Thyroglobulin (Tg) is the major glycoprotein produced by the thyroid gland, where it serves as a template for thyroid hormone synthesis and as an intraglandular store of iodine. Measurement of Tg levels in serum is of great practical importance in the follow-up of differentiated thyroid carcinoma (DTC), a setting in which elevated levels after total thyroidectomy are indicative of residual or recurrent disease. The most recent methods for serum Tg measurement are monoclonal antibody-based and are highly sensitive. However, major challenges remain regarding the interpretation of the results obtained with these immunometric methods, particularly in patients with endogenous antithyroglobulin antibodies or in the presence of heterophile antibodies, which may produce falsely low or high Tg values, respectively. The increased prevalence of antithyroglobulin antibodies in patients with DTC, as compared with the general population, raises the very pertinent possibility that tumor Tg may be more immunogenic. This inference makes sense, as the tumor microenvironment  is characterized by several changes that could induce posttranslational modification of many proteins, including Tg. Attempts to understand the structure of Tg have been made for several decades, but findings have generally been incomplete due to technical hindrances to analysis of such a large protein (660 kDa). This review article will explore the complex structure of Tg and the potential role of its marked heterogeneity in our understanding of normal thyroid biology and neoplastic processes. Thyroglobulin (Tg) is a high molecular mass protein produced exclusively by the thyroid follicular cells. Measurement of Tg levels in serum is of great clinical importance in medical practice, as part of the diagnostic workup for several benign conditions, but especially in the postoperative follow-up of differentiated thyroid cancer (DTC).Under normal conditions, only a very small amount of Tg bypasses intrathyroidal proteolysis and reaches the bloodstream in essentially intact form. Therefore, only with the advent of radioimmunoassay techniques in the late 1960s did measurement of the minute concentrations of Tg occurring in human serum become possible . This meAlthough modern assays based on monoclonal anti-Tg antibodies (TgAb) have enabled the development of highly sensitive and specific measurement techniques, some pitfalls persist in clinical practice. One of these drawbacks would be the variability between assays using different monoclonal antibodies, which may cause Tg levels to have an up to two-fold difference when the same sample is analyzed by different assays, even in the absence of endogenous TgAb . In addiAttempts to elucidate the structure of Tg date back to the 1950s. Since then, evidence has arisen that serum Tg is composed of a pool of polypeptide fragments which are highly heterogeneous in terms of size, but also exhibit differences in iodine content and in the distribution of glycosylation, and sulfation ,12. HoweTg is synthesized in the endoplasmic reticulum of the follicular cells, modified in the Golgi complex and secreted into the follicular lumen. The gene that codes for Tg has been mapped to chromosome 8. It is fairly conserved across mammal species, with some sequence homology between human Tg and that of other animals . Tg is kTg messenger RNA codes for a polypeptide chain consisting of 2,768 amino acid residues that will compose the backbone of a high molecular weight glycoprotein made up of two 330-kDa polypeptide chains. Mature Tg (660 kDa) is formed by linking two disulfide-bonds polypeptide chains ,16.Tg is divided into two regions: N-terminal and C-terminal . These rThe first 19 residues of the N-terminal end constitute the signal peptide, which directs the pre-polypeptide during posttranslational processing and secretion into the Golgi complex  Figure .Analysis of the polypeptide chain at the N-terminal end (1-2170) reveals an organized structure .There are three domain types in which the positions of cysteine residues are highly conserved. By forming disulfide bonds between monomers, these residues increase molecular stability and resistance to proteolysis . These dConversely, the C-terminal region (approximately 581 residues) does not exhibit internal homology, but it is similar to a protein in the acetylcholinesterase family  . FurtherTg accounts for over 75% of all thyroid proteins, and it is present in the colloid and in much of the intracellular material of the gland .The physiologic functions of Tg include providing a matrix for thyroid hormone synthesis and storing iodine in the form of the iodinated tyrosyl residues monoiodotyrosine (MIT) and diiodotyrosine (DIT), which are the precursors of the thyroid hormones T3 (triiodothyronine) and T4 (thyroxine). In addition, Tg also plays a role in modulating the expression of genes involved in the synthesis of other thyroid proteins (sodium-iodide symporter [NIS] and thyroid peroxidase [TPO]) and transcription factors involved in normal thyroid physiology  ,20.In addition to these physiologic roles, Tg is involved in the pathogenesis of several thyroid diseases, particularly autoimmune thyroiditis (in which it acts as an antigen) and DTC; in patients with DTC, Tg is used as a marker of residual disease or tumor recurrence after total thyroidectomy ,6.As noted above, Tg is the matrix for thyroid hormone synthesis. This process begins with formation of the polypeptide chain within the endoplasmic reticulum and continues with posttranslational modifications, which occur simultaneously: glycosylation and sulfation (primarily in the Golgi complex), iodination , and phosphorylation  ,22. The Tg undergoes extensive posttranslational modifications, including glycosylation, iodination, and phosphorylation. These modifications influence several aspects of normal Tg and thyroid hormone biosynthesis and play roles in various pathologic processes.Approximately 10% of the molecular mass of Tg is composed of carbohydrate residues . The glyThe major basic types of N-linked sugars are type A, or simple, which contain mannose and N-acetylglucosamine residues; and type B, or complex, which contain galactose, fucose, and sialic acid residues in addition to those of type A sugars. Other types include type C, which contain O-linked sugars, the residues of which are still largely unknown; and type D, which contain chains of the proteoglycan chondroitin sulfate. Type A and B sugars bind to Tg via asparagine residues, whereas type C and D sugars bind to serine residues .Oligosaccharides play roles in several thyroid functions. Notable roles include: influence on iodination and hormone synthesis; specific interactions with microsomes and membrane receptors; directing Tg to subcellular and extracellular compartments ; Tg immuRegarding the immunoreactivity of Tg, Fenouillet and cols. compared the Tg secreted by cells in culture to that extracted from thyroid tissues and found that the former exhibited fourfold less binding to polyclonal antibodies against native Tg. This difference was attributed to the greater amount of complex branched carbohydrates on secreted Tg as compared with thyroid-derived Tg. These carbohydrate chains appear to interfere with antigen-antibody recognition by masking regions of the polypeptide chain that constitute the main antigenic determinants . AnotherDespite advances, much remains to be explored regarding Tg glycosylation.Sulfation is a late posttranslational modification that takes place in the Golgi complex . SulfateThe role of these sulfated residues varies. They are involved in molecular conformation and protein interactions, take part in activation and deactivation of biological activities, and account for much of the negative charge of the Tg molecule ,30. HoweA role of sulfate in tumor dissemination and growth mechanisms has been speculated. Loss of sulfate has been documented in some tumor models, including pancreatic cancer . FurtherIn vitro studies conducted on FRTL-5 cells and using dog thyroid-derived Tg have suggested a potential role of this posttranslational modification in the Tg iodination process and in TSH-independent protein synthesis  or endogenous TgAb. The latter are much more prevalent in patients with DTC (25-30%) than in the healthy population (10%) . As mentThe presence of these endogenous anti-Tg antibodies in the follow up of DTC is an additional clinical challenge and may cause some degree of uncertainty either to the physician, regarding the status of the disease, or to the patient, causing anxiety, besides the increase in treatment costs due to the higher number of laboratory and imaging tests. Previous studies have shown that higher titers of anti-Tg antibodies are associated with higher risk of recurrence and have found that the higher the levels of these antibodies, the higher the chances of tumor recurrence -52. AlthAnother issue encountered in clinical practice is the wide variability in results when different methods are used for Tg measurement . As thesSeveral methods have been proposed in an attempt to bypass this issue, such as measurement of Tg mRNA in peripheral blood , use of One of the most promising attempts to escape the interference of TgAb on the Tg dosage is LC-MS/MS. In this technique, the entire serum protein is degraded with trypsin and the levels of Tg-specific peptides are used as a reference to quantify Tg . AlthougThus, the question remains whether polymorphisms in the Tg gene modifying the primary polypeptide sequence of the protein may affect the generation of target peptides to be identified by LC-MS/MS. In practice, this could really be a problem in view of recent studies that found two phenomena that may change the primary polypeptide sequence of Tg: different single-nucleotide polymorphisms in the Tg gene leading to an amino acid exchange  and somaIn addition, any posttranslational modifications may also cause loss of peptides of interest, preventing their identification by LC-MS/MS and resulting in falsely low or even negative values in the presence of disease. It is important to notice that in order for the generation of appropriate peptides to be impaired, it is sufficient that any posttranslational modification produces a trypitc fragment with a different charge/mass ratio, thus preventing its recognition by LC-MS/MS analysis . An examBesides, even if a hypothetic patient with metastatic thyroid tumor produces a Tg with this exact peptide sequence but with no glycosylation at Arginine position, this peptide will not be detected by LC-MS/MS. In fact, a recent study by Spencer and cols. showed the limitations of Tg identification by LC-MS/MS; this strategy, for example, fails to detect serum Tg levels in nearly one fourth of patients with positive TgAb and persistent/recurrent disease . In thatDespite the aforementioned issues, Tg measurement remains the cornerstone of follow-up of patients with DTC. Therefore, new techniques that can enhance its detection are essential. Modern methods, particularly those involving proteomics and mass spectrometry analysis , may hol


