U.S. Navy Surface Ship depot-level maintenance periods of performance were studied to develop a method for predicting maintenance durations. The need for the method has been highlighted by Navy leadership in recent media posts describing unacceptable maintenance delays and this research provides practitioners and decisionmakers with a reliable estimating tool. This study helps by putting forth a method that defines the rate of work accomplishment based on relevant variables. Using ordinary least squares models, this research revealed that the size of the contract obligation and the amount of shipyard work occurring simultaneously in the market are key variables in determining depot maintenance durations. With the knowledge found here, the next logical step is an optimization model for each U.S. Navy surface ship homeport.

Waste cooking oil (WCO) recycled asphalt is facing issues regarding insufficient thermal oxidation stability and aging resistance. In this research, glycerol esterification was adopted to pretreat WCO, and the consequences of this treatment on the aging resistance and thermal stability of WCO were analyzed. The impacts of varying levels of esterification of WCO on the high-temperature, low-temperature performances, fatigue properties, as well as aging resistance of recycled asphalt were investigated. Furthermore, the mechanisms of regeneration and anti-aging of deeply esterified WCO recycled asphalt were revealed by Fourier transform infrared spectroscopy (FTIR) and gel permeation chromatography (GPC) tests. The results indicated that variations in the physical properties of WCO during the aging process were reduced, and its aging resistance was improved following glycerol esterification therapy. The initial thermal decomposition temperature was increased by approximately 115°C, which resulted in the enhancement of thermal stability significantly. Recycled asphalt obtained from deeply esterified WCO exhibited superior high-temperature, low-temperature performances and fatigue properties. Moreover, the thermal oxidation stability and aging resistance of recycled asphalt with deep-esterified WCO could be promoted by reducing the oxidation and volatilization of light components during the aging process.

Non-viral mediated plasmid DNA transfection by electroporation (EP) is an established method for gene transfection. In this study, the usefulness of direct EP at an intradermal (i.d.) site (D_EP) with implanted electrodes to achieve a high protein expression level was investigated. In addition, D_EP application with various intervals with a low application voltage was also evaluated to confirm its effect on protein expression. A higher protein expression level was observed after green fluorescent protein (GFP)- and luciferase-encoding DNA were delivered by i.d. injection followed by D_EP application. When luciferase expression was observed with an in vivo imaging system, continuous expression was confirmed over 21 days after i.d. injection followed by D_EP at 100 V. This approach provided increased gene expression levels compared with conventional EP methods via the stratum corneum layer. In addition, the effect of application voltage on luciferase expression was investigated; two-time applications (repeated D_EP) at 20 V with 5 min intervals showed similar luciferase expression level to single D_EP application with 100 V. Histological observations showed the skin became thicker after a single D_EP at 100 V, whereas no apparent thickness changes was confirmed after repeated D_EP at 20 V with 5 min intervals. This study revealed that direct i.d. voltage application achieved high protein expression levels even at low voltages. Skin is a promising administration site for DNA vaccines, so this approach may be effective in DNA vaccine delivery into skin tissue.

There is a growing need to implement modern technologies, such as digital twinning, to improve the efficiency of transport fleet maintenance processes and maintain the company's operational capacity at the required level. Therefore, the paper reviews the existing literature to present an up-to-date and content-relevant analysis in this field. The proposed methodology is a systematic literature review using the Primo multi-search tool following Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines. The main inclusion criteria included the publication dates (studies published from 2012–2024) and studies published in English. This resulted in the selection of 201 of the most relevant papers in the area of investigation. Finally, selected articles in this review were categorized into seven groups: a) air transportation, b) railway transportation, c) land transportation (road), d) in-house logistics, e) water and intermodal transportation, f) supply chain operation, and g) other applications. One of the main advantages of the study is that the results are obtained from different scientific sources/databases thanks to using the multi-search tool. Moreover, a bibliometric analysis of the selected papers was performed. The results have led the authors to specify the main research problems and trends related to the analyzed area and to identify the main research gaps for future investigation from academic and engineering perspectives. In addition, based on the review results, a framework for DT in transportation system maintenance was developed. The study ends with conclusions and future research directions.

Maritime transport has adapted to recent political and economic shifts by addressing stringent pollution reduction requirements, redrawing transport routes for safety, reducing onboard technical incidents, managing data security risks and transitioning to autonomous vessels. The integration of AI-based technologies for fault diagnosis and decision-making, coupled with proper personnel training, has become essential for optimal ship operation, with AI-assisted predictive maintenance emerging as the key strategy to ensure onboard systems function within desired parameters and enhance equipment availability. This study proposes a machine-learning algorithm for evaluating onboard systems performance by analyzing sensor data and mapping it to fault patterns to estimate functional states, validated through tests on a seawater cooling system from an oil tanker, demonstrating operational efficiency and reliability. The immediate advantage is reduced time for fault diagnosis by rapidly assessing the system using operational data, the algorithm enabling real-time monitoring and fault data management to minimize efforts as part of predictive maintenance assisted by machine learning tools.

Preventive Maintenance (PM) is a periodic maintenance strategy, which has great results for devices in extending their life, increasing productivity, and most importantly, help avoid unexpected breakdowns and their costly consequence. A preventive maintenance scheduling (PMS) is determining the time for carrying out PM, and it represents a sensitive issue in terms of impact on production if the time for the PM process is not optimally distributed. In this study, hybrid heuristic methods were used to solve the PMS problem, as genetic algorithm and Tabu research were adopted. The optimal solution was reached in a short time compared to previous studies in which optimal methods were used, integer programming and nonlinear integer programming. Also, sensitivity analysis was applied to measure the robustness and strength of the method used, where an optimal solution was obtained for all experiments and in record time. This method can be used for power plants in privet or public sectors, to generate an optimal PMS, to save money, and to avoid water or electricity cuts.

Technological equipment in quarries that extract and deliver aggregates for different uses operates in a predetermined flow depending on the type of rocks exploited and the dimensional characteristics imposed on the final products. In this context, the interruptions in operation required to replace high-wear parts (such as the teeth of excavators and bucket loaders) must be limited as much as possible through technological solutions to increase their service life. The evolution of the wear of the teeth of the quarry equipment that come into direct contact with the rocks was concretely established in the production process, in parallel with the wear values obtained by simulating the wear phenomenon in laboratory conditions, in order to validate the data collected during the operation of the machines. Preventive-repetitive maintenance, within the activities of reconditioning the worn surfaces of the teeth, through the charging process by manual electric welding with covered electrodes, was applied directly to the machine, which led to the shortening of the interruptions in operation necessary to replace these spare parts.

This research seeks to provide local governments with a comprehensive alternative for the proper maintenance of roads, focusing on the surface and functional evaluation of pavements. It com-pares conventional methods of the International Roughness Index (IRI) and the Pavement Condi-tion Index (PCI) with novel methodologies that employ smart technologies. Road maintenance is essential for economic development, facilitating the circulation of services and resources. This re-search analyzes the efficiency of smart technologies in the maintenance of local roads in Arequipa, taking as a case study a 2 km section of the AR-780 highway in Polobaya. The International Roughness Indices (IRI) obtained through the Merlin Roughness Meter and the Roadroid applica-tion were compared, finding a minimum variation of 4.007% in the left lane and 8.5% in the right lane. Roadroid turned out to be 60 times faster than the conventional method, with a cost differ-ence of 220.11 soles. Both methods classified the road condition (PSI) as GOOD, validating the accuracy of Roadroid. In addition, the Pavement Condition Index (PCI) was evaluated with con-ventional methods and a DJI Mavic 2 Pro drone, finding a variation of 6.89%. The cost difference between the methodologies was 1,047.73 soles, and the use of the drone proved to be 10 times faster than visual inspection. Finally, it can be said that this study contributes to closing the knowledge gap regarding the use of smart technologies for better pavement management on local roads, so that the actors in charge of the roads can make decisions based on science and thus con-tribute to the well-being of the population.

The development of Artificial Intelligence-based tools is having a big impact on industry. In this context, the maintenance operations of important assets and industrial resources are deeply changing both from a theoretical and a practical perspective, even in the field of ship propulsion systems. Namely, conventional preventive maintenance schedules audits and checks at fixed times by using statistics on component failures, but it can be improved by a predictive maintenance based on the real component health status, which is inspected by proper sensors. In this way, time and costs are saved. More in details, data-driven models, through Machine Learning (ML) algorithms, generate the expected values of monitored variables for comparison with real measurements coming from the asset, hence for a diagnosis based on the difference between expectations and observations. Then, a ML-based fault detection starts with the choice of the ML algorithm. This process is often not the consequence of an in-depth deep analysis of the different algorithms available in the literature. For that reason, the authors propose a simple procedure to support a first implementation stage of the so-called Condition Based Maintenance (CBM): a quick benchmarking of the most suitable ML algorithms useful for fault detection. The algorithms are compared by taking into account not only the algorithm output error, shown by the Mean Squared Error between predictions and data, but also the response time, which is a crucial variable for maintenance purpose.

As a consequence of applying advanced maintenance practices, the theoretical probability of failures is relatively low. However, observation of low market intelligence and maintenance management has been reported. The experimental investigation is supported by findings from a survey targeting asset-intensive companies applying hydraulic power systems. Next, the study incorporates multidimensional data analysis using CA-AHC (Correspondance Analysis with Agglomerative Hierarchical Clustering) approach. The non-parametric machine learning models are used from generated feature subspace to extract features affecting maintenance performance indicators. The results support empirical evidence that equipment age increases the probability of failures. However, the novel findings show that number of maintenance personnel, equipment size measured by nominal working energy consumption, and activities dedicated to maintaining fluid cleanliness impact regression results of companies utilising hydraulic applications.

Aggregative multicellularity occurs when dispersed cells join together to form a highly cooperative unit, in contrast to clonal multicellular organisms formed by cells that remain in contact after descent from a single cell. Because aggregative groups may include non-relatives, aggregative multicellular organisms should be particularly vulnerable to the rise of cheater cells that take advantage of social goods without paying the costs, reducing cooperation, and even threatening extinction. We review the key mechanisms by which aggregative multicellular organisms control cheaters with a focus on the best studied aggregative organisms, Myxococcus xanthus and Dictyostelium discoideum. These include various passive and active mechanisms to maintain high relatedness within aggregates, to enforce cooperation on aggregate members, and the costs of cheating on other key functions. Ultimately, aggregative multicellular organisms are not that different from clonal organisms descended from a single cell.

Using data-driven models to solve predictive maintenance problems has been prevalent for original equipment manufacturers (OEMs). However, such models fail to solve two tasks that OEMs are interested in: (1) Making the well-built failure prediction models working on existing scenarios (vehicles, working conditions) adaptive to target scenarios. (2) Finding out the failure causes, furthermore, determining whether a model generates failure predictions based on reasonable causes. This paper investigates a comprehensive architecture towards making the predictive maintenance system adaptive and interpretable by proposing (1) an ensemble model dealing with time-series data consisting of a long short-term memory (LSTM) neural network and Gaussian threshold to achieve failure prediction one week in advance and (2) an online transfer learning algorithm and a meta learning algorithm, which render existing models adaptive to new vehicles with limited data volumes. (3) Furthermore, the Local Interpretable Model-agnostic Explanations (LIME) interpretation tool and super-feature methods are applied to interpret individual and general failure causes. Vehicle data from Isuzu Motors, Ltd., are adopted to validate our method, which include time-series data and histogram data. The proposed ensemble model yields predictions with 100% accuracy for our test data on engine stalling problem and is more rapidly adaptive to new vehicles with smaller error following application of either online transfer learning or the meta learning method. The interpretation methods help elucidate the global and individual failure causes, confirming the model credibility.

Predictive maintenance (PdM) represents a transformative approach to ensuring the security and reliability of critical infrastructure systems. This proactive maintenance strategy leverages advanced data analytics, machine learning, and sensor technology to anticipate and address potential failures before they occur. By continuously monitoring the health of infrastructure components and analyzing performance data, predictive maintenance enables timely interventions, minimizes unplanned downtimes, and enhances overall system resilience. This paper explores the application of predictive maintenance in safeguarding critical infrastructure, focusing on its impact on security, operational efficiency, and cost-effectiveness. Case studies demonstrate how PdM has been successfully implemented across various sectors, including transportation, energy, and utilities, highlighting its role in mitigating risks and extending the lifespan of essential assets. The findings underscore the importance of integrating predictive maintenance into security strategies to protect vital infrastructure from emerging threats and ensure uninterrupted service delivery.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

In this study, we present case studies to explore the dynamics of implementation and maintenance of health interventions. We analyze how specific interventions are built and eroded, how the building and erosion mechanisms are interconnected, and why we can see significantly different erosion rates across otherwise similar organizations. We use multiple comparative obesity prevention case studies to provide empirical information on the mechanisms of interest, and use qualitative systems modeling to integrate our evolving understanding into an internally consistent and transparent theory of the phenomenon. Our preliminary results identify reinforcing feedback mechanisms, including design of organizational processes, motivation of stakeholders, and communication among stakeholders, which influence implementation and maintenance of intervention components. Over time, these feedback mechanisms may drive a wedge between otherwise similar organizations, leading to distinct configurations of implementation and maintenance processes.

