The 2023 MDPI Annual Report has
been released!
 
26 pages, 684 KiB  
Systematic Review
Combination of Two Long-Acting Antipsychotics in Schizophrenia Spectrum Disorders: A Systematic Review
by Salvatore Cipolla, Pierluigi Catapano, Daniela D’Amico, Rocchina Monda, Nunzia Paola Sallusto, Francesco Perris, Valeria De Santis, Francesco Catapano, Mario Luciano and Andrea Fiorillo
Brain Sci. 2024, 14(5), 433; https://doi.org/10.3390/brainsci14050433 (registering DOI) - 26 Apr 2024
Abstract
Background: Up to 34% of patients with schizophrenia are resistant to several treatment trials. Lack of continuous and adequate treatment is associated with relapse, rehospitalization, a lower effect of antipsychotic therapy, and higher risk of side effects. Long-acting injectables antipsychotics (LAI APs) enhance [...] Read more.
Background: Up to 34% of patients with schizophrenia are resistant to several treatment trials. Lack of continuous and adequate treatment is associated with relapse, rehospitalization, a lower effect of antipsychotic therapy, and higher risk of side effects. Long-acting injectables antipsychotics (LAI APs) enhance compliance and improve clinical outcomes and quality of life in patients with schizophrenia, and thus it may be advisable to administer two LAI APs at the same time in cases of treatment-resistant schizophrenia. The purpose of this review is to summarize the available literature regarding the combined use of two LAI APs in patients with schizophrenia or other psychotic spectrum disorders. Methods: An extensive literature search for relevant articles regarding any combination of two long-acting injectable antipsychotics has been performed from inception up to 9 February 2024, on PubMed, Scopus and APA PsycInfo, according to the PRISMA statement. Only studies reporting combination of two LAI APs and its clinical outcome in patients with schizophrenia and related disorders were selected. Results: After the selection process, nine case reports, four case series and two observational retrospective studies were included in the final analysis. All patients treated with dual LAI APs reported a good response, and no new or unexpected adverse effects due to the combination of two LAIs were reported. Different drug combinations were used, and the most frequent association resulted in aripiprazole monohydrate + paliperidone palmitate once monthly (32 times). Conclusions: Our review highlights that the treatment regimen with two concurrent LAI APs is already widely used in clinical practice and is recognized as providing a promising, effective, and relatively safe therapeutic strategy for treating the schizophrenia spectrum disorders. Full article
22 pages, 9814 KiB  
Article
Ten Years of Mediterranean Monk Seal Stranding Records in Greece under the Microscope: What Do the Data Suggest?
by Maria Solanou, Aliki Panou, Irida Maina, Stefanos Kavadas and Marianna Giannoulaki
Animals 2024, 14(9), 1309; https://doi.org/10.3390/ani14091309 (registering DOI) - 26 Apr 2024
Abstract
This paper presents the results of an analysis of stranding events of the Mediterranean monk seal Monachus monachus over a decade. The analysis involved categorization according to the cause of stranding and seasonality, the identification of hotspot stranding areas and an assessment of [...] Read more.
This paper presents the results of an analysis of stranding events of the Mediterranean monk seal Monachus monachus over a decade. The analysis involved categorization according to the cause of stranding and seasonality, the identification of hotspot stranding areas and an assessment of possible correlations between stranding events and environmental/climatic patterns using time series analysis. Moreover, Generalized Additive Models (GAMs) were applied to explore the effects of the size of small-scale fishing grounds, the number of species sightings, and the occurrence of reproduction sites on “human-related” strandings. Finally, special focus was put on the central part of the eastern Ionian Sea for the assessment of stranding hotspot areas by means of the Multi-Criteria Decision Analysis (MCDA) approach, based on different kinds of spatial information such as anthropogenic pressures and the location of breeding sites and feeding grounds. Time series analysis results revealed that oscillation indices, during the first half of the year, and sea surface temperature (SST) in the Mediterranean from October to December were positively correlated with monk seal stranding events. GAMs underlined that areas combining extended small-scale fishery grounds and a higher number of sightings were more likely to cause more strandings. Regarding spatial analyses, the central Aegean Sea was highlighted as a hotspot for “human-related strandings”, while the MCDA approach emphasized that the southern coasts of Cephalonia and the gulf between Lefkada and mainland Greece were susceptible to subadult strandings. Full article
22 pages, 2630 KiB  
Article
Dual Role of NMDAR-Containing NR2A and NR2B Subunits in Alzheimer’s Disease
by Iu Raïch, Jaume Lillo, Joan Biel Rebassa, Toni Capó, Arnau Cordomí, Irene Reyes-Resina, Mercè Pallàs and Gemma Navarro
Int. J. Mol. Sci. 2024, 25(9), 4757; https://doi.org/10.3390/ijms25094757 (registering DOI) - 26 Apr 2024
Abstract
Alzheimer’s disease (AD) is the main cause of dementia worldwide. Given that learning and memory are impaired in this pathology, NMDA receptors (NMDARs) appear as key players in the onset and progression of the disease. NMDARs are glutamate receptors, mainly located at the [...] Read more.
Alzheimer’s disease (AD) is the main cause of dementia worldwide. Given that learning and memory are impaired in this pathology, NMDA receptors (NMDARs) appear as key players in the onset and progression of the disease. NMDARs are glutamate receptors, mainly located at the post-synapse, which regulate voltage-dependent influx of calcium into the neurons. They are heterotetramers, and there are different subunits that can be part of the receptors, which are usually composed of two obligatory GluN1 subunits plus either two NR2A or two NR2B subunits. NR2A are mostly located at the synapse, and their activation is involved in the expression of pro-survival genes. Conversely, NR2B are mainly extrasynaptic, and their activation has been related to cell death and neurodegeneration. Thus, activation of NR2A and/or inactivation of NR2B-containing NMDARS has been proposed as a therapeutic strategy to treat AD. Here, we wanted to investigate the main differences between both subunits signalling in neuronal primary cultures of the cortex and hippocampus. It has been observed that Aβ induces a significant increase in calcium release and also in MAPK phosphorylation signalling in NMDAR-containing NR2B subunits in cortical and hippocampal neurons. However, while NMDAR-containing NR2A decreases neuronal death and favours cell viability after Aβ treatment, NMDAR-containing NR2B shows higher levels of cytotoxicity and low levels of neuronal survival. Finally, it has been detected that NMDAR has no effect on pTau axonal transport. The present results demonstrate a different role between GluNA and GluNB subunits in neurodegenerative diseases such as Alzheimer’s. Full article
14 pages, 1361 KiB  
Article
Corrosion Resistance and Conductivity of Ta-Nb-N-Coated 316L Stainless Steel as Bipolar Plates for Proton Exchange Membrane Fuel Cells
by Qizhong Li, Chuan Ding, Mai Yang, Meijun Yang, Tenghua Gao, Song Zhang, Baifeng Ji, Takashi Goto and Rong Tu
Coatings 2024, 14(5), 542; https://doi.org/10.3390/coatings14050542 (registering DOI) - 26 Apr 2024
Abstract
The large-scale application of stainless steel (SS) bipolar plates (BPs) in proton exchange membrane fuel cells (PEMFCs) is mainly limited by insufficient corrosion resistance and electrical conductivity. In this work, Ta-Nb-N coatings were prepared on 316L SS substrates by unbalanced magnetron sputtering to [...] Read more.