For urgent need to the transition to sustainable development, it is of great significance to explore the driving role of green credit policies in innovation performance. This study uses a sample of Chinese A-share listed companies from 2004 to 2019 and constructs a quasi-natural experiment based on the Green Credit Guidelines issued by the China Banking Regulatory Commission in 2012. PSM-DID method is employed to examine the innovation impact of green credit policies in both green credit-restricted and non-restricted industries, thereby exploring the its mechanism of influence on firm innovation performance. The results show that after the implementation of Guidelines, it promotes a company’s innovation output, significantly enhances its innovation performance, especially in terms of quantity-based incentives. However, the incentive effect on quality-based incentives is relatively limited. Secondly, by increasing the level of risk-taking within the enterprise and strengthening external environmental regulations, the green credit policy can further enhance its promotion effect on corporate innovation performance. Finally, the promotion effect of green credit policies is more significant for state-owned enterprises and large-scale enterprises. The research results help to break through the bottleneck of corporate innovation with the coordination of environmental protection and economy, which further improve the sustainability of economic development. With the deepening development of industrialization and urbanization, environmental pollution has been increasing . It is uIn oder to achieve the dual goals of stable growth and environmental optimization, China economy can transform towards green environmental protection by green finance to guide resources . By intrThis paper takes green credit as a representative of green finance to explore the impact and mechanism of green credit policies on corporate innovation performance. Taking the green credit policy as an exogenous shock variable, the PSM-DID model is used to investigate its different effects on innovation performance between green credit-restricted and non-restricted industries, and empirically analyze the motivation and restraint of Guidelines on corporate innovation performance. Secondly, this paper further explores the potential regulatory mechanisms, which is also the innovation point of this study. Many complex uncertainties, as the long cycle, large investment and uncertain conversion of innovation, may have important influences on innovation decision-making. Enterprises have dual roles as economic part and social part. As the external pressure, the government environmental regulation may stimulate or force companies to change the traditional production methods with high energy consumption and emission, thus achieving technological transformation and upgrading. From the risk-taking level of enterprise and environmental regulation, the paper studies the potential mechanisms that affect the actual effectiveness of green credit policies, in order to explore better ways to play the role of green finance in supporting corporate innovation performance.There are some potential marginal contributions of this study: 1) deepening the integration of green credit and innovation-driven development, the study explores the actual effects and problems of green credit policies on corporate innovation performance, and provides references for further improvement of relevant theories and system construction; 2) Most present studies have explored the role of financing constraints, but innovation uncertainty and other regulatory tools are lack of consideration. Matching government environmental regulation with the risk-taking and innovation capabilities of enterprise, the study finds out the innovation constraints faced by enterprises, and provides diversified paths for the green credit policies in coordinating environmental protection and economic goals.China has been formally implementing the green credit policy since 2007, and the issuance of Guidelines transformed it from a voluntary to a mandatory policy in 2012, establishing a series of standards for financial institutions and enterprises. Green credit differs from other types of policies as it introduces resources into the clean industry field to achieve environmental governance goals. In the process of green credit, financial institutions incorporate enterprise environmental performance into the credit assessment system, and use loan interest rates to control enterprise funding sources, thereby influencing innovative behaviors such as R&D investment. Moreover, companies with good environmental risk management often receive higher return quotas, which attract more investors to invest in enterprises with better environmental performance.The impact of green credit policy is mainly achieved through its incentive and constraint effects. Firstly, it incentivizes clean industries by incorporating enterprise environmental risk management into the credit assessment system, which controls the financing opportunities for enterprises . As a reHypothesis 1: The implementation of Green Credit Guidelines has a significant positive impact on innovation performance in green credit-restricted industries.Easing financing constraints, Guidelines provide some enterprises with opportunities to obtain more borrowing funds, and promotes their innovation investment. However, subjective foresight is the main factor guiding behavior in reality, but the future is full of uncertainties . TherefoHypothesis 2: The higher the risk-taking level is, the more significant the promotion of innovation is after the implementation of Green Credit Guidelines.2 emissions and the probability of extreme events [Environmental regulation is a crucial governmental tool for the environment protection, playing a significant role in reducing COe events . While se events  suggestse events . Since ee events . Converse events , 30. BasHypothesis 3: The stronger the environmental regulation is, the more significant the innovation effect will be after the implementation of Green Credit Guidelines.Due to China’s unique institutional background, there may be some differences between state-owned enterprises and non-state-owned enterprises in terms of resource acquisition, which may result in uneven innovation output. Therefore, this paper further analyzes the impact of green credit policies on innovation output from the perspective of enterprise property rights. State-owned enterprises are more likely to obtain the trust of financial institutions such as banks due to government support, as well as funding at lower thresholds and costs . HoweverHypothesis 4: The promotion effect on innovation performance will be more significant for state-owned enterprises after the implementation of Green Credit Guidelines.According to the Schumpeterian hypothesis, enterprise size are also factors that affect whether companies undergo technological change . BecauseHypothesis 5: The promotion effect on innovation performance will be more significant for large-scale enterprises after the implementation of Green Credit Guidelines.This paper examines all A-share listed companies from 2004 to 2019, using data sources such as the Guotai-An (CSMAR) database and China Environmental Statistics Yearbook. To ensure accuracy, the study excludes certain samples based on the following criteria: (1) exclude listed companies in the financial industry; (2) exclude ST, *ST and companies with missing important variables; (3) truncate continuous variables in the model at the 1% and 99% levels to exclude the influence of outliers. Data processing is completed with Stata16.0.Compared with static comparison or traditional difference methods, the difference-in-difference method (DID) compares the difference before and after the unimplemented group with the difference before and after the implemented group, which can effectively avoid endogeneity issues of policy as an explanatory variable. The paper takes panel data of A-share listed companies as the research sample and controls for unobservable individual and time heterogeneous factors that may affect innovation performance by leveraging the exogeneity of the explanatory variable.The DID method was used to investigate the effect of green credit on innovation, as shown in the following equation:it represents the innovation performance of the i-th listed company in the t-th year measured by the number of patent applications. To measure the quality and quantity of enterprise innovation, the paper uses the number of invention patent applications (Inva), utility model patent applications (Uma), and the total number of patents . To address the problem of right-skewed distribution of the dependent variable and eliminate the impact of extreme data, the paper adds 1 to the number of patent applications and takes the logarithm to obtain LnTotal, LnInva, and LnUma.The dependent variable PatentThe core explanatory variable is the green credit policy, industry attributes, and their interaction term. To satisfy the requirements of the double difference method, two dummy variables, Post and Treat, were set. Post is a time variable; it is set to 0 before the implementation of Green Credit Guidelines (t<2012) and set to 1 after its implementation (t≥2012). Treat indicates whether the i-th company belongs to the green credit-restricted industry. Industries identified as A-class risks in the Green Credit Guidelines are considered to be restricted by green credit policies. The experimental group (Treat = 1) consists of companies in these industries, while the control group (Treat = 0) consists of companies not in these industries.Risk-taking level of enterprises: the paper uses earnings volatility as the most commonly used measure of enterprise risk-taking. The higher the