The in vitro cultivation of M. leprae has not been possible since it was described as causing leprosy, and the limitation of animal models for clinical aspects makes studies on leprosy and bacteria-human host interaction a challenge. Our aim was to standardize the ex vivo skin model (hOSEC) to maintenance and study of M. leprae as an alternative animal model. Bacillary suspensions were inoculated into human skin explants and sustained in DMEM medium until 60 days. Explants were evaluated by RT-PCR-16SrRNA, and cytokines gene expression. Viability and infectivity of bacilli recovered from explant (D28 and D60) were evaluated using the Shepard’s model. All explants were RT-PCR-16srRNA positive. Viability and infectivity of recovered bacilli from explants, analyzed after 5 months of inoculation in mice showed an average positivity of 31%, being the highest positivity in the D28 groups (80%). Furthermore, our work showed different pattern in cytokines gene expression (TGF-β, IL-10, IL-8 and TNF-α) in the presence of alive or dead bacilli. Although changes can be made for improve future experiments, our results have demonstrated that it is possible to use the hOSEC to maintain M. leprae for 60 days, interacting with the host system, an important step in the development of experimental models for studies on the biology of the bacillus, its interactions, and drug susceptibility.

This review paper aims to understand the current processing plant maintenance systems and further identify on-stream phased array corrosion mapping (PACM) to reduce turnaround maintenance (TAM) activity during plant operations. Reducing the TAM duration and extending the TAM interval are common goals of most researchers. Thus, a detailed review was performed to understand the maintenance systems and the problems faced. Furthermore, a review of the current PACM application and the possibility of applying it during on-stream inspection was also per-formed. PACM has better detectability for localized corrosion, and the results can be obtained for a range of thicknesses, which is the main advantage of this method. The challenge is to apply it to a surface with high temperatures, owing to the greater probe contact and the limitation of ultrasonic properties. This literature review provides a more precise direction for future research to evaluate PACM on piping that can be utilized in inspection during plant operation at elevated temperatures. Detecting and monitoring corrosion growth without shutdown.

As a conceptual model of disease mechanisms, a disease map integrates available knowledge and is applied for data interpretation, predictions and hypothesis generation. It is possible to model disease mechanisms on different levels of granularity and adjust the approach to the goals of a particular project. This rich environment together with requirements for high-quality network reconstruction makes it challenging for new curators and groups to be quickly introduced to the development methods. In this review, we offer a step-by-step guide for developing a disease map within its mainstream pipeline that involves using the CellDesigner tool for creating and editing diagrams and the MINERVA Platform for online visualisation and exploration. We also describe how the Neo4j graph database environment can be used for managing and querying efficiently such a resource. For assessing the interoperability and reproducibility we apply FAIR principles.

Background and Aim: Tacrolimus is highly effective in intractable ulcerative colitis, but maintenance may be problematic. This study examined 52-week maintenance and adverse events. Methods: This retrospective study of patients who used tacrolimus from April 2009 to December 2021 (N = 136) examined remission induction rates and background factors in the remission (n = 108) and non-remission groups (n = 28); 52-week maintenance; drug-specific maintenance (azathioprine [n = 58] vs tacrolimus [n = 12] and vs biological product [Bio, n = 8]); and adverse events. Results: The mean observation period was 1230175 days. Remission occurred in 72.7%. Significant differences were observed in sex and endoscopic score (before treatment and 2 weeks after tacrolimus trough levels). Maintenance rate at 52 weeks was 61.6%; significant differences were observed in sex, hospitalization duration, and prednisolone during hospitalization (P < 0.05). Drug-specific 52-week maintenance was 67% with azathioprine, 54% with tacrolimus, and 37% with Bio. No tacrolimus-related serious adverse events occurred that led to discontinuation. Discussion: Remission was more common in women with improved endoscopic scores after tacrolimus trough levels and patients with improved endoscopic scores after tacrolimus therapy. Remission maintenance was more common in women with a long hospitalization at remission and high total steroid dose. Results suggest that treatment with adequate prednisolone use during the period with more inflammation may improve subsequent maintenance. Conclusions: In intractable ulcerative colitis, tacrolimus can induce remission even in patients who cannot use azathioprine for maintenance. Remission can be maintained with azathioprine, tacrolimus, or a Bio.

The good management of the building maintenance should be based on the regular maintenance work. Repair works are often not carried out or there are shifts in time, which causes degradation of the building. The article presents a method of planning renovation works of a MUBAR (maintenance Management in an Un-renovated Building with Abandoning Renovation) based on the consequences in case of their lack. No renovation work on individual elements in a building can cause a threat to the stability of the building structure, risking the lives of users, continuing damage to the building by damaging further elements, or even a building disaster. The method can also be applied to historic buildings. Often, due to abandonment of repairs caused most often by lack of the owner, improper manager or irresponsible users, degradation of these objects occurs. The consequences of neglected renovation of buildings lead to irreversible processes of their destruction. The aim of the article is to present the developed method of planning renovation works based on the consequences of lack of renovation works.

Neurodegenerative diseases are universally marked by the accumulation of misfolded protein. Neurons respond to these proteostatic disturbances by sequestering, and thus inactivating, toxic misfolded proteins into a perinuclear organelle called the aggresome. The aggresome can be subsequently degraded in bulk by autophagy, a process termed aggrephagy. The formation of protein aggregates has historically been considered a spontaneous and unregulated process, but emerging research has instead discovered a diverse cohort of regulatory proteins that mediate protein aggregation. Chaperones are the first proteins to respond to misfolded proteins, and do so by recognizing the aberrant exposure of hydrophobic domains. When chaperones are unable to correctly refold proteins, their substrates are transferred to ubiquitin ligating machinery to catalyze polyubiquitination. Although ubiquitin chains typically direct proteins towards proteasomes, severe proteotoxic stress can overwhelm, or even directly inhibit, proteasomes. As an alternative to proteasomal degradation, misfolded proteins are redirected towards the mitotic organizing center (MTOC) and, following retrograde transport by dynein, are packaged and sequestered within an intermediate filament (IF) cage to form the aggresome. The biogenesis of the aggresome is thus a highly regulated event, and a better understanding of the mechanisms facilitating this process will provide critical insight into neurodegenerative disease.

This study investigates the application of frequency augmentation techniques to improve condition-based maintenance (CBM+) systems for airborne weapon systems, focusing on the predictive accuracy of velocity and acceleration parameters. Utilizing MIL-STD-1553B MUX data from 138 sorties of fixed-wing aircraft, we explored six augmentation methods, including traditional interpolations (linear, quadratic, cubic spline) and advanced machine learning models (K-Nearest Neighbor, LSTM, and Bi-LSTM). Our findings indicate that while traditional methods like linear interpolation are more effective for velocity parameters, advanced ML techniques, particularly Bi-LSTM, provide better results for acceleration parameters, which exhibit more complex and rapid variability. The study underscores the necessity of tailoring augmentation approaches to specific parameter characteristics and highlights the potential of ML models in capturing intricate patterns within time-series data. These insights are critical for advancing CBM+ systems in military avionics, enhancing reliability and operational efficiency through improved data processing strategies. Future work should explore more performant augmentation techniques, such as by integrating multi-dimensional datasets, and explore ways to develop automated tools for a more powerful predictive maintenance framework.

Burnout is common in many countries and is associated with several other problems, such as depression, anxiety, insomnia and memory deficits, and prospectively it predicts long-term sick-leave, cardiovascular disease and death. Clinical burnout or its residual symptoms often last several years and a common assumption is that recovery takes a long time by nature despite full time sick-leave and absence of work stress. Literature suggests models that hypothetically explain the development, but not maintenance, of the syndrome. Based on cognitive and behavioral principles and stress theory this paper describes a theoretical model explaining how clinical burnout can develop and be maintained. While the development of clinical burnout is mainly explained by prolonged stress reactions and disturbed recovery processes due to work related stressors, maintenance of the syndrome is particularly explained by prolonged stress reactions and disturbed recovery processes due to the new context of experiencing burnout and being on sick-leave. Worry about acquired memory deficits, passivity and excessive sleep, shame, fear of stress reactions, and the perception of not being safe are examples of responses that can contribute to the maintenance. The model has important implications for research and how to intervene clinical burnout.

Single-stand selective monofunctional uracil DNA glycosylase 1 (SMUG1) works to remove uracil and certain oxidized bases from DNA during base excision repair (BER). This review provides a historical characterization of SMUG1 and 5-hydroxymethyl-2'-deoxyuridine (5-hmdU) one important substrate of this enzyme. Biochemical and structural analyses provide remarkable insight into the mechanism of this glycosylase revealing SMUG1 has a unique helical wedge which influences damage recognition during repair. Rodent studies suggest that, while SMUG1 shares substrate specificity with another uracil glycosylase UNG2, loss of SMUG1 can have unique cellular phenotypes. This review highlights the multiple roles SMUG1 may play in preserving genome stability, and how the loss of SMUG1 activity may promote cancer. Finally, we discuss recent studies indicating SMUG1 has moonlighting functions beyond BER, playing a critical role in RNA processing including the RNA component of telomerase.

Predictive maintenance technologies have emerged as a transformative force in retail supply chain management, offering the potential to significantly enhance operational efficiency, reduce costs, and improve customer satisfaction. This study explores the implementation and impact of predictive maintenance within the retail sector, focusing on its benefits, challenges, technological tools, and future directions. The findings indicate that predictive maintenance enables a proactive approach to equipment management, leading to substantial reductions in downtime and maintenance costs, extended equipment lifespan, and enhanced sustainability through reduced energy consumption and waste. However, the adoption of these technologies is not without challenges. High initial costs, the need for specialized skills in data analytics and IoT, issues with data quality and reliability, organizational resistance, and cybersecurity concerns present significant barriers to successful implementation. Technological tools such as IoT sensors, data analytics platforms, machine learning algorithms, and digital twins are crucial for the effective functioning of predictive maintenance systems, providing real-time data monitoring and analysis that improve decision-making and maintenance planning. The study also highlights promising future trends, including advancements in AI, machine learning, IoT, and blockchain technologies, which are expected to further enhance predictive maintenance capabilities. To fully realize the potential of predictive maintenance, companies must address the identified challenges, invest in workforce development, and implement robust data security measures. Future research should focus on exploring these advancements, understanding the broader environmental impacts, and conducting cross-industry analyses to identify best practices. Overall, while predictive maintenance offers substantial benefits, its successful integration requires a nuanced approach that balances technological innovation with strategic and operational considerations.

We present 4 cases of patients diagnosed with multiple myeloma initially treated without monoclonal antibodies. It was decided to provide the benefit of the drug after maintenance with lenalidomide was initiated to consolidate the post-maintenance response followed by monitoring without any kind of treatment. In this series of 4 cases 100% of the patients achieved a strict complete response with undetectable Minimal Residual Disease (MRD) for flow cytometry after post-maintenance consolidation with daratumumab regardless of the scheme used as induction/consolidation, as well as whether they had received HSCT. Until the last follow-up the patients are under surveillance with no evidence of progression. It should be noted that 3 of 4 of these patients debuted with high-risk disease.

Making sustainable business models, especially in manufacturing, is a key approach for organizations to adopt in order to create more sustainable processes. New technologies are needed to implement new policies that can minimize the economic, environmental, and social consequences of industrial activity. Sustainable maintenance is decisive to guarantee the availability, reliability, and safety of assets, surpassing traditional maintenance policies and embracing the principles of the circular economy. The main objective of Maintenance 4.0 is to increase the lifespan and availability of the equipment by preventing unplanned downtime, reducing planned shutdowns, and improving safety. This research focuses on the integration of advanced Industry 4.0 tools with conventional monitoring and control techniques in process industries. The article suggests that while complex neural networks might provide good predictions, simpler solutions can generalize well and have lower prediction errors because they can capture the underlying relationships between variables in a specific asset better. The combination of maintenance function, Industry 4.0 tools, and advanced statistical solutions to obtain sustainable processes can facilitate organizational change and aid decision-making in equipment management. These solutions seek to reduce interruptions and expenses through the unnecessary utilization of labor and spare parts. All these considerations improve communication and data processing, resulting in improved maintenance of a hydrogen compressor in the petrochemical industry.

