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Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world.
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most exciting work published in the various research areas of the journal.
This study investigated the synthesis and functional characteristics of Fe3O4@Ag core–shell nanoparticles, focusing on the impact of amino functionalization on their structural and chemical properties. Utilizing self-assembly methods driven by electrostatic interactions, we achieved the effective adsorption of Ag
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This study investigated the synthesis and functional characteristics of Fe3O4@Ag core–shell nanoparticles, focusing on the impact of amino functionalization on their structural and chemical properties. Utilizing self-assembly methods driven by electrostatic interactions, we achieved the effective adsorption of Ag nanoparticles into Fe3O4 cores previously modified with silane (APTES) or polymer (PEI) precursors. Our results elucidate how the type of amino precursor affects the surface charge and subsequent adsorption dynamics, revealing that PEI-modified Fe3O4 nanoparticles exhibit more substantial Ag nanoparticle adsorption than those modified with APTES. This enhanced adsorption was attributed to the higher density of the amine groups introduced by PEI, which also affected the electrostatic properties of the nanoparticles, as evidenced by their zeta-potential values. Moreover, this study highlighted the role of electrostatic attraction in the self-assembly process, facilitating a controlled synthesis environment that enhances the stability and functionality of nanoparticles for potential biomedical and catalytic applications. This research not only advances our understanding of nanoparticle behavior under different surface chemistries but also demonstrates the importance of surface engineering in optimizing nanoparticle performance for targeted applications.
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Abnormalities in sperm nuclei and chromatin can interfere with normal fertilization, embryonic development, implantation, and pregnancy. We aimed to study the impact of H2BFWT gene variants in sperm DNA on ICSI outcomes in couples undergoing ART treatment. One hundred and nineteen partners were
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Abnormalities in sperm nuclei and chromatin can interfere with normal fertilization, embryonic development, implantation, and pregnancy. We aimed to study the impact of H2BFWT gene variants in sperm DNA on ICSI outcomes in couples undergoing ART treatment. One hundred and nineteen partners were divided into pregnant (G1) and non-pregnant (G2) groups. After semen analysis, complete DNA was extracted from purified sperm samples. The sequence of the H2BFWT gene was amplified by PCR and then subjected to Sanger sequencing. The results showed that there are three mutations in this gene: rs7885967, rs553509, and rs578953. Significant differences were shown in the distribution of alternative and reference alleles between G1 and G2 (p = 0.0004 and p = 0.0020, respectively) for rs553509 and rs578953. However, there was no association between these SNPs and the studied parameters. This study is the first to shed light on the connection between H2BFWT gene variants in sperm DNA and pregnancy after ICSI therapy. This is a pilot study, so further investigations about these gene variants at the transcriptional and translational levels will help to determine its functional consequences and to clarify the mechanism of how pregnancy can be affected by sperm DNA.
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Stroke is the second most common cause of death worldwide, and it greatly impacts the quality of life for survivors by causing impairments in their upper limbs. Due to the difficulties in accessing rehabilitation services, immersive virtual reality (IVR) is an interesting approach
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Stroke is the second most common cause of death worldwide, and it greatly impacts the quality of life for survivors by causing impairments in their upper limbs. Due to the difficulties in accessing rehabilitation services, immersive virtual reality (IVR) is an interesting approach to improve the availability of rehabilitation services. This systematic review evaluates the technological characteristics of IVR systems used in the rehabilitation of upper limb stroke patients. Twenty-five publications were included. Various technical aspects such as game engines, programming languages, headsets, platforms, game genres, and technical evaluation were extracted from these papers. Unity 3D and C# are the primary tools for creating IVR apps, while the Oculus Quest (Meta Platforms Technologies, Menlo Park, CA, USA) is the most often used headset. The majority of systems are created specifically for rehabilitation purposes rather than being readily available for purchase (i.e., commercial games). The analysis also highlights key areas for future research, such as game assessment, the combination of hardware and software, and the potential integration incorporation of biofeedback sensors. The study highlights the significance of technological progress in improving the effectiveness and user-friendliness of IVR. It calls for additional research to fully exploit IVR’s potential in enhancing stroke rehabilitation results.