degree of earnings volatility, the higher the level of risk-taking, and vice versa. Drawing on existing research, Roa is adjusted by annual-industry mean to mitigate the effects of economic cycles and industry factors.Environmental regulation: Environmental protection investment (EPI) is a direct government investment in environmental management in various regions, which is the main means of governance in China. Thus, the paper uses EPI/GDP as the measurement indicator to avoid measurement errors caused by regional economic differences. The larger the investment of environmental protection is, the greater the environmental regulation in the region where the enterprise is located.i, t-1. to control for other individual characteristics that may affect innovation performance of companies. These variables include enterprise size (Size), Return on Assets (Roa), debt level (Lev), cash ratio (Cash), years since establishment (Age), proportion of independent directors (Ind), CEO duality , Institutional Ownership (Inst), number of employees (Employee), revenue growth rate (Growth), free cash flow (Fcf), separation of ownership and control (Sep), book-to-market ratio (MtB), number of board members (Board), and fixed asset ratio (Ppe) in Drawing on existing research, the paper includes a series of control variables XFigs The DID model is an effective method for evaluating the macroeconomic policies. Based on the PSM-DID model, This study employs the nearest neighbor matching method to estimate propensity scores with a Logit model, as shown in Based on the established DID model, the study obtains the regression results between the green credit policy and innovation output of enterprises. In Column (1), the coefficient of the interaction term Post×Treat is 0.191, which is significant at the 1% level. This indicates that the Guidelines significantly increase the total patent applications in green credit-restricted industries, highlighting the promotion effect on these industries’ innovation performance. The coefficient of Post is 0.364, which is also significant at the 1% level, suggesting that the Guidelines significantly improve the innovation performance of non-restricted industries. Meanwhile, in Column (3), the interaction term and post coefficient are both significantly positive, indicating that the Guidelines significantly increase the output of green credit-restricted industry innovation. In Columns (1) and (3), the post coefficient is greater than the interaction term Post×Treat, which indicates that for non-restricted industries, the impact of the Guidelines on enterprise innovation performance is more pronounced in this group.However, in Column (2), the coefficient of the interaction term Post×Treat is not significant, while the coefficient of Post is significant at the 1% level. This suggests that the policy effect of the Guidelines on innovation quality is heterogeneous across different industries. Specifically, the Guidelines have a significant positive impact on the innovation quality of non-restricted industries, but do not have a significant promotion effect on the green credit-restricted industries.Based on the analysis, the study can confirm Hypothesis 1. The implementation of the Guidelines results in a significant improvement in the innovation performance of both green credit-restricted and non-restricted industries. In particular, it has a strong positive impact on the innovation output of non-restricted industries. However, its effect is limited on the number of invention patents for green credit-restricted industries. Hence, the Guidelines plays a more significant role in promoting the quantity of innovation in these industries.As there are various matching methods for the DID model, including nearest neighbor matching and caliper matching, this paper reports regression results after changing the matching method of the control variables from nearest neighbor matching to caliper matching. The fixed effects of the overall sample for the experimental group and control group are reported in The main effect in the study shows that the Guidelines has a significant promoting effect on enterprise innovation. Based on this, this paper draws on Aiken’s interaction effects  to furthThe risk-taking level of enterprises is a crucial factor in determining their financing opportunities and project selection process. Enterprises with high risk-taking levels are more likely to attract investment and other resources due to their ability to withstand risks and compensate for losses. By increasing trust between shareholders and managers, decision-makers are more inclined to seek risk. Based on the risk-taking level of each company, this paper constructs an interaction term between the risk-taking level and green credit-restricted industries before and after the Guidelines.The research finds that as consumers’ pursuit gradually shifts towards green and healthy directions, the explicit cost-effectiveness declines significantly in direct environmental governance. Under environmental regulations, companies are more inclined to choose technological innovation as a way to respond actively, thereby promoting innovation output. Therefore, this paper further analyzes the regulatory mechanism of environmental regulations on the Guidelines and enterprise innovation performance. Specifically, it constructs an interaction term between environmental regulations and green credit-restricted industries before and after the Guidelines.This paper analyzes how heterogeneity in property rights might affect the effectiveness of green credit policies in China. State-owned enterprises are generally considered more credible in financing opportunities from banks and other financial institutions, which could result in different policy effects between state-owned and non-state-owned enterprises under this Guidelines. Therefore, this study divides the sample into state-owned and non-state-owned enterprises based on property rights and compares their innovation levels before and after the Guidelines. In this paper, the median of the sample size is used as the threshold to distinguish small-scale enterprises from large-scale ones. The study examines whether differences in enterprise size affect the effectiveness of the Guidelines. Regression results in The study enriches the relevant research on the effect of green credit policy on stimulating enterprise innovation, which finds that after the Guidelines, the overall innovation performance of enterprises has been improved, and it is more pronounced in non-restricted industries. However, this promotion effect is only manifested in the numbers of innovation output, and the effect on innovation quality is not significant. Furthermore, since innovation needs high input and long cycles, the ability to bear unknown risks is one of the factors that affect the enterprise innovation. Better risk-taking abilities can enhance the incentive effect of green credit policy on enterprise innovation output. From an external perspective, although the stronger in environmental regulatory leads to an increase in compliance cost expenditures for companies, the innovation compensation effect will bring about a rise in capital returns in the long run. Secondly, through heterogeneity analysis, the paper finds that differences in property rights and enterprise size also effect the innovation performances of differen enterprises by the Guidelines, among which state-owned and large-scale green credit-restricted enterprises are more sensitive to this policy, and the promotion is more significant.This study holds some the policy implications that green credit policy can better promote enterprise innovation performance, which is a win-win policy that advances the coordination of environment and economy, but its policy effect needs to be fully realized with a better matching institutional system. According to the mechanism analysis, better the risk-taking capacity and environmental regulations are both ways to further enhance the Guidelines effect on innovation performance. The green credit policy plays an important role in the realization of China’s 3060 dual carbon goals, and contributes to the development strategy of an innovative and environment friendly country. Therefore, the following recommendations are proposed:In order to seek upgrading measures to meet social needs, enterprises play the leading role in innovation with social responsibilities. Firstly, they should public the environmental Information actively for the business goal of environmental and economic benefits. Secondly, avoiding excessive reliance on indirect borrowing from banks, enterprises would seek for more financing channels as venture capital funds and government support with strong risk management to reduce the uncertainty of innovative projects. Moreover, they also need full use of funds invested in research actively for innovative transformation.The government focuses on the effectiveness of credit policies and improves a more sound green credit system. Firstly, based on regional differences in development and capabilities, differentiated green credit systems should be established, tailored to local conditions and enterprises. Thus, differential development routes are created to match financial supply. Secondly, the green credit market would be expanded to stimulate the enterprise innovation enthusiasm and connect banks with other green finance markets as carbon finance, thus providing more financial support for green innovative enterprises with an information sharing platform. Furthermore, the research shows that mandatory environmental regulations can further enhance the effect of credit policies on innovative transformation. Therefore, various environmental regulatory measures should be combined to an incentive guidance mechanism, which will provide more informations under a reasonable evaluation system and increase the cost of rent-seeking behaviors with mandatory measures.Based on comprehensive and accurate environmental and risk assessment, financial institutions should establish differentiated credit management systems through digital information platforms, forming a dynamic adjustment system of credit resources. This system could solve the information asymmetry and lift the constraint on restricted enterprises with different treatments, and aim to provide more suitable and effective financial support for enterprises.S1 Data(XLSX)Click here for additional data file.


