The 2023 MDPI Annual Report has
been released!
 
Article
Enhancing Botnet Detection in Network Security Using Profile Hidden Markov Models
by Rucha Mannikar and Fabio Di Troia
Appl. Sci. 2024, 14(10), 4019; https://doi.org/10.3390/app14104019 (registering DOI) - 9 May 2024
Abstract
A botnet is a network of compromised computer systems, or bots, remotely controlled by an attacker through bot controllers. This covert network poses a threat through large-scale cyber attacks, including phishing, distributed denial of service (DDoS), data theft, and server crashes. Botnets often [...] Read more.
A botnet is a network of compromised computer systems, or bots, remotely controlled by an attacker through bot controllers. This covert network poses a threat through large-scale cyber attacks, including phishing, distributed denial of service (DDoS), data theft, and server crashes. Botnets often camouflage their activity by utilizing common internet protocols, such as HTTP and IRC, making their detection challenging. This paper addresses this threat by proposing a method to identify botnets based on distinctive communication patterns between command and control servers and bots. Recognizable traits in botnet behavior, such as coordinated attacks, heartbeat signals, and periodic command distribution, are analyzed. Probabilistic models, specifically Hidden Markov Models (HMMs) and Profile Hidden Markov Models (PHMMs), are employed to learn and identify these activity patterns in network traffic data. This work utilizes publicly available datasets containing a combination of botnet, normal, and background traffic to train and test these models. The comparative analysis reveals that both HMMs and PHMMs are effective in detecting botnets, with PHMMs exhibiting superior accuracy in botnet detection compared to HMMs. Full article
18 pages, 3736 KiB  
Article
Bovine Serum Albumin Effect on Collapsing PNIPAM Chains in Aqueous Solutions: Spin Label and Spin Probe Study
by Georgii A. Simenido, Ekaterina M. Zubanova, Evgenii A. Ksendzov, Sergei V. Kostjuk, Peter S. Timashev and Elena N. Golubeva
Polymers 2024, 16(10), 1335; https://doi.org/10.3390/polym16101335 (registering DOI) - 9 May 2024
Abstract
The influence of bovine serum albumin (BSA) on collapsing poly(N-isopropylacrylamide) (PNIPAM) chains was studied with turbidimetry and spin probe and spin label electron paramagnetic resonance spectroscopy. An increased ratio of collapsed chains in aqueous solutions in the narrow temperature region near [...] Read more.
The influence of bovine serum albumin (BSA) on collapsing poly(N-isopropylacrylamide) (PNIPAM) chains was studied with turbidimetry and spin probe and spin label electron paramagnetic resonance spectroscopy. An increased ratio of collapsed chains in aqueous solutions in the narrow temperature region near the LCST appeared in the presence of 2.5–10 wt% BSA. The spin probe EPR data indicate that the inner cavities of the BSA dimers are probably responsive to the capture of small hydrophobic or amphiphilic molecules, such as TEMPO nitroxyl radical. The observed features of the structure and dynamics of inhomogeneities of aqueous PNIPAM-BSA solutions, including their mutual influence on the behavior of the polymer and protein below the LCST, should be considered when developing and investigating PNIPAM-based drug delivery systems. Full article
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12 pages, 895 KiB  
Review
Photocatalytic Bacterial Destruction and Mineralization by TiO2-Based Photocatalysts: A Mini Review
by Paulina Rokicka-Konieczna and Antoni W. Morawski
Molecules 2024, 29(10), 2221; https://doi.org/10.3390/molecules29102221 (registering DOI) - 9 May 2024
Abstract
This work presents an overview of the reports on the bacterial cell photocatalytic destruction and mineralization process in the presence of TiO2-based photocatalysts. The presented research included experiments conducted in air and water. Numerous works confirmed that a photocatalytic process with [...] Read more.
This work presents an overview of the reports on the bacterial cell photocatalytic destruction and mineralization process in the presence of TiO2-based photocatalysts. The presented research included experiments conducted in air and water. Numerous works confirmed that a photocatalytic process with TiO2 led to bacteria and their organic residues’ mineralization. Additionally, based on the obtained results, a possible two-stage mechanism of photocatalytic mineralization in the presence of TiO2-based materials was proposed. To help future studies, challenges of photocatalytic microorganism mineralization are also proposed. There are some aspects that need to be addressed, such as the lack of standardization of conducted research or relatively small amount of research on photocatalytic microorganism mineralization. According to our best knowledge, in the available literature, no work regarding a summary of previous research on photocatalytic bacterial mineralization process was found. Full article
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18 pages, 1370 KiB  
Review
An Overview of Hydrothermally Synthesized Titanate Nanotubes: The Factors Affecting Preparation and Their Promising Pharmaceutical Applications
by Ranim Saker, Hadi Shammout, Géza Regdon, Jr. and Tamás Sovány
Pharmaceutics 2024, 16(5), 635; https://doi.org/10.3390/pharmaceutics16050635 (registering DOI) - 9 May 2024
Abstract
Recently, titanate nanotubes (TNTs) have been receiving more attention and becoming an attractive candidate for use in several disciplines. With their promising results and outstanding performance, they bring added value to any field using them, such as green chemistry, engineering, and medicine. Their [...] Read more.