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Idiopathic pulmonary fibrosis is a fatal interstitial lung disease for which effective drug therapies are lacking. Senegenin, an effective active compound from the traditional Chinese herb Polygala tenuifolia Willd, has been shown to have a wide range of pharmacological effects. In this
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Idiopathic pulmonary fibrosis is a fatal interstitial lung disease for which effective drug therapies are lacking. Senegenin, an effective active compound from the traditional Chinese herb Polygala tenuifolia Willd, has been shown to have a wide range of pharmacological effects. In this study, we investigated the therapeutic effects of senegenin on pulmonary fibrosis and their associated mechanisms of action. We found that senegenin inhibited the senescence of epithelial cells and thus exerted anti-pulmonary-fibrosis effects by inhibiting oxidative stress. In addition, we found that senegenin promoted the expression of Sirt1 and Pgc-1α and that the antioxidative and antisenescent effects of senegenin were suppressed by specific silencing of the Sirt1 and Pgc–1α genes, respectively. Moreover, the senegenin-induced effects of antioxidation, antisenescence of epithelial cells, and antifibrosis were inhibited by treatment with Sirt1 inhibitors in vivo. Thus, the Sirt1/Pgc-1α pathway exerts its antifibrotic effect on lung fibrosis by mediating the antioxidative and antisenescent effects of senegenin.
Full article
Sexual and reproductive health (SRH) services’ underutilization by men remains a global public health challenge. SRH problems constitute major health challenges in that they form almost one-seventh of the disease burden and contribute to higher and earlier morbidity among men. We, therefore, invited
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Sexual and reproductive health (SRH) services’ underutilization by men remains a global public health challenge. SRH problems constitute major health challenges in that they form almost one-seventh of the disease burden and contribute to higher and earlier morbidity among men. We, therefore, invited subject matter experts to collaborate in co-creating intervention strategies to enhance men’s utilization of SRH services. We employed the nominal group technique (NGT) for data collection. The NGT is a structured method that involves gathering a group of people to discuss a problem for the purpose of achieving a group consensus and planning actions for the selected problem. The participants who were purposively sampled included researchers, scientists, academics, clinicians, and policymakers. The participants suggested the need to improve men’s knowledge, provide healthcare resources such as equipment, medical supplies, and SRH-trained male healthcare workers, deal with healthcare workers’ negative attitudes through training and capacitation, and destigmatize socially constructed gender norms that deter men from seeking medical help. These important intervention strategies can be implemented to encourage men’s use of SRH services. Men’s current underutilization of SRH services requires the urgent implementation of evidence-based interventions. Collaborating with SRH experts in identifying appropriate intervention strategies can assist program managers and policymakers in designing SRH services tailored to men’s sexual health needs.
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Recently, an outbreak of Ips sexdentatus (Börner, 1776) has caused considerable damage in the pine forests of the Czech Republic. As historical data on the biology of this pest are scarce due to its rare occurrence in recent decades, our work focused on
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Recently, an outbreak of Ips sexdentatus (Börner, 1776) has caused considerable damage in the pine forests of the Czech Republic. As historical data on the biology of this pest are scarce due to its rare occurrence in recent decades, our work focused on monitoring flight activity and voltinism and investigating methods for monitoring its activity during the growing season. Observations were conducted from March to September 2021 and 2022 at three sites using 12 Theysohn traps with four types of pheromone lures (ACUMIPROTECT, ACUWIT, SEXOWIT and Pheagr IAC) together with data loggers to record weather conditions. The first beetles occurred in early May (daily mean temperatures above 13 °C). After the first egg laying stage, females re-emerged to establish a sister brood. The maximum flight activity appeared between late June and mid-July (daily mean temperatures about 20 °C), and the offspring occurred at the turn of June/July and in the first half of August. Since then, flight activity had a downward trend and quietened in September. According to the data, monitoring of I. sexdentatus should be conducted between May and September using the ACUMIPROTECT pheromone bait exhibiting the highest capturing efficacy. In future, however, the behavior of I. sexdentatus might alter due to climate change.
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To achieve rapid post-earthquake repair of self-centering ribbed floor flat-beam frame structures, a ductile hybrid joint consisting of dog-bone-shaped, weakened, energy-dissipating steel bars connected to the upper and lower column sections through high-strength threads is proposed based on the damage control design concept.