The large-scale application of stainless steel (SS) bipolar plates (BPs) in proton exchange membrane fuel cells (PEMFCs) is mainly limited by insufficient corrosion resistance and electrical conductivity. In this work, Ta-Nb-N coatings were prepared on 316L SS substrates by unbalanced magnetron sputtering to improve corrosion resistance and conductivity. The Ta-Nb-N coatings had a dense structure without obvious defects. In simulated PEMFC cathode environments consisting of 0.5 M H2SO4 + 2 ppm HF at 70 ± 0.5 °C, which is harsher than the U.S. Department of Energy specification, the corrosion current density of Ta-Nb-N-coated BPs was reduced to 2.2 × 10−2 Acm−2. Ta-Nb-N-coated samples showed better electrical conductivity than 316L SS, which had an excellent interfacial contact resistance of 9.2 mΩcm2. In addition, the Ta-Nb-N-coated samples had a water contact angle of 100.7°, showing good hydrophobicity for water management. These results indicate that Ta-Nb-N coatings could be a promising material for BPs. Full article
(This article belongs to the Special Issue Advances in Thin Films for Energy Storage and Conversion)
16 pages, 1109 KiB  
Article
Illumina Sequencing and Metabolomic Analysis Explored the Effects of the Mixed Silage of Rice Straw and Chinese Cabbage Waste on Fecal Microorganisms and Metabolites in Hu Sheep
by Chuang Li, Zhiqi Lu, Ruxin Qi, Zhenbin Zhang, Yue Lu, Muhammad Hammad Zafar, Kailun Yang and Mengzhi Wang
Fermentation 2024, 10(5), 233; https://doi.org/10.3390/fermentation10050233 (registering DOI) - 26 Apr 2024
Abstract
Silage is the most important component of a ruminant diet and has important production and health significance in ruminant production. The aim of the research was to investigate how the mixed silage of Chinese cabbage waste and rice straw (mixed silage) impacts the [...] Read more.
Silage is the most important component of a ruminant diet and has important production and health significance in ruminant production. The aim of the research was to investigate how the mixed silage of Chinese cabbage waste and rice straw (mixed silage) impacts the fecal microorganisms and metabolites in Hu sheep using Illumina sequencing and metabolomic analysis. A total of 16 Hu sheep (8 rams and 8 ewes) weighing about 39 kg and 5.5 months old were used as experimental sheep and divided into two groups (4 rams and 4 ewes, n = 8) using the principle of randomized trials: the control group with peanut sprouts, corn husks, and sorghum husks as roughage and the silage group with the mixed silage as roughage. There were no significant differences in the average daily gain (ADG), dry matter intake (DMI), or feed conversion rate (FCR) between the control group and the mixed silage groups (p > 0.05). Microbiome results showed that 15 microorganisms such as Ruminococcaceae UCG 010, Breznakia, Erysipelothrix, Desulfovibrio, Succiniclasticum, and Shuttleworthia were significantly different between the two groups. In addition, metabolomics showed that the mixed silage modulated the concentrations and metabolic pathways of metabolites in the manure. Significantly different metabolites were mainly enriched in amino acid anabolism (“glycine, serine, and threonine metabolism”, “valine, leucine, and isoleucine biosynthesis”, “arginine biosynthesis”, etc.), nucleic acid metabolism (pyrimidine metabolism). In conclusion, the addition of mixed silage to the diet of Hu sheep can alter the structure of the hindgut microflora and regulate the metabolism of amino acids and nucleotides, which affects health performance. Full article
(This article belongs to the Special Issue Application of Fermentation Technology in Animal Nutrition)
20 pages, 3031 KiB  
Article
microRNA and the Post-Transcriptional Response to Oxidative Stress during Neuronal Differentiation: Implications for Neurodevelopmental and Psychiatric Disorders
by Behnaz Khavari, Michelle M. Barnett, Ebrahim Mahmoudi, Michael P. Geaghan, Adam Graham and Murray J. Cairns
Life 2024, 14(5), 562; https://doi.org/10.3390/life14050562 (registering DOI) - 26 Apr 2024
Abstract
Oxidative stress is one of the most important environmental exposures associated with psychiatric disorders, but the underlying molecular mechanisms remain to be elucidated. In a previous study, we observed a substantial alteration of the gene expression landscape in neuron-like cells that were differentiated [...] Read more.
Oxidative stress is one of the most important environmental exposures associated with psychiatric disorders, but the underlying molecular mechanisms remain to be elucidated. In a previous study, we observed a substantial alteration of the gene expression landscape in neuron-like cells that were differentiated from SH-SY5Y cells after or during exposure to oxidative stress, with a subset of dysregulated genes being enriched for neurodevelopmental processes. To further explore the regulatory mechanisms that might account for such profound perturbations, we have now applied small RNA-sequencing to investigate changes in the expression of miRNAs. These molecules are known to play crucial roles in brain development and response to stress through their capacity to suppress gene expression and influence complex biological networks. Through these analyses, we observed more than a hundred differentially expressed miRNAs, including 80 previously reported to be dysregulated in psychiatric disorders. The seven most influential miRNAs associated with pre-treatment exposure, including miR-138-5p, miR-96-5p, miR-34c-5p, miR-1287-5p, miR-497-5p, miR-195-5p, and miR-16-5p, supported by at least 10 negatively correlated mRNA connections, formed hubs in the interaction network with 134 genes enriched with neurobiological function, whereas in the co-treatment condition, miRNA-mRNA interaction pairs were enriched in cardiovascular and immunity-related disease ontologies. Interestingly, 12 differentially expressed miRNAs originated from the DLK1-DIO3 location, which encodes a schizophrenia-associated miRNA signature. Collectively, our findings suggest that early exposure to oxidative stress, before and during prenatal neuronal differentiation, might increase the risk of mental illnesses in adulthood by disturbing the expression of miRNAs that regulate neurodevelopmentally significant genes and networks. Full article
(This article belongs to the Section Genetics and Genomics)
27 pages, 1976 KiB  
Article
Business Process Reengineering with a Circular Economy PDCA Model from the Perspective of Manufacturing Industry
by Milena Nebojša Rajić, Zorana Zoran Stanković, Marko V. Mančić, Pedja Miroslav Milosavljević and Rado Maksimović
Processes 2024, 12(5), 877; https://doi.org/10.3390/pr12050877 (registering DOI) - 26 Apr 2024
Abstract
In times of increasing awareness of sustainability and the need for efficient business processes, this study explores the integration of business process reengineering with circular economy principles within Serbian manufacturing organizations. Addressing the need for sustainable development, the research aims to propose and [...] Read more.
In times of increasing awareness of sustainability and the need for efficient business processes, this study explores the integration of business process reengineering with circular economy principles within Serbian manufacturing organizations. Addressing the need for sustainable development, the research aims to propose and validate a model that harmonizes business process reengineering with the circular economy to improve environmental and organizational performance. The study conducted an extensive survey and analysis across 135 manufacturing organizations in Serbia, assessing their readiness and current practices in adopting circular economy strategies through business process reengineering, utilizing the Plan-Do-Check-Act (PDCA) model. The findings reveal a moderate level of integration, with an average implementation score of 44.70% across surveyed organizations. Notably, organizations with ISO 9001 and ISO 14001 certifications demonstrated higher levels of model implementation. The study highlights the potential of integrating business process reengineering with circular economy principles as a path to sustainable manufacturing. It also highlights the need for targeted strategies to improve management commitment, resource allocation, and participation in sustainable practices. The research contributes valuable insights for policymakers, industry stakeholders, and academic discourse, advocating for a more systematic approach to embedding circular economy principles within organizational processes for a sustainable future. Full article
(This article belongs to the Section Manufacturing Processes and Systems)
Show Figures

