The 2023 MDPI Annual Report has
been released!
 
3 pages, 166 KiB  
Editorial
Special Issue “Diagnosis and Treatment of Rare Diseases”
by Álvaro Hermida-Ameijeiras
J. Clin. Med. 2024, 13(9), 2574; https://doi.org/10.3390/jcm13092574 (registering DOI) - 27 Apr 2024
Abstract
Rare diseases (RDs) represent a large and heterogeneous group of low-prevalence conditions, and 473 million people could be affected worldwide [...] Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Rare Diseases)
14 pages, 1652 KiB  
Article
Fetal Hypoglycemia Induced by Placental SLC2A3-RNA Interference Alters Fetal Pancreas Development and Transcriptome at Mid-Gestation
by Victoria C. Kennedy, Cameron S. Lynch, Amelia R. Tanner, Quinton A. Winger, Ahmed Gad, Paul J. Rozance and Russell V. Anthony
Int. J. Mol. Sci. 2024, 25(9), 4780; https://doi.org/10.3390/ijms25094780 (registering DOI) - 27 Apr 2024
Abstract
Glucose, the primary energy substrate for fetal oxidative processes and growth, is transferred from maternal to fetal circulation down a concentration gradient by placental facilitative glucose transporters. In sheep, SLC2A1 and SLC2A3 are the primary transporters available in the placental epithelium, with SLC2A3 [...] Read more.
Glucose, the primary energy substrate for fetal oxidative processes and growth, is transferred from maternal to fetal circulation down a concentration gradient by placental facilitative glucose transporters. In sheep, SLC2A1 and SLC2A3 are the primary transporters available in the placental epithelium, with SLC2A3 located on the maternal-facing apical trophoblast membrane and SLC2A1 located on the fetal-facing basolateral trophoblast membrane. We have previously reported that impaired placental SLC2A3 glucose transport resulted in smaller, hypoglycemic fetuses with reduced umbilical artery insulin and glucagon concentrations, in addition to diminished pancreas weights. These findings led us to subject RNA derived from SLC2A3-RNAi (RNA interference) and NTS-RNAi (non-targeting sequence) fetal pancreases to qPCR followed by transcriptomic analysis. We identified a total of 771 differentially expressed genes (DEGs). Upregulated pathways were associated with fat digestion and absorption, particularly fatty acid transport, lipid metabolism, and cholesterol biosynthesis, suggesting a potential switch in energetic substrates due to hypoglycemia. Pathways related to molecular transport and cell signaling in addition to pathways influencing growth and metabolism of the developing pancreas were also impacted. A few genes directly related to gluconeogenesis were also differentially expressed. Our results suggest that fetal hypoglycemia during the first half of gestation impacts fetal pancreas development and function that is not limited to β cell activity. Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Treatment of Pregnancy Complications)
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25 pages, 2233 KiB  
Article
A Comparative Analysis of Sediment Concentration Using Artificial Intelligence and Empirical Equations
by Muhammad Ashraf Khalid, Abdul Razzaq Ghumman and Ghufran Ahmed Pasha
Hydrology 2024, 11(5), 63; https://doi.org/10.3390/hydrology11050063 (registering DOI) - 27 Apr 2024
Abstract
Morphological changes in canals are greatly influenced by sediment load dynamics, whose estimation is a challenging task because of the non-linear behavior of the sediment concentration variables. This study aims to compare different techniques including Artificial Intelligence Models (AIM) and empirical equations for [...] Read more.
Morphological changes in canals are greatly influenced by sediment load dynamics, whose estimation is a challenging task because of the non-linear behavior of the sediment concentration variables. This study aims to compare different techniques including Artificial Intelligence Models (AIM) and empirical equations for estimating sediment load in Upper Chenab Canal based on 10 years of sediment data from 2012 to 2022. The methodology involves utilization of a newly developed empirical equation, the Ackers and White formula and AIM including 20 neural networks with 10 training functions for both Double and Triple Layers, two Artificial Neuro-Fuzzy Inference System (ANFIS), Particle Swarm Optimization, and Ensemble Learning Random Forest models. Sensitivity analysis of sediment concentration variables has also been performed using various scenarios of input combinations in AIM. A state-of-the-art optimization technique has been used to identify the parameters of the empirical equation, and its performance is tested against AIM and the Ackers and White equation. To compare the performance of various models, four types of errors—correlation coefficient (R), T-Test, Analysis of Variance (ANOVA), and Taylor’s Diagram—have been used. The results of the study show successful application of Artificial Intelligence (AI) and empirical equations to capture the non-linear behavior of sediment concentration variables and indicate that, among all models, the ANFIS outperformed in simulating the total sediment load with a high R-value of 0.958. The performance of various models in simulating sediment concentration was assessed, with notable accuracy achieved by models AIM11 and AIM21. Moreover, the newly developed equation performed better (R = 0.92) compared to the Ackers and White formula (R = 0.88). In conclusion, the study provides valuable insights into sediment concentration dynamics in canals, highlighting the effectiveness of AI models and optimization techniques. It is suggested to incorporate other AI techniques and use multiple canals data in modeling for the future. Full article
23 pages, 1275 KiB  
Article
How the Ethylene Biosynthesis Pathway of Semi-Halophytes Is Modified with Prolonged Salinity Stress Occurrence?
by Miron Gieniec, Zbigniew Miszalski, Piotr Rozpądek, Roman J. Jędrzejczyk, Małgorzata Czernicka and Michał Nosek
Int. J. Mol. Sci. 2024, 25(9), 4777; https://doi.org/10.3390/ijms25094777 (registering DOI) - 27 Apr 2024
Abstract
The mechanism of ethylene (ET)–regulated salinity stress response remains largely unexplained, especially for semi-halophytes and halophytes. Here, we present the results of the multifaceted analysis of the model semi-halophyte Mesembryanthemum crystallinum L. (common ice plant) ET biosynthesis pathway key components’ response to prolonged [...] Read more.