Recently, titanate nanotubes (TNTs) have been receiving more attention and becoming an attractive candidate for use in several disciplines. With their promising results and outstanding performance, they bring added value to any field using them, such as green chemistry, engineering, and medicine. Their good biocompatibility, high resistance, and special physicochemical properties also provide a wide spectrum of advantages that could be of crucial importance for investment in different platforms, especially medical and pharmaceutical ones. Hydrothermal treatment is one of the most popular methods for TNT preparation because it is a simple, cost-effective, and environmentally friendly water-based procedure. It is also considered as a strong candidate for large-scale production intended for biomedical application because of its high yield and the special properties of the resulting nanotubes, especially their small diameters, which are more appropriate for drug delivery and long circulation. TNTs’ properties highly differ according to the preparation conditions, which would later affect their subsequent application field. The aim of this review is to discuss the factors that could possibly affect their synthesis and determine the transformations that could happen according to the variation of factors. To fulfil this aim, relevant scientific databases (Web of Science, Scopus, PubMed, etc.) were searched using the keywords titanate nanotubes, hydrothermal treatment, synthesis, temperature, time, alkaline medium, post treatment, acid washing, calcination, pharmaceutical applications, drug delivery, etc. The articles discussing TNTs preparation by hydrothermal synthesis were selected, and papers discussing other preparation methods were excluded; then, the results were evaluated based on a careful reading of the selected articles. This investigation and comprehensive review of different parameters could be the answer to several problems concerning establishing a producible method of TNTs production, and it might also help to optimize their characteristics and then extend their application limits to further domains that are not yet totally revealed, especially the pharmaceutical industry and drug delivery. Full article
(This article belongs to the Special Issue Advanced Pharmaceutical Excipients Used in Solid Dosage Forms)
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9 pages, 2268 KiB  
Brief Report
Evaluation of Anti-Inflammatory Activity in Methanolic Seed Extracts of International Sorghum bicolor L. Resources
by Da Ye Ham, Ji Won Seo, Hong Ju Choi, Jiu Park, Na Young Kim, Myong Jo Kim, Chang Yeon Yu and Eun Soo Seong
Agronomy 2024, 14(5), 997; https://doi.org/10.3390/agronomy14050997 (registering DOI) - 9 May 2024
Abstract
Sorghum is an important cereal with high value as a health food ingredient because it contains various phenolic compounds. Anti-inflammatory activity was assessed using 12 sorghum resources collected from various countries to explore their potential as medicinal resources. The findings revealed that, at [...] Read more.
Sorghum is an important cereal with high value as a health food ingredient because it contains various phenolic compounds. Anti-inflammatory activity was assessed using 12 sorghum resources collected from various countries to explore their potential as medicinal resources. The findings revealed that, at extract concentrations of 25 µg/mL and 50 µg/mL, cell survival rates were observed to be between 70 and 80% for most varieties, with the exception of K159081. In the analysis of anti-inflammatory activity, measured by the rate of nitric oxide (NO) production, sorghum varieties K159041 and K159081 exhibited NO production rates of 0.46 ± 0.38% and 2.58 ± 0.20%, respectively, indicating significant anti-inflammatory properties. The investigation into anti-inflammatory effects also included examining the expression of the inducible nitric oxide synthase (iNOS) gene, which is related to the inflammatory response triggered by LPS in macrophages. Varieties K159041, K159048, K159077, K159078, K159081, K159089, and K159096 were analyzed for this purpose. Further, an expression test of the cyclooxygenase 2 (COX-2) gene revealed values less than 0.4 in K159077, K159081, and K159089, suggesting these sorghum lines possess higher anti-inflammatory activity compared to others. Additionally, the expression analysis of tumor necrosis factor alpha (TNF-α), a gene identified as an inflammatory cytokine, showed that the mRNA levels in the lines K159048, K159077, K159078, K159088, K159089, K159093, and K159096 were expressed at lower levels relative to other sorghum resources, categorizing them as having high anti-inflammatory activity. Notably, the K159081 line exhibited the lowest expression level of all genes associated with inflammation, marking it as a valuable medicinal resource with potential development as an anti-inflammatory agent. Full article
(This article belongs to the Section Plant-Crop Biology and Biochemistry)
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17 pages, 7129 KiB  
Review
On-Chip Supercontinuum Generation Pumped by Short Wavelength Fiber Lasers
by Peng Chen, Zhe Long, Qi Cheng, Maozhuang Song, Wei Wang, Ruixue Liu, Zheng Zhang, Kai Xia, Zhen Yang, Lei Qian, Shengchuang Bai, Xunsi Wang, Peilong Yang, Peipeng Xu, El Sayed Yousef and Rongping Wang
Photonics 2024, 11(5), 440; https://doi.org/10.3390/photonics11050440 (registering DOI) - 9 May 2024
Abstract
Supercontinuum (SC) generation pumped by fiber lasers with short wavelengths below 2.0 μm is important since it can provide a compact light source for various applications. We review the progress of SC generation in various materials regarding the formation of the waveguides and [...] Read more.
Supercontinuum (SC) generation pumped by fiber lasers with short wavelengths below 2.0 μm is important since it can provide a compact light source for various applications. We review the progress of SC generation in various materials regarding the formation of the waveguides and point out the existing issues in the current investigations and possible solutions in the future. Full article
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25 pages, 3186 KiB  
Article
Adaptive Multi-Criteria Selection for Efficient Resource Allocation in Frugal Heterogeneous Hadoop Clusters
by Basit Qureshi
Electronics 2024, 13(10), 1836; https://doi.org/10.3390/electronics13101836 (registering DOI) - 9 May 2024
Abstract
Efficient resource allocation is crucial in clusters with frugal Single-Board Computers (SBCs) possessing limited computational resources. These clusters are increasingly being deployed in edge computing environments in resource-constrained settings where energy efficiency and cost-effectiveness are paramount. A major challenge in Hadoop scheduling is [...] Read more.