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To achieve rapid post-earthquake repair of self-centering ribbed floor flat-beam frame structures, a ductile hybrid joint consisting of dog-bone-shaped, weakened, energy-dissipating steel bars connected to the upper and lower column sections through high-strength threads is proposed based on the damage control design concept. By moving the ductile energy-dissipating zone out to the locally weakened section of the energy-dissipating steel bars and the locally unbonded prestressed steel bars in the core area, the residual deformation was limited and the seismic performance improved. Based on the working principle of hybrid joints, low cycle loading tests were conducted on two joint specimens to analyze the influence of lateral prestress on the seismic performance of the hybrid joints. Numerical modeling methods were used to compare the position of the energy-dissipating steel bars in the composite layer and the friction performance of the joints. The research results indicated that the hybrid joint had stable load bearing, deformation, and energy dissipation capabilities, with damage being primarily concentrated in the energy-dissipating steel bars. Even at an inter-story displacement angle of 5.5%, the upper and lower column segments remained elastic. After unloading, the connection seam at the joint was closed, and the self-centering performance was good. When the inter-story displacement angle reached 5.5%, the lateral prestress increased from 150 kN to 250 kN, the ultimate bearing capacity of the joint increased by 16.3%, and the cumulative energy consumption increased by 30.0%. The influence of the friction coefficient of the joint surface on the structural performance was set at a threshold of 0.7. When it was less than the threshold, the ultimate bearing capacity and initial stiffness of the joint increased with the increase in the friction coefficient. After reaching the threshold, the increase in the ultimate bearing capacity of the joint slowed down, and the rate of stiffness degradation gradually accelerated. This joint showed excellent seismic performance and can thus achieve post-earthquake repair of structures.
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Kentaro Ochiai, Neal Bhutiani, Atsushi Ikeda, Abhineet Uppal, Michael G. White, Oliver Peacock, Craig A. Messick, Brian K. Bednarski, Yi-Qian Nancy You, John M. Skibber, George J. Chang and Tsuyoshi Konishi
Cancers2024, 16(11), 2093; https://doi.org/10.3390/cancers16112093 (registering DOI) - 31 May 2024
Total neoadjuvant therapy (TNT) is a novel strategy for rectal cancer that administers both (chemo)radiotherapy and systemic chemotherapy before surgery. TNT is expected to improve treatment compliance, tumor regression, organ preservation, and oncologic outcomes. Multiple TNT regimens are currently available with various combinations
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Total neoadjuvant therapy (TNT) is a novel strategy for rectal cancer that administers both (chemo)radiotherapy and systemic chemotherapy before surgery. TNT is expected to improve treatment compliance, tumor regression, organ preservation, and oncologic outcomes. Multiple TNT regimens are currently available with various combinations of the treatments including induction or consolidation chemotherapy, triplet or doublet chemotherapy, and long-course chemoradiotherapy or short-course radiotherapy. Evidence on TNT is rapidly evolving with new data on clinical trials, and no definitive consensus has been established on which regimens to use for improving outcomes. Clinicians need to understand the advantages and limitations of the available regimens for multidisciplinary decision making. This article reviews currently available evidence on TNT for rectal cancer. A decision making flow chart is provided for tailor-made use of TNT regimens based on tumor location and local and systemic risk.
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The global demand for protein is on an upward trajectory, and peanut protein powder has emerged as a significant player, owing to its affordability and high quality, with great future market potential. However, the industry currently lacks efficient methods for rapid quality testing.
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The global demand for protein is on an upward trajectory, and peanut protein powder has emerged as a significant player, owing to its affordability and high quality, with great future market potential. However, the industry currently lacks efficient methods for rapid quality testing. This research paper addressed this gap by introducing a portable device with employed near-infrared spectroscopy (NIR) to quickly assess the quality of peanut protein powder. The principal component analysis (PCA), partial least squares (PLS), and generalized regression neural network (GRNN) methods were used to construct the model to further enhance the accuracy and efficiency of the device. The results demonstrated that the newly established NIR method with PLS and GRNN analysis simultaneously predicted the fat, protein, and moisture of peanut protein powder. The GRNN model showed better predictive performance than the PLS model, the correlation coefficient in calibration (Rcal) of the fat, the protein, and the moisture of peanut protein powder were 0.995, 0.990, and 0.990, respectively, and the residual prediction deviation (RPD) were 10.82, 10.03, and 8.41, respectively. The findings unveiled that the portable NIR spectroscopic equipment combined with the GRNN method achieved rapid quantitative analysis of peanut protein powder. This advancement holds a significant application of this device for the industry, potentially revolutionizing quality testing procedures and ensuring the consistent delivery of high-quality products to fulfil consumer desires.
