Aliya , Fleming Jason B. , Permuth Jennifer B.
Published: January 2024

BACKGROUND: While multiple cyst features are evaluated for stratifying pancreatic intraductal papillary mucinous neoplasms (IPMN), cyst size is an important factor that can influence treatment strategies. When magnetic resonance imaging (MRI) is used to evaluate IPMNs, no universally accepted sequence provides optimal size measurements. T2-weighted coronal/axial have been suggested as primary measurement sequences; however, it remains unknown how well these and maximum all-sequence diameter measurements correlate with pathology size. This study aims to compare agreement and bias between IPMN long-axis measurements on seven commonly obtained MRI sequences with pathologic size measurements. METHODS: This retrospective cohort included surgically resected IPMN cases with preoperative MRI exams. Long-axis diameter tumor measurements and the presence of worrisome features and/orhigh-risk stigmata were noted on all seven MRI sequences. MRI size and pathology agreement and MRI inter-observer agreement involved concordance correlation coefficient (CCC) and intraclass correlation coefficient (ICC), respectively. The presence of worrisome features and high-risk stigmata were compared to the tumor grade using kappa analysis. The Bland-Altman analysis assessed the systematic bias between MRI-size and pathology. RESULTS: In 52 patients (age 68 ± 13 years, 22 males), MRI sequences produced mean long-axis tumor measurements from 2.45–2.65 cm. The maximum MRI lesion size had a strong agreement with pathology (CCC = 0.82 (95% CI: 0.71–0.89)). The maximum IPMN size was typically observed on the axial T1 arterial post-contrast and MRCP coronal series and overestimated size versus pathology with bias +0.34 cm. The radiologist interobserver agreement reached ICCs 0.74 to 0.91 on the MRI sequences. CONCLUSION: The maximum MRI IPMN size strongly correlated with but tended to overestimate the length compared to the pathology, potentially related to formalin tissue shrinkage during tissue processing.
Artificial Intelligence and Panendoscopy—Automatic Detection of Clinically Relevant Lesions in Multibrand Device-Assisted Enteroscopy
Authors: Mendes Francisco , Mascarenhas Miguel , Ribeiro Tiago , Afonso João , Cardoso Pedro , Martins Miguel , Cardoso Hélder , Andrade Patrícia , Ferreira João P. S. , Mascarenhas Saraiva Miguel , Macedo Guilherme
Published: January 2024

Device-assisted enteroscopy (DAE) is capable of evaluating the entire gastrointestinal tract, identifying multiple lesions. Nevertheless, DAE’s diagnostic yield is suboptimal. Convolutional neural networks (CNN) are multi-layer architecture artificial intelligence models suitable for image analysis, but there is a lack of studies about their application in DAE. Our group aimed to develop a multidevice CNN for panendoscopic detection of clinically relevant lesions during DAE. In total, 338 exams performed in two specialized centers were retrospectively evaluated, with 152 single-balloon enteroscopies (Fujifilm®, Porto, Portugal), 172 double-balloon enteroscopies (Olympus®, Porto, Portugal) and 14 motorized spiral enteroscopies (Olympus®, Porto, Portugal); then, 40,655 images were divided in a training dataset (90% of the images, n = 36,599) and testing dataset (10% of the images, n = 4066) used to evaluate the model. The CNN’s output was compared to an expert consensus classification. The model was evaluated by its sensitivity, specificity, positive (PPV) and negative predictive values (NPV), accuracy and area under the precision recall curve (AUC-PR). The CNN had an 88.9% sensitivity, 98.9% specificity, 95.8% PPV, 97.1% NPV, 96.8% accuracy and an AUC-PR of 0.97. Our group developed the first multidevice CNN for panendoscopic detection of clinically relevant lesions during DAE. The development of accurate deep learning models is of utmost importance for increasing the diagnostic yield of DAE-based panendoscopy.
Increased Collagen I/Collagen III Ratio Is Associated with Hemorrhage in Brain Arteriovenous Malformations in Human and Mouse
Authors: Shabani Zahra , Schuerger Joana , Zhu Xiaonan , Tang Chaoliang , Ma Li , Yadav Alka , Liang Rich , Press Kelly , Weinsheimer Shantel , Schmidt Annika , Wang Calvin , Sekhar Abinav , Nelson Jeffrey , Kim Helen , Su Hua
Published: January 2024