Every firm is devoted to polishing and fine-tuning its maintenance strategy. More exactly, when we develop robust and efficient preventive and conditional maintenance approaches, our objective is to combine performance and robustness to increase maintenance decision-making. This, in turn, leads to a reduction in system failures and a subsequent drop in related expenses. This impulse drives the origin of this essay: to provide fresh criteria that allow us to improve and optimize maintenance techniques. Furthermore, our study has been realistically utilized via the deployment of condition-based maintenance (CBM) techniques, which are commonly regarded as a critical lever that allows firms to gain a competitive advantage in the context of the fourth industrial revolution. Combining both perfect and imperfect maintenance actions into CBM strategies appears to be an effective technique to obtain high economic performance and robustness in the maintenance strategies of the companies. Following this idea, we propose and optimize in this paper a set of criteria enabling the combined assessment of the mean economic performance and the resilience of various kinds of maintenance techniques. The advantage of the proposed criterion is that it adapts to different types of maintenance strategies and provides access to a simple and relevant evaluation model. Thanks to this new criterion, we will be able to choose the better maintenance strategies that have more performance and robustness between these strategies for a system with more or less stable behavior. The Monte Carlo Method is incorporated into the comparative assessment of maintenance methods, adding a layer to the evaluation of the performance and robustness of each adaptation in decision-making.

Currently, software development is more associated with families of configurable software rather than the single implementation of a product. Due to the numerous possible combinations in a software product line, testing these families of software product lines (SPLs) is a difficult undertaking (SPL). Moreover, the presence of optional features makes the testing of SPLs impractical. Several features are presented in SPLs, but due to the environment's time and financial constraints, these features are rendered unfeasible. Testing subsets of configured products is thus one approach to solving this issue. In order to reduce testing effort and get better results, alternative methods of testing SPLs are required, such as the combinatorial interaction testing (CIT) technique. Unfortunately CIT method produces unscalable solutions for large size SPLs with excessive constraints. The CIT method costs more because of feature combinations. The optimization of the various conflicting testing objectives, such as reducing the cost and configuration number, have also been considered. In this article, we have proposed a search-based software engineering solution using multi-objective optimization algorithms (MOEAs). In particular, the research is applied to different types of MOEA methods; Indicator-Based Evolutionary Algorithm (IBEA), Multi-objective Evolutionary Algorithm based on Decomposition (MOEA/D), Non-Dominated Sorting Genetic Algorithm II (NSGAII), NSGAIII, and Strength Pareto Evolutionary Algorithm 2 (SPEA2). The results of the algorithms are examined in the context of distinct objectives and two quality indicators. The results revealed how feature model attributes, implementation context and the number of objectives affect the performance of the algorithms.

Telomeres are crucial structures that preserve genome stability. Their progressive erosion over rounds of DNA duplication determines senescence of cells and organisms. Telomere length homeostasis is critical for cancer development then telomere maintenance mechanisms are established targets in cancer treatment. Besides telomere elongation, telomere’s dysfunction impinges on intracellular signalling pathways, in particular DNA damage signalling and repair affecting cancer cell survival and proliferation. This review summarizes and discusses about the recent findings in anti-cancer drug development targeting different “telosome” components.

Packaging of the eukaryotic DNA genome with histone and other proteins forms a chromatin structure that regulates the outcome of all DNA mediated processes. The cellular pathways that ensure genomic stability detect and repair DNA damage through mechanisms which are critically dependent upon chromatin structures established by histones and, particularly, transient histone post-translational modifications . Though subject to a range of modifications, histone methylation is especially crucial for DNA damage repair as the methylated histones often form platforms for subsequent repair protein binding at damaged sites. In this review, we highlight and discuss how histone methylation impacts the maintenance of genome integrity through effects related to DNA repair and repair pathway choice.

In the manufacturing industry, orders are typically scheduled and delivered through batches, and the probability of machine failure under high-load operation is high. On this basis, we focus on a single machine batch scheduling problem with a maintenance interval (SMBSP-MI). The studied problem is expressed by three-field representation as 1|B,MI|\sum{F_j+\mu}m, and the optimization objective is to minimize total flow time and delivery costs. Firstly, 1|B,MI|\sum{F_j+\mu}m is proved to be NP-hard by Turing reduction. Secondly, shortest processing time (SPT) order is shown the optimal scheduling of SMBSP-MI, and a dynamic programming algorithm based on SPT (DPA-SPT) with the time complexity of O(n^3T_1) is proposed. A small-scale example is designed to verify the feasibility of DPA-SPT. Finally, DPA-SPT is approximated to a fully-polynomial dynamic programming approximation algorithm based on SPT (FDPAA-SPT) by intervals partitioning technique. The proposed FDPAA-SPT runs in O(\frac{n^5}{\varepsilon^2})\ time with the approximation (1+\varepsilon).

Aim. The aim of this study is to compare data from two cohorts separated by a 17-year interval. We assessed the prevalence and severity of symptoms with the “dialysis symptom index” in these two groups recruited in 2007 and 2024 to determine how advancements in dialysis therapy have influenced symptom burden’s prevalence and severityMethods. We conducted a cross-sectional study of patients receiving thrice weekly, in-center hemodialysis. The population, recruited between February and March 2007, was comprised of patients receiving maintenance hemodialysis at the outpatient dialysis unit of our hospital. This dialysis facility is staffed by academic nephrologists. In May 2024, in the same unit, another population sample was recruited and studied as in 2007. Study coordinators administered the Dialysis Symptom Index (DSI) during the dialysis treatment. The DSI is made up of 30 questions, each of which addresses a specific physical or emotional symptom. Patients were asked to report symptoms that had been present at any time during the previous week by responding “yes” or “no”. For symptoms that were present, the patient was then asked to describe the symptom severity on a five-point Likert scale (1= not bothersome to 5=bothers very much). We generated a total symptom burden score that represents the total number of symptoms reported as being present, as well as a total symptom severity score that represents the sum of individual severity scores assigning a severity score of zero for symptoms that were not present. Results. We studied 71 patients in 2007 and 61 patients in 2024. The demographic, clinical and laboratory characteristics of the two study populations did not differ significantly. The total symptom burden score did not differ significantly between 2007 and 2024. The prevalence of most symptoms was similar in the two groups. The prevalence of constipation, decreased interest in sex and difficulty becoming sex aroused was higher in 2024 than in 2007. The total symptom severity was similar in the two periods. The severity of most symptoms was similar in the two groups. The severity of decreased interest in sex and difficulty becoming sex aroused was higher in 2024 than in 2007. Conclusion. The present study shows that, 17 years apart, the prevalence and severity of the symptom burden in patients on maintenance hemodialysis has not changed significantly. These results suggest that effort should be made to design adequate studies on the causes and pathogenesis of physical and emotional symptoms of patients on chronic hemodialysis and, once the underlying mechanisms are identified, it is amenable that high-quality studies on possible therapeutic pharmacological and non-pharmacological interventions will be performed.

The rapid growth of the aviation industry has progressively heightened the importance of airport maintenance management. There is an increasing need for a comprehensive system that considers the diverse requirements of various stakeholders. Existing research has primarily focused on the technological advancements of optimization models, with limited applicability in practice. In this study, we introduce the Condition Cases Optimization (CCO) to address these limitations while incorporating multi-facility and multi-year network optimization models. We developed condition index, Serviceability Level, integrated assessment indices and performance models for decision-making criteria. We categorize conditions into three classes and propose a practical decision-making strategy that can flexibly adapt to budget constraints. Sensitivity analysis highlights the impact of initial budget, maintenance methods, costs, and thresholds on decision outcomes. Through a case study we validate the effectiveness and practicality of the CCO method as an efficient decision-making tool.

Convolutional Neural Networks combined with autonomous drones are increasingly seen as enablers of partially automating the aircraft maintenance visual inspection process. Such an innovative concept can have a significant impact on aircraft operations. Through supporting aircraft maintenance engineers detect and classify a wide range of defects, the time spent on inspection can significantly be reduced. Examples of defects that can be automatically detected include aircraft dents, paint defects, cracks and holes, and lightning strike damage. Additionally, this concept could also increase the accuracy of damage detection and reduce the number of aircraft inspection incidents related to human factors like fatigue and time pressure. In our previous work, we have applied a recent Convolutional Neural Network architecture known by MASK R-CNN to detect aircraft dents. MASK-RCNN was chosen because it enables the detection of multiple objects in an image while simultaneously generating a segmentation mask for each instance. The previously obtained F1 and F2 scores were 62.67% and 59.35% respectively. This paper extends the previous work by applying different techniques to improve and evaluate prediction performance experimentally. The approaches uses include (1) Balancing the original dataset by adding images without dents; (2) Increasing data homogeneity by focusing on wing images only; (3) Exploring the potential of three augmentation techniques in improving model performance namely flipping, rotating, and blurring; and (4) using a pre-classifier in combination with MASK R-CNN. The results show that a hybrid approache combining MASK R-CNN and augmentation techniques leads to an improved performance with an F1 score of (67.50%) and F2 score of (66.37%)

With the rapid development of global offshore wind power, the demand for offshore wind power operation and maintenance is also increasing. Wisdomization of offshore wind farms is a practical need to improve the operation level and benefit of offshore wind farms. This paper first introduces the current development situation and characteristics of global offshore wind power, and expounds the current situation and main challenges of offshore wind power operation and maintenance market. Therefore, our paper discusses the innovation of offshore wind power operation and maintenance from the aspects of operation and maintenance management of offshore wind power, monitoring and analysis technology of units, far-reaching wind field monitoring and operation and maintenance risks. Then, combined with information technology and lean management concept, a smart operation and maintenance management platform for wind farms in far-reaching sea areas is built to explore centralized and intelligent operation and maintenance management mode, improve operation and maintenance efficiency of wind farms in far-reaching sea areas, and minimize operation and maintenance costs. Finally, through the research on the characteristics of 5G technology, combined with the practical experience of operation and maintenance, and in view of the characteristics of offshore wind farms, we analyze and propose several typical application scenarios of 5G technology in the intelligent operation and maintenance of offshore wind farms, which provides a new solution for the efficient operation and maintenance of offshore wind farms.

The present paper deals with research on maintenance strategy and maintenance process improvement procedures to increase the efficiency and quality of the production system. It includes the design of maintenance performance indicators relevant to today's manufacturing systems to track improvements in the sustainable development of the manufacturing system. There are also the basic principles of maintenance strategy with linkages to the manufacturing system and selecting the strategy for the organization. The paper emphasizes maintenance management auditing and quality implementation in maintenance. Further, there is the process of changing the maintenance strategy described. This process includes reassessing the criticality of machines and equipment and their design units, then resource and capacity planning and input for maintenance management. It describes the impact of changing the maintenance management organization and maintenance capacity considering the change of strategy and the evaluation of maintenance choice alternatives, together with an analysis of the optimization procedure, which has an impact on social implication. The paper concludes by presenting the achieved impacts of maintenance strategy are: (1) increase in production efficiency (10%), (2) quality improvement in production (20%), (3) performance improvement (30%), (4) reduction of maintenance process costs (35%).

Recent technological advancements such as IoT and Big Data have granted industries extensive access to data, opening up new opportunities for integrating Artificial Intelligence (AI) across various applications to enhance production processes. We can cite two critical areas where AI can play a key role in industry such as product quality control and predictive maintenance. This paper presents a survey of AI applications in the domain of Industry 4.0, with a specific focus on product quality control and predictive maintenance. Experiments were conducted using two datasets, incorporating different machine learning and deep learning models from the literature. Furthermore, this paper provides an overview of the AI solution development approach for product quality control and predictive maintenance. This approach includes several key steps, such as data collection, data analysis, model development, model explanation, and model deployment.

This paper proposes a solution for the development of microclimate monitoring for Low Voltage / High Voltage switchgear using the PRTG Internet of Things (IoT) platform. This IoT-based real time monitoring system can enable predictive maintenance to reduce the risk of electrical station malfunctions due to unfavorable environmental conditions. The combination of humidity and dust can lead to unplanned electrical discharges along the isolators inside a low or medium voltage electric table. If no predictive measures are taken, the situation may deteriorate and lead to significant damage inside and outside the switchgear cell. Thus, the mentioned situation can lead to unprogrammed maintenance interventions that can conduct to the change of the entire affected switchgear cell. Using a low-cost and efficient system, the climate conditions inside and outside the switchgear is monitored and transmitted remotely to a monitoring center. From the results obtained using a 365-day time interval, we can conclude that the proposed system is integrated successfully in the switchgear maintaining process, having as result the reducing of maintenance costs.

Predictive maintenance (PM) algorithms are widely applied for detecting operational anomalies on industrial processes to trigger maintenance before a possible breakdown; however, much less focus has been devoted to the use of such PM predictions as feedback in automated process control mechanisms. They usually integrate preventive solutions to protect the machines, usually causing downtimes. The premise of this study is to develop a holistic adaptive process scheduling mechanism that incorporates PM analysis as a safety component to optimize the operation mode of an industrial process toward preventing breakdowns while maintaining its availability and operational state, thereby reducing downtimes. As PM is largely a data-driven approach; hence, relies on the setup, we first compare different PM approaches and identify a one-class support vector machine (OCSVM) as the best performing option for the anomaly detection on our setup. Then, we propose a novel pipeline to integrate maintenance predictions into a real-time adaptive process scheduling mechanism. It schedules for the most suitable operation, i.e., optimizing for machine health and process efficiency, according to the abnormal readings. To demonstrate the pipeline on action, we implement our approach on a small-scale conveyor belt system utilizing our Internet of Things (IoT) framework. The results show that our PM-based adaptive process control provides an efficient process with less or no downtime. We also conclude that a PM approach does not provide sufficient efficiency without its integration into an autonomous planning process.