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Víctor Martínez-Rosas, Gabriel Navarrete-Vázquez, Daniel Ortega-Cuellar, Roberto Arreguin-Espinosa, Verónica Pérez de la Cruz, Ernesto Calderón-Jaimes, Sergio Enríquez-Flores, Carlos Wong-Baeza, Isabel Baeza-Ramírez, Laura Morales-Luna, Montserrat Vázquez-Bautista, Miriam Abigail Rojas-Alarcón, Beatriz Hernández-Ochoa and Saúl Gómez-Manzo
Molecules2024, 29(11), 2585; https://doi.org/10.3390/molecules29112585 (registering DOI) - 31 May 2024
Metronidazole (MTZ) is the most common drug used against Trichomonas vaginalis (T. vaginalis) infections; however, treatment failures and high rates of recurrence of trichomoniasis have been reported, suggesting the presence of resistance in T. vaginalis to MTZ. Therefore, research into new
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Metronidazole (MTZ) is the most common drug used against Trichomonas vaginalis (T. vaginalis) infections; however, treatment failures and high rates of recurrence of trichomoniasis have been reported, suggesting the presence of resistance in T. vaginalis to MTZ. Therefore, research into new therapeutic options against T. vaginalis infections has become increasingly urgent. This study investigated the trichomonacidal activity of a series of five imidazole carbamate compounds (AGR-1, AGR-2, AGR-3, AGR-4, and AGR-5) through in vitro susceptibility assays to determine the IC50 value of each compound. All five compounds demonstrated potent trichomonacidal activity, with IC50 values in the nanomolar range and AGR-2 being the most potent (IC50 400 nM). To gain insight into molecular events related to AGR-induced cell death in T. vaginalis, we analyzed the expression profiles of some metabolic genes in the trophozoites exposed to AGR compounds and MTZ. It was found that both AGR and MTZ compounds reduced the expression of the glycolytic genes (CK, PFK, TPI, and ENOL) and genes involved in metabolism (G6PD, TKT, TALDO, NADHOX, ACT, and TUB), suggesting that disturbing these key metabolic genes alters the survival of the T. vaginalis parasite and that they probably share a similar mechanism of action. Additionally, the compounds showed low cytotoxicity in the Caco-2 and HT29 cell lines, and the results of the ADMET analysis indicated that these compounds have pharmacokinetic properties similar to those of MTZ. The findings offer significant insights that can serve as a basis for future in vivo studies of the compounds as a potential new treatment against T. vaginalis.
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Background: Advanced non-small-cell lung cancer (NSCLC) can be treated with novel targeted therapies that are tailored to the genetic characteristics of malignancy. While tissue-based genomic testing is considered the gold standard for the detection of oncogenic driver mutations, several challenges like inadequate tissue
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Background: Advanced non-small-cell lung cancer (NSCLC) can be treated with novel targeted therapies that are tailored to the genetic characteristics of malignancy. While tissue-based genomic testing is considered the gold standard for the detection of oncogenic driver mutations, several challenges like inadequate tissue availability, the invasiveness of procuring tumors, and prolonged turnaround time of analysis are encountered. Considering these limitations, guidelines have recognized liquid biopsies using circulating cell-free DNA (cfDNA) as a useful tool to complement conventional tissue testing. Even though cfDNA next-generation sequencing (NGS) can have high sensitivity and specificity, optimal patient benefit requires the interpretation of the molecular profiling results in the context of clinical and diagnostic features to achieve the best outcomes. Case Descriptions: In this case series, we present six patients with advanced NSCLC whose plasma or tissue biopsy samples were analyzed with commercially available comprehensive NGS assays that elucidate the role of testing at various time points in the treatment journey. In all six cases, comprehensive genomic profiling (CGP) provided clinically useful information to guide treatment decisions. Conclusion: Adding to the existing real-world evidence, this case series reinforces that CGP-driven treatment strategies in advanced NSCLC, coupled with other available clinical information, can optimize treatment decisions.
