The genitourinary syndrome of menopause (GSM) is a widely occurring condition affecting millions of women worldwide. The current treatment of GSM involves the use of orally or vaginally administered estrogens, often with the risk of endometrial hyperplasia. The utilization of progestogens offers a means to counteract the effects of estrogen on the endometrial tissue, decreasing unwanted side effects and improving therapeutic outcomes. In this study, a norethindrone acetate (NETA)-loaded, hollow, cylindrical, and sustained release platform has been designed, fabricated, and optimized for implantation in the uterine cavity as a counter-estrogenic intervention in the treatment of GSM. The developed system, which comprises ethyl cellulose (EC) and polycaprolactone (PCL), has been statistically optimized using a two-factor, two-level factorial design, with the mechanical properties, degradation, swelling, and in vitro drug release of NETA from the device evaluated. The morphological characteristics of the platform were further investigated through scanning electron microscopy in addition to cytocompatibility studies using NIH/3T3 cells. Results from the statistical design highlighted the platform with the highest NETA load and the EC-to-PCL ratio that exhibited favorable release and weight loss profiles. The drug release data for the optimal formulation were best fitted with the Peppas–Sahlin model, implicating both diffusion and polymer relaxation in the release mechanism, with cell viability results noting that the prepared platform demonstrated favorable cytocompatibility. The significant findings of this study firmly establish the developed platform as a promising candidate for the sustained release of NETA within the uterine cavity. This functionality serves as a counter-estrogenic intervention in the treatment of GSM, with the platform holding potential for further advanced biomedical applications. Full article

The bitter drug, warfarin, has a narrow therapeutic index (NTI) and is used in paediatrics and geriatrics. The aim of this feasibility study was to formulate the taste-masked warfarin-containing pellets to be applicable for dose personalisation and to improve patient compliance, as well as to investigate the effect of the core type (PharSQ^® Spheres M, CELPHERE™ CP-507, and NaCl) on the warfarin release from the Kollicoat^® Smartseal taste-masking-coated pellets. The cores were successfully drug-loaded and coated in a fluid-bed coater with a Wurster insert. An increase in particle size and particle size distribution was observed by optical microscopy. In saliva-simulated pH, at the Kollicoat^® Smartseal level of 2 mg/cm², none of the pellets demonstrated drug release, confirming their efficient taste-masking. However, in a stomach-simulated pH, a faster drug release was observed from PharSQ^® Spheres M- and CELPHERE™ CP-507-coated pellets in comparison with NaCl cores. Additional experiments allowed us to explain the slower drug release from NaCl-containing pellets because of the salting-out effect. Despite the successful taste masking, the drug release from pellets was relatively slow (not more than 91% per 60 min), allowing for further formulation improvements. Full article

The COVID-19 pandemic has resulted in millions of fatalities worldwide. The case of pediatric cancer patients stands out since, despite being considered a population at risk, few studies have been carried out concerning symptom detection or the description of the mechanisms capable of modifying the course of the COVID-19 disease, such as the interaction and response between the virus and the treatment given to cancer patients. By synthesizing existing studies, this paper aims to expose the treatment challenges for pediatric patients with COVID-19 in an oncology context. Additionally, this updated review includes studies that utilized the antiviral agents Remdesivir and Paxlovid^TM in pediatric cancer patients. There is no specific treatment designed exclusively for pediatric cancer patients dealing with COVID-19, and it is advisable to avoid self-medication to prevent potential side effects. Managing COVID-19 in pediatric cancer patients is indeed a substantial challenge. New strategies, such as chemotherapy application rooms, have been implemented for children with cancer who were positive for COVID-19 but asymptomatic since the risk of disease progression is greater than the risk of complications from SARS-CoV-2. Full article