The mechanism of ethylene (ET)–regulated salinity stress response remains largely unexplained, especially for semi-halophytes and halophytes. Here, we present the results of the multifaceted analysis of the model semi-halophyte Mesembryanthemum crystallinum L. (common ice plant) ET biosynthesis pathway key components’ response to prolonged (14 days) salinity stress. Transcriptomic analysis revealed that the expression of 3280 ice plant genes was altered during 14-day long salinity (0.4 M NaCl) stress. A thorough analysis of differentially expressed genes (DEGs) showed that the expression of genes involved in ET biosynthesis and perception (ET receptors), the abscisic acid (ABA) catabolic process, and photosynthetic apparatus was significantly modified with prolonged stressor presence. To some point this result was supported with the expression analysis of the transcript amount (qPCR) of key ET biosynthesis pathway genes, namely ACS6 (1-aminocyclopropane-1-carboxylate synthase) and ACO1 (1-aminocyclopropane-1-carboxylate oxidase) orthologs. However, the pronounced circadian rhythm observed in the expression of both genes in unaffected (control) plants was distorted and an evident downregulation of both orthologs’ was induced with prolonged salinity stress. The UPLC-MS analysis of the ET biosynthesis pathway rate-limiting semi-product, namely of 1-aminocyclopropane-1-carboxylic acid (ACC) content, confirmed the results assessed with molecular tools. The circadian rhythm of the ACC production of NaCl-treated semi-halophytes remained largely unaffected by the prolonged salinity stress episode. We speculate that the obtained results represent an image of the steady state established over the past 14 days, while during the first hours of the salinity stress response, the view could be completely different. Full article
(This article belongs to the Special Issue Molecular Regulatory Mechanisms of Salinity Tolerance in Plants 2.0)
23 pages, 1763 KiB  
Article
Methamphetamine and the Synthetic Cathinone 3,4-Methylenedioxypyrovalerone (MDPV) Produce Persistent Effects on Prefrontal and Striatal Microglial Morphology and Neuroimmune Signaling Following Repeated Binge-like Intake in Male and Female Rats
by Erin K. Nagy, Paula F. Overby, Jonna M. Leyrer-Jackson, Vincent F. Carfagno, Amanda M. Acuña and M. Foster Olive
Brain Sci. 2024, 14(5), 435; https://doi.org/10.3390/brainsci14050435 (registering DOI) - 27 Apr 2024
Abstract
Psychostimulants alter cellular morphology and activate neuroimmune signaling in a number of brain regions, yet few prior studies have investigated their persistence beyond acute abstinence or following high levels of voluntary drug intake. In this study, we examined the effects of the repeated [...] Read more.
Psychostimulants alter cellular morphology and activate neuroimmune signaling in a number of brain regions, yet few prior studies have investigated their persistence beyond acute abstinence or following high levels of voluntary drug intake. In this study, we examined the effects of the repeated binge-like self-administration (96 h/week for 3 weeks) of methamphetamine (METH) and 21 days of abstinence in female and male rats on changes in cell density, morphology, and cytokine levels in two addiction-related brain regions—the prefrontal cortex (PFC) and dorsal striatum (DStr). We also examined the effects of similar patterns of intake of the cocaine-like synthetic cathinone derivative 3,4-methylenedioxypyrovalerone (MDPV) or saline as a control. Robust levels of METH and MDPV intake (~500–1000 infusions per 96 h period) were observed in both sexes. We observed no changes in astrocyte or neuron density in either region, but decreases in dendritic spine densities were observed in PFC pyramidal and DStr medium spiny neurons. The microglial cell density was decreased in the PFC of METH self-administering animals, accompanied by evidence of microglial apoptosis. Changes in microglial morphology (e.g., decreased territorial volume and ramification and increased cell soma volume) were also observed, indicative of an inflammatory-like state. Multiplex analyses of PFC and DStr cytokine content revealed elevated levels of various interleukins and chemokines only in METH self-administering animals, with region- and sex-dependent effects. Our findings suggest that voluntary binge-like METH or MDPV intake induces similar cellular perturbations in the brain, but they are divergent neuroimmune responses that persist beyond the initial abstinence phase. Full article
14 pages, 1558 KiB  
Article
Severity of Omicron Subvariants and Vaccine Impact in Catalonia, Spain
by Víctor López de Rioja, Luca Basile, Aida Perramon-Malavez, Érica Martínez-Solanas, Daniel López, Sergio Medina Maestro, Ermengol Coma, Francesc Fina, Clara Prats, Jacobo Mendioroz Peña and Enric Alvarez-Lacalle
Vaccines 2024, 12(5), 466; https://doi.org/10.3390/vaccines12050466 (registering DOI) - 27 Apr 2024
Abstract
In the current COVID-19 landscape dominated by Omicron subvariants, understanding the timing and efficacy of vaccination against emergent lineages is crucial for planning future vaccination campaigns, yet detailed studies stratified by subvariant, vaccination timing, and age groups are scarce. This retrospective study analyzed [...] Read more.