The Italian Stone Pine (Pinus pinea L.) is one of the most employed ornamental trees in towns with Mediterranean climates. For example, in the city of Rome, Pinus is the most common genus, with more than 51,000 trees. This study investigates technical and economic features of maintenance operations of Stone Pines and evaluates the productivity and costs of the observed yards. Pruning and felling are the most frequent management operations of trees in towns and this study analyzes the features of these operations carried out in 14 work sites. The operations were carried out either with aerial platforms (19 trees) or ascending the crown by tree-climbing (6 trees). The operations were sampled with time studies (12 trees for pruning and 13 for felling). Work time was measured from the beginning of operations to the transport of the residual biomass to the collection and loading point, using centesimal stopwatches and video recording. The total residual biomass was weighed or assessed. Total observation time amounted to 63.1 hours. The evaluation of the costs of each work site considered the fixed and the variable costs and the costs for the labor force. A Multiple Linear Regression model (statistics: determination coefficient R2: 0.74, adjusted R2: 0.67, p-value < 0.001) which utilizes four regressors easily evaluable before the work, was adopted to predict the gross time of the operations. This paper can contribute to optimize trees maintenance methods in urban sites and to assess the potential residual wood biomass attainable from urban forestry maintenance in the city of Rome.

As construction costs continue to rise and adequate amounts of funding continues to be a challenge, the allocation of resources is of critical importance when it comes to the maintenance and rehabilitation (M&R) of highway infrastructure. A Life Cycle Assessment (LCA) methodology is presented here that integrates realistic traffic conditions in the operational phase to compare M&R scenarios over the analysis period of a 26-km stretch of Interstate-495. Pavement International Roughness Index (IRI) were determined using AASHTO’s PavementME System. Meanwhile, vehicle fuel consumption and emission factors were calculated using a combination of Google Maps®, the U.S. EPA’s Motor Vehicle Emission Simulator, the SHRP2 Naturalistic Driving Study, and MassDOT’s Transportation Data Management System. The evaluation of pavement performance with realistic traffic conditions, varying M&R strategies and material characteristics was quantified in terms of Life Cycle Cost (LCC), Global Warming Potential (GWP) and Cumulative Energy Demand (CED) for both agencies and users. The inclusion of realistic traffic conditions into the use phase of the LCA resulted in a 6.4% increase in CED and GWP when compared to baseline conditions simulated for a week long operation duration. Results from this study show that optimization of M&R type, material selection and timing may lead to a 2.72% decrease in operations cost and 47.6% decrease in construction/maintenance costs.

The present work provides continuity with studies where currently the industrial market is characterized by a highly variable demand in terms of quantities and flexibility of manufacturing or mass customization, which translates into a more demanding production context in terms of the continuous changes required to the production systems, the effect of which results in an increase in the fatigue subjected to the machines that make up the production systems. On the other hand, current production systems tend to use highly communicative and sensorized cyber-physical systems; these characteristics can be used to integrate them into decision-assisted systems in order to improve the availability of the industrial plant. The assisted system developed focuses on collecting and taking advantage of historical knowledge of industrial plant failures and breakdowns. By ideally integrating the Reliability Centered Maintenance (RCM) methodology and Case-Based Reasoning (CBR) algorithms implemented in a Java application, it is possible to design maintenance plans adjusted to a real and changing operational context of any industrial plant. As a result, faster and more accurate decisions are made, as they are based on data. This article focuses on improving certain aspects of the developed assisted system by adding more value to it by incorporating Fuzzy Logic (FL) techniques. The aim is to improve the way of entering information about risk factors and their relative importance, by incorporating natural language, instead of a numerical score, resulting in increased precision in the calculation of the Risk Priority Number (RPN) of the new cases incorporated into the assisted system.

In the realm of smart manufacturing, equipment plays a pivotal role, impacting the efficiency and quality of production. Ensuring equipment availability and optimal performance is crucial, necessitating effective maintenance strategies. This paper addresses the complexities of smart device maintenance, which often involves collaboration between multiple entities like device owners, manufacturers, suppliers, and external maintenance services. To enhance this cooperative maintenance, we propose a novel maintenance system based on permissioned blockchain technology, offering superior security and reliability compared to conventional cloud-based platforms. Our contributions include developing an integrated maintenance system framework for smart manufacturing, which facilitates interactions among diverse stakeholders. Additionally, we have developed a prototype of this maintenance system, serving as a practical model for real-world application. Our research primarily demonstrates the practicality and advantages of using permissioned blockchain for maintenance systems in the manufacturing sector, paving the way for more secure, efficient, and collaborative maintenance practices.

All kinds of vessels consist of dozens of complex machineries with rotating parts and electric motors that operate continuously in a harsh environment with excess temperature and humidity, vibration, fatigue and load. A breakdown or malfunction in one of these machineries can significantly impact the vessel’s operation and safety and consequently, the safety of the crew and the environment. To maintain operational efficiency and seaworthiness, the shipping industry invests substantial resources in preventive maintenance and repairs. This research presents the economic and technical benefits of predictive maintenance over to traditional preventive maintenance, and repair by replacement approaches in the maritime domain. By leveraging modern technology and Artificial Intelligence, we can analyze real-time operating conditions of machinery, enabling early detection of potential damages and allowing for effective planning of future maintenance and repair activities. In this paper, we propose and develop a Convolutional Neural Network that is fed with raw vibration measurements acquired in a laboratory environment from the ball bearings of a motor. Then, we investigate whether the proposed network can accurately detect the functional state of ball bearings and categorize any possible failures present, contributing to improved maintenance practices in the shipping industry.

Wind power is one of the most important sources of renewable energy available today. A large part of the wind energy cost is due to the cost of maintaining wind power equipment. When a wind turbine component fails to function, it might need to be replaced under the less than ideal circumstances. This is known as corrective maintenance. To minimize unnecessary costs, a more active maintenance policy based on the life expectancy of the key components is preferred. Optimal scheduling of preventive maintenance activities requires advanced mathematical modeling. In this paper, an optimal preventive maintenance algorithm is designed using the renewal-reward theorem. In the multi-component setting, our approach involves a new idea of virtual maintenance which allows us to treat each replacement event as a renewal event even if some components are not replaced by new ones. The proposed optimization algorithm is applied to a four-component model of a wind turbine and the optimal maintenance plans are computed for various initial conditions. The modeling results showed clearly the benefit of PM planning compared to pure CM strategy (about 30% lower maintenance cost).

This study investigated the breakdown trend in an automated production with an aim to recommend the application of Reliability-centered maintenance (RCM) for an improved productivity via a new preventive maintenance (PM) program. Individual Section-forming machine (ISM): a glass blowing machine for making glass bottles was used as the case study of an automated production system. The machine parts and the working mechanisms were analysed with a special focus on methods of processes and procedures that will enable the ISM maintenance department run more effective and achieve its essential goal of ensuring effective machine operation and reducing machine downtime. In this work, information is provided on the steps and procedures to identify critical components of the ISM using Failure Modes and Effect Analysis (FMEA) as a tool to develop an optimal maintenance program based on the reliability data of the equipment’s functional components. A relationship was established between the failure rate of the machine components and the maintenance costs such that using the recommended PM program, an evidence of improvement in the machine’s availability, safety and cost-effectiveness will result into an increase in the company’s profit margin.

Artificial Intelligence (AI) models are expected to have a great impact in the manufacturing industry, optimizing time and resource cost by enabling applications such as predictive maintenance (PM) of production machines. A necessary condition for this is the availability of high quality data collected as close as possible to the process in question. With the advent of 5G equipped multi sensor platforms (MSPs), high sampling rate data can be collected and transmitted for processing in real time. This poses a data security challenge, since this data may give valuable insight into confidential business information of companies. Federated learning (FL) enables the training of AI models with data from multiple sources without it leaving the shop floor, by utilizing distributed computing resources available on premise. This paper introduces an architecture of FL based on data collected from 5G MSPs for enabling PM in industrial environments and discusses its potential benefits and challenges.

(1) Methadone is a chiral synthetic opioid primarily used to treat heroin and prescription-opioid addiction: the (R)-enantiomer (Levomethadone) activates the µ-opioid receptor more potently than the (S)-enantiomer, which is a more potent blocker of the hERG potassium channels, resulting in QTc prolongation. The purpose of this study is to assess the effect of methadone on the QTc interval and to investigate the benefits of Levomethadone. (2) The electrocardiograms of 165 patients taking methadone at various dosages and for different periods of time were examined: the QTc value was manually measured and then adjusted using Bazett's formula. (3) Data analysis revealed a linear association between the dosage of methadone and QTc length; no correlation was found between the QTc value and gender, age, or duration of therapy. 14% of the sample (23 patients) showed a prolongation of the QTc interval. 10 of the 23 patients with QTc elongation underwent a change of therapy from Methadone to Levomethadone: in 90% of these patients, a normalization in the QTc length was established. (4) This study confirmed the role of methadone, specifically its dosage, in QTc prolongation and the efficiency of Levomethadone as an adequate therapeutic substitute in these circumstances. This study validates the importance of a careful electrocardiographic monitoring in methadone-treated patients.

This study uses a wind turbine case study to showcase an architecture for implementing a distributed digital twin in which all important aspects of a predictive maintenance solution in a DT use a fog computing paradigm, and the typical predictive maintenance DT is improved to offer better asset utilization and management through real time condition monitoring, predictive analytics, and health management of selected components of Wind turbines in a wind farm.. Digital twin (DT) is a technology that sits at the intersection of Internet of Things, Cloud Computing and Software Engineering to provide a suitable tool for replicating physical objects in the digital space. This can facilitate the implementation of asset management in manufacturing systems through predictive maintenance solutions leveraged by Machine Learning (ML). With DTs, a solution architecture can easily use data and software to implement asset management solutions such as Condition Monitoring and Predictive Maintenance using acquired sensor data from physical objects and computing capabilities in the digital space. While DT offers a good solution, it is an emerging technology that could be improved with better standards, architectural framework, and implementation methodologies. Researchers in both academia and industry have showcased DT implementations with different levels of success. However, DTs remain limited in standards and architectures that offer efficient predictive maintenance solutions with real time sensor data, and intelligent DT capabilities. An appropriate feedback mechanism is also needed to improve asset management operations.

Buildings are subject to intrinsic and extrinsic failures at all stages of the construction process, i.e., design to occupancy (i.e., use) as several failure types can affect them. There are three basic steps for researching building failures: listing, cataloging, and solving/deciding whether highlighting the least invasive and lowest cost intervention. Therefore, this research presents some methods used in construction for the intervention prioritization and seeks to illustrate the most suitable methodology for different settings failure x diagnosis x intervention. Therefore, the most traditional tools are shown: BASICO, SWIFT, FEMEA, AAF, and GUT matrix, where a critical assessment of the strengths and weaknesses is carried out. After that, a case study on maintenance services for the moisture on the building facades was performed. Finally, the GUT matrix and the FMEA method are the best results

In today's business world, many companies have realized that consumer feedback evaluations play a crucial part in shaping the company's future activities. The hotel and tourism industries are well-known examples where the user feedback has become crucial. Even though most accommodations want their clients to express their opinions about their services, these reviews are nevertheless carefully reviewed by them. This manual approach is time demanding and error prone, the level of expertise of the individual analyzing the evaluations determines the quality of the manual analysis. This research focuses on the development of a tool-based support system that analyzes text-based customer evaluations and then highlights the maintenance issues identified in the reviews, removing the need to manually evaluate and analyze the customer reviews. The process includes data preparation, sentiment analysis, and a fully trained deep learning model to extract critical insights. Using sentiment analysis techniques after data preprocessing and trained deep learning model, an accuracy of 96\% was achieved, and this paper discusses how this technology helps to meet the needs of accommodation management by completing activities efficiently. This might save management time and helps to save money without losing clients, allowing them to enhance their additional sales.

In the field of industrial process monitoring, more and more interest is being shown in specific process categories. These include time-varying processes, that is, those processes whereby the response one receives as output from the system depends on when the input signal is sent into it. There are many reasons for this process variability and such contexts are not always analyzed with this operational characteristic at their core. At the same time, interest in certain categories of techniques is also becoming more prominent, to meet certain application needs. Among these, clustering and unsupervised techniques in general are gaining ground. This is largely due to the difficulty of finding fault data with which to train, for example, supervised models. On the other hand, the clustering technique, on which this contribution focuses, also makes it possible to compensate for the lack of complete knowledge of the structure of the process itself. With these two considerations in mind, this contribution proposes a literature review on the topic of clustering applied in time-varying contexts, in the maintenance field. The aim is to present an overview of the main fields of study, the role of clustering in this context and the main clustering techniques used.