Efficient resource allocation is crucial in clusters with frugal Single-Board Computers (SBCs) possessing limited computational resources. These clusters are increasingly being deployed in edge computing environments in resource-constrained settings where energy efficiency and cost-effectiveness are paramount. A major challenge in Hadoop scheduling is load balancing, as frugal nodes within the cluster can become overwhelmed, resulting in degraded performance and frequent occurrences of out-of-memory errors, ultimately leading to job failures. In this study, we introduce an Adaptive Multi-criteria Selection for Efficient Resource Allocation (AMS-ERA) in Frugal Heterogeneous Hadoop Clusters. Our criterion considers CPU, memory, and disk requirements for jobs and aligns the requirements with available resources in the cluster for optimal resource allocation. To validate our approach, we deploy a heterogeneous SBC-based cluster consisting of 11 SBC nodes and conduct several experiments to evaluate the performance using Hadoop wordcount and terasort benchmark for various workload settings. The results are compared to the Hadoop-Fair, FOG, and IDaPS scheduling strategies. Our results demonstrate a significant improvement in performance with the proposed AMS-ERA, reducing execution time by 27.2%, 17.4%, and 7.6%, respectively, using terasort and wordcount benchmarks. Full article
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10 pages, 3665 KiB  
Article
Development and Validation of a Prediction Model for Acute Hypotensive Events in Intensive Care Unit Patients
by Toshiyuki Nakanishi, Tatsuya Tsuji, Tetsuya Tamura, Koichi Fujiwara and Kazuya Sobue
J. Clin. Med. 2024, 13(10), 2786; https://doi.org/10.3390/jcm13102786 (registering DOI) - 9 May 2024
Abstract
Background: Persistent hypotension in the intensive care unit (ICU) is associated with increased mortality. Predicting acute hypotensive events can lead to timely intervention. We aimed to develop a prediction model of acute hypotensive events in patients admitted to the ICU. Methods: [...] Read more.
Background: Persistent hypotension in the intensive care unit (ICU) is associated with increased mortality. Predicting acute hypotensive events can lead to timely intervention. We aimed to develop a prediction model of acute hypotensive events in patients admitted to the ICU. Methods: We included adult patients admitted to the Nagoya City University (NCU) Hospital ICU between January 2018 and December 2021 for model training and internal validation. The MIMIC-III database was used for external validation. A hypotensive event was defined as a mean arterial pressure < 60 mmHg for at least 5 min in 10 min. The input features were age, sex, and time-series data for vital signs. We compared the area under the receiver-operating characteristic curve (AUROC) of three machine-learning algorithms: logistic regression, the light gradient boosting machine (LightGBM), and long short-term memory (LSTM). Results: Acute hypotensive events were found in 1325/1777 (74.6%) and 2691/5266 (51.1%) of admissions in the NCU and MIMIC-III cohorts, respectively. In the internal validation, the LightGBM model had the highest AUROC (0.835), followed by the LSTM (AUROC 0.834) and logistic regression (AUROC 0.821) models. Applying only blood pressure-related features, the LSTM model achieved the highest AUROC (0.843) and consistently showed similar results in external and internal validation. Conclusions: The LSTM model using only blood pressure-related features had the highest AUROC with comparable performance in external validation. Full article
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23 pages, 1877 KiB  
Review
Blockchain for Organ Transplantation: A Survey
by Elif Calik and Malika Bendechache
Blockchains 2024, 2(2), 150-172; https://doi.org/10.3390/blockchains2020008 (registering DOI) - 9 May 2024
Abstract
As blockchain becomes more widely used, a growing number of application fields are becoming interested in blockchain to benefit from its decentralised nature, invariability, security, transparency, quick transaction capabilities, and cost-effectiveness. Blockchain has a wide range of applications and uses in healthcare. Distributed [...] Read more.
As blockchain becomes more widely used, a growing number of application fields are becoming interested in blockchain to benefit from its decentralised nature, invariability, security, transparency, quick transaction capabilities, and cost-effectiveness. Blockchain has a wide range of applications and uses in healthcare. Distributed ledger technology facilitates the secure transfer of patient medical records, manages the medicine supply chain, and creates an efficient, transparent, safe, and effective way of communicating data across global healthcare. The organ transplantation process (OTP) is one of the healthcare areas that benefit from the use of such technology to make its process more secure and transparent. In this article, we put forward a systematic literature review analysis on the application of blockchain to the OTP. Additionally, we address and highlight the barriers and challenges that arise while using blockchain technology for the OTP. We also offer some suggestions for future developments that would enhance blockchain’s implementation in the OTP domain. Full article
(This article belongs to the Special Issue Feature Papers in Blockchains)
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20 pages, 1207 KiB  
Review
Driver Mutations in Pancreatic Cancer and Opportunities for Targeted Therapy
by Olamide T. Olaoba, Temitope I. Adelusi, Ming Yang, Tessa Maidens, Eric T. Kimchi, Kevin F. Staveley-O’Carroll and Guangfu Li
Cancers 2024, 16(10), 1808; https://doi.org/10.3390/cancers16101808 (registering DOI) - 9 May 2024
Abstract
Pancreatic cancer is the sixth leading cause of cancer-related mortality globally. As the most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) represents up to 95% of all pancreatic cancer cases, accounting for more than 300,000 deaths annually. Due to the lack [...] Read more.