In the current COVID-19 landscape dominated by Omicron subvariants, understanding the timing and efficacy of vaccination against emergent lineages is crucial for planning future vaccination campaigns, yet detailed studies stratified by subvariant, vaccination timing, and age groups are scarce. This retrospective study analyzed COVID-19 cases from December 2021 to January 2023 in Catalonia, Spain, focusing on vulnerable populations affected by variants BA.1, BA.2, BA.5, and BQ.1 and including two national booster campaigns. Our database includes detailed information such as dates of diagnosis, hospitalization and death, last vaccination, and cause of death, among others. We evaluated the impact of vaccination on disease severity by age, variant, and vaccination status, finding that recent vaccination significantly mitigated severity across all Omicron subvariants, although efficacy waned six months post-vaccination, except for BQ.1, which showed more stable levels. Unvaccinated individuals had higher hospitalization and mortality rates. Our results highlight the importance of periodic vaccination to reduce severe outcomes, which are influenced by variant and vaccination timing. Although the seasonality of COVID-19 is uncertain, our analysis suggests the potential benefit of annual vaccination in populations >60 years old, probably in early fall, if COVID-19 eventually exhibits a major peak similar to other respiratory viruses. Full article
(This article belongs to the Special Issue COVID-19 and Vaccination Strategies in Global Health)
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14 pages, 3764 KiB  
Article
The Formation–Structure–Functionality Relationship of Catalyst Layers in Proton Exchange Membrane Fuel Cells
by Donglei Yang, Nitul Kakati, Mrittunjoy Sarker, Felipe Mojica and Po-Ya Abel Chuang
Energies 2024, 17(9), 2093; https://doi.org/10.3390/en17092093 (registering DOI) - 27 Apr 2024
Abstract
Understanding the relationship between the formation, structure, and functionality of catalyst layers is crucial for designing catalyst layers with specific high-current-density operations. In this study, we investigated the impact of the ionomer-to-carbon (I/C) ratio and solid content on transport properties. We conducted fuel [...] Read more.
Understanding the relationship between the formation, structure, and functionality of catalyst layers is crucial for designing catalyst layers with specific high-current-density operations. In this study, we investigated the impact of the ionomer-to-carbon (I/C) ratio and solid content on transport properties. We conducted fuel cell performance and diagnostic measurements to demonstrate the combined effects of the I/C ratio and solid content on the mass transport, particularly oxygen transport. To elucidate the roles of the I/C ratio and solid content in catalyst layer formation, we utilized dynamic light scattering and rheological measurements. By analyzing the local and global structure of ionomer-Pt/C assemblages in the catalyst inks, we observed that the I/C ratio and solid content influence the competition between homo-aggregation and hetero-aggregation, the strengths of inter- and intra-cluster bonds, and the rigidity and connectivity of the particulate structure. Additionally, high-shear-application simulations tend to reduce the connectivity of the particulate network and induce cluster densification, unless the global structure is mechanically stable and resilient. Based on this understanding, we established the formation–structure–functionality relationship for catalyst layers, thereby providing fundamental insights for designing catalyst layers tailored to specific functionalities. Full article
(This article belongs to the Special Issue Advances in Hydrogen Energy III)
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12 pages, 631 KiB  
Review
Paediatric Atopic Dermatitis: The Unexpected Impact on Life with a Specific Look at the Molecular Level
by Silvia Artusa, Giorgia Mazzuca, Giorgio Piacentini, Riccardo Castagnoli, Gian Luigi Marseglia, Angelo Pietrobelli and Luca Pecoraro
Int. J. Mol. Sci. 2024, 25(9), 4778; https://doi.org/10.3390/ijms25094778 (registering DOI) - 27 Apr 2024
Abstract
Atopic dermatitis (AD) is a condition with a multifactorial aetiology that affects the skin. It most often begins at preschool age and involves the skin. The disease’s main symptom is intense itching, which occurs especially at night and affects the child’s sleep, negatively [...] Read more.
Atopic dermatitis (AD) is a condition with a multifactorial aetiology that affects the skin. It most often begins at preschool age and involves the skin. The disease’s main symptom is intense itching, which occurs especially at night and affects the child’s sleep, negatively impacting the quality of life of affected children and, consequently, their families. The difficulty in resting during the night leads to many problems during the day, particularly behavioural disorders and difficulties in paying attention at school, which results in learning impairment. The unexpected symptoms of AD are caused by pathophysiological processes that include many molecular pathways and inflammatory cytokines such as IL-31, IL-1, IL-2, TNF-a, and IL-6. Drawing on a comprehensive review of the literature in PubMed/MedLine, our review offers an in-depth exploration of both the psychosocial impacts of AD and the molecular processes that contribute to this disorder. Full article
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25 pages, 3325 KiB  
Review
Secreted Aspartic Proteinases: Key Factors in Candida Infections and Host-Pathogen Interactions
by Grazyna Bras, Dorota Satala, Magdalena Juszczak, Kamila Kulig, Ewelina Wronowska, Aneta Bednarek, Marcin Zawrotniak, Maria Rapala-Kozik and Justyna Karkowska-Kuleta
Int. J. Mol. Sci. 2024, 25(9), 4775; https://doi.org/10.3390/ijms25094775 (registering DOI) - 27 Apr 2024
Abstract
Extracellular proteases are key factors contributing to the virulence of pathogenic fungi from the genus Candida. Their proteolytic activities are crucial for extracting nutrients from the external environment, degrading host defenses, and destabilizing the internal balance of the human organism. Currently, the [...] Read more.