Background: The increase in the collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. Activated microglia enhance inflammation-induced fibrosis. Hypotheses: The COL I/COL III ratio in human and mouse brain arteriovenous malformations (bAVMs) is associated with bAVM hemorrhage, and the depletion of microglia decreases the COL I/COL III ratio and hemorrhage. Method: COL I, COL III, and hemorrhages were analyzed in 12 human bAVMs and 6 control brains, and mouse bAVMs induced in three mouse lines with activin receptor-like kinase 1 (n = 7) or endoglin (n = 7) deleted in the endothelial cells or brain focally (n = 5). The controls for the mouse study were no-gene-deleted litter mates. Mouse bAVMs were used to test the relationships between the Col I/Col III ratio and hemorrhage and whether the transient depletion of microglia reduces the Col I/Col III ratio and hemorrhage. Results: The COL I/COL III ratio was higher in the human and mouse bAVMs than in controls. The microhemorrhage in mouse bAVMs was positively correlated with the Col I/Col III ratio. Transient depletion of microglia reduced the Col I/Col III ratio and microhemorrhage. Conclusions: The COL I/COL III ratio in the bAVMs was associated with bAVM hemorrhage. The depletion of microglia reduced the bAVM Col I/Col III ratio and hemorrhage.
The Establishment of Current Transient of Nucleation and Growth under Diffusion-Controlled Electrocrystallisation: A Microreview
Authors: Luo Gong , Yuan Yuan , Cai Jiaqi , Yuan Guohui , Li Ning
Published: January 2024

In this microreview, the importance of electrochemical phase formation is outlined. Further, the establishment of current transition during electrochemical nucleation and growth is explored. First, the microreaction kinetic process of electrocrystallisation and the rate-controlling steps of electrodeposition are carefully discussed. Then, the current transient formulation under electrochemical polarisation-controlled electrocrystallisation is summarised. Finally, a summary of the process for calculating the current transient formulation of nucleation and growth under diffusion-controlled electrocrystallisation is explained in detail.
Artificial Intelligence in Predicting Microsatellite Instability and KRAS, BRAF Mutations from Whole-Slide Images in Colorectal Cancer: A Systematic Review
Authors: Guitton Theo , Allaume Pierre , Rabilloud Noémie , Rioux-Leclercq Nathalie , Henno Sébastien , Turlin Bruno , Galibert-Anne Marie-Dominique , Lièvre Astrid , Lespagnol Alexandra , Pécot Thierry , Kammerer-Jacquet Solène-Florence
Published: January 2024

Mismatch repair deficiency (d-MMR)/microsatellite instability (MSI), KRAS, and BRAF mutational status are crucial for treating advanced colorectal cancer patients. Traditional methods like immunohistochemistry or polymerase chain reaction (PCR) can be challenged by artificial intelligence (AI) based on whole slide images (WSI) to predict tumor status. In this systematic review, we evaluated the role of AI in predicting MSI status, KRAS, and BRAF mutations in colorectal cancer. Studies published in PubMed up to June 2023 were included (n = 17), and we reported the risk of bias and the performance for each study. Some studies were impacted by the reduced number of slides included in the data set and the lack of external validation cohorts. Deep learning models for the d-MMR/MSI status showed a good performance in training cohorts (mean AUC = 0.89, [0.74–0.97]) but slightly less than expected in the validation cohort when available (mean AUC = 0.82, [0.63–0.98]). Contrary to the MSI status, the prediction of KRAS and BRAF mutations was less explored with a less robust methodology. The performance was lower, with a maximum of 0.77 in the training cohort, 0.58 in the validation cohort for KRAS, and 0.82 AUC in the training cohort for BRAF.
Diagnostic Methods in Forensic Pathology: Autoptic Findings and Immunohistochemical Study in Cases of Sudden Death Due to a Colloid Cyst of the Third Ventricle
Authors: Montana Angelo , Busardò Francesco Paolo , Tossetta Giovanni , Goteri Gaia , Castaldo Pasqualina , Basile Giuseppe , Bambagiotti Giulia
Published: January 2024