Coronavirus disease 2019 (COVID-19) can lead to persistent and debilitating symptoms referred to as Post-Acute sequelae of SARS-CoV-2 infection (PASC) This broad symptomatology lasts for months after the acute infection and impacts physical and mental health and everyday functioning. In the present study, we aimed to evaluate the prevalence and predictors of long-term impairment of working ability in non-elderly people hospitalised for COVID-19. Methods: This cross-sectional study involved 322 subjects hospitalised for COVID-19 from 1 March 2020 to 31 December 2022 in the University Hospital of Bari, Apulia, Italy, enrolled at the time of their hospital discharge and followed-up at a median of 731 days since hospitalization (IQR 466–884). Subjects reporting comparable working ability and those reporting impaired working ability were compared using the Mann-Whitney test (continuous data) and Fisher’s test or Chi-Square test (categorical data). Multivariable analysis of impaired working ability was performed using a logistic regression model. Results: Among the 322 subjects who were interviewed, 184 reported comparable working ability (57.1%) and 134 reported impaired working ability (41.6%) compared to the pre-COVID-19 period. Multivariable analysis identified age at hospital admission (OR 1.02, 95% CI 0.99 to 1.04), female sex (OR 1.90, 95% CI 1.18 to 3.08), diabetes (OR 3.73, 95% CI 1.57 to 9.65), receiving oxygen during hospital stay (OR 1.76, 95% CI 1.01 to 3.06), and severe disease (OR 0.51, 95% CI 0.26 to 1.01) as independent predictors of long-term impaired working ability after being hospitalised for COVID-19. Conclusions: Our findings suggest that PASC promotes conditions that could result in decreased working ability and unemployment. These results highlight the significant impact of this syndrome on public health and the global economy, and the need to develop clinical pathways and guidelines for long-term care with specific focus on working impairment. Full article

Directed evolution is a pivotal strategy for new antibody discovery, which allowed the generation of high-affinity Fabs against gliadin from two antibody libraries in our previous studies. One of the libraries was exclusively derived from celiac patients’ mRNA (immune library) while the other was obtained through a protein engineering approach (semi-immune library). Recent advances in high-throughput DNA sequencing techniques are revolutionizing research across genomics, epigenomics, and transcriptomics. In the present work, an Oxford Nanopore in-lab sequencing device was used to comprehensively characterize the composition of the constructed libraries, both at the beginning and throughout the phage-mediated selection processes against gliadin. A customized analysis pipeline was used to select high-quality reads, annotate chain distribution, perform sequence analysis, and conduct statistical comparisons between the different selection rounds. Some immunological attributes of the most representative phage variants after the selection process were also determined. Sequencing results revealed the successful transfer of the celiac immune response features to the immune library and the antibodies derived from it, suggesting the crucial role of these features in guiding the selection of high-affinity recombinant Fabs against gliadin. In summary, high-throughput DNA sequencing has improved our understanding of the selection processes aimed at generating molecular binders against gliadin. Full article

Tomato (Solanum lycopersicum) is the most important vegetable and fruit crop in the family Solanaceae worldwide. Numerous pests and pathogens, especially viruses, severely affect tomato production, causing immeasurable market losses. In Taiwan, the cultivation of tomato crops is mainly threatened by insect-borne viruses, among which pepper veinal mottle virus (PVMV) is one of the most prevalent. PVMV is a member of the genus Potyvirus of the family Potyviridae and is non-persistently transmitted by aphids. Its infection significantly reduces tomato fruit yield and quality. So far, no PVMV-resistant tomato lines are available. In this study, we performed nitrite-induced mutagenesis of the PVMV tomato isolate Tn to generate attenuated PVMV mutants. PVMV Tn causes necrotic lesions in Chenopodium quinoa leaves and severe mosaic and wilting in Nicotiana benthamiana plants. After nitrite treatment, three attenuated PVMV mutants, m4-8, m10-1, and m10-11, were selected while inducing milder responses to C. quinoa and N. benthamiana with lower accumulation in tomato plants. In greenhouse tests, the three mutants showed different degrees of cross-protection against wild-type PVMV Tn. m4-8 showed the highest protective efficacy against PVMV Tn in N. benthamiana and tomato plants, 100% and 97.9%, respectively. A whole-genome sequence comparison of PVMV Tn and m4-8 revealed that 20 nucleotide substitutions occurred in the m4-8 genome, resulting in 18 amino acid changes. Our results suggest that m4-8 has excellent potential to protect tomato crops from PVMV. The application of m4-8 in protecting other Solanaceae crops, such as peppers, will be studied in the future. Full article