Pancreatic cancer is the sixth leading cause of cancer-related mortality globally. As the most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) represents up to 95% of all pancreatic cancer cases, accounting for more than 300,000 deaths annually. Due to the lack of early diagnoses and the high refractory response to the currently available treatments, PDAC has a very poor prognosis, with a 5-year overall survival rate of less than 10%. Targeted therapy and immunotherapy are highly effective and have been used for the treatment of many types of cancer; however, they offer limited benefits in pancreatic cancer patients due to tumor-intrinsic and extrinsic factors that culminate in drug resistance. The identification of key factors responsible for PDAC growth and resistance to different treatments is highly valuable in developing new effective therapeutic strategies. In this review, we discuss some molecules which promote PDAC initiation and progression, and their potential as targets for PDAC treatment. We also evaluate the challenges associated with patient outcomes in clinical trials and implications for future research. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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11 pages, 2511 KiB  
Article
Highly Stable Hybrid Pigments Prepared from Organic Chromophores and Fluorinated Hydrotalcites
by Magali Hernández, Carlos Felipe, Ariel Guzmán-Vargas, José Luis Rivera and Enrique Lima
Colorants 2024, 3(2), 125-135; https://doi.org/10.3390/colorants3020009 (registering DOI) - 9 May 2024
Abstract
Structural hydroxide groups in layered magnesium–aluminum double hydroxides were partially replaced by fluoride ions. Fluorinated and fluorine-free materials were used as hosts for two dyes, carminic acid and hydroxyl naphthol blue, resulting in a hybrid pigment color palette. The pigments were produced by [...] Read more.
Structural hydroxide groups in layered magnesium–aluminum double hydroxides were partially replaced by fluoride ions. Fluorinated and fluorine-free materials were used as hosts for two dyes, carminic acid and hydroxyl naphthol blue, resulting in a hybrid pigment color palette. The pigments were produced by two ways, either incorporating chromophore during the synthesis of the layered double hydroxide or in a post-synthesis step through the memory effect of the LDHs. Additionally, the pigments were protected with a magnesium hydroxide phase to prevent the color from fading over time. The pigments were stable for periods as long as 10 years. The color properties of the pigments were significantly influenced by the host of dye since the presence of fluorine directly influences the acid–base properties of the layered double hydroxides. The pigments conferred their color to white cream in the preparation of colored creams. The colored creams acquired the color of the layered pigment. Full article
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13 pages, 1083 KiB  
Article
Proposal and Validation of a New Index to Assess the Difficulty of Lower Third Molar Extraction
by Paula Hermida-Cabrera, Belén Lima-Sánchez, Vanessa Montoya-Salazar, Luis-Guillermo Oliveros-López, Pedro Alomar-Velasco, José-Luis Gutiérrez-Pérez, Daniel Torres-Lagares and María Baus-Domínguez
Dent. J. 2024, 12(5), 138; https://doi.org/10.3390/dj12050138 (registering DOI) - 9 May 2024
Abstract
There is no current consensus on the parameters that determine the difficulty of mandibular third molar extraction in terms of the time required, which is essential to prevent complications and optimize the time of the intervention. This study aims to obtain, using the [...] Read more.
There is no current consensus on the parameters that determine the difficulty of mandibular third molar extraction in terms of the time required, which is essential to prevent complications and optimize the time of the intervention. This study aims to obtain, using the mathematical method of multiple linear regression, an equation that allows estimating the extraction time of a lower third molar according to its complexity, as well as to validate this equation in a sample of external wisdom teeth. Methods: A prospective cohort study on a sample of patients of the Master of Oral Surgery of the University of Seville in which multiple linear regression coefficients were calculated with a subsequent validation study of the results in the sample of patients operated in the Hospital Palmaplanas of Mallorca. Results: The regression line obtained after applying the statistical methodology to the cohort of patients from the University of Seville obtained significant dependent variables such as depth, roots, and odontosection. Once applied to the cohort of patients from the Palmaplanas Hospital in Mallorca, a regression coefficient was obtained between the data received and the estimated 0.770. Conclusions: The formula proposed in this article presents significant validity in the prediction of the surgical time of extraction of the lower third molars included. Full article
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16 pages, 2242 KiB  
Article
Oral Delivery of Liraglutide-Loaded Zein/Eudragit-Chitosan Nanoparticles Provides Pharmacokinetic and Glycemic Outcomes Comparable to Its Subcutaneous Injection in Rats
by Jeferson Ziebarth, Letícia Marina da Silva, Ariane Krause Padilha Lorenzett, Ingrid Delbone Figueiredo, Paulo Fernando Carlstrom, Felipe Nunes Cardoso, André Luiz Ferreira de Freitas, Amanda Martins Baviera and Rubiana Mara Mainardes
Pharmaceutics 2024, 16(5), 634; https://doi.org/10.3390/pharmaceutics16050634 (registering DOI) - 9 May 2024
Abstract
Liraglutide (LIRA) is a glucagon-like peptide-1 (GLP-1) receptor agonist renowned for its efficacy in treating type 2 diabetes mellitus (T2DM) and is typically administered via subcutaneous injections. Oral delivery, although more desirable for being painless and potentially enhancing patient adherence, is challenged by [...] Read more.