The colloid cyst is a non-malignant tumor growth made of a gelatinous material covered by a membrane of epithelial tissue. It is usually located posterior to the foramen of Monro, in the anterior aspect of the third ventricle of the brain. Due to its location, it can cause obstructive hydrocephalus, increased intracranial pressure, and sudden cardiac death, catecholamine-mediated, through hypothalamus compression. All the mechanisms are still controversial, but the role of catecholamine has been confirmed with histological findings that highlighted myocardial injury (coagulative myocytolysis and contraction band necrosis, CBN). This study presents a case of sudden death in a previously healthy 22-year-old male due to a colloid cyst of the third ventricle. A complete autopsy was performed, highlighting in the brain an abundant quantity of cerebrospinal fluid (CSF) and a 2 cm pale grayish-green rounded cyst formation partially filling and distending the third ventricle. The diagnosis was confirmed through immunohistochemical investigation: positivity for Periodic acid-Schiff (PAS) staining and CK7 expression. In cases such as the one reported here, a combined approach of autopsy, histology, and immunohistochemistry is mandatory in order to identify the neoformation’s location and morpho-structural characteristics for a correct differential diagnosis, as well as to identify the cause of death.
Impact of Non-Surgical Periodontal Treatment on the Concentration and Level of MRP-8/14 (Calprotectin) as an Inflammatory Biomarker in Women with Periodontitis and Rheumatoid Arthritis: A Quasi-Experimental Study
Authors: Popoca-Hernández Elena Aurora , Martínez-Martínez Rita Elizabeth , González-Amaro Roberto Fidencio , Niño-Moreno Perla del Carmen , Ayala-Herrera José Luis , Jerezano-Domínguez Alberto Vinicio , Espinosa-Cristóbal Leon Francisco , Márquez-Corona María de Lourdes , Espinosa-de Santillana Irene Aurora , Medina-Solís Carlo Eduardo
Published: January 2024

The aim of this study was to evaluate the impact of non-surgical periodontal treatment (NS-PT) on periodontal parameters and inflammatory biomarkers in the concentration and level of calprotectin (CLP) in women with periodontitis and rheumatoid arthritis (RA). In this quasi-experimental study, we evaluated 30 women (mean age: 52.0 ± 5.8 years) with periodontitis and RA who had been diagnosed and treated for RA for more than 3 years and whose activity markers remained at similar values without significant reduction over three consecutive months. Patients underwent NS-PT, which included plaque control, scaling, and root planing. Serum and saliva samples, periodontal indices, RA activity markers, Disease Activity Score-28 (DAS28), the erythrocyte sedimentation rate (ESR), and the C-reactive protein (CRP) and CLP contents were measured at the beginning of the study and 6 and 12 weeks after NS-PT. Parametric and nonparametric tests were used in the analysis. The mean age was 52.0 ± 5.8 years. Compared to the baseline results, all periodontal indices were significantly reduced 6 and 12 weeks after NS-PT (p < 0.001). DAS28 was also significantly reduced after 12 weeks (p < 0.0001). Similarly, the serum CLP concentration decreased 6 and 12 weeks after NS-PT (p < 0.0001). Of the patients, 100% presented lower levels of CRP and ESR (p < 0.0001). Overall, NS-PT reduced inflammation and disease activity, highlighting the importance of oral health in the control and treatment of systemic diseases such as RA and confirming that NS-PT effectively reduces periodontitis activity and plays a key role in modulating RA activity. Therefore, NS-PT should be considered as an adjunct treatment for RA.
Investigating the Impact of Vitamin A and Amino Acids on Immune Responses in Celiac Disease Patients
Authors: Fallah Shayan , Asri Nastaran , Nikzamir Abdolrahim , Ahmadipour Shokoufeh , Sadeghi Amir , Rostami Kamran , Rostami-Nejad Mohammad
Published: January 2024

Amino acids (AAs) and vitamin imbalances are observed in celiac disease (CD). This study evaluated the plasma profile of vitamin A and AAs and the expression level of IL-2, IL-4, IL-10, IL-12 and TGFβ in CD patients. A total of 60 children and adults with CD and 40 healthy controls (HCs) were included. The plasma profile of Vitamin A and AAs and the mRNA expression levels of target genes were assessed. Active adult patients exhibited a decrease in Vitamin A levels (p = 0.04) and an increase in IL-2 (p = 0.008) and IL-12 (p = 0.007) mRNA expression compared to the HCs. The treated adult patients showed elevated Serine (p = 0.003) and Glycine (p = 0.04) levels, as well as increased IL-12 (p < 0.0001) mRNA expression, and a decrease in Tryptophan (p = 0.04) levels relative to the controls. Additionally, the treated adult patients had higher plasma levels of Threonine compared to both the active (p = 0.04) and control (p = 0.02) subjects, and the increased mRNA expression of IL-4 (p = 0.01) in comparison to the active patients. In active children with CD, the IL-2 mRNA level was found to be higher than in the controls (p < 0.0001) and in the treated children (p = 0.005). The treated children with CD exhibited decreased plasma levels of Tryptophan (p = 0.01) and Isoleucine (p = 0.01) relative to the controls, and the increased mRNA expression of TGFβ (p = 0.04) relative to the active patients. Elevated levels of specific AAs (Serine, Glycine, Threonine) in the treated CD patients suggested their potential to improve intestinal damage and inflammation, while decreased levels of Tryptophan and Isoleucine highlighted the need for dietary intervention.
Path Planning and Tracking Control of Tracked Agricultural Machinery Based on Improved A* and Fuzzy Control
Authors: Liu Lixing , Wang Xu , Wang Xiaosa , Xie Jinyan , Liu Hongjie , Li Jianping , Wang Pengfei , Yang Xin
Published: January 2024