The design of exterior lighting is crucial for automotive manufacturers to ensure the visibility and safety of the driver. This article proposes a new strategy to control and diagnose one or more exterior lighting functions in electric vehicles by maximising the electrical faults that are detected and their transfer over a single-wire. The outcome is a decreased system cost and an additional method for vehicle lighting infrastructure control and diagnosis. Virtual simulation tools are used to explore the correlation between master-slave architecture and the effectiveness of the single-wire approach to comply with safety and regulatory demands. Safety-related and non-safety-related needs are explored to properly assess lighting functions, internal logic, and fault-case scenarios. Furthermore, assessing the viability of minimizing wire harness utilization while retaining the diagnostic capabilities for the controlled lighting sources, thereby simultaneously reducing the vehicle’s overall weight. This approach aims to concurrently decrease the overall weight of the vehicle. This work has three main contributions: (1) the development of efficient and reliable lighting systems in electric vehicles, a critical factor for achieving optimal performance, ensuring customer satisfaction, meeting regulatory compliance, and enhancing cost-effectiveness in automotive lighting systems. (2) Framework for future development and implementation of lighting systems in electric vehicles. (3) Simulation of the hardware architecture associated with the system strategy to achieve the desired system strategy for effectively applying the single-wire approach. Light-emitting diode (LED) solutions have emerged as a key focus for meeting these objectives. LED lighting possesses attributes well-suited to long life, high reliability, excellent vibration and shock performance, optimised power consumption, and a compact package for the optical design. The rapid adoption of vehicle electrification, coupled with advancements in solid-state lighting sources, has established a solid foundation for the widespread implementation of LED-based exterior lighting. These solid-state light sources provide enhanced efficiency in terms of thermal management, optical performance, and overall reliability. The design and development of external lighting equipment types are continuously expanding, aiming to achieve greater flexibility across hardware, software, and optics to meet the demands of emerging functions like Adaptive Frontlight Systems (AFS) and comply with ECE regulations [The automotive industry’s scope for COulations ,2,3,4.As the primary light source exterior vehicle lighting equipment utilizes either solid-state lighting sources or traditional bulbs. The former category features the latest vehicle architectures, while the latter appears in older or more affordable vehicles. Solid-state lighting sources are silicon-based illumination sources, such as LEDs, LASERs, and OLEDs. The overall efficiency of solid-state lighting, regardless of the driver type, is influenced by the need for voltage and electrical current regulation. This regulation process impacts the overall efficiency of the system, which can range from around 50% for linear regulators to over 80% for DC/DC switching regulators. The utilization of DC/DC switching regulators presents the potential for significant efficiency gains, particularly in optimizing power efficiency for hybrid vehicles [LED lighting has managed to bridge the gap in optical performance with lens losses and comply with regulations as per the United Nations Economic Commission for Europe (UNECE-R 123) requirements. The AFS and Glare-Free High Beam (GFHB)  are contDetecting faults and failures in LED-based lighting components presents one of the most challenging aspects of system efficiency. The primary issue is the number of control and feedback loops over independent wire control, resulting in a complex deadlock. In fig  an IntelWhile it addresses a different automotive system, Ref.  examinesTo develop efficient and reliable lighting systems in electric vehicles, which is crucial for optimal performance, maintaining customer satisfaction, ensuring regulatory compliance, and ensuring cost-effectiveness in automotive lighting systems.To guide future development and implementation of lighting systems in electric vehicles.To propose a hardware architecture that can employ the one-wire fault detection method and validate it through simulation.This paper proposes a new strategy to control and diagnose one or more exterior lighting functions in electric vehicles with a single-wire instead of many. As the backbone of the electrical and electronic architecture, the power supply, control, and diagnostics are critical components in modern automotive lighting systems. Due to their improved quality, reliability, and efficiency, light-emitting diodes (LEDs) have become the default choice for automotive lighting systems. This study employs virtual simulation tools to investigate the relationship between master-slave architecture and how the single-wire approach satisfies safety and regulatory demands. Through the analysis of internal logic and fault case scenarios, the article presents safety-related and non-safety-related lighting functional approaches, demonstrating the benefits of the single line approach. This work has three main contributions:This paper is organised into four sections. Conventional incandescent lamps used in automotive headlights do not require the utilisation of specialised electronics. Headlights based on LED, HID (high-intensity discharge), or Xenon require dedicated drivers to charge the loads and achieve start-up. The dedicated drivers boost the input voltage level up to the LED string voltage, more than 12 V, and up to thousands of volts to generate the electrical arc for HID or xenon. Regarding efficiency, LED loads exhibit minimal radiation losses but experience significant heat losses, as presented in High beam (main beam);Low beam (dipped beam);Fog lamps;Turn indicators (direction indicator);Daytime running lights;Position lights;Side-markers;Auxiliary lamps, such as dedicated cornering lights or signature lighting.Front-lighting system topologies vary depending on desired architectural constraints and the composition of features. Basic lighting can be driven directly with wire control, as shown in Projection of navigation data ;Dynamic lane assist (highlight of vehicle width on narrow passages);The highlight of warnings, road signs, and vehicle state.Network-enabled headlights provide the capability of leveraging the use of high-resolution systems with symbol projection to achieve fully automatic control. Some of the functions are:Rear lamps are the most crucial lights from a safety perspective and are designed to provide the state and dynamic behaviour intended to be conveyed by the vehicle user. Safety-related functions for rear lighting are direction indicators, brake lights, reversing lights, and fog lighting. Similar to front-lighting, solid-state lighting sources are used to leverage the regulatory constraints and add on the OEM -specific light signature for branding enhancement, merged and controlled as well by ADAS features and passive safety needs such as brake light detection. They are linked with the complexity and overall vehicle needs, which need to be controlled either by wire, communication bus, or a mix to attain the required reaction time .By design, they can be divided into six or more individual components to achieve the desired styling and surface coverage; one function, for example, the turn indicators, is used on the same side, with one section on the fender and another on the trunk. From a styling perspective, these components add a visually appealing look to the overall design. From a regulation perspective, dividing a function adds constraints for architecture control . The arrFor certain lighting functions, diagnostics or fault detection systems are mandatory to ensure compliance with regional regulations  and safety compliance based on ISO2626262 . Based oFault detection is utilized to promptly notify the driver in real-time in the event of any light failures, triggering the system to enter a fail-safe state. Light failures refer to LED malfunctions, power supply losses, and common electrical issues like open loads, short circuits, and internal failures within driving components. The electronic control unit internally conveys and assesses these failures through diagnostic tests. For instance, in the case of LEDs, the electronic control unit compares the actual current consumption and voltage across the LED string with pre-defined, coded values established during the design phase. This meticulous evaluation ensures the precise detection of any anomalies or deviations from expected performance. This ensures regulations set the required visibility targets, and address safety requirements, and take proper measures. For the most critical functions, such as low beams, if the control between the transmitter body unit—vehicle controller unit—and the lighting unit is lost, the safe state of the lighting unit is the low beam activation, and they remain active until control is reestablished, ensuring continuous functionality ,18. WithWhen the same load is used for the same function, the control architecture for driving the lighting can be implemented either through buses or wired control systems. The first approach is usually the simplest to adopt, but it comes at a higher cost due to the need for a dedicated transceiver and software integration. In contrast, the wired solution is more optimised from a cost perspective and can be driven in an analogue manner . A crossThe vehicle control unit receives user requests, which are acquired through steering column switches or by environment sensors such as rain, light, or objects in complex architectures. It compares that