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Refugees and asylum seekers bring with them a plurality of cultures, traditions, and values that could prove crucial in influencing perceived health needs, requests for intervention, or willingness to undergo specific health treatments. Although studies have focused on the health consequences of forced
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Refugees and asylum seekers bring with them a plurality of cultures, traditions, and values that could prove crucial in influencing perceived health needs, requests for intervention, or willingness to undergo specific health treatments. Although studies have focused on the health consequences of forced migration, in recent years, there has been a lack of information on how refugees and asylum seekers represent their experiences of perceived health needs and elements that influence well-being, in a community context. This study aims to explore the experience of refugees and asylum seekers in an Italian multicultural community about perceived health needs. A qualitative phenomenological study was conducted with an interpretive approach. The data were collected using a semi-structured face-to-face interview. The interviews were transcribed, read thoroughly, and analyzed. Nineteen refugees and asylum seekers were interviewed. Three main themes were extracted: (1) the centrality of the family to feel healthy; (2) feeling part of a community; and (3) stability and security. The results confirm that health needs, experiences, and different cultural representations of health and illness should be read and addressed with a culturally competent vision. This study was not registered.
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Kenta Yamamoto, Shin-Ichi Sawada, Satoru Shindo, Shin Nakamura, Young M. Kwon, Nazanin Kianinejad, Saynur Vardar, Maria Hernandez, Kazunari Akiyoshi and Toshihisa Kawai
Gels2024, 10(6), 377; https://doi.org/10.3390/gels10060377 (registering DOI) - 31 May 2024
Osteoclast stimulatory transmembrane protein (OC-STAMP) plays a pivotal role in the promotion of cell fusion during osteoclast differentiation (osteoclastogenesis) in the context of pathogenic bone resorption. Thus, it is plausible that the suppression of OC-STAMP through a bioengineering approach could lead to the
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Osteoclast stimulatory transmembrane protein (OC-STAMP) plays a pivotal role in the promotion of cell fusion during osteoclast differentiation (osteoclastogenesis) in the context of pathogenic bone resorption. Thus, it is plausible that the suppression of OC-STAMP through a bioengineering approach could lead to the development of an effective treatment for inflammatory bone resorptive diseases with minimum side effects. Here, we synthesized two types of spermine-bearing (Spe) cationic glucan dendrimer (GD) gels (with or without C12) as carriers of short interfering RNA (siRNA) to silence OC-STAMP. The results showed that amphiphilic C12-GD-Spe gel was more efficient in silencing OC-STAMP than GD-Spe gel and that the mixture of anti-OC-STAMP siRNA/C12-GD-Spe significantly downregulated RANKL-induced osteoclastogenesis. Also, local injection of anti-OC-STAMP-siRNA/C12-GD-Spe could attenuate bone resorption induced in a mouse model of periodontitis. These results suggest that OC-STAMP is a promising target for the development of a novel bone regenerative therapy and that C12-GD-Spe gel provides a new nanocarrier platform of gene therapies for osteolytic disease.
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Mycoplasma capricolum subsp. capricolum (Mcc) and Mycoplasma capricolum subsp. capripneumoniae (Mccp) are pathogens that affect large and small ruminants. Indeed, Mcc affects both sheep and goats, causing contagious agalactia (CA). Mccp affects only goats, causing contagious caprine pleuropneumonia (CCPP). CA and CCPP are
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Mycoplasma capricolum subsp. capricolum (Mcc) and Mycoplasma capricolum subsp. capripneumoniae (Mccp) are pathogens that affect large and small ruminants. Indeed, Mcc affects both sheep and goats, causing contagious agalactia (CA). Mccp affects only goats, causing contagious caprine pleuropneumonia (CCPP). CA and CCPP are mainly controlled using inactivated Mcc and Mccp vaccines. However, producing the vaccine with the Mccp strain is complex, fastidious, and costly due to the slow growth of the bacterium. In this study, we present new oil-adjuvanted and inactivated Mcc and Mccp vaccines for sheep and goats against CA and CCPP. The vaccines were evaluated for safety and efficacy using experimental infection. A serological response was observed one week after of the first vaccination of sheep and goats with Mcc and goats with Mccp. The vaccinated animals were subsequently challenged with the virulent Mcc MOR20 strain. The Mcc vaccine was demonstrated to provide robust protection when the animals were challenged with Mcc MOR20. Cross-protection against the Mcc MOR20 challenge was also obtained with the Mccp vaccine. This finding revealed, for the first time, the safety and efficacy of an inactivated Mcc vaccine against contagious agalactia and cross-protection between Mcc and Mccp strains.