In order to improve the efficiency of agricultural machinery operations and reduce production costs, this article proposes a path planning algorithm based on the improved A* algorithm (IA*) and a tracking controller based on fuzzy sliding mode variable structure control (F-SMC) to meet the operation requirements of tracked agricultural machinery. Firstly, we introduce a heuristic function with variable weights, a penalty, and a fifth-order Bezier curve to make the generated path smoother. On this basis, the ant colony algorithm is introduced to further optimize the obtained path. Subsequently, based on fuzzy control theory and sliding mode variable structure control theory, we established a kinematic model for tracked agricultural machinery as the control object, designed a fuzzy sliding mode approaching law, and preprocessed it to reduce the time required for sliding mode control to reach the chosen stage. The simulation experiment of path planning shows that compared with A*, the average reduction rate of the path length for IA* is 5.51%, and the average reduction rate of the number of turning points is 39.01%. The path tracking simulation experiment shows that when the driving speed is set to 0.2 m/s, the adjustment time of the F-SMC controller is reduced by 0.99 s and 1.42 s compared to the FUZZY controller and PID controller, respectively. The variance analysis of the adjustment angle shows that the minimum variance of the F-SMC controller is 0.086, and the error converges to 0, proving that the vehicle trajectory is smoother and ultimately achieves path tracking. The field test results indicate that the path generated by the IA* algorithm can be tracked by the F-SMC controller in the actual environment. Compared to the A* algorithm and FUZZY controller, the path tracking time reduction rate of IA* and F-SMC is 29.34%, and the fuel consumption rate is reduced by 2.75%. This study is aimed at providing a feasible approach for improving the efficiency of tracked agricultural machinery operations, reducing emissions and operating costs.
Research on Yaw Stability Control Strategy Based on Direct Slip Rate Allocation
Authors: Li Jing , Luo Jin , Guo Shiyao , Feng Baidong
Published: January 2024

This paper deals with the integrated control of trajectory tracking and yaw stability for autonomous vehicles. Firstly, a nonlinear vehicle dynamics model is established. The MPC algorithm was used to determine the best front wheel angle. The PID control algorithm is used to ensure the accuracy of longitudinal speed tracking. The sliding mode control algorithm is used to generate additional yaw moment and optimize the distribution of longitudinal tire force. In order to ensure the most effective distribution of the driving torque of the four wheels of the vehicle, the PID algorithm is used to track and manage the longitudinal slip rate of each tire on the bottom layer. Simulation tools such as MATLAB/Simulink and Carsim are used to verify the effectiveness of the multi-closed-loop integrated control technology. Compared with the general control strategy (no slip rate control), the trajectory error of this control algorithm is reduced by 55.6%, which indicates that it has advantages in obtaining a high tracking accuracy and ensuring the stability of autonomous vehicles.
Underwater Image Restoration through Color Correction and UW-Net
Authors: Awan Hafiz Shakeel Ahmad , Mahmood Muhammad Tariq
Published: January 2024

The restoration of underwater images plays a vital role in underwater target detection and recognition, underwater robots, underwater rescue, sea organism monitoring, marine geological surveys, and real-time navigation. In this paper, we propose an end-to-end neural network model, UW-Net, that leverages discrete wavelet transform (DWT) and inverse discrete wavelet transform (IDWT) for effective feature extraction for underwater image restoration. First, a color correction method is applied that compensates for color loss in the red and blue channels. Then, a U-Net based network that applies DWT for down-sampling and IDWT for up-sampling is designed for underwater image restoration. Additionally, a chromatic adaptation transform layer is added to the net to enhance the contrast and color in the restored image. The model is rigorously trained and evaluated using well-known datasets, demonstrating an enhanced performance compared with existing methods across various metrics in experimental evaluations.
Post-Cancellation-Based LLR Refining for MIMO Multiple ARQ Systems
Authors: Park Sangjoon
Published: January 2024