request with the previous states of the same driving cycle. The lighting controller unit receives the request and based on the load status, proceeds to restart and turn on the lights. If a fault is detected, it stores the data trouble code (DTC) and provides the status to a higher level, and the user is notified with either a telltale or a message in the dashboard for the light status, active or in failure. According to regulations, not all lights require a dedicated telltale indicator. Hence, some data are displayed on the dashboard with a generic message to check the light(s).Electrical and electronic architecture control, for the same load utilisation manages two different functions, for example, daytime running lights (DRL) and front position lights (FPL) on the front side of the vehicle. Or brake light (or stop lamps) and rear position lamps (RPL) on the rear side , in someThe electrical and electronic architecture must incorporate driver ICs utilising field-effect transistors . These components detect typical output failures, including open loads and short circuits. The microcontroller drives the respective outputs based on pre-defined criteria or latches them for protection if needed. Based on With the increased amount of wires, the probability of false status increases, and the complexity of defending them according to the system failure management and evaluation analysis (S-FMEA), resolving this issue is deemed highly challenging and often presents significant difficulties. When the function 1 status is failing, resembling a short circuit to the battery, while the actual load is working properly, the vehicle controller unit will assume the failure is true, and the user will be notified. For improved control strategy and cost reduction scope, some OEMs migrated towards a PWM feedback line to inform the transmitter body unit about the status of both functions in a more contained manner and immune to failure, like in PWM-based codification provides a functional range for the function status, individually and with dedicated values: 0% duty cycle for the failure to the ground (SCC−), and 100% duty cycle for the short circuit to the battery failure (SCC+). The PWM coding can be customised to meet the specific requirements of the OEMs, particularly when multiple functions are combined on the same feedback line; the codification example is shown in An error margin or a locking feature should be integrated based on the PWM frequency usage, typically 100 Hz or 200 Hz.The error margin in Issues and efficiency requirements as innovation drivers are continuously emerging in the automotive industry. Wire-harness layout and functional management are critical aspects that address these evolving needs. Exploring innovative system design and management approaches is crucial for achieving this. One approach is to integrate control and failure management into a single line, which results in a streamlined architecture with several benefits. Combining these two critical components in a smoother package improves system efficiency and performance. This innovation-driven need highlights the importance of continuous improvements and adopting new and innovative ideas to enhance system design and performance. The proposed strategy was evaluated using Matlab-Simulink (version R2021a), using a constant current controller in the receiver body unit to regulate the stability and flux of the LEDs. An open load serial failure with the LEDs is generated to reflect the most common failure type. The overall schematic is shown in In addition to the current controller, the receiver body unit contains a linear regulator control manager (LRCM), The evaluation of the proposed concept is aimed at demonstrating the compatibility and possibility of coexisting shared functionality over the same wire for input function control (FC) and output failure status (FS). In The transmitter body unit and receiver body unit input and output stages were designed to reflect the indent concept scope and functionality. In contrast, a comprehensive model approach would contain a push-pull topology for the control line to segregate the possible overlap in Cost-effectiveness is associated with the reduction of the harness and the number of pins on both the transceiver and receiver electronic control units. In The solution adoption on a vehicle platform is based on an expected amount of vehicles sold of one million; hence, the cost reduction between the architecture with dedicated PWM  and the The proposed innovative work in this paper, with the scope of reducing costs and enhancing efficiency in automotive systems, has the potential to offer significant benefits for vehicle manufacturers and suppliers of the equipment. Although the cost savings will vary for each manufacturer due to their unique architecture and strategies, reducing pins, wire harnesses, and vehicle weight will substantially impact the industry. This state-of-the-art work can be particularly effective for OEMs that sell a large volume of vehicles. Although additional electronics may be required for adoption, the standardisation of the block control over time will help balance investment amortisation over time. The resulting reduction in the bill-of-materials, associated costs, and improvements in efficiency provide significant benefits for suppliers and manufacturers alike, making this an innovation-driven approach worth considering for future automotive systems.The holistic model, the single-wire approach from this article, has the control and diagnostic capability shared and provides valuable insight for enhancing the overall safety and efficiency of the automotive systems. With no functional degradation, safety failure or regulation compliance failure, it portrays advantages for moving towards a more efficient approach. The lighting system design and control are studied and simulated to conclude the findings by contrasting the behaviour of control and diagnostic capability between the current models used and the hybrid proposal. The system approach for sharing the responsibility between the receiver and transmitter body units provides a sensing failure-free environment where one unit takes the overall responsibility when the other is in degraded mode.Simulations carried out revealed the overall system structure and behaviour to attain the expected functionality desired for the intended scope of supervising the lighting sources and coding with the duty cycle in a push-pull communication, the sensed state. Based on the findings, we have concluded that no degradation is encountered by reducing the number of wires and sharing the responsibility at the system level.In the future, we may consider extending the incipient fault detection technique presented by Deep Principal Component Analysis (DPCA) using the framework presented in .


Continuous fiber-reinforced thermoplastic composites (CFRTPCs) have advantages such as high specific strength, high specific modulus, corrosion resistance, and recyclability and are widely used in the fields of aerospace, rail transit, new energy, and so on. However, traditional methods for preparing CFRTPCs, such as placement and molding, rely more on forming molds, resulting in high manufacturing costs and a slow response speed, which limits the promotion and application of the new generation of CFRTPCs with complex configurations and designable performance. Three-dimensional printing can efficiently create products with multiple materials, complex structures, and integrated functions, introducing new ways and opportunities for the manufacturing of CFRTPCs. However, poor mechanical properties are the bottleneck problem in achieving 3D printing of CFRTPCs. This paper summarizes the research status of the fused deposition modeling (FDM) 3D printing process and the corresponding mechanical properties of CFRTPCs. The focus is on analyzing the influences of the FDM process parameters, such as the material type, printing temperature, speed parameters, layer thickness, scanning space, stacking direction, and fiber volume content, on the mechanical properties of CFRTPCs. Finally, the main problems and future prospects of current CFRTPCs-FDM are analyzed and forecasted, providing new references and ideas for 3D printing of high-performance CFRTPCs. Continuous Fiber-Reinforced Thermoplastic Composites (CFRTPCs), composed of reinforcing fiber and matrix resin through certain forming processes, have advantages such as high specific strength, high specific modulus, corrosion resistance, fatigue resistance, recyclability, good damping and shock absorption, designable performance, and multifunctional integration ,2,3. As The traditional process methods for preparing CFRTPCs , glass fiber (GF), and Kevlar fiber (KF); commonly used thermoplastic resins include polylactic acid (PLA), acrylonitrile butadiene styrene copolymers (ABS), polyamide (commonly known as nylon) (PA), and polyether ether ketone (PEEK). Different fiber/resin combinations result in significant differences in the mechanical properties of the 3D printed CFRTPCs due to the different interphase interface properties. Oztan et al.  used CF The above research indicates that the material properties of fibers and resins, as well as their interfacial properties, are important factors affecting the mechanical properties of CFRTPCs. To improve the mechanical properties, on the one hand, efforts can be made to develop high-performance fibers and matrices and expand the material system; on the other hand, fiber modification technology can be combined to make the fiber surface rougher or undergo chemical reactions to generate new polar groups to promote matrix impregnation of the fibers and improve the interfacial bonding performance between the fibers and the matrix.