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Pore water pressure (PWP) response is significant for evaluating the earth dams’ stability, and PWPs are, therefore, generally monitored. However, due to the soil heterogeneity and its non-linear behavior within earths, the PWP is usually difficult to estimate and predict accurately in order
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Pore water pressure (PWP) response is significant for evaluating the earth dams’ stability, and PWPs are, therefore, generally monitored. However, due to the soil heterogeneity and its non-linear behavior within earths, the PWP is usually difficult to estimate and predict accurately in order to detect a pathology or anomaly in the behavior of an embankment dam. This study endeavors to tackle this challenge through the application of diverse machine learning (ML) techniques in estimating the PWP within an existing earth dam. The methods employed include random forest (RF) combined with simulated annealing (SA), multilayer perceptron (MLP), standard recurrent neural networks (RNNs), and gated recurrent unit (GRU). The prediction capability of these techniques was gauged using metrics such as the coefficient of determination (R2), mean square error (MSE), and CPU training time. It was found that all the considered ML methods could give satisfactory results for the PWP estimation. Upon comparing these methods within the case study, the findings suggest that, in this study, multilayer perceptron (MLP) gives the most accurate PWP prediction, achieving the highest coefficient of determination (R2 = 0.99) and the lowest mean square error (MSE = 0.0087) metrics. A sensitivity analysis is then presented to evaluate the models’ robustness and the hyperparameter’s influence on the performance of the prediction model.
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As the Internet of Things (IoT) continues to evolve, securing IoT networks and devices remains a continuing challenge. Anomaly detection is a crucial procedure in protecting the IoT. A promising way to perform anomaly detection in the IoT is through the use of
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As the Internet of Things (IoT) continues to evolve, securing IoT networks and devices remains a continuing challenge. Anomaly detection is a crucial procedure in protecting the IoT. A promising way to perform anomaly detection in the IoT is through the use of machine learning (ML) algorithms. There is a lack of studies in the literature identifying optimal (with regard to both effectiveness and efficiency) anomaly detection models for the IoT. To fill the gap, this work thoroughly investigated the effectiveness and efficiency of IoT anomaly detection enabled by several representative machine learning models, namely Extreme Gradient Boosting (XGBoost), Support Vector Machines (SVMs), and Deep Convolutional Neural Networks (DCNNs). Identifying optimal anomaly detection models for IoT anomaly detection is challenging due to diverse IoT applications and dynamic IoT networking environments. It is of vital importance to evaluate ML-powered anomaly detection models using multiple datasets collected from different environments. We utilized three reputable datasets to benchmark the aforementioned machine learning methods, namely, IoT-23, NSL-KDD, and TON_IoT. Our results show that XGBoost outperformed both the SVM and DCNN, achieving accuracies of up to 99.98%. Moreover, XGBoost proved to be the most computationally efficient method; the model performed 717.75 times faster than the SVM and significantly faster than the DCNN in terms of training times. The research results have been further confirmed by using our real-world IoT data collected from an IoT testbed consisting of physical devices that we recently built.
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Schnitzler syndrome is a rare disorder characterized by a chronic urticarial rash associated with immunoglobulin M (IgM) monoclonal gammopathy. Schnitzler syndrome shares strong clinicopathologic similarities with monogenic IL-1-mediated autoinflammatory disorders and is now considered an acquired adult-onset autoinflammatory disease. The spectacular effect of
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Schnitzler syndrome is a rare disorder characterized by a chronic urticarial rash associated with immunoglobulin M (IgM) monoclonal gammopathy. Schnitzler syndrome shares strong clinicopathologic similarities with monogenic IL-1-mediated autoinflammatory disorders and is now considered an acquired adult-onset autoinflammatory disease. The spectacular effect of interleukin-1 inhibitors demonstrates the key role of this cytokine in the pathogenesis of the disease. However, the physiopathology of Schnitzler syndrome remains elusive, and the main question regarding the relationship between autoinflammatory features and monoclonal gammopathy is still unanswered. The purpose of this narrative review is to describe what is currently known about the pathogenesis of this peculiar disease, as well as to address its diagnosis and management.