Timely detection of surface damages on wind turbine blades is imperative for minimising downtime and avoiding possible catastrophic structural failures. With recent advances in drone technology, a large number of high-resolution images of wind turbines are routinely acquired and subsequently analysed by experts to identify imminent damages. Automated analysis of these inspection images with the help of machine learning algorithms can reduce the inspection cost, thereby reducing the overall maintenance cost arising from the manual labour involved. In this work, we develop a deep learning based automated damage suggestion system for subsequent analysis of drone inspection images. Experimental results demonstrate that the proposed approach could achieve almost human level precision in terms of suggested damage location and types on wind turbine blades. We further demonstrate that for relatively small training sets advanced data augmentation during deep learning training can better generalise the trained model providing a significant gain in precision.

With the rapid development of electric vehicles, the infrastructure for charging stations is also expanding quickly, and the failure rate of charging piles is increasing. To address the effective operation and maintenance of charging stations, a method based on the XGBoost algorithm for electric vehicle DC charging stations is proposed. An operation and maintenance system is con-structed based on state analysis, considering the operation status of the charging station and users' charging habits. Factors such as driving and charging habits, road traffic, and charging station equipment are taken into account. The training sample data is established using historical data, online monitoring data, and external environmental data, and the charging station status evaluation model is trained using the XGBoost algorithm. Based on the condition assessment results, a risk assessment model is established in combination with fault parameters. Risk tracking of the charging station is conducted using the lack of power supply (ENC), evaluating the risk level of each station, and determining the operation and maintenance order. The optimal opera-tion and maintenance model for DC charging stations, aimed at achieving both economic and reliable goals, is constructed to determine the operation and maintenance schedule for each sta-tion. The results of the case study demonstrate that the state evaluation and operation and maintenance strategy can significantly improve the reliability of the system and the overall ben-efits of operation and maintenance while meeting the required standards.

Since the first description of bisphosphonate-related osteonecrosis of the jaw (BRONJ) numerous research groups have focused on possible pathological mechanisms including the suppression of the bone turnover of the jaw, antiangiogenic effects and soft tissue toxicity. In our review we focused on summarizing the role of the soft tissues in the development and progression of BRONJ. The biological behavior of fibroblasts can be significantly influenced by bisphosphonates (BP) such as a concentration dependent reduction of cell viability. High concentrations of BP can induce apoptosis and necrosis of the cells. Comparable effects could be detected for keratinocytes. Compared to non-nitrogen containing bisphosphonates nitrogen-containing BP have worse effects on cell biology by blocking the mevalonate pathway. Next to this the cell architecture and the expression levels of several genes and proteins are significantly disturbed by BP. These inhibitory effects of BP are in accordance with BP related reduced angiogenesis and neovascularization and could underline the hypothesis that inhibition of fibroblasts and keratinocytes results in delayed wound healing and can induce and trigger BRONJ.

Structural Maintenance of Chromosomes (SMC) complexes are an evolutionary conserved protein family. In most eukaryotes, three SMC complexes have been characterized: cohesin, condensin, and SMC5-6 complexes. These complexes are involved in a plethora of functions and defects in SMC genes can lead to increased risk of chromosomal abnormalities, infertility, and cancer. To investigate th evolution of SMC complex genes in mammals, we analyzed their selective patterns in an extended phylogeny. Signals of positive selection were identified for condensin NCAPG, for two SMC5/6 complex genes (SMC5 and NSMCE4A) and for all cohesin genes with almost exclusive meiotic expression (RAD21L1, REC8, SMC1B, and STAG3). For the latter, evolutionary rates correlate with expression during female meiosis and most positively selected sites fall in intrinsically disordered regions (IDRs). Our results support growing evidence that IDRs are fast evolving and that most likely contribute to adaptation through modulation of phase separation. We suggest that the natural selection signals identified in SMC complexes may be the result of different selective pressures: a host-pathogen arms race in the condensin and SMC5/6 complexes, and an intragenomic conflict similar to that described for centromeres and telomeres for meiotic cohesin genes.

In today's business world, many companies have realized that consumer feedback evaluations play a crucial part in shaping the company's future activities. The hotel and tourism industries are well-known examples where the user feedback has become crucial. Even though most accommodations want their clients to express their opinions about their services, these reviews are nevertheless carefully reviewed by them. This manual approach is time demanding and error prone, the level of expertise of the individual analyzing the evaluations determines the quality of the manual analysis. This research focuses on the development of a tool-based support system that analyzes text-based customer evaluations and then highlights the maintenance issues identified in the reviews, removing the need to manually evaluate and analyze the customer reviews. The process includes data preparation, sentiment analysis, and a fully trained deep learning model to extract critical insights. Using sentiment analysis techniques after data preprocessing and trained deep learning model, an accuracy of 96% was achieved, and this paper discusses how this technology helps to meet the needs of accommodation management by completing activities efficiently. This might save management time and helps to save money without losing clients, allowing them to enhance their additional sales.

Grinding processes’ stochastic nature poses a challenge in predicting the quality of the resulting surfaces. Post-production measurements for form, surface roughness, and circumferential waviness are commonly performed due to infeasibility in measuring all quality parameters during the grinding operation. Therefore, it is challenging to diagnose the root cause of quality deviations in real-time resulting from variations in the machine’s operating condition. This paper introduces a novel approach to predicting the overall quality of the individual parts. The grinder is equipped with sensors to implement condition-based maintenance and is induced with five frequently occurring failure conditions for the experimental test runs. The crucial quality parameters are measured for the produced parts. Fuzzy c-means (FCM) and Hotelling’s T-squared (T2) have been evaluated to generate quality labels from the multi-variate quality data. Benchmarked random forest regression models are trained using fault diagnosis feature set and quality labels. Quality labels from the T2 statistic of quality parameters are preferred over FCM approach for their repeatability. The model, trained from T2 labels achieves more than 94% accuracy when compared to the measured ring disposition. The predicted overall quality using the sensors’ feature set is compared against the threshold to reach a trustworthy maintenance decision.

Performing predictive maintenance (PdM) is challenging for many reasons. Dealing with large datasets which may not contain run-to-failure data (R2F) complicates PdM even more. When no R2F data are available, identifying condition indicators (CIs), estimating the health index (HI), and thereafter, calculating a degradation model for predicting the remaining useful lifetime (RUL) are merely impossible using supervised learning. In this paper, a 3 dof delta robot used for pick and place task is studied. In the proposed method, autoencoders (AEs) are used to predict when maintenance is required based on the signal sequence distribution and anomaly detection, which is vital when no R2F data is available. Due to the sequential nature of the data, non-linearity of the system, and correlations between parameter time series, convolutional layers are used for feature extraction. Thereafter, a sigmoid function is used to predict the probability of having an anomaly given CIs acquired from AEs. This function can be manually tuned given the sensitivity of the system or optimized by solving a minimax problem. Moreover, the proposed architecture can be used for fault localization for the specified system. Additionally, the proposed method is capable of calculating RUL using Gaussian process (GP), as a degradation model, given HI values as its input.

The significance of virtual reality (AR/VR/MR) technology stands out because it can be used in various construction fields such as urban design, construction review, maintenance and education, etc. As to prove this, conglomerates such as Facebook, Google, Sony, Microsoft, and Samsung are increasing their investments to preoccupy the virtual reality market and are competing to dominate the contents and platform market. Virtual reality technology has a concept that collectively refers to VR (Virtual Reality), AR (Augmented Reality), and MR (Mixed Reality), but technically, the two technologies are strictly separated. While VR technology is an immersive virtual environment using computer graphic technology, AR technology is a more advanced technology that combines real data and VR data, and MR technology is a technology that combines both AR and VR. In Korea, Republic of, the use of BIM (Building Information Modeling), a 3D information model, becomes mandatory and based on this, the demand for a new market where VR/AR/MR technologies and advanced sensing equipment are combined increases. This study implemented a building maintenance platform using AR based on 5G, and developed matching technology between BIM of the building maintenance platform and AR equipment. Besides this study implemented the technology to enhance the matching rate of the matching technology and carried out the process to enhance the matching rate empirically through continuous tests. As a result, the initial target of 90% matching rate could be improved to 96%. Based on this, it is expected that effective EV (Optimum Life Cycle Cost) could be achieved at a lower cost compared to the previous one by using it for maintenance monitoring after construction and completion of the building, and can be used as an effective solution in the aspect of building maintenance as well.

The aim of this paper is to use deep learning tools to innovate pre-trained object detection models to improve the accuracy of non-destructive testing (NDT) of civil aviation maintenance. First, this thesis classifies object defects for NDT, such as cracks, undercut, etc. Nowadays, thesis surveys innovation deep-learning methods technology is used to improve the defect detection performance inferencing capability, increase the accuracy and efficiency of automatic identification which in enhanced the safety and reliability of aircraft fuselage in future, mark hidden cracks and solve the challenges that cannot be identified by manual inspection. Second, recent mainstream techniques the YOLOv4 neural network to the graphics card GPU core operator to speed up the recognition of defect images is being applied to the non-destructive inspection process of aircraft maintenance on A, C and D-Level, fully validating the deep learning model's powerful defect detection target capability. The attention-based YOLOv4 algorithm is improved by applying a one-stage attention mechanism to the YOLOv4, thereby improving the accuracy of the innovation model. Finally, thesis improved YOLOv4 based on an attention mechanism is proposed for object detection NDT via the deep learning method to effectively improve and shorten the inspection anomaly detection method for automatic detection sensor systems.

Acute myeloid leukemias are characterized by genetic alterations that lead to a complete or partial block at various stages of myeloid differentiation, leading to continual proliferation of myeloid progenitor cells. These alterations can include a well-documented chromosomal translocation that leads to the synthesis of the PML-retinoic acid receptor fusion protein that leads to a block in differentiation and the ability to induce differentiation with all-trans retinoic acid and other small molecules. In essence, in large part, the disease is due to stem cell-like cells that are blocked in their ability to undergo terminal differentiation to more mature, non-proliferative cell types. We discovered a long non-coding RNA (lncRNA), lncRNAp53int1, encoded from the first intron of the p53 tumor suppressor gene. Interestingly, lncRNAp53int1 appears to play an important regulatory role in maintaining the undifferentiated and proliferative state in a manner independent from p53 gene expression. lncRNAp53int1 is expressed at high levels in proliferating, undifferentiated promyelocytes and its levels fall significantly during their terminal differentiation to non-proliferating granulocytes or macrophages. Furthermore, forced overexpression of lncRNAp53int1 blocks terminal differentiation. The observation that the expression of this lncRNA is repressed during terminal differentiation of human leukemic cells and its expression blocks differentiation of leukemic myeloid progenitor cells, is likely to have clinical implications with regards to differentiation therapy for myeloid leukemia. Ongoing research aims to identify the molecular partners that it associates with and the signaling pathways that this lncRNA participates in with the long-term goal of identifying molecules that inhibit lncRNAp53int1 activity and serve as potential therapeutic drugs. The goal of this mini-review is to disseminate these novel and interesting findings to readers and to describe where we think this research is headed and the impact it can have on myeloid leukemias.

Modern engineering faces challenges in ensuring technical standards for service, durability, and sustainability. Political, administrative, and budgetary factors, coupled with climate change, pose tasks to structural integrity, affecting industries and economies. Marine infrastructures represent a strategic asset of the country as it handles a large part of the economic exchanges. This article analyzes five essential factors that play a fundamental role in the performance analysis of coastal structures: Chloride-induced corrosion, degradation models, maintenance strategies, monitoring, and climate change. Starting with reinforcement corrosion, considered as the main cause of distress, particularly in coastal zones for the long-term behavior of structures. Additional pressure from the influences of climate change is becoming evident and extreme, leading to reduction in capacity. To guarantee the lifespan, degradation models contribute by estimating the long-term performance of the asset as a strategic piece to the development of effective maintenance solutions. Additionally, quantifying the condition of the structure from monitoring data, plays a crucial part that provides information on the current situation of the structure. Finally, this review summarizes the challenges associated with the maintenance of aging marine structures considering aspects such as corrosion, monitoring, and the future challenges this area will face due to climate change.

Prediction models in mobility and transportation maintenance systems have been dramatically improved through using machine learning methods. This paper proposes novel machine learning models for an intelligent road inspection. The traditional road inspection systems based on the pavement condition index (PCI) are often associated with the critical safety, energy and cost issues. Alternatively, the proposed models utilize surface deflection data from falling weight deflectometer (FWD) tests to predict the PCI. Machine learning methods are the single multi-layer perceptron (MLP) and radial basis function (RBF) neural networks as well their hybrids, i.e., Levenberg-Marquardt (MLP-LM), scaled conjugate gradient (MLP-SCG), imperialist competitive (RBF-ICA), and genetic algorithms (RBF-GA). Furthermore, the committee machine intelligent systems (CMIS) method was adopted to combine the results and improve the accuracy of the modeling. The results of the analysis have been verified through using four criteria of average percent relative error (APRE), average absolute percent relative error (AAPRE), root mean square error (RMSE), and standard error (SD). The CMIS model outperforms other models with the promising results of APRE=2.3303, AAPRE=11.6768, RMSE=12.0056, and SD=0.0210.