Cellular and humoral immunity exhibit dynamic adaptation to the mutating SARS-CoV-2 virus. It is noteworthy that immune responses differ significantly, influenced by whether a patient has received vaccination or whether there is co-occurrence of naturally acquired and vaccine-induced immunity, known as hybrid immunity. The different immune reactions, conditional on vaccination status and the viral variant involved, bear implications for inflammatory responses, patient outcomes, pathogen transmission rates, and lingering post-COVID conditions. Considering these developments, we have performed a review of recently published literature, aiming to disentangle the intricate relationships among immunological profiles, transmission, the long-term health effects post-COVID infection poses, and the resultant clinical manifestations. This investigation is directed toward understanding the variability in the longevity and potency of cellular and humoral immune responses elicited by immunization and hybrid infection. Full article

The hepatitis E virus is a serious health concern worldwide, with 20 million cases each year. Growing numbers of autochthonous HEV infections in industrialized nations are brought on via the zoonotic transmission of HEV genotypes 3 and 4. Pigs and wild boars are the main animal reservoirs of HEV and play the primary role in HEV transmission. Consumption of raw or undercooked pork meat and close contact with infected animals are the most common causes of hepatitis E infection in industrialized countries. However, during the past few years, mounting data describing HEV distribution has led experts to believe that additional animals, particularly domestic ruminant species (cow, goat, sheep, deer, buffalo, and yak), may also play a role in the spreading of HEV. Up to now, there have not been enough studies focused on HEV infections associated with animal milk and the impact that they could have on the epidemiology of HEV. This critical analysis discusses the role of domestic ruminants in zoonotic HEV transmissions. More specifically, we focus on concerns related to milk safety, the role of mixed farming in cross-species HEV infections, and what potential consequences these may have on public health. Full article

Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen that causes severe abortions in sows and high piglet mortality, resulting in huge economic losses to the pig industry worldwide. The emerging and novel PRRSV isolates are clinically and biologically important, as there are likely recombination and pathogenic differences among PRRSV genomes. Furthermore, the NADC34-like strain has become a major epidemic strain in some parts of China, but the characterization and pathogenicity of the latest strain in Inner Mongolia have not been reported in detail. In this study, an NADC34-like strain (CHNMGKL1-2304) from Tongliao City, Inner Mongolia was successfully isolated and characterized, and confirmed the pathogenicity in pigs. The phylogenetic tree showed that this strain belonged to sublineage 1.5 and had high homology with the strain JS2021NADC34. There is no recombination between CHNMGKL1-2304 and any other domestic strains. Animal experiments show that the CHNMGKL1-2304 strain is moderately virulent to piglets, which show persistent fever, weight loss and high morbidity but no mortality. The presence of PRRSV nucleic acids was detected in both blood, tissues, nasal and fecal swabs. In addition, obvious pathological changes and positive signals were observed in lung, lymph node, liver and spleen tissues when subjected to hematoxylin–eosin (HE) staining and immunohistochemistry (IHC). This report can provide a basis for epidemiological investigations and subsequent studies of PRRSV. Full article

The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan–Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23–0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16–0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02–2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk. Full article