Extracellular proteases are key factors contributing to the virulence of pathogenic fungi from the genus Candida. Their proteolytic activities are crucial for extracting nutrients from the external environment, degrading host defenses, and destabilizing the internal balance of the human organism. Currently, the enzymes most frequently described in this context are secreted aspartic proteases (Saps). This review comprehensively explores the multifaceted roles of Saps, highlighting their importance in biofilm formation, tissue invasion through the degradation of extracellular matrix proteins and components of the coagulation cascade, modulation of host immune responses via impairment of neutrophil and monocyte/macrophage functions, and their contribution to antifungal resistance. Additionally, the diagnostic challenges associated with Candida infections and the potential of Saps as biomarkers were discussed. Furthermore, we examined the prospects of developing vaccines based on Saps and the use of protease inhibitors as adjunctive therapies for candidiasis. Given the complex biology of Saps and their central role in Candida pathogenicity, a multidisciplinary approach may pave the way for innovative diagnostic strategies and open new opportunities for innovative clinical interventions against candidiasis. Full article
(This article belongs to the Special Issue Microbial Proteases: Structure, Function and Role in Pathogenesis)
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20 pages, 11589 KiB  
Article
Experimental Evaluation of an SDR-Based UAV Localization System
by Cristian Codău, Rareș-Călin Buta, Andra Păstrăv, Paul Dolea, Tudor Palade and Emanuel Puschita
Sensors 2024, 24(9), 2789; https://doi.org/10.3390/s24092789 (registering DOI) - 27 Apr 2024
Abstract
UAV communications have seen a rapid rise in the last few years. The drone class of UAV has particularly become more widespread around the world, and illicit behavior using drones has become a problem. Therefore, localization, tracking, and even taking control of drones [...] Read more.
UAV communications have seen a rapid rise in the last few years. The drone class of UAV has particularly become more widespread around the world, and illicit behavior using drones has become a problem. Therefore, localization, tracking, and even taking control of drones have also gained interest. Knowing the frequency of a target signal, its position can be determined (as the angle of arrival with respect to a fixed receiver point) using radio frequency-based localization techniques. One such technique is represented by the subspace-based algorithms that offer highly accurate results. This paper presents the implementation of the MUSIC algorithm on an SDR-based system using a uniform circular antenna array and its experimental evaluation in relevant outdoor environments for drone localization. The results show the capability of the system to indicate the AoA of the target signal. The results are compared with the actual direction computed from the log files of the drone application and validated with a professional direction-finding solution (i.e., Narda SignalShark equipped with the automatic direction-finding antenna). Full article
(This article belongs to the Section Communications)
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15 pages, 4594 KiB  
Article
Intra-Examiner Reliability and Validity of Sagittal Cervical Spine Mensuration Methods Using Deep Convolutional Neural Networks
by Mohammad Mehdi Hosseini, Mohammad H. Mahoor, Jason W. Haas, Joseph R. Ferrantelli, Anne-Lise Dupuis, Jason O. Jaeger and Deed E. Harrison
J. Clin. Med. 2024, 13(9), 2573; https://doi.org/10.3390/jcm13092573 (registering DOI) - 27 Apr 2024
Abstract
Background: The biomechanical analysis of spine and postural misalignments is important for surgical and non-surgical treatment of spinal pain. We investigated the examiner reliability of sagittal cervical alignment variables compared to the reliability and concurrent validity of computer vision algorithms used in the [...] Read more.
Background: The biomechanical analysis of spine and postural misalignments is important for surgical and non-surgical treatment of spinal pain. We investigated the examiner reliability of sagittal cervical alignment variables compared to the reliability and concurrent validity of computer vision algorithms used in the PostureRay® software 2024. Methods: A retrospective database of 254 lateral cervical radiographs of patients between the ages of 11 and 86 is studied. The radiographs include clearly visualized C1–C7 vertebrae that were evaluated by a human using the software. To evaluate examiner reliability and the concurrent validity of the trained CNN performance, two blinded trials of radiographic digitization were performed by an extensively trained expert user (US) clinician with a two-week interval between trials. Then, the same clinician used the trained CNN twice to reproduce the same measures within a 2-week interval on the same 254 radiographs. Measured variables included segmental angles as relative rotation angles (RRA) C1–C7, Cobb angles C2–C7, relative segmental translations (RT) C1–C7, anterior translation C2–C7, and absolute rotation angle (ARA) C2–C7. Data were remotely extracted from the examiner’s PostureRay® system for data collection and sorted based on gender and stratification of degenerative changes. Reliability was assessed via intra-class correlations (ICC), root mean squared error (RMSE), and R2 values. Results: In comparing repeated measures of the CNN network to itself, perfect reliability was found for the ICC (1.0), RMSE (0), and R2 (1). The reliability of the trained expert US was in the excellent range for all variables, where 12/18 variables had ICCs ≥ 0.9 and 6/18 variables were 0.84 ≤ ICCs ≤ 0.89. Similarly, for the expert US, all R2 values were in the excellent range (R2 ≥ 0.7), and all RMSEs were small, being 0.42 ≤ RMSEs ≤ 3.27. Construct validity between the expert US and the CNN network was found to be in the excellent range with 18/18 ICCs in the excellent range (ICCs ≥ 0.8), 16/18 R2 values in the strong to excellent range (R2 ≥ 0.7), and 2/18 in the good to moderate range (R2 RT C6/C7 = 0.57 and R2 Cobb C6/C7 = 0.64. The RMSEs for expert US vs. the CNN network were small, being 0.37 ≤ RMSEs ≤ 2.89. Conclusions: A comparison of repeated measures within the computer vision CNN network and expert human found exceptional reliability and excellent construct validity when comparing the computer vision to the human observer. Full article
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22 pages, 9247 KiB  
Article
Ultrasonic-Assisted Decoloration of Polysaccharides from Seedless Chestnut Rose (Rosa sterilis) Fruit: Insight into the Impact of Different Macroporous Resins on Its Structural Characterization and In Vitro Hypoglycemic Activity
by Guangjing Chen, Meiwen Sun, Kaiwen Chen, Lisha Wang and Juyan Sun
Foods 2024, 13(9), 1349; https://doi.org/10.3390/foods13091349 (registering DOI) - 27 Apr 2024
Abstract
Pigments within polysaccharides pose significant challenges when analyzing their structural characteristics and evaluating their biological activities, making decolorization a crucial step in purifying these biomolecules. In this research, a novel approach using ultrasound-assisted static adsorption with macroporous resins was employed to decolorize polysaccharides [...] Read more.