Although evolutionary transitions of individuality have been extensively theorized, little attention has been paid to the origin of levels of organization within organisms. How and why do specialized cells become organized into specialized tissues or organs? What spurs a transition in organizational level in cases where the function is already present in constituent cell types? We propose a model for this kind of evolutionary transition in terms of two key features of cellular self-maintenance: metabolic constraints on functional performance and the capacity for metabolic complementation between parenchymal and supporting cells. These features suggest a scenario whereby pre-existing specialized cell types are integrated into tissues when changes to the internal or external environment favor offloading metabolic burdens from a primary specialized cell type onto supporting cells. We illustrate this process of “supra-functionalization” using the nervous system and the pancreas as examples. The model reveals distinctive concerns for explaining this kind of evolutionary transition—instead of the suppression of “cheating” by components, the issue is how a tissue comes under modular genetic control as a distinct body part—and also points to a novel form of evolutionary complexity-increasing ratchet.

Interpretation of increased gain in the bovine animals is difficult to be validated due to inherent genetic variation to meet their requirement for energy and protein, and those may relate to the bull species, e.g., Thai swamp buffalo. Therein, the study aimed at investigating and predicting protein requirement systems, with providing abundant energy intake 2.20 Mcal/kg DM for maintenance and growth of Thai swamp buffaloes using the comparative prolonged feeding trial for 90 days. Sixteen bull Thai swamp buffaloes at the initial (Age: 18-24 months; BW: 233 ± 25.0 kg) were as-signed into four treatment groups, four buffaloes each, fed 5.42, 6.96, 8.94, and 10.71% DM crude protein (CP). CP intake, BW, and physiological fluid were determined. The net CP requirements for maintenance and growth of Thai swamp buffaloes were 5.41 g CP/kg W0.75 and 0.46 g CP/g average daily gain (ADG), respectively. Our results indicated that CP requirement increases, when BW increases. An increased dietary CP resulted in an increased number at blood urine nitrogen (N), N absorption, total volatile fatty acid, urinary purine derivative, and the microbial N. Notably, the net CP requirement for growth of Thai swamp buffalo was higher than it reported in NRC, but the maintenance was lower.

A comprehensive Energy Audit of a Maintenance facility was performed to assess its energy performance and identify scope for improvement. The facility’s Energy Use Intensity (EUI) for 2022 was 404 kWh/m2 — more than double the Benchmark EUI for Maintenance facilities (151 kWh/m2) recommended by EnergyStar. Furthermore, the Load Factor for 2022 was 0.22, which is lower than the recommended minimum of 0.75 for an efficient building. The audit encompassed an in-depth evaluation of the building's structural and operational characteristics, comprising HVAC systems, lighting, building envelope, and energy-intensive machinery. An energy model of the building was developed to emulate the baseline building energy performance for 2022. Following the energy model's development and validation, an analysis was conducted to identify energy-intensive areas and opportunities for optimization. Energy Efficiency Measures were then formulated, focusing on improving energy efficiency while focusing on energy consumption reduction and GHG emission reduction. Results demonstrated the potential of Energy Audits and Modeling to enable significant reductions in energy consumption and promote sustainable building practices. Among the Energy Efficiency Measures considered, re-sizing and decarbonizing HVAC equipment contributed the most to energy savings, with a 100% decrease in natural gas and 37% decrease in electricity use annually.

In the post-PARP inhibitor era, potential changes in tumor biology after maintenance therapy have not been well investigated in recurrent ovarian cancer. We reported a case with alterations in the clinical and histological features of multiple relapsed disease associated with PARP inhibitor maintenance therapy. The patient with high-grade serous carcinoma exhibited BRCA wildtype and homologous recombination proficiency status, and suffered from three recurrences and surgeries accordingly. Olaparib maintenance had been used during the second-line therapy. We compared the differences in clinics and pathology among three recurrences and relapsed lesions. Disease-free survivals were dramatically decreased after the exposure to olaparib. At exploration of quaternary cytoreduction, the relapsed tumor was characterized by a carcinomatosis-like metastasis pattern and an easy tendency of bleeding. Tumor cytopathological changes and alterations were observed in both the tumoral and non-tumoral stroma, among relapsed tumor tissues derived from secondary, tertiary and quaternary cytoreduction. Histopathology indicated hemorrhage, necrosis, atypical tumor cells, massive angiogenesis, and decreased CD8+ tumor-infiltrating lymphocytes, particularly in the third relapsed disease. To our knowledge, this is the first report to show a unique metastatic pattern of angiogenic burst after PARP inhibitor maintenance therapy in ovarian cancer, which seemed to trigger invasive tumor growth and immune suppression. Further prospective studies and translational research focusing cytoreductive surgery after PARP inhibitor could progressively lead to an understanding of the biological behavior and metastatic patterns.

Arabic is present in the Arab world and beyond. It is used as an official (or co-official) language in the Arab World (this refers to the twenty-two member states of the Arab League). Also, Arabic has the status of a national language in Mali, Niger, and Senegal. Besides, it is spoken in linguistic enclaves in Nigeria, Cyprus, Turkey, Uzbekistan, Iran, and Afghanistan. In addition, it is employed as the liturgical language in Muslim countries and countries with a Muslim minority all over Africa and Asia. As a result of the migration to Western countries since the end of the nineteenth century, Arabs and Arabic has been present in such countries. The presence of Arabs in Western countries raises the following question: Are these Arabs language maintainers or language shifters? The present article is an attempt to answer this question through reviewing a number of studies that have dealt with Arabic language maintenance among the Arabs living in Western countries (namely the United States of America, the United Kingdom, Canada, Australia, New Zealand, Sweden, Greece, and France), deducing from these studies the major trends in Arabic language maintenance among these Arabs, and providing a critique of the studies.

Denture wearers often complain about jeopardized function and reduced quality of life due to lack of prosthesis’ retention. Implant retained mandibular overdentures, on 2 non-connected implants (2IOD) are well-proven solutions to overcome these issues. We prospectively assessed 69 patients and scrutinized clinical records until at least 7 years of function. Thirty-six were retained on Locator ® Abutments (LA) and thirty-tree on Ball Abutments (BA). Both systems were compared regarding the type, amount and total cost of required maintenance. One implants was lost, yielding 98.7% survival after 7 years. In total 438 technical issues occurred: 121 (27.35%) in BA and 317 (72.4%) in LA. Out of these, 343 events (78%) were solved chairside: 191 (43.6%) were replacements of retention caps, 113 (25.8%) were minor acrylic repairs, in 26 (5.9%) pressure ulcers had to be relieved and 13 (3%) related to abutments. LA required 179 insert replacements compared to 12 in the BA group. The overall initial treatment cost was 3850 euro. The average total maintenance cost in relation to the initial cost for the LA and BA groups was 19.11% (range 0% - 82.24%) and 18.91% (range 0% - 113.26%) respectively (P=0.540). Conclusions: The 7-years maintenance costs for a 2IOD is acceptable when the patient is regularly checked and professionally maintained. Most events are easily solvable chairside, but a few patients required more expensive interventions, regardless of the type of attachment used.

The present paper deals with research of maintenance strategy and maintenance process improvement procedure to increase the efficiency and quality of the production system. It includes the design of maintenance performance indicators relevant to today's manufacturing systems to track improvements in the sustainable development of the manufacturing system. Describes the basic principles of maintenance strategy with linkages to the manufacturing system and selecting the right strategy for the organization. The paper emphasizes maintenance management auditing and quality implementation in maintenance. Further, there is the process of changing the maintenance strategy described. This process includes reassessing the criticality of machines and equipment and their design units, then resource and capacity planning and input for maintenance management. It is described the impact of changing the maintenance management organization and maintenance capacity in the light of the change of strategy and the evaluation of maintenance choice alternatives, together with an analysis of the optimization procedure. The paper concludes by presenting the achieved impact of maintenance strategy change on the production efficiency and production quality of the selected enterprise.

Modern war is sudden and rapid, and once the battle starts, the demand for equipment maintenance and guarantee will show an outburst situation, which puts equipment maintenance and guarantee capability to a severe test. To accurately grasp the civil-military integration of aviation maintenance and guarantee capabilities, it is necessary to evaluate their capabilities. To this end, the evaluation indicator system is established by using the three-dimensional indicator system construction model of "maintenance task → task demand → capability demand", and the evaluation method based on intuitionistic fuzzy entropy and normal grey cloud model is proposed, using intuitionistic fuzzy entropy theory to determine the expert weights and indicator weights, and the grey cloud model theory to determine the capability evaluation level. Finally, the application process of the evaluation model is demonstrated through specific examples, and the evaluation results are analyzed to verify the effectiveness of the evaluation model.

Modern war is sudden and rapid, and once the battle starts, the demand for equipment maintenance and guarantee will show an outburst situation, which puts equipment maintenance and guarantee capability to a severe test. To accurately grasp the civil-military integration of aviation maintenance and guarantee capabilities, it is necessary to evaluate their capabilities. To this end, the evaluation indicator system is established by using the three-dimensional indicator system construction model of "maintenance task → task demand → capability demand", and the evaluation method based on intuitionistic fuzzy entropy and normal grey cloud model is proposed, using intuitionistic fuzzy entropy theory to determine the expert weights and indicator weights, and the grey cloud model theory to determine the capability evaluation level. Finally, the application process of the evaluation model is demonstrated through specific examples, and the evaluation results are analyzed to verify the effectiveness of the evaluation model.

Background: The new therapeutic modality incorporating countermeasure against the most plausible environmental factor in inflammatory bowel disease, i.e., a plant-based diet, showed far better outcomes than current standards in inflammatory bowel disease. Infliximab is widely used for induction and subsequent scheduled maintenance therapy in patients with inflammatory bowel disease. However, the efficacy of infliximab diminishes over time. Objectives: To investigate the durability of scheduled infliximab maintenance therapy incorporating plant-based diet in inflammatory bowel disease. Methods: This was a prospective single-group trial at tertiary hospitals. Infliximab maintenance therapy was indicated in patients with severe or unresponsive to conventional therapy. Infliximab (5 mg/kg body weight) was infused every 8 weeks on an inpatient basis, and plant-based diet, a lacto-ovo-vegetarian diet, was served three or four times during hospitalization. Durability was assessed using the Kaplan-Meier method. Results: Twenty-four patients (16 with Crohn’s disease, eight with ulcerative colitis) were included: median age 27.5 years old, disease duration 53.5 months, and concomitant use of immunosuppressant 21%. Intensification of infliximab was employed in 46% of patients. There was no significant difference in durability rates between Crohn’s disease and ulcerative colitis. Durability rates were 87% at both 5 and 10 years. Plant-based diet score in the median follow-up period of 9.3 years, which indicates adherence to the plant-based diet, was significantly higher than the baseline score. Conclusions: Infliximab maintenance therapy incorporating plant-based diet yielded a high durability rate of 87% at 5 years in patients with Inflammatory bowel disease.

Evaluating mutation testing behavior can help decide whether refactoring successfully maintains the expected initial test results. Moreover, manually performing this analytical work is both time-consuming and prone to errors. This paper extends an approach to assess test code behavior and proposes a tool called MeteoR. This tool comprises an IDE plugin to detect issues that may arise during test code refactoring, reducing the effort required to perform evaluations. A preliminary assessment was conducted to validate the tool and ensure the proposed test code refactoring approach is adequate. By analyzing not only the mutation score but also the generated mutants in the pre- and post-refactoring process, results show that the approach is capable of checking whether the behavior of the mutants remains unchanged throughout the refactoring process. This proposal represents one more step toward the practice of test code refactoring. It can improve overall software quality, allowing developers and testers to safely refactor the test code in a scalable and automated way.

: In this study we evaluated, if single nucleotide polymorphisms (SNPs) in the genes encoding PTH, VDR, CYP24A1 and CYP27B1 are associated with Mandibular Retrognathism (MR). Samples from biologically-unrelated patients receiving orthodontic treatment were included in this study. Pre-orthodontic lateral cephalograms were used to determine the phenotype. Patients having a retrognathic mandible (SNB<78º) were selected as cases and those with an orthognathic mandible (SNB=78º–82º) were selected as controls. Genomic DNA was used for genotyping analysis of SNPs in PTH (rs694, rs6256 and rs307247), VDR (rs7975232), CYP24A1 (rs464653) and CYP27B1 (rs927650). Chi-squared or Fisher’s tests were used to compare genotype and allele distribution among groups. Haplotype analysis was performed for the SNPs in PTH. The established alpha was p<0.05. Multifactor dimensionality reduction (MDR) was used to identify SNP-SNP interactions. A total of 48 MR and 43 controls were included. In the genotype and allele distribution analysis, the SNPs rs694, rs307247 and rs464653 in were associated with MR (p<0.05). MDR analyses predicted the best interaction model for MR was rs694-rs927650, followed by rs307247-rs464653-rs927650. Some haplotypes in the PTH gene presented statistical significance. Our results suggest that SNPs in PTH, VDR, CYP24A1 and CYP27B1 genes are associated with the presence of mandibular retrognathism.