In multiple-input multiple-output (MIMO) multiple automatic repeat request (ARQ) systems, multiple streams with independent hybrid ARQ (HARQ) processes can be simultaneously sent. Thus, the interference from other streams can affect future retransmissions of a packet as well as the current transmission, and proper management of interference at the receiver is required. Therefore, in this paper, a post-cancellation-based log-likelihood ratio (LLR) refining scheme is proposed for MIMO multiple ARQ (MMARQ) systems. In the proposed scheme, after the end of the entire conventional reception procedure for packet decoding, LLR refining is performed for the non-terminated packets that will be sent during the next transmission time interval. For LLR refining, the packet cancellation is performed to cancel only the successfully decoded packets. Thus, the LLRs of the non-terminated packets are refined without any error propagation, including the inter-transmission error propagation. Consequently, the proposed scheme can compensate for the interference problem in MMARQ systems and improve system performance. In order to utilize the error detection results of decoded codewords, the proposed scheme should be performed after the end of the entire reception procedure for packet decoding. Therefore, as the post-processing scheme, the proposed scheme can be employed to any existing LLR-level combining-based MMARQ receiver without changing the original procedure. Simulation results verify that the proposed scheme can significantly improve the error performance and throughput of MMARQ systems, especially for hard-decision interference cancellation-based receivers and high-order modulation. In addition, compared with the conventional reception procedure, the proposed scheme requires a smaller computational complexity in most of the simulated SNR region. Therefore, the proposed LLR refining scheme can be considered as an effective and practical post-processing scheme for an MMARQ receiver.
Interface Contact Thermal Resistance of Die Attach in High-Power Laser Diode Packages
Authors: Deng Liting , Li Te , Wang Zhenfu , Zhang Pu , Wu Shunhua , Liu Jiachen , Zhang Junyue , Chen Lang , Zhang Jiachen , Huang Weizhou , Zhang Rui
Published: January 2024

The reliability of packaged laser diodes is heavily dependent on the quality of the die attach. Even a small void or delamination may result in a sudden increase in junction temperature, eventually leading to failure of the operation. The contact thermal resistance at the interface between the die attach and the heat sink plays a critical role in thermal management of high-power laser diode packages. This paper focuses on the investigation of interface contact thermal resistance of the die attach using thermal transient analysis. The structure function of the heat flow path in the T3ster thermal resistance testing experiment is utilized. By analyzing the structure function of the transient thermal characteristics, it was determined that interface thermal resistance between the chip and solder was 0.38 K/W, while the resistance between solder and heat sink was 0.36 K/W. The simulation and measurement results showed excellent agreement, indicating that it is possible to accurately predict the interface contact area of the die attach in the F-mount packaged single emitter laser diode. Additionally, the proportion of interface contact thermal resistance in the total package thermal resistance can be used to evaluate the quality of the die attach.
Optimal Control of Brushless Doubly Fed Wind Power Generator under Zero-Voltage Ride-Through
Authors: Xu Junyang , Nie Pengcheng
Published: January 2024

In the grid-connected operation dynamics of brushless doubly fed generators (BDFGs), a dip in the grid voltage is equivalent to suddenly adding a reverse voltage source at the parallel node. By deriving the expressions of the transient current of power winding (PW), control winding (CW), and rotor winding (RW) of a BDFG in the complex frequency domain under a natural state, it was concluded that the overshoot and oscillation time are affected by the CW voltage, the drop degree and phase of the grid voltage, and the rotor speed. Therefore, an optimal control strategy is proposed. A state model with the CW current as the state variable was constructed using the Pontryagin minimum principle. The finite-time integral value of the square of the electromagnetic torque was set as the objective function to achieve the minimum value that could suppress the overshoot and oscillation of the electromagnetic torque, and the optimal CW voltage command value was directly solved to accelerate the convergence of the BDFG’s physical quantities, thereby reducing the amplitude. Finally, the feasibility of the optimal control algorithm was verified using tests on an experimental platform.
Bio-Dealcoholization of Wines: Can Yeast Make Lighter Wines?
Authors: Afonso Sílvia Martins , Inês António , Vilela Alice
Published: January 2024

The relationship between climate change and viticulture has become increasingly apparent in recent years. Rising temperatures have been a critical factor in early grape ripening. This, in turn, has led to wines with imbalanced acidity and, more importantly, higher alcohol content and pH values. Today, consumers demand high-quality and healthy products, and this trend has extended to wine consumption. Consumers prefer wines with reduced alcohol content due to the health risks associated with alcohol consumption. To meet this demand, researchers have developed modified yeast strains that reduce wine alcohol content during fermentation. These strains ferment less sugar or redirect carbon metabolism. However, their use may pose challenges, such as producing undesired secondary metabolites that can affect wine characteristics. Additionally, consumers are still divided on using genetically modified organisms (GMOs) in food and beverages. This review examines the impact of climate change on wine quality and consumer perception, taking into account new technologies used to reduce wine alcohol content or produce low-alcohol-content wines, such as low-cost techniques like bio-dealcoholization performed by non-GMO wine yeast, Saccharomyces, and non-Saccharomyces.