Figure 1

13 pages, 1129 KiB  
Article
Frequency and Demographic Analysis of Odontogenic Tumors in Three Tertiary Institutions: An 11-Year Retrospective Study
by Asma Almazyad, Mohammed Alamro, Nasser Almadan, Marzouq Almutairi and Turki S. AlQuwayz
Diagnostics 2024, 14(9), 910; https://doi.org/10.3390/diagnostics14090910 (registering DOI) - 26 Apr 2024
Abstract
Odontogenic tumors (OTs) are distinct conditions that develop in the jawbones, exhibiting diverse histopathological features and variable clinical behaviors. Unfortunately, the literature on this subject in Saudi Arabia remains sparse, indicating a pressing need for more comprehensive data concerning the frequency, demographics, treatment [...] Read more.
Odontogenic tumors (OTs) are distinct conditions that develop in the jawbones, exhibiting diverse histopathological features and variable clinical behaviors. Unfortunately, the literature on this subject in Saudi Arabia remains sparse, indicating a pressing need for more comprehensive data concerning the frequency, demographics, treatment modalities, and outcomes of OTs. Objectives: The study aims to evaluate the frequency, demographic features, treatment, and outcomes of OTs across three tertiary medical centers. Methods and Material: OT cases were identified in King Abdulaziz Medical City (KAMC), King Fahad Medical City (KFMC), and Prince Sultan Military Medical City (PSMMC) from January 2010 to December 2021. Results: Ninety-two OT cases were identified from the anatomical pathology laboratories of three tertiary hospitals. KFMC contributed the highest number of cases (43.5%), followed by KAMC (30.4%) and PSMMC (26.1%). The median age of OT patients was 29 years (range: 5–83), with males representing more than half of the patients (56.5%). The mandible was the most frequent site of OT occurrence (72.5%), with ameloblastoma being the predominant OT (63.0%), followed by odontoma (19.5%). Among the treatment modalities, bone resection was employed the most (51.0%), followed by enucleation (25.6%). Notably, 11.5% of OT cases with available follow-up data exhibited recurrence, with ameloblastoma accounting for eight recurrent cases. Conclusions: Although OTs are relatively common in the jaws, they are rare in anatomical pathology laboratories and the general population. This study contributes valuable insights into the epidemiology characteristics, treatment trends, and recurrence rates of OTs in Saudi Arabia. Full article
(This article belongs to the Special Issue Advances in the Diagnosis of Oral and Maxillofacial Disease)
26 pages, 373 KiB  
Article
Canonical vs. Grand Canonical Ensemble for Bosonic Gases under Harmonic Confinement
by Andrea Crisanti, Luca Salasnich, Alessandro Sarracino and Marco Zannetti
Entropy 2024, 26(5), 367; https://doi.org/10.3390/e26050367 (registering DOI) - 26 Apr 2024
Abstract
We analyze the general relation between canonical and grand canonical ensembles in the thermodynamic limit. We begin our discussion by deriving, with an alternative approach, some standard results first obtained by Kac and coworkers in the late 1970s. Then, motivated by the Bose–Einstein [...] Read more.
We analyze the general relation between canonical and grand canonical ensembles in the thermodynamic limit. We begin our discussion by deriving, with an alternative approach, some standard results first obtained by Kac and coworkers in the late 1970s. Then, motivated by the Bose–Einstein condensation (BEC) of trapped gases with a fixed number of atoms, which is well described by the canonical ensemble and by the recent groundbreaking experimental realization of BEC with photons in a dye-filled optical microcavity under genuine grand canonical conditions, we apply our formalism to a system of non-interacting Bose particles confined in a two-dimensional harmonic trap. We discuss in detail the mathematical origin of the inequivalence of ensembles observed in the condensed phase, giving place to the so-called grand canonical catastrophe of density fluctuations. We also provide explicit analytical expressions for the internal energy and specific heat and compare them with available experimental data. For these quantities, we show the equivalence of ensembles in the thermodynamic limit. Full article
(This article belongs to the Special Issue Matter-Aggregating Systems at a Classical vs. Quantum Interface)
23 pages, 834 KiB  
Article
Joint Hybrid Beamforming Design for Millimeter Wave Amplify-and-Forward Relay Communication Systems
by Jinxian Zhao, Dongfang Jiang, Heng Wei, Bingjie Liu, Yifeng Zhao, Yi Zhang, Haoyuan Yu and Xuewei Liu
Appl. Sci. 2024, 14(9), 3713; https://doi.org/10.3390/app14093713 (registering DOI) - 26 Apr 2024
Abstract
Hybrid beamforming (HBF) has been regarded as one of the most promising technologies in millimeter Wave (mmWave) communication systems. In order to guarantee the communication quality in non-line-of-sight (NLOS) scenarios, joint HBF design for the mmWave amplify-and-forward (AF) relay communication system is studied [...] Read more.
Hybrid beamforming (HBF) has been regarded as one of the most promising technologies in millimeter Wave (mmWave) communication systems. In order to guarantee the communication quality in non-line-of-sight (NLOS) scenarios, joint HBF design for the mmWave amplify-and-forward (AF) relay communication system is studied in this paper. The ideal case is first considered where the mmWave half-duplex (HD) AF relay system operates with channel state information (CSI) accurately known. In order to tackle the non-convex problem, a manifold optimization (MO)-based alternating optimization algorithm is proposed, where an optimization problem containing only constant modulus constraints in Euclidean space can be converted to an unconstrained optimization problem in a Riemann manifold. Furthermore, considering more practical cases with estimation errors of CSI, we investigate the robust joint HBF design with the system operating in full-duplex (FD) mode to obtain higher spectral efficiency (SE). A null-space projection (NP) based self-interference cancellation (SIC) algorithm is developed to attenuate the self-interference (SI). Different from the traditional SI suppression algorithm, there’s no limit on the number of RF chains. Numerical results reveal that our proposed algorithms has a good convergence and can effectively deal with the influence of different CSI estimation errors. A significant performance improvement can be achieved in contrast with other approaches. Full article
(This article belongs to the Special Issue Novel Advances in Internet of Vehicles)
16 pages, 506 KiB  
Article
The Use of Technology Assisted by Artificial Intelligence Depending on the Companies’ Digital Maturity Level
by Gabriel Brătucu, Eliza Ciobanu, Ioana Bianca Chițu, Adriana Veronica Litră, Alexandra Zamfirache and Marius Bălășescu
Electronics 2024, 13(9), 1687; https://doi.org/10.3390/electronics13091687 (registering DOI) - 26 Apr 2024
Abstract
Major companies in the global market have made significant investments in artificial intelligence-assisted technology to increase the value of their products and services, which gives the implementation of artificial intelligence an extremely important role. Starting from these premises, the authors set out to [...] Read more.
Major companies in the global market have made significant investments in artificial intelligence-assisted technology to increase the value of their products and services, which gives the implementation of artificial intelligence an extremely important role. Starting from these premises, the authors set out to evaluate the transformation level of companies in terms of adopting technology based on artificial intelligence according to their level of digital maturity. For this purpose, qualitative research was used by deploying the inductive method, which allowed five distinct categories of companies with unique characteristics to be identified, generating an interval scale that illustrates the level of digital maturity and the ability to adopt and implement viable solutions based on artificial intelligence technology. This paper, in addition to identifying the digital transformation level of companies, offers solutions and recommendations for addressing the challenges encountered by the business environment, thus contributing to the understanding and development of strategies adapted to each situation that may appear on the market. Full article
22 pages, 18156 KiB  
Article
Research on Multi-Objective Optimization Design of University Student Center in China Based on Low Energy Consumption and Thermal Comfort
by Ming Liu, Yufei Que, Nanxin Yang, Chongyi Yan and Qibo Liu
Energies 2024, 17(9), 2082; https://doi.org/10.3390/en17092082 (registering DOI) - 26 Apr 2024
Abstract
Ensuring optimal building performance is vital for enhancing student activity comfort and fostering energy-saving initiatives toward low-carbon objectives. This paper focuses on university student centers in China, aiming to diminish building energy consumption while enhancing indoor thermal comfort. Parametric modeling of typical cases [...] Read more.
Ensuring optimal building performance is vital for enhancing student activity comfort and fostering energy-saving initiatives toward low-carbon objectives. This paper focuses on university student centers in China, aiming to diminish building energy consumption while enhancing indoor thermal comfort. Parametric modeling of typical cases is executed using the Grasshopper 1.0.0007 software package, and the simulation of building energy consumption and indoor thermal comfort relies on the Ladybug and Honeybee plug-in. Employing a multi-objective optimization design method and the Octopus multi-objective optimization algorithm, this study integrates numerical simulations and on-site surveys to analyze how factors like building form, orientation, envelope structure, and others impact the indoor and outdoor environment. A comprehensive optimization design approach is implemented for the building’s exterior components, including the walls, windows, roof, and shading system. After conducting a comparative analysis of the annual comprehensive energy consumption and indoor thermal comfort before and after the optimization plan, it is determined that implementing these measures reduces the annual comprehensive energy consumption of the building under study by 58.8% and extends the duration of indoor thermal comfort by 53.0%. This study presents a practical optimization design methodology for university student center architecture in China, aiding architects in decision making and advocating for energy-efficient building designs. Full article
(This article belongs to the Special Issue Optimizing Energy Efficiency and Thermal Comfort in Building)
Show Figures