Liraglutide (LIRA) is a glucagon-like peptide-1 (GLP-1) receptor agonist renowned for its efficacy in treating type 2 diabetes mellitus (T2DM) and is typically administered via subcutaneous injections. Oral delivery, although more desirable for being painless and potentially enhancing patient adherence, is challenged by the peptide’s low bioavailability and vulnerability to digestive enzymes. This study aimed to develop LIRA-containing zein-based nanoparticles stabilized with eudragit RS100 and chitosan for oral use (Z-ERS-CS/LIRA). These nanoparticles demonstrated a spherical shape, with a mean diameter of 238.6 nm, a polydispersity index of 0.099, a zeta potential of +40.9 mV, and an encapsulation efficiency of 41%. In vitro release studies indicated a prolonged release, with up to 61% of LIRA released over 24 h. Notably, the nanoparticles showed considerable resistance and stability in simulated gastric and intestinal fluids, suggesting protection from pH and enzymatic degradation. Pharmacokinetic analysis revealed that orally administered Z-ERS-CS/LIRA paralleled the pharmacokinetic profile seen with subcutaneously delivered LIRA. Furthermore, in vivo tests on a diabetic rat model showed that Z-ERS-CS/LIRA significantly controlled glucose levels, comparable to the results observed with free LIRA. The findings underscore Z-ERS-CS/LIRA nanoparticles as a promising approach for oral LIRA delivery in T2DM management. Full article
(This article belongs to the Special Issue Smart Nanotechnology to Enhancing Drug Delivery and Bioavailability)
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19 pages, 2297 KiB  
Article
Increased Prolylcarboxypeptidase Expression Can Serve as a Biomarker of Senescence in Culture
by Nicholas Glen Boullard, Jason J. Paris, Zia Shariat-Madar and Fakhri Mahdi
Molecules 2024, 29(10), 2219; https://doi.org/10.3390/molecules29102219 (registering DOI) - 9 May 2024
Abstract
Prolylcarboxypeptidase (PRCP, PCP, Lysosomal Pro-X-carboxypeptidase, Angiotensinase C) controls angiotensin- and kinin-induced cell signaling. Elevation of PRCP appears to be activated in chronic inflammatory diseases [cardiovascular disease (CVD), diabetes] in proportion to severity. Vascular endothelial cell senescence and mitochondrial dysfunction have consistently been shown [...] Read more.
Prolylcarboxypeptidase (PRCP, PCP, Lysosomal Pro-X-carboxypeptidase, Angiotensinase C) controls angiotensin- and kinin-induced cell signaling. Elevation of PRCP appears to be activated in chronic inflammatory diseases [cardiovascular disease (CVD), diabetes] in proportion to severity. Vascular endothelial cell senescence and mitochondrial dysfunction have consistently been shown in models of CVD in aging. Cellular senescence, a driver of age-related dysfunction, can differentially alter the expression of lysosomal enzymes due to lysosomal membrane permeability. There is a lack of data demonstrating the effect of age-related dysfunction on the expression and function of PRCP. To explore the changes in PRCP, the PRCP-dependent prekallikrein (PK) pathway was characterized in early- and late-passage human pulmonary artery endothelial cells (HPAECs). Detailed kinetic analysis of cells treated with high molecular weight kininogen (HK), a precursor of bradykinin (BK), and PK revealed a mechanism by which senescent HPAECs activate the generation of kallikrein upon the assembly of the HK–PK complex on HPAECs in parallel with an upregulation of PRCP and endothelial nitric oxide (NO) synthase (eNOS) and NO formation. The NO production and expression of both PRCP and eNOS increased in early-passage HPAECs and decreased in late-passage HPAECs. Low activity of PRCP in late-passage HPAECs was associated with rapid decreased telomerase reverse transcriptase mRNA levels. We also found that, with an increase in the passage number of HPAECs, reduced PRCP altered the respiration rate. These results indicated that aging dysregulates PRCP protein expression, and further studies will shed light into the complexity of the PRCP-dependent signaling pathway in aging. Full article
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29 pages, 13159 KiB  
Article
Preliminary Performance Analysis of Medium-Range Liquid Hydrogen-Powered Box-Wing Aircraft
by Giuseppe Palaia, Karim Abu Salem and Erasmo Carrera
Aerospace 2024, 11(5), 379; https://doi.org/10.3390/aerospace11050379 (registering DOI) - 9 May 2024
Abstract
This paper proposes a performance analysis of a medium-range airliner powered by liquid hydrogen (LH2) propulsion. The focus is on operating performance in terms of achievable payload and range. A non-conventional box-wing architecture was selected to maximize operating performance. An optimization-based [...] Read more.
This paper proposes a performance analysis of a medium-range airliner powered by liquid hydrogen (LH2) propulsion. The focus is on operating performance in terms of achievable payload and range. A non-conventional box-wing architecture was selected to maximize operating performance. An optimization-based multidisciplinary design framework was developed to retrofit a baseline medium-range box-wing aircraft by designing and integrating the fuel tanks needed to store the LH2; several solutions were investigated for tank arrangement and layout by means of sensitivity analyses. As a main outcome, a performance analysis of the proposed LH2-powered box-wing aircraft is provided, highlighting the impact of the introduction of this energy carrier (and the integration of the related tank systems) on aircraft operating performance; a comparative study with respect to a competitor LH2-retrofitted tube-and-wing aircraft is also provided, to highlight the main possible operating differences between the two architectures. The findings reveal that the retrofitted box-wing can achieve long-range flights at the cost of a substantially reduced payload, mainly due to the volume limitations imposed by the installation of LH2 tanks, or it can preserve payload capacity at the expense of a significant reduction in range, as the trade-off implies a reduction in on-board LH2 mass. Specifically, the studied box-wing configuration can achieve a range of 7100 km transporting 150 passengers, or shorter ranges of 2300 km transporting 230 passengers. The competitor LH2-retrofitted tube-and-wing aircraft, operating in the same category and compatible with the same airport apron constraints, could achieve a distance of 1500 km transporting 110 passengers. Full article
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15 pages, 2324 KiB  
Article
Confused about Rehabilitation? Multi-Faceted Approaches for Brain Injured Patients in a Confusional State
by Jesper Fabricius, Anna Birthe Andersen, Gitte Lindegård Munk and Hanne Kaae Kristensen
Hospitals 2024, 1(1), 50-64; https://doi.org/10.3390/hospitals1010005 - 9 May 2024
Abstract
Post-injury confusional state is a common phenomenon following acquired brain injury. A multi-faceted approach for decreasing confusion is recommended, but there is a paucity of research related to non-pharmacological management. The main objective was to present a conceptual model of multi-faceted approaches for [...] Read more.