The high demand for liquefied natural gas (LNG) requires more LNG carriers (LNGCs) to be in operation. During transportation, there is a high risk due to the required extremely low temperatures and the explosive nature of LNG cargo. Moreover, when there is a lack of experience in operating old LNGCs, there is a serious concern regarding operational accidents. A systematic maintenance strategy, especially for LNG cargo containment systems, is crucial for maintaining safe LNG transportation at sea. The purpose of this study is to develop preventive LNG cargo containment system maintenance models by using LNGC dock specifications from LNGCs of various ages. The dock specifications from a conventional LNGC repairing dock were analyzed using natural language processing techniques in order to develop preventive maintenance models of the LNG cargo containment system. From these results, and by considering the ship’s age, it was found that for young LNGCs the priority for repair should focus on checking routine consumable spare parts by tank inspections, whereas for older LNGCs the focus should be on tank condition maintenance rather than on other facilities. These results are expected to be useful in the development of a maintenance strategy of preventive LNG cargo containment systems in maritime LNG transportation.

The aim of this study was to compare the screw removal torque of mini conical prosthetic components and straight trunnion of indexed morse taper implants, after mechanical cycling. The sample consisted of 40 implants and 20 mini-conical prosthetic components (MC group) and 20 straight trunnion components (ST group). Each group consisted of 10 specimens, with 2 implants in each, and cobalt-chromium metallic crowns were screwed into each sample. The components of the MC group received a torque of 20 N.cm with a digital torque wrench and after 10 minutes were retightened with the same value as the initial torque. The components of the ST group received a torque of 30 N.cm, with a digital torque wrench and after 10 minutes, they were retightened with the same value. The screws of the respective crowns of the two groups received a torque of 10 N.cm and after 10 minutes were retightened with the same value. Each group was subjected to the fatigue test in a mechanical cycler at 2.000.000 cycles, with a load of 250 N and frequency of 4 Hz. At the end of the fatigue test, the loosening torque of each screw of the specimens was measured through a digital torque wrench. The data were analyzed by two-way ANOVA and Tukey test. In both groups, there were loss of torque. The results showed no statistic difference between MC and ST groups.

: Nanotechnology options to road surface maintenance offers several advantages compared to traditionally used materials. The small particle sizer of hydrophobic Nano-Silane modified Nano-Polymers (NSNP) enables these nanotechnology products to deeply penetrate existing road surfaces, sealing micro-cracks and render surfacings to be water-resistant for extended periods of time. In comparison, traditionally used products contain minimum partial sizes of about 1 – 5 microns, that provide a superficial protection that wears off in a relatively short period of time. These traditional products are often associated with vehicle contamination while drying and requires the re-instatement of road markings. None of these disadvantages are associated with applicable NSNP technologies that are quick drying, with no vehicle contamination risks and is equivalent to a “clear-seal” requiring no reinstatement of road markings. In a similar vein, pot-hole repairs can be done using applicable, easy to use, pre-packed and treated pot-hole repair kits that are water-repellent and quick-drying at a fraction of the costs of conventional cold-mix products. Resurfacing using NME binder slurries can be done labour-intensively on a pre-treated NSNP surfacing, restoring cracked surfacing and providing a water-resistant long-lasting protective layer without the removal of existing cracked areas. The implementation of nanotechnology solutions for road surface maintenance operations is directly associated with ease of use, labour-intensive operations, prevention of considerable deterioration in riding quality due to removal and manual re-instatement of cracked surfaces, time and cost savings and a reduction in the risk of water damage to the sub-structure. TRANSLATE with x English ArabicHebrewPolish BulgarianHindiPortuguese CatalanHmong DawRomanian Chinese SimplifiedHungarianRussian Chinese TraditionalIndonesianSlovak CzechItalianSlovenian DanishJapaneseSpanish DutchKlingonSwedish EnglishKoreanThai EstonianLatvianTurkish FinnishLithuanianUkrainian FrenchMalayUrdu GermanMalteseVietnamese GreekNorwegianWelsh Haitian CreolePersian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back TRANSLATE with x English ArabicHebrewPolish BulgarianHindiPortuguese CatalanHmong DawRomanian Chinese SimplifiedHungarianRussian Chinese TraditionalIndonesianSlovak CzechItalianSlovenian DanishJapaneseSpanish DutchKlingonSwedish EnglishKoreanThai EstonianLatvianTurkish FinnishLithuanianUkrainian FrenchMalayUrdu GermanMalteseVietnamese GreekNorwegianWelsh Haitian CreolePersian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back

Plants attained cellular homeostasis of phosphate (Pi) through an integrated response pathway regulated by different families of transcription factors including MYB, WRKY, bHLH and ZFP. The systemic response to Pi limitation showed the critical role played by inositol pyrophosphate (PP-InsPs) as signaling molecule and SPX (SYG1/PHO81/XPR1) domain proteins as sensor of cellular Pi status. Binding of SPX to PP-InsPs regulates the transcriptional activity of the MYB-CC proteins, phosphate starvation response factors (PHR/PHL) as the central regulator of Pi-deficiency response in plants. Vacuolar phosphate transporter, VPT may sense the cellular Pi status by its SPX domain, and vacuolar sequestration is activated under Pi replete condition and the stored Pi is an important resource to be mobilized under Pi deficiency. Proteomic approaches led to new discoveries of proteins associated with Pi-deficient response pathways and post-translational events that may influence plants in achieving Pi homeostasis. This review provides current understanding on the molecular mechanisms at the transcriptional and translational levels for achieving Pi homeostasis in plants highlighting the importance of DNA-protein and protein-protein interactions. The potential strategies for employing the CRISPR technology to modify the gene sequences of key regulatory and response proteins for attaining plant Pi homeostasis are discussed.

Patients undergoing dialysis through a permanent catheter often experience infection or malfunction. However, few studies have clarified the predictors of permanent catheter patency survival in patients undergoing hemodialysis. We assessed the relationship between parameters of body composition monitoring (BCM) determined before the initiation of dialysis and the patency survival of the permanent catheters inserted in 179 patients who commenced hemodialysis between January 14, 2020 and August 31, 2021. The relationships between permanent catheter patency at 6 weeks and BCM parameters, laboratory tests, age, sex, comorbidities, and medications at baseline were studied using Kaplan–Meier survival curves. Permanent catheter patency was observed to be superior at high extracellular-to-intracellular (ECW/ICW) ratio (P<0.005). After adjustment for covariates, the ECW/ICW ratio remained an independent factor associated with permanent catheter patency survival. When patients with non-patent catheters were subdivided into infection and malfunction groups, and the associations of BCM parameters were evaluated in those groups, the ECW/ICW ratio was not significantly associated with permanent catheter patency survival in the infection group (P = 0.327); instead, a significant association was found for the lean tissue index (P<0.001). In the malfunction group, the ECW/ICW ratio remained significantly associated with permanent catheter patency survival (P < 0.001).

Measuring the non-pathogenic Torque Teno Virus (TTV) load allows assessing the net immunosuppressive state after kidney transplantation (KTx). Currently, it is not known how exposure to maintenance immunosuppression affects TTV load. We hypothesized that TTV load is associated with the exposure to mycophenolic acid (MPA) and tacrolimus. We performed a prospective study including 54 consecutive KTx. Blood TTV load was measured by an in-house PCR at months 1 and 3. Together with doses and trough blood levels of tacrolimus and MPA, we calculate the coefficient of variability (CV), time in therapeutic range (TTR) and concentration/dose ratio (C/D) of tacrolimus, and the MPA-area under the curve (AUC-MPA) at the third month. TTV load at the first and third month discriminated those patients at risk of developing opportunistic infections between months 1 and 3 (AUC-ROC 0.723, 95%CI 0.559-0.905, p = 0.023) and between months 3 to 6 (AUC-ROC 0.778, 95%CI 0.599-0.957, p = 0.028), respectively, but not those at risk of acute rejection. TTV load did not relate to mean tacrolimus blood level, CV, TTR, C/D and AUC-MPA. To conclude, although TTV is a useful marker of net immunosuppressive status after KTx, it is not related to exposure to maintenance immunosuppression.

Patients under immunosuppressive therapy for kidney diseases or on maintenance hemodialysis are more susceptible to infection than the general population since loss of renal function per se was an immunocompromised condition. Of relevance, CT imaging plays a crucial role in the detection and management of pulmonary infectious diseases. We hence presented diverse CT findings of pulmonary infections in the above said patients collected during our arduous work against a wide range of pathogens including klebsiella pneumoniae, staphylococcus aureus, candida parapsilosis, aspergillus, cryptococcus, mucor, pneumocystis carinii, cytomegalovirus, mycobacterium and nocardia. Notably, the pulmonary pathological changes were either primary pneumonia or secondary to the catheter-associated bloodstream infection. For a descriptive purpose, pulmonary manifestations of Wegener’s granuloma, lung cancer and diffuse alveolar hemorrhage/infection in vasculitis were also examined. As such, we retrospectively elaborated most likely CT features of each individual pathogen and briefly covered the differential diagnosis as well. Arguably, combination of pattern recognition with knowledge of the clinical setting could make a presumptive diagnosis and early treatment even more convenient. From the experience of first-line nephrologists, our work could make a substantial contribution to the expeditious and efficacious management of pulmonary infections in the pertinent patient population.

Knowledge-based approaches are useful alternatives to predict the Failure Probability (FP) coping with the insufficient data, process integrity, and complexity issue in manufacturing systems. This study proposes a Fault Tree Analysis (FTA) approach as proactive knowledge-based technique to estimate the FP based maintenance planning with subjective information from domain experts. However, the classical-FTA still suffers from uncertainty and static structure limitations which poses a substantial dilemma in predicting FP. To deal with the uncertainty issues, a Fuzzy-FTA (FFTA) model was developed by statistical analysing the effective attributes such as experts' trait impacts, scales variation and, assorted membership and defuzzification functions. Besides, a Bayesian Network (BN) theory was conducted to overcome the static limitation of classical-FTA. The results of FFTA model revealed that the changes in decision attributes were not statistically significant on FP variation while BN model considering conditional rules to reflect the dynamic relationship between events had more impact on predicting FP. After all, the integrated FFTA-BN model was used in the optimization model to find the optimal maintenance intervals according to estimated FP and the total expected cost. As a practical example, the proposed model was implemented in a semi-automatic filling system in an automotive production line. The outcomes could be useful for upgrading the availability and safety of complex equipment in manufacturing systems.

This paper investigates optimal maintenance strategies for centrifugal compressors with electrical motor drivers using a Weibull analysis approach combined with rank regression, Fisher matrix, and median ranks. By leveraging data from Oreda 6, the study proposes a methodology to establish baseline intervals for corrective, preventive, predictive, and proactive maintenance in the absence of comprehensive historical data. The analysis reveals key Weibull parameters, including shape and scale factors, and calculates reliability metrics such as the mean time to failure (MTTF) and mean remaining life (MRL). The results suggest effective maintenance intervals and highlight the utility of Weibull analysis in enhancing maintenance strategies. This approach offers a robust framework for optimizing maintenance practices, even with limited historical data.

Background: Tacrolimus (TAC) effectively induces remission in refractory ulcerative colitis (UC). However, TAC therapy usually lasts for 3 months. Although azathioprine (AZA) is often used in maintenance therapy, the relapse rate remains high. Herein, we evaluated the efficacy of adalimumab (ADA) for remission maintenance in patients with UC after induction therapy with TAC. Methods: We prospectively enrolled patients with moderate-to-severe UC who achieved clinical remission after 3 months of TAC therapy with endoscopic non-mucosal healing (Cohort A). After TAC discontinuation, the remission maintenance rate for up to 1 year after starting ADA therapy was examined. We retrospectively enrolled patients with UC treated with TAC (Cohort B). Among patients in clinical remission after TAC treatment for 3 months, those who received AZA as remission maintenance therapy after TAC discontinuation constituted the AZA group. Patients in Cohort A who received ADA and AZA as remission maintenance therapy after TAC discontinuation constituted the ADA group. We compared the remission maintenance rates in AZA and ADA groups for up to 5 years after TAC discontinuation. Results: In Cohort A, of the 46 patients with UC treated with TAC, 17 were eligible for analysis after receiving ADA as remission maintenance therapy. A notable 88.2% (15/17) were still in remission 1 year after starting ADA. The ADA group (n=16) exhibited a significantly higher relapse-free rate than the AZA group (n=26) (p<0.05; log-rank test). Conclusion: Switching to ADA for remission maintenance in patients with refractory UC who achieved clinical remission with TAC is clinically useful.

Small RNAs (sRNA) are epigenetic regulators of essential biological processes that have been linked to the onset and progression of leukemia, including acute adult T-cell leukemia-lymphoma (ATLL) caused by the retrovirus Human T-lymphotropic virus type 1. Here, we describe the sRNA profile of a 30-year-old female with ATLL at diagnosis and after maintenance therapy, with the goal of correlating their expression levels with response to therapy.