A natural monkeypox virus infection may not induce sufficient neutralizing antibody responses in a subset of healthy individuals. The aim of this study was to evaluate monkeypox virus-neutralizing antibodies six months after infection and to assess the virological factors predictive of a poor immunological response. Antibodies were assessed using a plaque reduction neutralization test at six months from mpox infection; mpox cutaneous, oropharyngeal, and anal swabs, semen, and plasma samples were tested during infection. Overall, 95 people were included in the study; all developed detectable antibodies. People who were positive for the monkeypox virus for more days had higher levels of antibodies when considering all tested samples (p = 0.029) and all swabs (p = 0.005). Mpox cycle threshold values were not predictive of antibody titers. This study found that the overall days of monkeypox virus detection in the body, irrespective of the viral loads, were directly correlated with monkeypox virus neutralizing antibodies at six months after infection. Full article

The human papillomavirus is the most common sexually transmitted infection in the world. Most HPV infections clear spontaneously within 2 years of infection; however, persistent infection can result in a wide array of diseases, ranging from genital warts to cancer. Most cases of cervical, anal, and oropharyngeal cancers are due to HPV infection, with cervical cancer being one of the leading causes of cancer death in women worldwide. Screening is available for HPV and cervical cancer, but is not available everywhere, particularly in lower-resource settings. HPV infection disproportionally affects individuals living with HIV, resulting in decreased clearance, increased development of cancer, and increased mortality. The development of the HPV vaccine has shown a drastic decrease in HPV-related diseases. The vaccine prevents cervical cancer with near 100% efficacy, if given prior to first sexual activity. Vaccination uptake remains low worldwide due to a lack of access and limited knowledge of HPV. Increasing awareness of HPV and access to vaccination are necessary to decrease cancer and HPV-related morbidity and mortality worldwide. Full article

The skin is a complex tissue that provides a strong physical barrier against invading pathogens. Despite this, many viruses can access the skin and successfully replicate in either the epidermal keratinocytes or dermal immune cells. In this review, we provide an overview of the antiviral T cell biology responding to cutaneous viral infections and how these responses differ depending on the cellular targets of infection. Much of our mechanistic understanding of T cell surveillance of cutaneous infection has been gained from murine models of poxvirus and herpesvirus infection. However, we also discuss other viral infections, including flaviviruses and papillomaviruses, in which the cutaneous T cell response has been less extensively studied. In addition to the mechanisms of successful T cell control of cutaneous viral infection, we highlight knowledge gaps and future directions with possible impact on human health. Full article

Natural gas hydrate (NGH) is a potential future energy resource. More than 90% of NGH resources exist in the pore medium of seafloor sediments. During the development of deep-sea oil and gas fields, wellbore pipelines are often clogged due to the synthesis of gas hydrates, and the addition of thermodynamic inhibitors is a common solution to prevent hydrate synthesis. In this paper, the effects of two single inhibitors, sodium chloride and ethylene glycol, as well as hybrid inhibitors combining these two inhibitors on the synthesis of methane hydrates were investigated using the self-developed one-dimensional gas hydrate exploitation simulation test apparatus. The effects of single and hybrid inhibitors were investigated in terms of the hydrate synthesis volume and gas–water two-phase conversion rate. The results show that the hybrid inhibitor has a better inhibitory effect on hydrate synthesis with the same initial synthesis driving force. When the concentration of inhibitors is low, salt inhibitors can have a better inhibitory effect than alcohol inhibitors. However, in the mixed inhibitor experiment, increasing the proportion of ethylene glycol in the mixed inhibitor can more effectively inhibit the synthesis of hydrates than increasing the proportion of sodium chloride in the mixed inhibitor. Full article

Assessments of the hosting capacity of electricity distribution networks are of paramount importance, as they facilitate the seamless integration of rooftop photovoltaic systems into the grid, accelerating the transition towards a more carbon neutral and sustainable system. This paper employs a deep reinforcement learning-based approach to evaluate the real-time hosting capacity of low voltage distribution networks in a model-free manner. The proposed approach only requires real-time customer voltage data and solar irradiation data to provide a fast and accurate estimate of real-time hosting capacity at each customer connection point. This study addresses the imperative for accurate electrical models, which are frequently unavailable, in evaluating the hosting capacity of electricity distribution networks. To meet this challenge, the proposed approach utilizes a deep neural network-based, data-driven model of a low-voltage electricity distribution network. This proposed methodology incorporates model-free elements, enhancing its adaptability and robustness. In addition, a comparative analysis between model-based and model-free hosting capacity assessment methods is presented, highlighting their respective strengths and weaknesses. The utilization of the proposed hosting capacity estimation model enables distribution network service providers to make well-informed decisions regarding grid planning, leading to cost minimization. Full article