Post-injury confusional state is a common phenomenon following acquired brain injury. A multi-faceted approach for decreasing confusion is recommended, but there is a paucity of research related to non-pharmacological management. The main objective was to present a conceptual model of multi-faceted approaches for confusion, and secondly to investigate the rehabilitation outcome following these approaches. The setting is a specialized ward for rehabilitation of patients with severe cognitive difficulties following acquired brain injury. The conceptual model encompasses neurobehavioral strategies, pharmacological treatment, engagement in meaningful occupations, next of kin involvement, organizational demands, the physical environment, along with differential diagnostics. Patient cases are provided to illustrate the impact of each approach. A total of 141 of 281 patients were in a confusional state at admission. At discharge, 62% had emerged from the confusional state. Patients in a confusional state due to traumatic brain injury and subarachnoid hemorrhage had clinically important differences of >22 points in the functional independence measure from admission to discharge, following rehabilitation efforts based on the conceptual model. No clinically important difference was seen in patients with non-SAH stroke and patients with other types of brain injuries. The proposed conceptual model should be further evaluated in complex intervention studies. Full article
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13 pages, 6416 KiB  
Article
Evaluation of the Therapeutical Effect of Matricaria Chamomilla Extract vs. Galantamine on Animal Model Memory and Behavior Using 18F-FDG PET/MRI
by Roxana Iacob, Matei Palimariciuc, Tudor Florea, Cosmin Vasilica Pricope, Cristina Mariana Uritu, Bogdan Ionel Tamba, Teodor Marian Ionescu, Cati Raluca Stolniceanu, Wael Jalloul, Romeo Petru Dobrin, Lucian Hritcu, Oana Cioanca, Monica Hancianu, Alexandru Gratian Naum and Cipriana Stefanescu
Curr. Issues Mol. Biol. 2024, 46(5), 4506-4518; https://doi.org/10.3390/cimb46050273 - 9 May 2024
Abstract
The memory-enhancing activity of Matricaria chamomilla hydroalcoholic extract (MCE) is already being investigated by behavioral and biochemical assays in scopolamine-induced amnesia rat models, while the effects of scopolamine (Sco) on cerebral glucose metabolism are examined as well. Nevertheless, the study of the metabolic [...] Read more.
The memory-enhancing activity of Matricaria chamomilla hydroalcoholic extract (MCE) is already being investigated by behavioral and biochemical assays in scopolamine-induced amnesia rat models, while the effects of scopolamine (Sco) on cerebral glucose metabolism are examined as well. Nevertheless, the study of the metabolic profile determined by an enriched MCE has not been performed before. The present experiments compared metabolic quantification in characteristic cerebral regions and behavioral characteristics for normal, only diseased, diseased, and MCE- vs. Galantamine (Gal)-treated Wistar rats. A memory deficit was induced by four weeks of daily intraperitoneal Sco injection. Starting on the eighth day, the treatment was intraperitoneally administered 30 min after Sco injection for a period of three weeks. The memory assessment comprised three maze tests. Glucose metabolism was quantified after the 18F-FDG PET examination. The right amygdala, piriform, and entorhinal cortex showed the highest differential radiopharmaceutical uptake of the 50 regions analyzed. Rats treated with MCE show metabolic similarity with normal rats, while the Gal-treated group shows features closer to the diseased group. Behavioral assessments evidenced a less anxious status and a better locomotor activity manifested by the MCE-treated group compared to the Gal-treated group. These findings prove evident metabolic ameliorative qualities of MCE over Gal classic treatment, suggesting that the extract could be a potent neuropharmacological agent against amnesia. Full article
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12 pages, 1118 KiB  
Review
Advancements in Neurosurgical Intraoperative Histology
by Ali A. Mohamed, Emma Sargent, Cooper Williams, Zev Karve, Karthik Nair and Brandon Lucke-Wold
Tomography 2024, 10(5), 693-704; https://doi.org/10.3390/tomography10050054 - 9 May 2024
Abstract
Despite their relatively low incidence globally, central nervous system (CNS) tumors remain amongst the most lethal cancers, with only a few other malignancies surpassing them in 5-year mortality rates. Treatment decisions for brain tumors heavily rely on histopathological analysis, particularly intraoperatively, to guide [...] Read more.
Despite their relatively low incidence globally, central nervous system (CNS) tumors remain amongst the most lethal cancers, with only a few other malignancies surpassing them in 5-year mortality rates. Treatment decisions for brain tumors heavily rely on histopathological analysis, particularly intraoperatively, to guide surgical interventions and optimize patient outcomes. Frozen sectioning has emerged as a vital intraoperative technique, allowing for highly accurate, rapid analysis of tissue samples, although it poses challenges regarding interpretive errors and tissue distortion. Raman histology, based on Raman spectroscopy, has shown great promise in providing label-free, molecular information for accurate intraoperative diagnosis, aiding in tumor resection and the identification of neurodegenerative disease. Techniques including Stimulated Raman Scattering (SRS), Coherent Anti-Stokes Raman Scattering (CARS), Surface-Enhanced Raman Scattering (SERS), and Tip-Enhanced Raman Scattering (TERS) have profoundly enhanced the speed and resolution of Raman imaging. Similarly, Confocal Laser Endomicroscopy (CLE) allows for real-time imaging and the rapid intraoperative histologic evaluation of specimens. While CLE is primarily utilized in gastrointestinal procedures, its application in neurosurgery is promising, particularly in the context of gliomas and meningiomas. This review focuses on discussing the immense progress in intraoperative histology within neurosurgery and provides insight into the impact of these advancements on enhancing patient outcomes. Full article
(This article belongs to the Section Neuroimaging)
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7 pages, 207 KiB  
Article
Bacterial Contamination of Syringes and Fluids in Diagnostic and Interventional Neuroangiography
by Martin Wiesmann, Sophia Honecker, Claudia Fleu, Christiane Franz, Manuela Schmiech, Hani Ridwan, Franziska Bürkle, Omid Nikoubashman and Sebastian Lemmen
Tomography 2024, 10(5), 686-692; https://doi.org/10.3390/tomography10050053 - 9 May 2024
Abstract
(1) Background: Bacterial contamination has been shown to occur during angiographies, although data on its frequency and relevance are sparse. Our aim was to evaluate the incidence of bacterial contamination of syringes used under sterile conditions during neuroangiographies. We sought to differentiate between [...] Read more.