Pigments within polysaccharides pose significant challenges when analyzing their structural characteristics and evaluating their biological activities, making decolorization a crucial step in purifying these biomolecules. In this research, a novel approach using ultrasound-assisted static adsorption with macroporous resins was employed to decolorize polysaccharides extracted from seedless chestnut rose (Rosa sterilis S. D. Shi) fruit (RSP). Among the fourteen tested resins, AB-8, D101, D4020, HPD100, and S8 were identified as the most effective, demonstrating superior decoloration efficiency and polysaccharide recovery. Further examinations of RSPs treated with these five resins revealed distinct effects on their uronic acid levels, monosaccharide makeup, molecular weight, surface structure, and hypoglycemic properties. The RSP treated with HPD100 resin stood out for having the highest uronic acid content, smallest particle size, and lowest molecular weight, leading to the most notable inhibition of α-glucosidase activity through a mixed inhibition model. The application of HPD100 resin in the decolorization process not only potentially preserved the macromolecular structure of RSP but also enhanced its hypoglycemic efficacy. These findings provide a solid theoretical basis for further exploring RSP as a component of functional foods, underscoring the effectiveness of the ultrasound-assisted resin adsorption method in polysaccharide purification. Full article
21 pages, 6087 KiB  
Article
A Hidden Eruption: The 21 May 2023 Paroxysm of the Etna Volcano (Italy)
by Emanuela De Beni, Cristina Proietti, Simona Scollo, Massimo Cantarero, Luigi Mereu, Francesco Romeo, Laura Pioli, Mariangela Sciotto and Salvatore Alparone
Remote Sens. 2024, 16(9), 1555; https://doi.org/10.3390/rs16091555 (registering DOI) - 27 Apr 2024
Abstract
On 21 May 2023, a hidden eruption occurred at the Southeast Crater (SEC) of Etna (Italy); indeed, bad weather prevented its direct and remote observation. Tephra fell toward the southwest, and two lava flows propagated along the SEC’s southern and eastern flanks. The [...] Read more.
On 21 May 2023, a hidden eruption occurred at the Southeast Crater (SEC) of Etna (Italy); indeed, bad weather prevented its direct and remote observation. Tephra fell toward the southwest, and two lava flows propagated along the SEC’s southern and eastern flanks. The monitoring system of the Istituto Nazionale di Geofisica e Vulcanologia testified to its occurrence. We analyzed the seismic and infrasound signals to constrain the temporal evolution of the fountain, which lasted about 5 h. We finally reached Etna’s summit two weeks later and found an unexpected pyroclastic density current (PDC) deposit covering the southern lava flow at its middle portion. We performed unoccupied aerial system and field surveys to reconstruct in 3D the SEC, lava flows, and PDC deposits and to collect some samples. The data allowed for detailed mapping, quantification, and characterization of the products. The resulting lava flows and PDC deposit volumes were (1.54 ± 0.47) × 106 m3 and (1.30 ± 0.26) × 105 m3, respectively. We also analyzed ground-radar and satellite data to evaluate that the plume height ranges between 10 and 15 km. This work is a comprehensive analysis of the fieldwork, UAS, volcanic tremor, infrasound, radar, and satellite data. Our results increase awareness of the volcanic activity and potential dangers for visitors to Etna’s summit area. Full article
21 pages, 623 KiB  
Review
Advancements in the Understanding of Small-Cell Neuroendocrine Cervical Cancer: Where We Stand and What Lies Ahead
by Yan Wang, Hui Qiu, Rongjie Lin, Weiwei Hong, Jiahao Lu, Huan Ling, Xiaoge Sun and Chunxu Yang
J. Pers. Med. 2024, 14(5), 462; https://doi.org/10.3390/jpm14050462 (registering DOI) - 27 Apr 2024
Abstract
Small-cell neuroendocrine cervical carcinoma (SCNCC) is a rare yet aggressive gynecological malignancy associated with dismal clinical outcomes. Its rarity has led to a limited number of retrospective studies and an absence of prospective research, posing significant challenges for evidence-based treatment approaches. As a [...] Read more.
Small-cell neuroendocrine cervical carcinoma (SCNCC) is a rare yet aggressive gynecological malignancy associated with dismal clinical outcomes. Its rarity has led to a limited number of retrospective studies and an absence of prospective research, posing significant challenges for evidence-based treatment approaches. As a result, most gynecologic oncology centers have limited experience with this tumor, emphasizing the urgent need for a comprehensive review and summary. This article systematically reviews the pathogenesis, immunohistochemical and molecular characteristics, prognostic factors, and clinical management of gynecologic SCNCC. We specifically focused on reviewing the distinct genomic characteristics of SCNCC identified via next-generation sequencing technologies, including loss of heterozygosity (LOH), somatic mutations, structural variations (SVs), and microRNA alterations. The identification of these actionable genomic events offers promise for discovering new molecular targets for drug development and enhancing therapeutic outcomes. Additionally, we delve deeper into key clinical challenges, such as determining the optimal treatment modality between chemoradiation and surgery for International Federation of Gynecology and Obstetrics (FIGO) stage I phase patients within a precision stratification framework, as well as the role of targeted therapy within the homologous recombination (HR) pathway, immune checkpoint inhibitors (ICIs), and prophylactic cranial irradiation (PCI) in the management of SCNCC. Finally, we anticipate the utilization of multiple SCNCC models, including cancer tissue-originated spheroid (CTOS) lines and patient-derived xenografts (PDXs), to decipher driver events and develop individualized therapeutic strategies for clinical application. Full article
(This article belongs to the Section Evidence Based Medicine)
16 pages, 527 KiB  
Article
Measuring the Density Matrix of Quantum-Modeled Cognitive States
by Wendy Xiomara Chavarría-Garza, Osvaldo Aquines-Gutiérrez, Ayax Santos-Guevara, Humberto Martínez-Huerta, Jose Ruben Morones-Ibarra and Jonathan Rincon Saucedo
Quantum Rep. 2024, 6(2), 156-171; https://doi.org/10.3390/quantum6020013 (registering DOI) - 27 Apr 2024
Abstract
Inspired by the principles of quantum mechanics, we constructed a model of students’ misconceptions about heat and temperature, conceptualized as a quantum system represented by a density matrix. Within this framework, the presence or absence of misconceptions is delineated as pure states, while [...] Read more.