In this study, the influence of zinc oxide (ZnO) nanostructures with various morphologies on the performance of dye-sensitized solar cells (DSSCs) was investigated. Photo-electrodes were fabricated incorporating ZnO transport layers of distinct nanoscale morphologies—namely nanoparticles, microballs, spiky microballs, belts, and triangles—and their respective current–voltage characteristics were evaluated. It was observed that the DSSCs employing the triangular ZnO nanostructures, with a side length of approximately 30 nm, achieved the highest power conversion efficiency of 2.62%. This was closely followed by the DSSCs using spherical nanoparticles with an average diameter of approximately 20 nm, yielding an efficiency of 2.54%. In contrast, the efficiencies of DSSCs with microball and spiky microball ZnO nanostructures were significantly lower, measuring 0.31 and 1.79%, respectively. The reduction in efficiency for the microball-based DSSCs is attributed to the formation of micro-cracks within the thin film during the fabrication process. All DSSC configurations maintained a uniform active area of 4 mm². Remarkably, the highest fill factor of 59.88% was recorded for DSSCs utilizing the triangular ZnO morphology, with the spherical nanoparticles attaining a marginally lower fill factor of 59.38%. This investigation corroborates the hypothesis that reduced particle size in the transport layer correlates with enhanced DSSC performance, which is further amplified when the nanoparticles possess pointed geometries that induce strong electric fields due to elevated charge concentrations. Full article

This study presents two concepts for integrating a wave rotor combustor (WRC) into a baseline engine: the wave rotor pressure-gain cycle (WRPGC) and the wave rotor work cycle (WRWC). Performance parameters were calculated under different thermodynamic cycles, and a comparative analysis of the thermodynamic cycles was conducted, considering both the ideal- and actual-loss conditions. Furthermore, the impact of the WRC precompression ratio, turbine inlet temperature, and fixed peak cycle temperature on the thermodynamic-cycle performance was investigated. The results indicate that embedding a WRC into a baseline engine with a compressor pressure ratio higher than 24.0 does not lead to an improvement in the thermal efficiency. However, under a baseline engine pressure ratio of 3.6, the actual-loss WRC cycle achieves efficiency improvements of 40.5% and 49.5% in the WRPGC and WRWC, respectively, compared to the baseline engine cycle. Increasing the wave rotor precompression ratio or the turbine inlet temperature ratio results in greater performance improvements for the WRWC compared to the WRPGC. When the peak cycle temperature of the wave rotor is fixed, there exists a narrow pressure ratio range wherein the WRPGC outperforms the WRWC. Therefore, the WRPGC is more suitable for embedment in baseline engines with lower pressure ratios. Full article

When heating units are operated in winter, the extreme conditions, such as deep peak regulation and large extraction, can easily lead to a low unit load and severe icing in the wet cooling tower, which threatens the safe operation of the unit. Therefore, it is necessary to study the anti-freezing characteristics of the wet cooling tower. In this paper, a three-dimensional numerical model of a high-level, natural draft wet cooling tower is developed based on the constant heat load method. The influence of withdrawing a certain percentage of circulating water into the bypass on the cooling performance and anti-freezing characteristics of the high-level, natural draft wet cooling tower is investigated. The results show that as the percentage of circulating water bypass extraction increases, the temperature drop of circulating water in the tower continues to increase, but the lowest and the average water temperatures at the bottom of the packing continue to decrease. At the same time, the amount of circulating water entering the tower decreases, the pressure difference between the inside and outside of the tower under the same environmental conditions decreases, and the pumping force of the cooling tower decreases. If the circulating water bypass extraction percentage is less than 10%, it can prevent the circulating water from freezing at the bottom of the packing and, at the same time, try to reduce the temperature of the circulating water entering the condenser to ensure the efficiency of the unit. Full article