(1)Influence on the infiltration between fibers and resinsThe printing temperature directly affects the melt flow performance of the matrix resin after heating, affecting the mechanical properties of the CFRTPCs from two aspects:The printing temperature is too low, resulting in high viscosity and poor fluidity during resin melting, making it difficult to complete the printing work. The increase in printing temperature enhances the resin melt fluidity, making it easier to enter the interior of the fiber bundle, improving the degree of infiltration between the fibers and resin, and thus improving the forming quality of the workpiece. However, excessive temperature can easily lead to strong resin fluidity and even decomposition and vaporization, which is not conducive to 3D forming. In general, the reasonable range for 3D printing temperature selection is above the glass transition temperature of the resin material and below the thermal decomposition temperature. Tian et al.  confirme(2)Influence on the multi-interface bonding performance of CFRTPCsThree-dimensional printed CFRTPCs have multiple interfaces, as shown in (1)For the fiber/resin interface, a reasonable printing temperature is beneficial for the resin matrix to remain above the glass transition temperature for a relatively long time, which is conducive to the full infiltration between the resin and the fiber bundle, thereby obtaining a phase interface with good performance.(2)For the interface between resin wires, as shown in The speed parameters include the printing speed and substrate feeding speed. The printing speed refers to the movement speed of the printing head, which is also the wire output speed of continuous fibers at the printer nozzle. The printing speed determines the forming efficiency of the workpiece and the soaking time of the continuous fibers and molten resin in the printing head. For online infiltration co-extrusion, the substrate feeding speed refers to the volume of resin material entering the printing head per unit time. Since the nozzle inner diameter remains unchanged, the substrate feeding speed determines the impregnation pressure between the fiber and the molten matrix, and to some extent determines the fiber volume content of the product.When determining the speed parameters, it is necessary to comprehensively consider the nozzle diameter and the type and performance of the fiber and resin. In general, a lower printing speed and a higher substrate feeding speed can improve the impregnation pressure and degree, which is beneficial for improving the interfaces’ bonding performance. However, too low a printing speed can prolong the heating time of the resin matrix inside the nozzle, causing thermal decomposition of the resin and preventing normal printing. Excessive substrate feeding speed may cause the molten resin to overflow from the nozzle, affecting the normal printing work. Zeng et al.  also fouAs shown in For 3D printed CFRTPCs, Shan et al.  found thTherefore, when selecting the thickness of the printing layer, it is necessary to comprehensively consider the relationship between the material mechanical properties, printing accuracy, and printing efficiency and make a compromise.As shown in In the study of the 3D printing of CFRTPCs, Shan. et al.  found thz-axis represents the stacking direction. It can be seen that the standard test pieces with the same geometric shape have various stacking directions such as a flat normal direction, a side legislative direction, and a straight legislative direction. Three-dimensional prints with different stacking directions have different microstructures and mechanical properties.According to the different geometric shapes and performance requirements of the parts, different stacking directions can be used to stack and accumulate materials layer by layer. The stacking direction is also an important factor affecting the mechanical properties of CFRTPCs. As shown in Currently, most research on the stacking direction is mainly based on experiments. Chacón et. al. ,22,46 syReinforcing fibers are the main load-bearing phase of CFRTPCs, and their volume content directly determines the part’s mechanical properties. Normally, an increase in fiber volume content results in a significant improvement in the mechanical properties. The commonly used methods for calculating fiber content include thermogravimetric analysis , geometrTherefore, in future research, on the one hand, effective methods to increase the fiber volume content of 3D printed composite materials should be further explored; on the other hand, in-depth research should also be conducted on how to improve the sufficient infiltration and high porosity of fibers under high fiber volume content, in order to ultimately achieve effective printing of high fiber volume content composite materials with good mechanical properties, meeting the application requirements of complex engineering structures for high-performance composite materials.Structural topology optimization is an important means to achieve lightweight in CFRTPCs-FDM products, and fiber path planning aims to determine the distribution of continuous fibers within the product. The main challenge of CFRTPCs-FDM structural topology optimization and fiber path planning is the coupling between structural design and the fiber distribution. Due to the anisotropic mechanical properties of fibers, the change in the fiber distribution caused by the shape change of composite materials should be fully considered in the topology optimization process. There are two main ideas for topology optimization and path planning of a CFRTPCs-FDM structure. One is sequential optimization, which first considers the overall topological shape and then considers the fibers distribution. For example, Li et al.  and FeduThe other is a parallel optimization that considers both the structural design and fiber distribution. For example, Lee et al. ,53 propo(1)Microwave-heating-assisted CFRTPCs-FDMAt present, the 3D printing of composite materials mainly adopts the traditional electric heating method to melt and then solidify and deposit, which has a long curing time and a high energy consumption. Li et al.  applied (2)Ultrasonic-assisted CFRTPCs-FDMQiao et al.  proposedIn order to improve the bonding between the resin and the fiber and reduce the porosity to improve the printing quality of CFRTPCs, in addition to the above process improvements, scholars have also proposed assisted measures such as substrate ultrasonic vibration assistance, laser melting assistance, roller pressure followup assistance, and hot pressing post treatment to improve the mechanical properties of CFRTPCs–FDM.With the wide application of CFRTPCs-FDM, the recycling and remanufacturing of waste composite parts has become a problem that must be faced. The recovery technologies of carbon fiber composite materials are divided into three categories: the physical recovery method, the energy recovery method, and the chemical recovery method. The physical recovery method is to mill, cut, or crush the waste composite materials to obtain short fibers, particles, powders, and other substances. This method has the advantages of being low cost, a simple process, and having no pollution, which is only suitable for uncontaminated composite waste parts, and the strength of the fiber is seriously reduced after treatment, and the reuse value is low. So, it can only be used as some fillers and cannot become a material with high purity requirements. The energy recovery method is to incinerate waste composite materials to obtain heat energy. However, this method causes secondary pollution, which should be avoided as much as possible. The technology that can really further recycle and reuse fibers is the chemical recovery method. The method is to degrade the resin matrix into small molecular compounds or oligomers, so as to achieve separation from fibers and fillers. It can not only recover the reinforced fibers but also recover the resin as raw material. It is the most promising recovery method at present .The carbon fiber obtained by the chemical recovery method is usually in a messy and fluffy state, which is difficult to make into prepreg products with long tow lengths. Therefore, the recovered fiber is more suitable for nonwoven materials, cut into short fibers, or even ground into smaller particles or powders, added to the resin matrix for remanufacturing. At present, chopped-fiber-reinforced thermoplastic materials are widely used in the 3D printing of composite materials. Therefore, the recycled carbon fiber is particularly suitable for the 3D printing of chopped-fiber-reinforced composites. (1)The mechanical properties of 3D printed CFRTPCs are closely related to the properties of reinforcing fibers, matrix resins, and multiple interfaces. The influencing factors can be summarized into three aspects: the material type, the process principle, and the process parameters. The factors are coupled with each other, jointly determining the forming quality of CFRTPC products;(2)The impact of the above factors on the mechanical properties of 3D printed CFRTPCs is ultimately reflected in three aspects: the fiber volume content, the interface bonding strength, and the porosity. Compared with traditional forming processes, current 3D printed CFRTPCs still face prominent problems such as a low fiber volume content, a weak interface bonding strength, and a high porosity.