Figure 1

19 pages, 1874 KiB  
Article
Numerical Simulation of Fracturing Fluid Storage in Shale Reservoirs Based on Experimental Measurements of Stress Sensitivity of Hydraulic Fracture Network Conductivity
by Tianhao Wang and Fujian Zhou
Energies 2024, 17(9), 2083; https://doi.org/10.3390/en17092083 (registering DOI) - 26 Apr 2024
Abstract
Hydraulic fracturing is used in shale reservoir production, with low flowback rates and a large amount of fracturing fluid retained inside the reservoir. In this study, a stress sensitivity analysis experiment on the fracture inflow capacity was implemented to investigate the relationship between [...] Read more.
Hydraulic fracturing is used in shale reservoir production, with low flowback rates and a large amount of fracturing fluid retained inside the reservoir. In this study, a stress sensitivity analysis experiment on the fracture inflow capacity was implemented to investigate the relationship between the hydraulic fracture (HF) and natural fracture (NF) inflow capacities and effective stress. A three-dimensional shale reservoir model was also constructed to couple the experimentally obtained laws with the numerical model to investigate the effects of the connection and closure of the fracture network on the retention of the fracturing fluid. The results show that the stress sensitivity of natural fractures is two orders of magnitude higher than that of hydraulic fractures. The seepage-absorption effect of capillary forces is not the whole reason for the large amount of fracturing fluid retention. The closure of the fracture network formed by natural and hydraulic fractures during the production process led to the storage of a large amount of fracturing fluid, and this process maintained the stability of the water production rate during the steady water production period. Full article
(This article belongs to the Section H: Geo-Energy)
12 pages, 1112 KiB  
Article
Distinguishing Molecular Properties of OAT, OATP, and MRP Drug Substrates by Machine Learning
by Anisha K. Nigam, Jeremiah D. Momper, Anupam Anand Ojha and Sanjay K. Nigam
Pharmaceutics 2024, 16(5), 592; https://doi.org/10.3390/pharmaceutics16050592 (registering DOI) - 26 Apr 2024
Abstract
The movement of organic anionic drugs across cell membranes is partly governed by interactions with SLC and ABC transporters in the intestine, liver, kidney, blood–brain barrier, placenta, breast, and other tissues. Major transporters involved include organic anion transporters (OATs, SLC22 family), organic anion [...] Read more.
The movement of organic anionic drugs across cell membranes is partly governed by interactions with SLC and ABC transporters in the intestine, liver, kidney, blood–brain barrier, placenta, breast, and other tissues. Major transporters involved include organic anion transporters (OATs, SLC22 family), organic anion transporting polypeptides (OATPs, SLCO family), and multidrug resistance proteins (MRPs, ABCC family). However, the sets of molecular properties of drugs that are necessary for interactions with OATs (OAT1, OAT3) vs. OATPs (OATP1B1, OATP1B3) vs. MRPs (MRP2, MRP4) are not well-understood. Defining these molecular properties is necessary for a better understanding of drug and metabolite handling across the gut–liver–kidney axis, gut–brain axis, and other multi-organ axes. It is also useful for tissue targeting of small molecule drugs and predicting drug–drug interactions and drug–metabolite interactions. Here, we curated a database of drugs shown to interact with these transporters in vitro and used chemoinformatic approaches to describe their molecular properties. We then sought to define sets of molecular properties that distinguish drugs interacting with OATs, OATPs, and MRPs in binary classifications using machine learning and artificial intelligence approaches. We identified sets of key molecular properties (e.g., rotatable bond count, lipophilicity, number of ringed structures) for classifying OATs vs. MRPs and OATs vs. OATPs. However, sets of molecular properties differentiating OATP vs. MRP substrates were less evident, as drugs interacting with MRP2 and MRP4 do not form a tight group owing to differing hydrophobicity and molecular complexity for interactions with the two transporters. If the results also hold for endogenous metabolites, they may deepen our knowledge of organ crosstalk, as described in the Remote Sensing and Signaling Theory. The results also provide a molecular basis for understanding how small organic molecules differentially interact with OATs, OATPs, and MRPs. Full article
17 pages, 863 KiB  
Review
Navigating Post-Traumatic Osteoporosis: A Comprehensive Review of Epidemiology, Pathophysiology, Diagnosis, Treatment, and Future Directions
by Matthew B. Weiss, Shoaib A. Syed, Harris Z. Whiteson, Rahim Hirani, Mill Etienne and Raj K. Tiwari
Life 2024, 14(5), 561; https://doi.org/10.3390/life14050561 (registering DOI) - 26 Apr 2024
Abstract
Post-traumatic osteoporosis (PTO) presents a significant challenge in clinical practice, characterized by demineralization and decreased skeletal integrity following severe traumatic injuries. This literature review manuscript addresses the knowledge gaps surrounding PTO, encompassing its epidemiology, pathophysiology, risk factors, diagnosis, treatment, prognosis, and future directions. [...] Read more.
Post-traumatic osteoporosis (PTO) presents a significant challenge in clinical practice, characterized by demineralization and decreased skeletal integrity following severe traumatic injuries. This literature review manuscript addresses the knowledge gaps surrounding PTO, encompassing its epidemiology, pathophysiology, risk factors, diagnosis, treatment, prognosis, and future directions. This review emphasizes the complexity of the etiology of PTO, highlighting the dysregulation of biomineralization processes, inflammatory cytokine involvement, hormonal imbalances, glucocorticoid effects, vitamin D deficiency, and disuse osteoporosis. Moreover, it underscores the importance of multidisciplinary approaches for risk mitigation and advocates for improved diagnostic strategies to differentiate PTO from other musculoskeletal pathologies. This manuscript discusses various treatment modalities, including pharmacotherapy, dietary management, and physical rehabilitation, while also acknowledging the limited evidence on their long-term effectiveness and outcomes in PTO patients. Future directions in research are outlined, emphasizing the need for a deeper understanding of the molecular mechanisms underlying PTO and the evaluation of treatment strategies’ efficacy. Overall, this review provides a comprehensive overview of PTO and highlights avenues for future investigation to enhance clinical management and patient outcomes. Full article
(This article belongs to the Section Medical Research)
Show Figures