Inspired by the principles of quantum mechanics, we constructed a model of students’ misconceptions about heat and temperature, conceptualized as a quantum system represented by a density matrix. Within this framework, the presence or absence of misconceptions is delineated as pure states, while the probability of mixed states is also considered, providing valuable insights into students’ cognition based on the mental models they employ when holding misconceptions. Using the analysis model previously employed by Lei Bao and Edward Redish, we represented these results in a density matrix. In our research, we utilized the Zeo and Zadnik Thermal Concept Evaluation among 282 students from a private university in Northeast Mexico. Our objective was to extract information from the analysis of multiple-choice questions designed to explore preconceptions, offering valuable educational insights beyond the typical Correct–Incorrect binary analysis of classical systems. Our findings reveal a probability of 0.72 for the appearance of misconceptions, 0.28 for their absence, and 0.43 for mixed states, while no significant disparities were observed based on gender or scholarship status, a notable difference was observed among programs (p < 0.05). These results are consistent with the previous literature, confirming a prevalence of misconceptions within the student population. Full article
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26 pages, 23380 KiB  
Article
Monitoring Change and Recovery of an Embayed Beach in Response to Typhoon Storms Using UAV LiDAR
by Qiujia Lei, Xinkai Wang, Yifei Liu, Junli Guo, Tinglu Cai and Xiaoming Xia
Drones 2024, 8(5), 172; https://doi.org/10.3390/drones8050172 (registering DOI) - 27 Apr 2024
Abstract
The monitoring of beach topographical changes and recovery processes under typhoon storm influence has primarily relied on traditional techniques that lack high spatial resolution. Therefore, we used an unmanned aerial vehicle light detection and ranging (UAV LiDAR) system to obtain the four time [...] Read more.
The monitoring of beach topographical changes and recovery processes under typhoon storm influence has primarily relied on traditional techniques that lack high spatial resolution. Therefore, we used an unmanned aerial vehicle light detection and ranging (UAV LiDAR) system to obtain the four time periods of topographic data from Tantou Beach, a sandy beach in Xiangshan County, Zhejiang Province, China, to explore beach topography and geomorphology in response to typhoon events. The UAV LiDAR data in four survey periods showed an overall vertical accuracy of approximately 5 cm. Based on the evaluated four time periods of the UAV LiDAR data, we created four corresponding DEMs for the beach. We calculated the DEM of difference (Dod), which showed that the erosion and siltation on Tantou Beach over different temporal scales had a significant alongshore zonal feature with a broad change range. The tidal level significantly impacted beach erosion and siltation changes. However, the storm surge did not affect the beach area above the spring high-tide level. After storms, siltation occurred above the spring high-tide zone. This study reveals the advantage of UAV LiDAR in monitoring beach changes and provides novel insights into the impacts of typhoon storms on coastal topographic and geomorphological change and recovery processes. Full article
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20 pages, 7435 KiB  
Article
Experimental Research of Ultrasonic Cavitation Evolution Mechanism and Model Optimization of RUREMM on Cylindrical Surface
by Wenjun Tong and Lin Li
Processes 2024, 12(5), 884; https://doi.org/10.3390/pr12050884 (registering DOI) - 27 Apr 2024
Abstract
Micro-pits are widely used in the aerospace and tribology sectors on cylindrical surfaces and electrochemical micromachining which are of great significance for the high material removal rate, absence of tool wear, and mechanical stress, while facing significant challenges such as stray corrosion and [...] Read more.
Micro-pits are widely used in the aerospace and tribology sectors on cylindrical surfaces and electrochemical micromachining which are of great significance for the high material removal rate, absence of tool wear, and mechanical stress, while facing significant challenges such as stray corrosion and low machining efficiency. Aiming at the above problems, this paper proposes a comprehensive method called radial ultrasonic rolling electrochemical micromachining (RUREMM) in which an ultrasonic field has been added onto the cylindrical surface. First, a theoretical model was created to gain the rules of the formation and collapse of bubbles in the liquid medium. Second, to analyze the optimal size of the cathode electrode, the COMSOL5.2 simulation software was proposed to research the influence of the electric field on the different dimensions, and the influences of different parameters in RUREMM on material depth/diameter ratio and roughness are explored through processing experiments. Research results found that the cavitation bubble undergoes expansion, compression, collapse and oscillation, where the max deviation is less than 12.5%. The optimized size was chosen as 200 × 200 μm2 and an electrode spacing of 800 μm through a series of electric field model simulation analyses. Relevant experiments show that the minimum pits with a width of 212.4 μm, a depth of 21.8 μm, and a surface roughness (Ra) of 0.253 μm were formed due to the optimized parameters. The research results can offer theoretical references for fabricating micro-pits with enhanced surface quality and processing precision on cylindrical surfaces. Full article
(This article belongs to the Section Manufacturing Processes and Systems)
19 pages, 3578 KiB  
Article
Unraveling the Etiology of Dilated Cardiomyopathy through Differential miRNA–mRNA Interactome
by Fernando Bonet, Francisco Hernandez-Torres, Mónica Ramos-Sánchez, Maribel Quezada-Feijoo, Aníbal Bermúdez-García, Tomás Daroca, Elena Alonso-Villa, Carlos García-Padilla, Alipio Mangas and Rocio Toro
Biomolecules 2024, 14(5), 524; https://doi.org/10.3390/biom14050524 (registering DOI) - 27 Apr 2024
Abstract
Dilated cardiomyopathy (DCM) encompasses various acquired or genetic diseases sharing a common phenotype. The understanding of pathogenetic mechanisms and the determination of the functional effects of each etiology may allow for tailoring different therapeutic strategies. MicroRNAs (miRNAs) have emerged as key regulators in [...] Read more.