The investigation of the ignition delay of hydrocarbon fuel is highly valuable for enhancing combustion efficiency, optimizing fuel thermal efficiency, and mitigating pollutant emissions. This paper has developed a BP-MRPSO neural network model for studying hydrocarbon fuel ignition and clarified the novelty of this model compared to the traditional BP and ANN models from the literature. The model integrates the particle swarm optimization (PSO) algorithm with MapReduce-based parallel processing technology. This integration improves the prediction accuracy and processing efficiency of the model. Compared to the traditional BP model, the BP-MRPSO model can increase the average correlation coefficient, from 0.9745 to 0.9896. The R² value for predicting fire characteristics using this model can exceed 90%. Meanwhile, when the two hidden layers of both the BP and BP-MRPSO models consist of 9 and 8 neurons, respectively, the accuracy of the BP-MRPSO model is increased by 38.89% compared to the BP model. This proved that the new BP-MRPSO model has the capacity to handle large datasets while achieving great precision and efficiency. The findings could provide a new perspective for examining the properties of fuel ignition, which is expected to contribute to the development and assessment of aviation fuel ignition characteristics in the future. Full article

In the wake of the dual-carbon objective, the call for low-carbon attributes in integrated energy systems is ascending, with an amplified imperative to integrate wind and solar power efficiently. This study introduces an advanced low-carbon optimization framework for integrated energy systems, incorporating a sophisticated time-differentiated carbon accounting mechanism attentive to consumer emissions. A nuanced carbon accounting model is crafted to assess consumer emissions with greater accuracy. Predicated on these emissions, a refined low-carbon demand response model is articulated, factoring in the influence of carbon emission factors pertinent to electricity and heat procurement on user conduct. This model integrates the consideration of heat reclaimed from methanation processes, which in turn informs the carbon emission factors associated with purchased heat, and evaluates the subsequent optimization impact on the system. The proposed model is designed to curtail the system’s operational expenditures and is operationalized via the CPLEX solver. Through the establishment of various scenarios for evaluative comparison, the model is corroborated to substantially augment the system’s proficiency in assimilating wind and solar energy, markedly curtail carbon emissions, and facilitate a sustainable and cost-efficient operation of the integrated energy system. Full article

The development of green technology in the world is progressing extremely rapidly. New possibilities for obtaining energy from renewable sources are constantly being sought and existing solutions are being improved. The multifaceted potential of the seas and oceans is an important aspect being taken into account in the development of the energy systems of a number of economies. One dimension of action in this area is the orientation towards offshore wind energy and the construction of offshore wind farms for this purpose. The purpose of this article is to analyse the importance of offshore wind farms in Poland’s energy system and to assess public perception of the changes taking place in this dimension. The article is based on research and critical analysis of the available literature, legal regulations and industry reports, as well as on the results of our own surveys, the scientific findings of which were developed with the application of statistical instruments using PQstat software, ensuring the expected quality of results. The findings of the article indicate the significant importance of offshore wind farms in the creation of Poland’s energy mix, with differing public attitudes towards their construction. Furthermore, the results of the research indicate a differentiated attitude of society towards the construction of offshore wind farms. The main motivation for majority support of the measure in question are economic reasons, which are connected with the expectation of a real price reduction per 1 kW of energy, as well as increased attractiveness of the region due to investments in this area. The main concern with the measure relates to environmental aspects, with concerns about the functioning of ecosystems in light of the construction and subsequent operation of wind farms. Negative public opinion is also signalled in relation to the potential risk of landscape change in a direction that is undesirable for the studied developed coastal tourist region in Poland. Full article