(1) Background: Bacterial contamination has been shown to occur during angiographies, although data on its frequency and relevance are sparse. Our aim was to evaluate the incidence of bacterial contamination of syringes used under sterile conditions during neuroangiographies. We sought to differentiate between contamination of the outside of the syringes and the inside and to detect the frequency, extent and germ spectrum of bacterial contamination. (2) Methods: We prospectively collected 600 samples from 100 neuroangiographies. Per angiography, fluid samples from the three routinely used syringes as well as the syringes themselves were analyzed. We analyzed the frequency and extent of contamination and determined the germ spectrum. (3) Results: The majority of samples (56.9%) were contaminated. There was no angiography that showed no contamination (0%). The outer surfaces of the syringes were contaminated significantly more frequently and to a higher extent than the inner surfaces. Both the frequency and extent of contamination of the samples increased with longer duration of angiographic procedures. Most of the bacterial species were environmental or skin germs (87.7%). (4) Conclusions: Bacterial contamination is a frequent finding during neuroangiographies, although its clinical significance is believed to be small. Bacterial contamination increases with longer duration of angiographic procedures. Full article
19 pages, 14002 KiB  
Article
An Assessment of the Role of the Timex Sampling Strategy on the Precision of Shoreline Detection Analysis
by Siegmund Nuyts, Eugene J. Farrell, Sheena Fennell and Stephen Nash
Coasts 2024, 4(2), 347-365; https://doi.org/10.3390/coasts4020018 - 9 May 2024
Abstract
Remote video imagery using shoreline edge detection is widely used in coastal monitoring in order to acquire measurements of nearshore and swash features. Some of these systems are constrained by their long setup time, positioning requirements and considerable hardware costs. As such, there [...] Read more.
Remote video imagery using shoreline edge detection is widely used in coastal monitoring in order to acquire measurements of nearshore and swash features. Some of these systems are constrained by their long setup time, positioning requirements and considerable hardware costs. As such, there is a need for an autonomous low-cost system (~EUR 500), such as Timex cameras, that can be rapidly deployed in the field, while still producing the outcomes required for coastal monitoring. This research presents an assessment of the effect of the sampling strategy (time-lapse intervals) on the precision of shoreline detection for two low-cost cameras located in a remote coastal area in western Ireland, overlooking a dissipative beach–dune system. The analysis shows that RMSD in the detected shoreline is similar to other studies for sampling intervals ranging between 1 s and 30 s (i.e., RMSDmean for Camera 1 = 1.4 m and Camera 2 = 0.9 m), and an increase in the sampling interval from 1 s to 30 s had no significant adverse effect on the precision of shoreline detection. The research shows that depending on the intended use of the detected shorelines, the current standard of 1 s image sampling interval when using Timex cameras can be increased up to 30 s without any significant loss of accuracy. This positively impacts battery life and memory storage, making the systems more autonomous; for example, the battery life increased from ~10 days to ~100 days when the sampling interval was increased from 1 to 5 s. Full article
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14 pages, 586 KiB  
Review
Role of NR5A1 Gene Mutations in Disorders of Sex Development: Molecular and Clinical Features
by Giovanni Luppino, Malgorzata Wasniewska, Roberto Coco, Giorgia Pepe, Letteria Anna Morabito, Alessandra Li Pomi, Domenico Corica and Tommaso Aversa
Curr. Issues Mol. Biol. 2024, 46(5), 4519-4532; https://doi.org/10.3390/cimb46050274 (registering DOI) - 9 May 2024
Abstract
Disorders/differences of sex development (DSDs) are defined as broad, heterogenous groups of congenital conditions characterized by atypical development of genetic, gonadal, or phenotypic sex accompanied by abnormal development of internal and/or external genitalia. NR5A1 gene mutation is one of the principal genetic alterations [...] Read more.