The purpose of this Individually Randomized Group Treatment Trial was to compare an Acceptance and Commitment Therapy-based (ACT) group intervention and a Cog-nitive Behavioral Therapy-based (CBT) group intervention for weight loss maintenance in a sample of adult patients with obesity seeking treatment for weight loss. 155 over-weight adults (BMI: Kg/m2= 43.8[6.8]) attending a multidisciplinary rehabilitation program for weight loss were randomized into two conditions: ACT and CBT. Demo-graphical, physical, and clinical data were assessed at the beginning of the program (t0), at discharge (t1), and at 6-month follow-up (t2). The following measures were ad-ministered: The Acceptance and Action Questionnaire-II (AAQ-II) and the Clinical Outcome in Routine Evaluation-Outcome Measure (CORE-OM). Generalized linear mixed models were performed to assess differences between groups. Moderation ef-fects for gender and eating disorders (ED) have been considered. From baseline to dis-charge no significant differences between interventions were found, with the only ex-ception of an improvement in the CORE-OM total score and in the CORE-OM subjective well-being subscale for those in the CBT condition. From discharge to follow-up ACT group participants showed significant results in terms of weight loss maintenance, CORE-OM total score, and CORE-OM and AAQ-II’s wellbeing, symptoms, and psy-chological problems subscales. Gender moderated the effects of time and intervention on the CORE-OM’ subscale reporting the risk for self-harm or harm others. The pres-ence of an eating disorder moderated the effect of time and intervention on the CORE-OM total score, on the CORE-Om’ symptoms and psychological problems sub-scales, and on the AAQ-II. Patients who received the ACT intervention were more likely to achieve a ≥5% weight loss from baseline to follow-up and to maintain the weight loss after discharge. The ACT intervention was thus effective in maintaining weight loss over time.

The aim of this study has been to develop a novel two-level multi-objective genetic algorithm (GA) to optimize time series forecasting data for fans used in road tunnels by the Swedish Transport Administration (Trafikverket). Level 1 is for the process of forecasting time series cost data, while level 2 evaluates the forecasting. Level 1 implements either a multi-objective GA based on the ARIMA model or a multi-objective GA based on the dynamic regression model. Level 2 utilises a multi-objective GA based on different forecasting error rates to identify a proper forecasting. Our method is compared with using the ARIMA model only. The results show the drawbacks of time series forecasting using only the ARIMA model. In addition, the results of the two-level model show the drawbacks of forecasting using a multi-objective GA based on the dynamic regression model. A multi-objective GA based on the ARIMA model produces better forecasting results. In level 2, five forecasting accuracy functions help in selecting the best forecasting. Selecting a proper methodology for forecasting is based on the averages of the forecasted data, the historical data, the actual data and the polynomial trends. The forecasted data can be used for life cycle cost (LCC) analysis.

Social media HPV vaccination interventions show promise for increasing HPV vaccination rates. An important consideration for the implementation of effective interventions into real-world practice in the translation potential, or external validity, of the intervention. To this end, we conducted a systematic literature review to describe the current body of evidence regarding the external validity of social media HPV vaccination-related interventions. Constructs related to external validity were based on the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework. Seventeen articles published between 2006 and 2020 met inclusion criteria. Three researchers independently coded each article using a validated RE-AIM (reach, effectiveness/efficacy, adoption, implementation, maintenance) framework. Discrepant codes were discussed with a fourth reviewer to gain consensus. Of these 17 studies, three were pilot efficacy studies, 10 were RCTs to evaluate effectiveness, one was a population-based study, and three did not explicitly state which type of study was conducted. Reflecting this distribution of study types, across all studies the mean level of reporting RE-AIM dimensions varied with reach recording 90.8%, effectiveness (72.1%), adoption (40.3%), implementation (45.6%), and maintenance (26.5%). This review suggests that while the current HPV vaccination social media-driven interventions provide sufficient information on internal validity (reach and effectiveness), few have aimed to gather data on external validity needed to translate the interventions into real world implementation. Our data suggest that implementation research is needed to move HPV vaccination-related interventions into practice. Included in this review are recommendations for enhancing the design and reporting of these HPV vaccination social media-related interventions.

Background: This retrospective study evaluates the survival effects of metronomic maintenance therapy with fluoropyrimidine in patients with stage III colorectal cancer (CRC) according to epidermal growth factor receptor (EGFR) expression. Methods: We enrolled 197 patients with stage III CRC who had undergone radical resection and FOLFOX regimen adjuvant chemotherapy. The clinicopathological features and effects of metronomic maintenance therapy on survival according to treatment group and EGFR expression were analyzed. By conducting an in vitro cell line study and in vivo study through knockdout of EGFR gene, we analyzed the capacities of cell proliferation and migration. Results: Postoperative relapse and mortality were significantly more common in the FOLFOX group. Metronomic maintenance therapy was a significantly independent predictive factor of postoperative relapse and mortality, as well as a prognostic factor of disease-free survival and overall survival. The significant differences of survival between the two groups were only observed in patients with positive EGFR expression. Conclusions: The present study suggested EGFR expression as the prognostic factor in patients with stage III CRC receiving metronomic maintenance therapy. By analyzing EGFR expression, we can identify the potential candidates with optimal survival benefit from metronomic maintenance therapy in patients with stage III CRC.

The noradrenergic theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the upregulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the Brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test the above-mentioned theory, a study was conducted on a sample of 686 participants (395 controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC volume, attentional performance and a biological index of brain maintenance (BrainPAD – an objective measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on Reserve indices including education and occupational attainment. Volumetric variation across groups was also explored along with gender differences. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic (NA) hypothesis. The antithetic relationships were also tested across the neuromodulatory subcortical systems.Results supported by bayesian modelling showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance across the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on the noradrenergic system (e.g. cognitive-attentive training, physical exercise, pharmacological and dietary interventions) may yield important clinical benefits to mitigate cognitive impairment with age and disease.

Background & aims It is documented that low protein and amino-acid dietary intake is related to poorer cognitive health and increased risk of dementia. Degradation of the neuromodulatory pathways, (comprising the cholinergic, dopaminergic, serotoninergic and noradrenergic systems) is observed in neurodegenerative diseases and impairs the proper biosynthesis of key neuromodulators from micro-nutrients and amino acids. How these micro-nutrients are linked to neuromodulatory pathways in healthy adults is less studied. The Locus Coeruleus–Noradrenergic System (LC-NA) is the earliest subcortical structure affected in Alzheimer’s disease, showing marked neurodegeneration, but is also sensitive for age-related changes. The LC-NA system is critical for supporting attention and cognitive control, functions that are enhanced both by tyrosine administration and chronic tyrosine intake. The purpose of this study was to 1) investigate whether the dietary intake of tyrosine, the key precursor for noradrenaline (NA), is related to LC integrity 2) whether LC integrity mediates the reported association between tyrosine intake and higher cognitive performance (measured with Trail Making Test – TMT), and 3) whether LC integrity relates to an objective measure of brain maintenance (BrainPAD). Methods The analyses included 398 3T MRIs of healthy participants from the Berlin Aging Study II to investigate the relationship between LC integrity and habitual dietary tyrosine intake-daily average (HD-Tyr-IDA). As a control procedure, the same analyses were repeated on other main seeds of the neuromdulatory subcortical system (Dorsal and Medial Raphe, Ventral Tegmental Area and Nucleus Basalis of Meynert). In the same way, the relationships between the five nuclei and BrainPAD were tested. Results Results show that HD-Tyr-IDA is positively associated with LC integrity. Similarly, LC integrity disproportionally relates to better brain maintenance (BrainPAD). Mediation analyses reveal that only LC, relative to the other nuclei tested, mediates the relationship between HD-Tyr-IDA I and performance in the TMT and between HD-Tyr-IDA and BrainPAD. Conclusions These findings provide the first evidence linking tyrosine intake with LC-NA system integrity and its correlation with neuropsychological performance. This study strengthens the role of diet for maintaining brain and cognitive health and supports the noradrenergic theory of cognitive reserve. Within this framework, adequate tyrosine intake might increase the resilience of LC-NA system functioning, by preventing degeneration and supporting noradrenergic metabolism required for LC function and neuropsychological performance.

A correlation of basic science and clinical symptoms in the human to propose a new theory for how the vestibular system works Neil S. Longridge Professor Emeritus, Division of Otolaryngology Department of Surgery, Faculty of Medicine, University of British Columbia Vancouver, BC CANADA *Arthur I. Mallinson, Clinical Associate Professor, Division of Otolaryngology Department of Surgery, Faculty of Medicine, University of British Columbia Vancouver, BC CANADA NS Longridge † *AI Mallinson † These authors contributed equally to this work. ABSTRACT; Bipedalism is unique among mammals. Until modern times, a fall and resulting leg fracture could be fatal. Balance maintenance after a destabilizing event requires instantaneous decision-making. The vestibular system plays an essential role in this process, initiating an emergency response. The afferent otolithic neural response is the first directionally oriented information to reach the cortex, and can then be used to initiate an appropriate protective response. Some vestibular efferent axons feed directly into the type I vestibular hair cells. This allows for rapid vestibular feedback via the striated organelle (STO), which has been largely ignored in most texts. We propose that this structure is essential in emergency fall prevention, and also that the system of sensory detection and resultant motor response works by having efferent movement information transmitted to the maculae simultaneously with the movement commands. This results in the otolithic membrane positioning itself precisely for the planned movement, and any error is due to an unexpected external cause. Error is fed back via the vestibular afferent system. The efferent system through the STO causes macular otolithic membrane movement which occurs simultaneously with the initiating motor command. As a result, no vestibular afferent activity occurs unless an error must be dealt with.

Purpose: To assess the utility of measurement of the computed tomography (CT) attenuation value (CTav) in predicting tumor necrosis in hepatocellular carcinoma (HCC) patients who achieve a complete response (CR), defined using modified Response Evaluation Criteria in Solid Tumors (mRECIST), after lenvatinib treatment. Method: We compared CTav in arterial phase CT images with postoperative histopathology in four patients who underwent HCC resection after lenvatinib treatment, to determine CTav thresholds indicative of histological necrosis (N-CTav). Next, we confirmed the accuracy of the determined N-CTav in 15 cases with histopathologically proven necrosis in surgical specimens. Furthermore, the percentage of the tumor with N-CTav, i.e. the N-CTav occupancy rate, assessed using Image J software in 30 tumors in 12 patients with CR out of 571 HCC patients treated with lenvatinib, and its correlation with local recurrence following CR were examined. Results: Receiver operating characteristic (ROC) curve analysis revealed an optimal cut-off value of CTav of 30.2 HU, with 90.0% specificity and 65.0% sensitivity in discriminating between pathologically identified necrosis and degeneration, with a CTav of less than 30.2 HU indicating necrosis after lenvatinib treatment (N30-CTav). Furthermore, the optimal cut-off value of 30.6% for the N30-CTav occupancy rate by ROC analysis was a significant indicator of local recurrence following CR with 76.9% specificity and sensitivity (area under the ROC curve; 0.939), with the CR group with high N30-CTav occupancy (&gt;30.6%) after lenvatinib treatment showing significantly lower local recurrence (8.3% at 1 year) compared with the low (&lt;30.6%) N30-CTav group (P&lt;0.001, 61.5% at 1 year). Conclusion: The cut-off value of 30.2 HU for CTav (N30-CTav) might be appropriate for identifying post-lenvatinib necrosis in HCC, and an N30-CTav occupancy rate of &gt;30.6% might be a　predictor of maintenance of CR. Use of these indicators have the potential to impact systemic chemotherapy for HCC.

Background: This retrospective study evaluate the survival effects of metronomic maintenance therapy with fluoropyrimidine in patients with stage III colorectal cancer (CRC) according to epidermal growth factor receptor (EGFR) expression. Methods: We enrolled 197 patients with stage III CRC who had undergone radical resection and FOLFOX regimen adjuvant chemotherapy. The clinicopathological features and effects of metronomic maintenance therapy on survival according to treatment group and EGFR expression were analyzed. By conducting an in vitro cell line study and in vivo study through knockdout of EGFR gene, we analyzed the capacities of cell proliferation and migration. Results: Postoperative relapse and mortality were significantly more common in the FOLFOX group. Metronomic maintenance therapy was a significantly independent predictive factor of postoperative relapse and mortality, as well as a prognostic factor of disease-free survival and overall survival. We also demonstrated that EGFR-knockout Caco2 cells are more sensitive to the inhibition effect of fluoropyrimidine than the control those. Conclusions: The present study suggested EGFR expression as the prognostic factor in patients with stage III CRC receiving metronomic maintenance therapy. By analyzing EGFR expression and treatment strategies, we can identify the potential candidates with optimal survival benefit from metronomic maintenance therapy in patients with stage III CRC.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.