Figure 1

9 pages, 367 KiB  
Article
Icarifil® in Association with Daily Use of Tadalafil (5 mg) versus Standard Tadalafil Daily Dose (5 mg) or Alone: Results from a Controlled, Randomized Clinical Trial
by Tommaso Cai, Fabrizio Palumbo, Carlos Miacola, Carlo Ceruti, Michele Rizzo, Giovanni Liguori, Luca Gallelli and Alessandro Palmieri
J. Clin. Med. 2024, 13(9), 2564; https://doi.org/10.3390/jcm13092564 (registering DOI) - 26 Apr 2024
Abstract
Background: The management of erectile dysfunction (ED) shows several grey zones and new treatments are required to reduce the percentage of patients discontinuing treatment. Here, we aim to evaluate the role of a natural mixture named Icarifil® (L-Citrulline, L-Carnitine, Eruca vesicaria [...] Read more.
Background: The management of erectile dysfunction (ED) shows several grey zones and new treatments are required to reduce the percentage of patients discontinuing treatment. Here, we aim to evaluate the role of a natural mixture named Icarifil® (L-Citrulline, L-Carnitine, Eruca vesicaria, Panax ginseng, Tribulus terrestris, Turnera diffusa, Taurine, Vitamin E, Zinc) in the management of patients with ED. Methods: From September 2022 to March 2023, all patients attending 3 urological institutions due to ED were randomized to receive the following for 3 months: Icarifil® 1 sachet every 24 h (Group 1) or Icarifil® 1 sachet + tadalafil 5 mg 1 tablet every 24 h (Group 2) or tadalafil 5 mg 1 tablet daily (Group 3). All patients underwent urologic visits and dedicated questionnaires (IIEF-5, SEP-2, SEP-3) at enrollment and at the follow-up evaluation (3 months). Patient-Reported Outcomes (PROs) at the follow-up evaluation were used. The primary endpoint was the difference in the questionnaires at the follow-up visit compared to the one at enrollment among the study groups. Results: In the per-protocol analysis, 52 patients in Group 1, 55 in Group 2 and 57 in Group 3 were analyzed. At the follow-up evaluation, IIEF-5 scores improved in all the 3 groups between enrollment and the follow-up evaluation, but a statistically significant difference was reported between Group 2 (+7.4) and Group 1 (+4.1) or Group 3 (+5.1), (p < 0.001; p < 0.001). Moreover, 47 patients (94.0%) in Group 2 showed an improvement in the SEP questionnaires, when compared with the baseline, while 29 in Group 1 (56.9%) and 42 in Group 3 (82.3%) showed a statistically significant difference (p = 0.004; p = 0.003) among the groups. The PRO analysis reported better efficacy and patient satisfaction in Group 2 when compared with Group 1 or Group 3. Conclusions: In conclusion, Icarifil® is able to improve penile erectile function in mild–moderate ED and significantly improve the clinical efficacy of daily used tadalafil 5 mg. Icarifil® could represent an interesting alternative treatment in patients experiencing adverse effects or with contraindications for chronic treatment with PDE5-is. Full article
(This article belongs to the Section Reproductive Medicine & Andrology)
21 pages, 20070 KiB  
Article
Biodegradation Study of Styrene–Butadiene Composites with Incorporated Arthrospira platensis Biomass
by Marius Bumbac, Cristina Mihaela Nicolescu, Traian Zaharescu, Ion Valentin Gurgu, Costel Bumbac, Elena Elisabeta Manea, Ioana Alexandra Ionescu, Bogdan-Catalin Serban, Octavian Buiu and Crinela Dumitrescu
Polymers 2024, 16(9), 1218; https://doi.org/10.3390/polym16091218 (registering DOI) - 26 Apr 2024
Abstract
The preparation of polymer composites that incorporate material of a biogenic nature in the polymer matrices may lead to a reduction in fossil polymer consumption and a potentially higher biodegradability. Furthermore, microalgae biomass as biogenic filler has the advantage of fast growth and [...] Read more.
The preparation of polymer composites that incorporate material of a biogenic nature in the polymer matrices may lead to a reduction in fossil polymer consumption and a potentially higher biodegradability. Furthermore, microalgae biomass as biogenic filler has the advantage of fast growth and high tolerance to different types of culture media with higher production yields than those provided by the biomass of terrestrial crops. On the other hand, algal biomass can be a secondary product in wastewater treatment processes. For the present study, an SBS polymer composite (SBSC) containing 25% (w/w) copolymer SBS1 (linear copolymer: 30% styrene and 70% butadiene), 50% (w/w) copolymer SBS2 (linear copolymer: 40% styrene and 60% butadiene), and 25% (w/w) paraffin oil was prepared. Arthrospira platensis biomass (moisture content 6.0 ± 0.5%) was incorporated into the SBSC in 5, 10, 20, and 30% (w/w) ratios to obtain polymer composites with spirulina biomass. For the biodegradation studies, the ISO 14855-1:2012(E) standard was applied, with slight changes, as per the specificity of our experiments. The degradation of the studied materials was followed by quantitatively monitoring the CO2 resulting from the degradation process and captured by absorption in NaOH solution 0.5 mol/L. The structural and morphological changes induced by the industrial composting test on the materials were followed by physical–mechanical, FTIR, SEM, and DSC analysis. The obtained results were compared to create a picture of the material transformation during the composting period. Thus, the collected data indicate two biodegradation processes, of the polymer and the biomass, which take place at the same time at different rates, which influence each other. On the other hand, it is found that the material becomes less ordered, with a sponge-like morphology; the increase in the percentage of biomass leads to an advanced degree of degradation of the material. The FTIR analysis data suggest the possibility of the formation of peptide bonds between the aromatic nuclei in the styrene block and the molecular residues resulting from biomass biodegradation. It seems that in industrial composting conditions, the area of the polystyrene blocks from the SBS-based composite is preferentially transformed in the process. Full article