(3)The fiber volume content is determined by a combination of speed parameters, layer thickness, scanning space, stacking direction, and so on. The pores of workpieces can be divided into macroscopic pores caused by the minimum bending radius or scanning overlap of the fibers and microscopic pores existing in continuous fibers, matrix resin, and interphase interface connections. Three-dimensional printed CFRTPCs have multiple interfaces: a fiber/resin interface and a resin interface between and within layers. Good interface bonding characteristics are conducive to reducing the porosity, improving the stress transfer efficiency, and interlaminar shear strength at the interface.Compared with traditional preparation processes, the mechanical properties of 3D printed CFRTPCs are still relatively poor. This paper analyzes and reviews the current research status of the 3D printing of CFRTPCs from the perspective of mechanical properties, and draws the following conclusions:(1)It is necessary to explore the rheological and time-dependent behavior of composite materials in the multiple states of FDM from a more microscopic perspective, so as to construct a mechanical model that accurately describes the complex rheological properties of materials and reveal the melting deposition mechanism of CFRTPCs at the molecular/atomic level, to realize scientific prediction of the mechanical properties of 3D printed CFRTPCs.(2)The data show that 50% to 60% of the structural failures in composite materials are closely related to interlayer damage. The bonding ability of the CFRTPCs’ 3D printing multi-interface  determines the interlaminar mechanical properties of the CFRTPCs to a large extent. Therefore, it is necessary to further study the interface cross scale coupling model of CFRTPCs-FDM, in order to reveal the regulatory mechanism of the interface from the microstructure to the macroscopic performance.(3)Researchers have established a relatively effective numerical simulation model for the traditional forming process of composite materials, achieving prediction and simulation of their mechanical behavior under typical load conditions. However, numerical simulations for the 3D printing of CFRTPCs are relatively lacking. Effective finite element and molecular dynamic models should be established based on the rheological mechanism and interface model of CFRTPCs-FDM to achieve effective simulation and prediction of 3D printed CFRTPCs properties.(4)The 3D printing of CFRTPCs has anisotropic characteristics, and the stacking direction and fiber orientation seriously affect the optimal load-bearing condition of the product. Therefore, it is necessary to carry out configuration design in combination with topology optimization, develop five-axis 3D printing equipment, adjust the stacking direction in real time, and use a path planning algorithm to realize the controllable layout of the fiber direction, so as to realize the integrated design and manufacturing of CFRTPCs in terms of “performance–configuration–process”.(5)It is necessary to explore and develop new process principles and improvement methods for the 3D printing of CFRTPCs, innovate CFRTPCs’ 3D printing equipment, and further improve the mechanical properties. Also needed is to develop new materials and improve the material system and, on the basis of the tensile, bending, and compression properties, further enrich the quality evaluation methods of the 3D printing of CFRTPCs, such as the impact properties, wear properties, creep properties, fatigue properties, and damage evolution laws.However, the existing research mainly focuses on analyzing the relevant factors through experimental methods along the lines of equipment development, experimental design, and result comparison, and exploring the optimal process methods and parameters under the relevant material types. In the future, research on CFRTPCs-FDM may focus on the following aspects:


Obsessive-compulsive disorder (OCD) is a mental disorder in which patients who suffer from it have repetitive and undesirable thoughts, feelings, ideas, sensations (obsessions) and behaviors that drive them to do something over and over again (compulsions).Often the person tries to get rid of the obsessive thoughts through compulsions, but this only provides short-term relief. Not carrying out the obsessive rituals can cause enormous anxiety and suffering.To describe a 23-year-old male patient, who suffers from anxiety and mood symptoms, reacts to ego-dystonic obsessive ideas and sexual content, of months of evolution, and who manages to calm down through compulsive masturbation or watching sexual videos on the internet. All this clinic negatively interferes with their quality of life, asking the patient for medical help to calm these ideas.We carried out a review in Pubmed with the terms Antiandrogens and TOC, in order to make a better description of the clinical case.After several treatment attempts , reaching maximum doses according to clinical guidelines, and with poor therapeutic response, it was decided to discuss the case with the endocrinology department of our hospital, deciding to start treatment with antiandrogens, in order to alleviate the persistent intrusive ideas of a sexual nature. The administration of antiandrogens in men can cause a decrease or increase in the development or involution of secondary sexual characteristics in men, reducing the activity or function of accessory sexual organs, and hyposexuality, with decreased sexual desire or libido.After several weeks, there was improvement in the obsessive symptoms with a decrease in compulsive rituals. However, after the 3rd mo, some symptoms reappeared, but not with the same severity and intensity as before treatment. In addition, we cannot ignore the adverse effects that have occurred, such as involution of secondary sexual characteristics. However, and taking into account the negative repercussion that this clinic had on the patient’s quality of life, the benefit obtained exceeded the risk, having noted clear improvement with this therapy, and maintaining evolutionary controls by both psychiatry and endocrinology.Patients suffering from obsessive-compulsive disorder can be effectively treated with anti-androgenic pharmacological agents with various modes of action. The most effective group of such agents is the long-acting analogues of the gonadotropin-releasing hormone. The objective of this review is to elucidate the possibility of using such powerful anti-androgenic agents in the treatment of obsessive-compulsive disorder.None Declared


In this article, a chaotic computing paradigm is investigated for the parameter estimation of the autoregressive exogenous (ARX) model by exploiting the optimization knacks of an improved chaotic grey wolf optimizer (ICGWO). The identification problem is formulated by defining a mean square error-based fitness function between true and estimated responses of the ARX system. The decision parameters of the ARX model are calculated by ICGWO for various populations, generations, and noise levels. The comparative performance analyses with standard counterparts indicate the worth of the ICGWO for ARX model identification, while the statistical analyses endorse the efficacy of the proposed chaotic scheme in terms of accuracy, robustness, and reliability. Parameter estimation plays an important role in system identification, which is the frontier of research in signal processing . It is wAmong these techniques, metaheuristics have gained significant attraction in recent decades for system identification. As presented in The second domain is human-based techniques which were used for optimization. In teaching–learning-based optimization , inspireThe third domain is evolutionary techniques applied to optimization problems. In differential evolution , an optiThe fourth domain includes physics-based techniques applied for optimization. In big bang big crunch , two phaThe fifth domain is nature-inspired techniques used in optimization. In the water cycle algorithm , the behChaos theory relates the chaotic dynamics of systems with initial conditions and unstable periodic motions . It is aCombining chaos in metaheuristics increases the exploration and exploitation of optimization techniques. Various chaotic metaheuristics were presented in the literature. In , a chaotGrey wolf optimizer (GWO) has gained significant attention in recent years due to its flexibility, scalability, and few parameters . It is aIn , a modifThe autoregressive exogenous model (ARX) is used in different engineering problems such as time series data prediction , pneumatThe parameter estimation problem of a system represented by the ARX model is investigated through optimization knacks of an improved chaotic grey wolf optimizer (ICGWO).The performance of the proposed ICGWO scheme is examined in detail through comparison with the conventional counterparts for various generations, populations, and noise levels.The statistical analysis through multiple independent trials confirms the accurate and robust performance of the ICGWO over the GWO, CGWO, and AGWO.The accurate estimation for a practical example of a temperature process system further validates the convergent performance of the ICGWO.The current study is a novel investigation exploring the potential of chaotic maps through an ICGWO for effective parameter estimation of ARX structure. The innovative contributions of the proposed study are as follows:The remainder of the article is structured as follows: ARX mathematical structure is presented in The ARX structure effectively model various engineering and applied sciences problems such as time series prediction, pneumatic positioning system, wheeled robots, MIMO systems, and behavior modeling ,80,81,82The output from Solving (3) as presented in (4)(4) can be rearranged as presented in (5)The information vectors are defined in (6) and (7).The parameter vectors are presented in (8) and (9).The overall information and parameter vectors are given in (10) and (11), respectively.The identification model of ARX system presented in GWO is a recently proposed metaheuristic inspired by social hierarchy and the hunting behavior of grey wolves. Grey wolves are apex predators and prefer to live in a pack size of five to twelve on average with a strict dominant hierarchy. The leaders are male and female and responsible for decisions regarding hunting, the place for sleep, time for waking up, etc. The leader wolf is dominant, and the pack should follow his/her orders. The leader wolves may