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Clear-cell Renal-Cell Carcinoma (ccRCC) is the most common type of renal-cell carcinoma (RCC). In many cases, RCC patients manifest the first symptoms during the advanced stage of the disease. For this reason, immunotherapy appears to be one of the dominant treatments to achieve
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Clear-cell Renal-Cell Carcinoma (ccRCC) is the most common type of renal-cell carcinoma (RCC). In many cases, RCC patients manifest the first symptoms during the advanced stage of the disease. For this reason, immunotherapy appears to be one of the dominant treatments to achieve a resolution. In this review, we focus on the presentation of the main immune checkpoint proteins that act as negative regulators of immune responses, such as PD-1, CTLA-4, LAG-3, TIGIT, and TIM-3, and their respective inhibitors. Interleukin-2, another potential component of the treatment of ccRCC patients, has also been covered. The synergy between several immunotherapies is one of the main aspects that unites the conclusions of research in recent years. To date, the combination of several immunotherapies enhances the efficacy of a monotherapy, which often manifests important limitations. Immunotherapy aimed at restoring the anti-cancer immune response in ccRCC, involved in the recognition and elimination of cancer cells, may also be a valid solution for many other types of immunogenic tumors that are diagnosed in the final stages.
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Endothelial cells (ECs) line the inner surface of all blood vessels and form a barrier that facilitates the controlled transfer of nutrients and oxygen from the circulatory system to surrounding tissues. Exposed to both laminar and turbulent blood flow, ECs are continuously subject
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Endothelial cells (ECs) line the inner surface of all blood vessels and form a barrier that facilitates the controlled transfer of nutrients and oxygen from the circulatory system to surrounding tissues. Exposed to both laminar and turbulent blood flow, ECs are continuously subject to differential mechanical stimulation. It has been well established that the shear stress associated with laminar flow (LF) is atheroprotective, while shear stress in areas with turbulent flow (TF) correlates with EC dysfunction. Moreover, ECs show metabolic adaptions to physiological changes, such as metabolic shifts from quiescence to a proliferative state during angiogenesis. The AMP-activated protein kinase (AMPK) is at the center of these phenomena. AMPK has a central role as a metabolic sensor in several cell types. Moreover, in ECs, AMPK is mechanosensitive, linking mechanosensation with metabolic adaptions. Finally, recent studies indicate that AMPK dysregulation is at the center of cardiovascular disease (CVD) and that pharmacological targeting of AMPK is a promising and novel strategy to treat CVDs such as atherosclerosis or ischemic injury. In this review, we summarize the current knowledge relevant to this topic, with a focus on shear stress-induced AMPK modulation and its consequences for vascular health and disease.
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Phenotypic variation analysis and comprehensive evaluation are important tools for selecting provenances of forest trees, which, in turn, is crucial for genetic improvement of forest trees. The study analyzed eight needle-leaf and fourteen tracheid trait indexes of ten provenances of Qinghai spruce forest
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Phenotypic variation analysis and comprehensive evaluation are important tools for selecting provenances of forest trees, which, in turn, is crucial for genetic improvement of forest trees. The study analyzed eight needle-leaf and fourteen tracheid trait indexes of ten provenances of Qinghai spruce forest stands. Multiple comparisons, correlation analysis, cluster analysis, and principal component analysis were used to evaluate the differences in needle-leaf and tracheid traits among the different provenances. The study found significant differences in the needle-leaf and tracheid traits among the provenances. All traits included 50 pairs of positive and 26 pairs of negative correlations. The coefficient of variation for the tracheid trait (18.86%) was higher than that for the needle-leaf trait (17.20%). A comprehensive evaluation of needle-leaf and tracheid traits was conducted using principal component analysis. The study demonstrated that the degree of variation in needle-leaf and tracheid traits among the provenances of Qinghai spruce was extensive, with a multitude of sources of variation. Therefore, it is crucial to strengthen the selection of good provenances in the early seed selection process. The results of the comprehensive evaluation can be utilized as a foundation for the selection of good provenances for carbon sequestration and timber properties.