(This article belongs to the Special Issue Biodegradable Polymer Composites: Fabrication and Applications II)
12 pages, 611 KiB  
Article
Association of Polymorphisms in PD-1 and LAG-3 Genes with Acute Myeloid Leukemia
by Lamjed Mansour, Mashael Alqahtani, Ali Aljuaimlani, Jameel Al-Tamimi, Nouf Al-Harbi and Suliman Alomar
Medicina 2024, 60(5), 721; https://doi.org/10.3390/medicina60050721 (registering DOI) - 26 Apr 2024
Abstract
Background and objectives: Acute myeloid leukemia (AML) is a hematological malignancy characterized by uncontrolled proliferation of immature myeloid cells. Immune checkpoint molecules such as programmed cell death protein 1 (PD-1) and lymphocyte activation gene-3 (LAG-3) are essential for controlling anti-tumor immune responses. This [...] Read more.
Background and objectives: Acute myeloid leukemia (AML) is a hematological malignancy characterized by uncontrolled proliferation of immature myeloid cells. Immune checkpoint molecules such as programmed cell death protein 1 (PD-1) and lymphocyte activation gene-3 (LAG-3) are essential for controlling anti-tumor immune responses. This study aims to explore the correlation between specific genetic variations (SNPs) in the PDCD1 (rs2227981) and LAG3 (rs12313899) genes and the likelihood of developing AML in the Saudi population. Material and methods: total of 98 Saudi AML patients and 131 healthy controls were genotyped for the PDCD1 rs2227981 and LAG3 rs12313899 polymorphisms using TaqMan genotyping assays. A logistic regression analysis was conducted to evaluate the relationship between the SNPs and AML risk using several genetic models. Results: The results revealed a significant association between the PDCD1 rs2227981 polymorphism and increased AML risk. In AML patients, the frequency of the G allele was considerably greater than in healthy controls (OR = 1.93, 95% CI: 1.31–2.81, p = 0.00080). The GG and AG genotypes were associated with a very high risk of developing AML (p < 0.0001). In contrast, no significant association was observed between the LAG3 rs12313899 polymorphism and AML risk in the studied population. In silico analysis of gene expression profiles from public databases suggested the potential impact of PDCD1 expression levels on the overall survival of AML patients. Conclusions: This study provides evidence for the association of the PDCD1 rs2227981 polymorphism with an increased risk for AML in the Saudi population. Full article
(This article belongs to the Section Genetics and Molecular Medicine)
12 pages, 750 KiB  
Article
Pomegranate Juice Clarification Using Ultrafiltration: Influence of the Type of Variety and Degree of Ripeness
by Asunción M. Hidalgo, José A. Macario, Marta Abellán-Baeza, Teresa Sánchez-Moya, Rubén López-Nicolás and Fulgencio Marín-Iniesta
Separations 2024, 11(5), 134; https://doi.org/10.3390/separations11050134 (registering DOI) - 26 Apr 2024
Abstract
Fruit consumption guarantees the supply of most of the necessary nutrients for a complete and balanced diet, as it is a relevant source of vitamins, minerals, and antioxidants. In particular, pomegranate has very interesting medicinal properties, such as an anti-inflammatory effect and the [...] Read more.
Fruit consumption guarantees the supply of most of the necessary nutrients for a complete and balanced diet, as it is a relevant source of vitamins, minerals, and antioxidants. In particular, pomegranate has very interesting medicinal properties, such as an anti-inflammatory effect and the protection of the cardiovascular system, among others. During pomegranate juice production, it appears cloudy and must be clarified to remove suspended solids such as colloids and high-molecular weight tannins. The membrane clarification process is a cost-effective alternative to the conventional methods, resulting in a high-quality product. In this work, the clarification of pomegranate juice using the Triple System Model F1 membrane module was carried out for the Mollar and Wonderful varieties with early and late maturity. Three ultrafiltration membranes with different molecular weight cut-off and different chemical compositions were used. The rejection coefficient and permeate flux (which represent the selectivity of the membranes and the process efficiency, respectively) were measured. GR-40PP showed the best results in terms of membrane selectivity and process efficiency, achieving adequate physicochemical juice parameters. Regarding the comparison of the maturity degree, in general terms, the Mollar variety showed better results. Ripe pomegranates showed greater selectivity, while the process efficiency was higher for the early samples. Full article
(This article belongs to the Section Analysis of Natural Products and Pharmaceuticals)
Show Figures