Dilated cardiomyopathy (DCM) encompasses various acquired or genetic diseases sharing a common phenotype. The understanding of pathogenetic mechanisms and the determination of the functional effects of each etiology may allow for tailoring different therapeutic strategies. MicroRNAs (miRNAs) have emerged as key regulators in cardiovascular diseases, including DCM. However, their specific roles in different DCM etiologies remain elusive. Here, we applied mRNA-seq and miRNA-seq to identify the gene and miRNA signature from myocardial biopsies from four patients with DCM caused by volume overload (VCM) and four with ischemic DCM (ICM). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used for differentially expressed genes (DEGs). The miRNA–mRNA interactions were identified by Pearson correlation analysis and miRNA target-prediction programs. mRNA-seq and miRNA-seq were validated by qRT-PCR and miRNA–mRNA interactions were validated by luciferase assays. We found 112 mRNAs and five miRNAs dysregulated in VCM vs. ICM. DEGs were positively enriched for pathways related to the extracellular matrix (ECM), mitochondrial respiration, cardiac muscle contraction, and fatty acid metabolism in VCM vs. ICM and negatively enriched for immune-response-related pathways, JAK-STAT, and NF-kappa B signaling. We identified four pairs of negatively correlated miRNA–mRNA: miR-218-5p-DDX6, miR-218-5p-TTC39C, miR-218-5p-SEMA4A, and miR-494-3p-SGMS2. Our study revealed novel miRNA–mRNA interaction networks and signaling pathways for VCM and ICM, providing novel insights into the development of these DCM etiologies. Full article
(This article belongs to the Section Molecular Genetics)
15 pages, 929 KiB  
Article
Exploring Data Input Problems in Mixed Reality Environments: Proposal and Evaluation of Natural Interaction Techniques
by Jingzhe Zhang, Tiange Chen, Wenjie Gong, Jiayue Liu and Jiangjie Chen
Future Internet 2024, 16(5), 150; https://doi.org/10.3390/fi16050150 (registering DOI) - 27 Apr 2024
Abstract
Data input within mixed reality environments poses significant interaction challenges, notably in immersive visual analytics applications. This study assesses five numerical input techniques: three benchmark methods (Touch-Slider, Keyboard, Pinch-Slider) and two innovative multimodal techniques (Bimanual Scaling, Gesture and Voice). An experimental design was [...] Read more.
Data input within mixed reality environments poses significant interaction challenges, notably in immersive visual analytics applications. This study assesses five numerical input techniques: three benchmark methods (Touch-Slider, Keyboard, Pinch-Slider) and two innovative multimodal techniques (Bimanual Scaling, Gesture and Voice). An experimental design was employed to compare these techniques’ input efficiency, accuracy, and user experience across varying precision and distance conditions. The findings reveal that multimodal techniques surpass slider methods in input efficiency yet are comparable to keyboards; the voice method excels in reducing cognitive load but falls short in accuracy; and the scaling method marginally leads in user satisfaction but imposes a higher physical load. Furthermore, this study outlines these techniques’ pros and cons and offers design guidelines and future research directions. Full article
17 pages, 1345 KiB  
Review
Machine Learning and Deep Learning Strategies for Chinese Hamster Ovary Cell Bioprocess Optimization
by Tiffany-Marie D. Baako, Sahil Kaushik Kulkarni, Jerome L. McClendon, Sarah W. Harcum and Jordon Gilmore
Fermentation 2024, 10(5), 234; https://doi.org/10.3390/fermentation10050234 (registering DOI) - 27 Apr 2024
Abstract
The use of machine learning and deep learning has become prominent within various fields of bioprocessing for countless modeling and prediction tasks. Previous reviews have emphasized machine learning applications in various fields of bioprocessing, including biomanufacturing. This comprehensive review highlights many of the [...] Read more.
The use of machine learning and deep learning has become prominent within various fields of bioprocessing for countless modeling and prediction tasks. Previous reviews have emphasized machine learning applications in various fields of bioprocessing, including biomanufacturing. This comprehensive review highlights many of the different machine learning and multivariate analysis techniques that have been utilized within Chinese hamster ovary cell biomanufacturing, specifically due to their rising significance in the industry. Applications of machine and deep learning within other bioprocessing industries are also briefly discussed. Full article
(This article belongs to the Special Issue Feature Review Papers in Fermentation Process Design 2023)
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12 pages, 3292 KiB  
Article
Spatial Distribution of Macrophage and Lymphocyte Subtypes within Tumor Microenvironment to Predict Recurrence of Non-Muscle-Invasive Papillary Urothelial Carcinoma after BCG Immunotherapy
by Julius Drachneris, Mindaugas Morkunas, Mantas Fabijonavicius, Albertas Cekauskas, Feliksas Jankevicius and Arvydas Laurinavicius
Int. J. Mol. Sci. 2024, 25(9), 4776; https://doi.org/10.3390/ijms25094776 (registering DOI) - 27 Apr 2024
Abstract
Non-muscle-invasive papillary urothelial carcinoma (NMIPUC) of the urinary bladder is the most common type of bladder cancer. Intravesical Bacille Calmette–Guerin (BCG) immunotherapy is applied in patients with a high risk of recurrence and progression of NMIPUC to muscle-invasive disease. However, the tumor relapses [...] Read more.