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South Korea is a rapidly aging society with the lowest fertility rates among the OECD economies. It is projected to become a super-aged society in 2025, with the share of individuals older than 65 reaching twenty percent. These developments make it important to
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South Korea is a rapidly aging society with the lowest fertility rates among the OECD economies. It is projected to become a super-aged society in 2025, with the share of individuals older than 65 reaching twenty percent. These developments make it important to analyze the determinants of health outcomes in older individuals. In this study, we identified the determinants of subjective and objective health outcomes among senior individuals in South Korea. We used self-rated health and life satisfaction scores as the two subjective health status indicators, while the number of chronic diseases was the objective one. We ran Tobit multivariate regressions of all three indicators on a set of factors related to the older citizens’ physical, economic, and social characteristics. Active employment status and willingness to work in the future were positively related to self-rated health level but were not statistically related to life satisfaction, while income positively affected both subjective health status indicators. Age did not appear to affect satisfaction with life. Active leisure activities were positively related to both self-rated health and life satisfaction. In contrast, passive leisure, such as watching TV, was negatively related to both health status indicators while being associated with an increased number of chronic diseases. Our findings suggest that older South Koreans view employment primarily as a means of financial support rather than as an opportunity for active social engagement.
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Acemetacin (ACM) is a new non-steroidal anti-inflammatory drug with anti-inflammatory, analgesic, and antipyretic effects. However, the poor water solubility and gastrointestinal side effects limit its use. Recently, the co-amorphous (CAM) strategy has attracted great interest to improve solubility for poorly water-soluble drugs, and
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Acemetacin (ACM) is a new non-steroidal anti-inflammatory drug with anti-inflammatory, analgesic, and antipyretic effects. However, the poor water solubility and gastrointestinal side effects limit its use. Recently, the co-amorphous (CAM) strategy has attracted great interest to improve solubility for poorly water-soluble drugs, and basic amino acids have the potential to protect the gastrointestinal tract. In order to develop a highly efficient and low-toxic ACM formulation, we prepared ACM CAM systems, with basic amino acids (lysine, arginine, and histidine) as co-formers, using a cryo-milling method. The solid-state behaviors of the ACM CAM systems were characterized by polarizing light microscopy, differential scanning calorimetry, and powder X-ray diffraction. Fourier transform infrared spectroscopy and molecular docking were carried out to understand the formation mechanism. Moreover, the gastro-protective effects of ACM CAM systems were evaluated in a rat gastric ulcer model. The results demonstrated that the CAM systems improved the dissolution rates of ACM compared with the neat amorphous counterpart. Furthermore, ACM CAM systems are significantly effective in mitigating the ACM-induced gastric ulcer in rats, and the ulcer inhibition rates were almost 90%. More importantly, this study provided a useful method for mitigating drug-induced gastrointestinal damage and broadened the applications of drug–amino acid CAM systems.
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We have been encouraging practicing gynecologists to adopt molecular diagnostics tests, PCR, and cancer biomarkers, as alternatives enabled by these platforms, to traditional Papanicolaou and colposcopy tests, respectively. An aliquot of liquid-based cytology was used for the molecular test [high-risk HPV types, (HR
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We have been encouraging practicing gynecologists to adopt molecular diagnostics tests, PCR, and cancer biomarkers, as alternatives enabled by these platforms, to traditional Papanicolaou and colposcopy tests, respectively. An aliquot of liquid-based cytology was used for the molecular test [high-risk HPV types, (HR HPV)], another for the PAP test, and one more for p16/Ki67 dual-stain cytology. A total of 4499 laboratory samples were evaluated, and we found that 25.1% of low-grade samples and 47.9% of high-grade samples after PAP testing had a negative HR HPV-PCR result. In those cases, reported as Pap-negative, 22.1% had a positive HR HPV-PCR result. Dual staining with p16/Ki67 biomarkers in samples was positive for HR HPV, and 31.7% were also positive for these markers. Out of the PCR results that were positive for any of these HR HPV subtypes, n 68.3%, we did not find evidence for the presence of cancerous cells, highlighting the importance of performing dual staining with p16/Ki67 after PCR to avoid unnecessary colposcopies. The encountered challenges are a deep-rooted social reluctance in Mexico to abandon traditional Pap smears and the opinion of many specialists. Therefore, we still believe that colposcopy continues to be a preferred procedure over the dual-staining protocol.
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