Graphical abstract

24 pages, 23162 KiB  
Article
An Experimental Procedure to Study the High-Speed Orthogonal Cutting of Unidirectional GFRP
by Martina Panico, Luca Boccarusso, Antonio Formisano, Giuseppe Villani and Antonio Langella
J. Manuf. Mater. Process. 2024, 8(3), 87; https://doi.org/10.3390/jmmp8030087 (registering DOI) - 26 Apr 2024
Abstract
The aim of this paper is to establish a valid procedure for better understanding all of the phenomena associated with the high-speed machining of glass fiber-reinforced plastic (GFRP) composites. Both rectangular and circular specimens were machined at high cutting speeds (up to 50 [...] Read more.
The aim of this paper is to establish a valid procedure for better understanding all of the phenomena associated with the high-speed machining of glass fiber-reinforced plastic (GFRP) composites. Both rectangular and circular specimens were machined at high cutting speeds (up to 50 m/min) in order to understand what occurred for all values of fiber orientation angles during machining operations. An innovative testing methodology was proposed and studied to investigate the phenomenon of burr formation and thus understand how to avoid it during machining operations. To this end, the forces arising during the machining process and the roughness of the resulting surface were carefully studied and correlated with the cutting angle. Additionally, the cutting surface and chip morphology formed during cutting tests were examined using a high-speed camera. Close correlations were found between the variations in the cutting forces’ signals and the trends of the surface roughness and the morphology of the machined surface. Full article
Show Figures