Disorders/differences of sex development (DSDs) are defined as broad, heterogenous groups of congenital conditions characterized by atypical development of genetic, gonadal, or phenotypic sex accompanied by abnormal development of internal and/or external genitalia. NR5A1 gene mutation is one of the principal genetic alterations implicated in causing DSD. This review outlines the role of NR5A1 gene during the process of gonadal development in humans, provides an overview of the molecular and functional characteristics of NR5A1 gene, and discusses potential clinical phenotypes and additional organ diseases due to NR5A1 mutations. NR5A1 mutations were analyzed in patients with 46,XY DSD and 46,XX DSD both during the neonatal and pubertal periods. Loss of function of the NR5A1 gene causes several different phenotypes, including some associated with disease in additional organs. Clinical phenotypes may vary, even among patients carrying the same NR5A1 variant, indicating that there is no specific genotype–phenotype correlation. Genetic tests are crucial diagnostic tools that should be used early in the diagnostic pathway, as early as the neonatal period, when gonadal dysgenesis is the main manifestation of NR5A1 mutation. NR5A1 gene mutations could be mainly associated with amenorrhea, ovarian failure, hypogonadism, and infertility during puberty. Fertility preservation techniques should be considered as early as possible. Full article
(This article belongs to the Special Issue Complex Molecular Mechanism of Monogenic Diseases 2.0)
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15 pages, 652 KiB  
Article
Sustainable Sheep and Goat Farming in Arid Regions of Jordan
by Faisal Al-Barakeh, Ashraf Omar Khashroum, Radi A. Tarawneh, Fatima A. Al-Lataifeh, Azzam N. Al-Yacoub, Moammar Dayoub and Khaled Al-Najjar
Ruminants 2024, 4(2), 241-255; https://doi.org/10.3390/ruminants4020017 (registering DOI) - 9 May 2024
Abstract
This study examines the sustainability of livestock farming in Jordan’s arid regions, focusing on smallholder Awassi sheep and Baladi goat farming. It assesses breeders, economic factors, herd productivity, and sustainability, evaluating the vitality of these breeds by examining reproductive success through birth and [...] Read more.
This study examines the sustainability of livestock farming in Jordan’s arid regions, focusing on smallholder Awassi sheep and Baladi goat farming. It assesses breeders, economic factors, herd productivity, and sustainability, evaluating the vitality of these breeds by examining reproductive success through birth and survival rates. In 2021–2022, a total of 53 traditional Awassi sheep and Baladi goat farms in Northern Jordan’s Mafraq Governorate were surveyed using a comprehensive questionnaire to gather data on breeders’ information, farm economics, and herd indicators. Dry seasons in arid lands are tough on sheep and goats, with limited fodder and water availability harming their health and reproductive capacity. While wet seasons bring relief, they can also introduce diseases. Special care for these animals throughout the year is crucial to maintain healthy herds in arid regions. Linear models were employed to analyze sample data, with variance and correlation tests used to explore relationships among variables. Additionally, chi-squared analysis was utilized to assess the impact of male replacement plans on these herds. The main outcomes of this study reveal that breeder indicators pose challenges to the sustainability and growth of Awassi sheep and Baladi goat farming. Conversely, economic indicators suggest a blend of financial stability alongside obstacles related to profitability and resource ownership. Breeder age emerges as a significant factor in livestock herd management, influenced by elements such as experience, resource availability, and adherence to traditional practices. Experience notably influences breeders’ decisions regarding male insemination replacements, likely due to acquired skills. Crop cultivation is shown to reduce fodder costs, thereby enhancing profitability for each young animal sold and consequently increasing the breeders’ returns. Winter conditions elevate animal mortality rates due to cold stress, while other animals within herds contribute to increased kid mortality by facilitating disease transmission. Breeder experience significantly impacts lamb survival, underscoring its importance in ensuring proper care. Increasing ewe proportions within herds enhances lamb production and lowers lamb mortality rates. Effective ram management and yearling lamb sales further contribute to herd health and productivity. A higher proportion of goats within a herd positively correlates with the number of young yearlings sold but inversely affects breeding males and overall kid numbers, indicating a delicate balance that influences herd productivity and mortality rates. Sheep (92.5%) and goat herds (90.6%) demonstrate reproductive success, indicative of superior long-term vitality. While sheep excel in birth rates, survival, and sales, they exhibit lower ewe and lambing percentages. Goat farming demonstrates high birth rates, sales, and overall success but requires particular attention to ensuring kid survival, especially during the winter months. Improving the characteristics of the Awassi sheep and Baladi goat flocks is crucial for ensuring sustainability, achievable through proper care practices in dry lands. In conclusion, despite the challenges, there are promising opportunities to enhance sheep and goat farming in Jordan. Effective management, informed by the breeders’ experience and economics, is crucial. Empowering small-scale herders and implementing targeted interventions, like winter mortality solutions and selective breeding, is vital for sustainable growth. Full article
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14 pages, 6325 KiB  
Article
The Postmortem Evaluation of Anatomical Thymic Parameters in the Context of Age, Cause of Death, Sex, and Body Mass Index in the Elderly Human Population
by Richaela Denlinger, Julia H. Smith, Joseph Lyle, Ian Clapp, Chandrika Janumpalli, Sydney Amick and Malgorzata Simm
Lymphatics 2024, 2(2), 83-96; https://doi.org/10.3390/lymphatics2020007 (registering DOI) - 9 May 2024
Abstract
The studies of thymic structure were performed predominantly in cohorts of younger individuals. Here, we established a cohort of body donors whose age at the time of death ranged from 57 to 103 to study the relationship between thymic structure and factors that, [...] Read more.
The studies of thymic structure were performed predominantly in cohorts of younger individuals. Here, we established a cohort of body donors whose age at the time of death ranged from 57 to 103 to study the relationship between thymic structure and factors that, in the younger subjects, have shown to affect the organ’s anatomy, including the presence of the organ’s capsule, its weight, size of the left and right lobes, and a transverse diameter. We explored the relationships between these thymic parameters and the subjects’ age, sex, and cause of death (COD), asking how the thymus in the elderly differed from the organ’s macro-anatomy in a broader and younger human population, and whether age, sex, COD, and BMI could influence the thymic parameters in the elderly. Our analyses revealed that the thymic size but not thymic weight in the KYCOM cohort differed significantly from the younger individuals. The size of the thymus in males progressively decreased, but in females, the size of the right lobe increased. The encapsulated thymus was detected with a higher frequency in females than males. We found no associations between thymic parameters and the person’s COD, age, or sex. However, the person’s BMI was associated with thymic weight, suggesting that obesity may influence the aging of the immune system. Full article
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