Non-muscle-invasive papillary urothelial carcinoma (NMIPUC) of the urinary bladder is the most common type of bladder cancer. Intravesical Bacille Calmette–Guerin (BCG) immunotherapy is applied in patients with a high risk of recurrence and progression of NMIPUC to muscle-invasive disease. However, the tumor relapses in about 30% of patients despite the treatment, raising the need for better risk stratification. We explored the potential of spatial distributions of immune cell subtypes (CD20, CD11c, CD163, ICOS, and CD8) within the tumor microenvironment to predict NMIPUC recurrence following BCG immunotherapy. Based on analyses of digital whole-slide images, we assessed the densities of the immune cells in the epithelial–stromal interface zone compartments and their distribution, represented by an epithelial–stromal interface density ratio (IDR). While the densities of any cell type did not predict recurrence, a higher IDR of CD11c (HR: 0.0012, p-value = 0.0002), CD8 (HR: 0.0379, p-value = 0.005), and ICOS (HR: 0.0768, p-value = 0.0388) was associated with longer recurrence-free survival (RFS) based on the univariate Cox regression. The history of positive repeated TUR (re-TUR) (HR: 4.93, p-value = 0.0001) and T1 tumor stage (HR: 2.04, p-value = 0.0159) were associated with shorter RFS, while G3 tumor grade according to the 1973 WHO classification showed borderline significance (HR: 1.83, p-value = 0.0522). In a multivariate analysis, the two models with a concordance index exceeding 0.7 included the CD11c IDR in combination with either a history of positive re-TUR or tumor stage. We conclude that the CD11c IDR is the most informative predictor of NMIPUC recurrence after BCG immunotherapy. Our findings highlight the importance of assessment of the spatial distribution of immune cells in the tumor microenvironment. Full article
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23 pages, 739 KiB  
Article
An Innovative Probiotic-Based Supplement to Mitigate Molecular Factors Connected to Depression and Anxiety: An In Vitro Study
by Sara Ferrari, Simone Mulè, Giorgia Rosso, Francesca Parini, Rebecca Galla, Claudio Molinari and Francesca Uberti
Int. J. Mol. Sci. 2024, 25(9), 4774; https://doi.org/10.3390/ijms25094774 (registering DOI) - 27 Apr 2024
Abstract
The gut–brain axis is a bidirectional relationship between the microbiota and the brain; genes related to the brain and gut synaptic formation are similar. Research on the causal effects of gut microbiota on human behavior, brain development, and function, as well as the [...] Read more.
The gut–brain axis is a bidirectional relationship between the microbiota and the brain; genes related to the brain and gut synaptic formation are similar. Research on the causal effects of gut microbiota on human behavior, brain development, and function, as well as the underlying molecular processes, has emerged in recent decades. Probiotics have been shown in several trials to help reduce anxiety and depressive symptoms. Because of this, probiotic combinations have been tested in in vitro models to see whether they might modulate the gut and alleviate depression and anxiety. Therefore, we sought to determine whether a novel formulation might affect the pathways controlling anxiety and depression states and alter gut barrier activities in a 3D model without having harmful side effects. Our findings indicate that B. bifidum novaBBF7 10 mg/mL, B. longum novaBLG2 5 mg/mL, and L. paracasei TJB8 10 mg/mL may influence the intestinal barrier and enhance the synthesis of short-chain fatty acids. Additionally, the probiotics studied did not cause neuronal damage and, in combination, exert a protective effect against the condition of anxiety and depression triggered by L-Glutamate. All these findings show that probiotics can affect gut function to alter the pathways underlying anxiety and depression. Full article
(This article belongs to the Special Issue Molecular Pharmacology of Antidepressants)
16 pages, 6529 KiB  
Article
Numerical Simulation of Stress Disturbance Mechanism Caused by Hydraulic Fracturing of Shale Formation
by Yinghui Zhu, Heng Zheng, Yi Liao and Ruiquan Liao
Processes 2024, 12(5), 886; https://doi.org/10.3390/pr12050886 (registering DOI) - 27 Apr 2024
Abstract
Characterizing changes in rock properties is essential for the hydraulic fracture and re-fracture parameter optimization of shale formations. This paper proposed a hydraulic fracturing model to investigate the changes in rock properties during hydraulic fracturing using SPH, and the changes in the stress [...] Read more.
Characterizing changes in rock properties is essential for the hydraulic fracture and re-fracture parameter optimization of shale formations. This paper proposed a hydraulic fracturing model to investigate the changes in rock properties during hydraulic fracturing using SPH, and the changes in the stress field and rock properties were quantitatively characterized. The simulation results indicated that the minimum horizontal principal stress increased by 10 MPa~15 MPa during fracture propagation, which is the main reason for the uneven propagation in multi-fracture propagation. Affected by the stress disturbance, the stimulated area was divided into four parts based on the changes in Young’s modulus and permeability; the more seriously the stress disturbance was affected, the higher the permeability of the stimulated zone was, and the smaller the stimulated zone was. Meanwhile, a zone with reduced permeability appeared due to the compression effect caused by the high injection pressure, and this increased with the increase in stress disturbance. The main reason for this was that strain formed because of the compression effect from the high injection pressure. The higher the stress disturbance, the higher the accumulated strain. This new model provides a new method for fracture parameter optimization, which also provides a foundation for the re-fracture parameter optimization of shale formations. Full article
(This article belongs to the Special Issue Advanced Fracturing Technology for Oil and Gas Reservoir Stimulation)

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