Figure 1

21 pages, 623 KiB  
Review
Phthalates: The Main Issue in Quality Control in the Beverage Industry
by Alessia Iannone, Cristina Di Fiore, Fabiana Carriera, Pasquale Avino and Virgilio Stillittano
Separations 2024, 11(5), 133; https://doi.org/10.3390/separations11050133 (registering DOI) - 26 Apr 2024
Abstract
Phthalate esters (PAEs) are a group of chemicals used to improve the flexibility and durability of plastics. The chemical properties and the resistance to high temperatures promote their degradation and release into the environment. Food and beverages can be contaminated by PAEs through [...] Read more.
Phthalate esters (PAEs) are a group of chemicals used to improve the flexibility and durability of plastics. The chemical properties and the resistance to high temperatures promote their degradation and release into the environment. Food and beverages can be contaminated by PAEs through the migration from packaging material because they are not covalently bound to plastic and also via different kinds of environmental sources or during processing. For instance, alcoholic drinks in plastic containers are a particular risk, since the ethanol contained provides a good solubility for PAEs. According to its role as an endocrine disruptor compound and its adverse effects on the liver, kidney, and reproductive and respiratory systems, the International Agency on Research Cancer (IARC) classified di-(2-ethylhexyl) phthalate (DEHP) as a possible human carcinogen. For this reason, to control human exposure to PAEs, many countries prohibited their use in food as non-food substances. For example, in Europe, the Commission Regulation (EU) 2018/2005 restricts the use of DEHP, dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), and diisobutyl phthalate (DiBP) to a concentration equal to or below 0.1 by weight in plasticizers in articles used by consumers or in indoor areas. There are reports from the US Food and Drug Administration (FDA) that some beverages (and food as well), particularly fruit juices, contain high levels of phthalates. In some cases, the deliberate adulteration of soft drinks with phthalate esters has been reported. This paper would like to show the difficulties of performing PAE analysis in beverage matrices, in particular alcoholic beverages, as well as the main solutions provided for quality control in the industrial branches. Full article
(This article belongs to the Section Analysis of Food and Beverages)
8 pages, 2717 KiB  
Article
Caesarean Section Scar and Placental Location at the First Trimester of Pregnancy—A Prospective Longitudinal Study
by Egle Savukyne, Mindaugas Kliucinskas, Laura Malakauskiene and Kristina Berskiene
Medicina 2024, 60(5), 719; https://doi.org/10.3390/medicina60050719 (registering DOI) - 26 Apr 2024
Abstract
Background and Objectives: This study aims to report the location of the placenta in the first trimester of pregnancy in groups of women according to the number of previous caesarean deliveries and the visibility of the caesarean scar niche. Materials and Methods: [...] Read more.
Background and Objectives: This study aims to report the location of the placenta in the first trimester of pregnancy in groups of women according to the number of previous caesarean deliveries and the visibility of the caesarean scar niche. Materials and Methods: The prospective observational research included adult women aged 18 to 41 years during pregnancy after one or more previous caesarean sections (CSs). Transvaginal (TVS) and transabdominal sonography (TAS) was used to examine the uterine scar and placental location during 11–14 weeks. The CS scar niche (“defect”) was bordered in the sagittal plane as a notch at the previous CS scar’s site with a depth of 2.0 mm or more. A comparative analysis of the placental location (high or low and anterior or posterior) was performed between groups of women according to the CS number and the CS scar niche. Results: A total of 122 participants were enrolled during the first-trimester screening. The CS scar defect (“niche”) was visible in 40.2% of cases. In cases after one previous CS, the placenta was low in the uterine cavity (anterior or posterior) at 77.4%, and after two or more CSs, it was at 67.9%. Comparing the two groups according to the CS scar niche, the placenta was low in 75.5% of cases in the participant group with a CS scar niche and in 75% of cases without a CS scar niche (p = 0.949). Conclusions: The number of previous caesarean deliveries has no effect on the incidence rate of low-lying placentas in the first trimester. Moreover, the presence of the CS scar niche is not associated with anterior low-lying placentas. Full article
(This article belongs to the Section Obstetrics and Gynecology)
Show Figures

Figure 1

12 pages, 1110 KiB  
Communication
A New Full Digital Workflow for Fixed Prosthetic Rehabilitation of Full-Arch Edentulism Using the All-on-4 Concept
by João Martins, João Rangel, Miguel de Araújo Nobre, Ana Ferro, Mariana Nunes, Ricardo Almeida and Carlos Moura Guedes
Medicina 2024, 60(5), 720; https://doi.org/10.3390/medicina60050720 (registering DOI) - 26 Apr 2024
Abstract
(1) Background: Recent digital workflows are being developed for full-arch rehabilitations supported by implants with immediate function. The purpose of this case series is to describe a new digital workflow for the All-on-4 concept. (2) Methods: The patients were rehabilitated using [...] Read more.
(1) Background: Recent digital workflows are being developed for full-arch rehabilitations supported by implants with immediate function. The purpose of this case series is to describe a new digital workflow for the All-on-4 concept. (2) Methods: The patients were rehabilitated using the All-on-4 concept with a digital workflow including computerized tomography scanning, intra-oral scanning, and CAD-CAM production of the temporary prosthesis, with the 3D printing of stackable guides (base guide, implant guide, and prosthetic guide). The passive fit of the prostheses and the time to perform the rehabilitations were evaluated. (3) Results: The digital workflow allowed for predictable bone reduction, the insertion of implants with immediate function, and the connection of an implant-supported prosthesis with immediate loading. The time registered to perform the full-arch rehabilitations (implant insertion, abutment connection, prosthesis connection) was below 2 hours and 30 min. No passive fit issues were noted. (4) Conclusions: within the limitation of this case series, the digital workflow applied to the All-on-4 concept using stackable base-, implant-, and prosthetic guides constitutes a potential alternative with decreased time for the procedure without prejudice of the outcome. Full article
(This article belongs to the Section Dentistry)

Open Access Journals

Browse by Indexing Browse by Subject Selected Journals
Back to TopTop