not be the strongest, but it is the best in terms of management. Hunting is the second interesting behavior of grey wolves after social hierarchy. The main steps of hunting in grey wolves are approaching the prey after tracking and chasing it, harassing the prey until it stops moving after pursuing and encircling, and finally, attack towards the prey.ICGWO is an improved version of GWO for solving optimization problems. Its mathematical model is presented below.In this step, the fittest solution In this step, the wolves encircle the prey as presented in (13) and (14).In this step, the positions from the three best solutions In this step, the hunting step is terminated based on To maintain the diversity, a logistic map is used such that the algorithm avoids the local minimum values during optimization. Its mapping is presented in (25).First, the parameters of ICGWO were set. Then, the best fitness solutions were assigned to In this section, the experimental analysis of ICGWO for the ARX model is presented. The analysis was conducted on several variations of populations (ken from  and presThe noise A statistical study of ICGWO against GWO, AGWO, and CGWO at The investigation of ICGWO is further explored in terms of average fitness values for all scenarios of To validate the performance of the proposed methodology, an ARX-based LD-Didactic temperature process plant model is considered. The authors of  describeThe convergence curves for all noise levels at The results presented in In this article, the strength of GWO and its various variants CGWO, AGWO, and ICGWO is exploited for parameter estimation of the ARX structure required to model various engineering and applied sciences processes. The decision parameters of the ARX model were optimized over various populations, generations, and noise levels. The logistic chaotic map along with the improved convergence factor were fused in GWO. The ICGWO is robust, accurate, and convergent for the parameter estimation of the ARX system. The convergence plots and statistical analysis through the ample number of autonomous trials confirmed that ICGWO performs better in terms of convergence and robustness as compared to conventional counterparts of the standard GWO, an improved GWO, and a simple chaotic GWO. The accurate estimation of ARX parameters reflecting the LD-Didactic temperature process plant model further validates the better performance of ICGWO. Future studies can extend the application of the proposed scheme to solve problems such as PV solar panels, constraint-preserving mixers, and real-time estimation of harmonics in nonlinear loads ,94,95,96


The rapidly evolving COVID-19 public health emergency has disrupted and challenged traditional healthcare, rehabilitation services, and treatment delivery worldwide. This perspective paper aimed to unite experiences and perspectives from an international group of rehabilitation providers while reflecting on the lessons learned from the challenges and opportunities raised during the COVID-19 pandemic. We discuss the global appreciation for rehabilitation services and changes in access to healthcare, including virtual, home-based rehabilitation, and long-term care rehabilitation. We illustrate lessons learned by highlighting successful rehabilitation approaches from the US, Belgium, and Japan. One in every three people will need rehabilitation services at some point in their lifetime . Yet, noIn addition to barriers to healthcare and rehabilitation services –8, the iAlthough the COVID-19 pandemic resulted in an accelerated publication rate in rehabilitation, with 18% of all publications published between 2019 and 2022 including the term “rehabilitation” , only recently, there has been a first collection of publications addressing the challenges and opportunities of health systems, rehabilitation care, and COVID-19 . TherefoIn January 2023, COVID-19 was diagnosed in more than 660 million individuals in 229 countries and territories around the globe, resulting in 6.7 million deaths and over 638 million recoveries . Though Differences in how countries responded to the pandemic and adjusted their rehabilitation services demonstrate variability in healthcare systems and priorities , 32. ForThis was not a global response; in other parts of the world rehabilitation services were deemed more of a priority. A registry-based study from Norway, including 1310 hospitalized patients with traumatic brain injury (TBI), demonstrated that the direct pathway to early specialized rehabilitation was maintained during 2020–2021 . SimilarOne of the most significant transformations in the delivery of healthcare services due to the pandemic has been innovation in remote delivery of care, including the use of telehealth. What seemed improbable pre-pandemic is now becoming an option of care currently reimbursable by insurances for individuals with limited access to physical healthcare facilities in many countries . RehabilMany professional associations and some government agencies across the globe  areThe growth of telehealth and other remote services is not only seen with COVID-19 patients but also within the healthcare system for medically vulnerable individuals and persons with limited access to healthcare in isolated areas of the world, including rural areas and parts of the world impacted by disaster and war. Telehealth has been shown to support patient-provider communication when face-to-face interaction is not possible . TeleheaTelehealth, home-based rehabilitation programs, and various web-based interventions were introduced early in some medical centers in the US , 48 and In Japan, dedicated virtual consultation services were introduced early in the pandemic through the Japanese Infectious Disease Prevention Act, where public health centers became responsible for infectious disease control and prevention , 56. An Despite the many benefits to telehealth, barriers to telehealth access were also noted. In some cases, patients who were receiving care at home did not have the resources  to engage in telehealth sessions. The lack of resources in low-income countries could explain why approaches of telehealth were limited in e.g., Tanzania . Indeed,Furthermore, telehealth, was noted to not be conducive to all types of conditions and rehabilitation services. For example, in speech-language pathology, online swallowing tests were recommended only as screenings; full evaluations and interventions were discouraged. In physical therapy, requests to allow therapists to treat patients remotely were deemed impractical or even unsafe. As a result, in the U.S., Centers for Medicare & Medicaid Services motioned to deny payment for certain types of telehealth services.During this process, many allied health professionals became strong advocates, not only for their patients but also for their profession. On several occasions, professionals took action by writing letters to Ministries of Health and introducing protocols that would inform safe practice. These actions allowed allied health professionals in Europe, for example, working with the National Health System, to notify state officials and administrators as to what rehabilitation specialty consists of and what allied health care professionals do.Long-term care facilities (LTCFs) inhabiting vulnerable populations, including the elderly and persons with disability, are at significant risk for massive outbreaks of viruses, including COVID-19 . COVID-1Dominiek Savio is one of the most prominent institutes for more than 500 children and adults with physical disabilities in Belgium, a country in which on May 3rd 2020, 53% of all deaths due to COVID-19 were in care homes . Given oAt the onset of the pandemic, the board of directors selected a group of three persons that were given authority to make decisions and implement measures against the spread of the virus. The two medical doctors of the institute provided the team with the latest updates via their network. Challenges could be tackled within the organization with the support of their medical team, including 2 medical doctors, 28 nurses, and 5 healthcare providers. Because of the fast-shrinking supply of personal protective equipment (PPE), residents safely produced face masks in the workshop. Proactive actions that supported a timely response to the pandemic was the initiative taken one year before the onset of the COVID-19 pandemic, to sensitize employees on the importance of hygiene .Despite the lockdown, all patients received the treatments and rehabilitation they needed while considering the well-being of both patients and employees. Initiatives such as the Chatbus, i.e., a bus separated in two parts by a plastic wall allowed contact between residents and visitors. Infographics were created and distributed to allow residents to make informed decisions about vaccination and PPE. Through the pandemic, the team adjusted their strategies, and in January 2022, they reduced the burden on the staff and residents by limiting the amount of PPE to Filtering Face Piece 2 masks. The call center “Coronafoon” allowed to collect and monitor the number of positive cases and provide timely information to the leadership team. The implementation of an emergency plan with a barometer which incorporates four main principles  gives guidance and trust for the future. The years of investment in solidarity and commitment amongst employees to improve the quality of life of persons with a disability proved its impact.Similar strategies were observed in Japan, which presented low mortality and morbidity rates in care homes . For exaThe COVID-19 pandemic offered insights into how different countries across the globe prioritize rehabilitation. Those countries that were not able to provide continued rehabilitation services during the pandemic are expected to suffer from detrimental consequences, including increased rates of chronic diseases, growing healthcare costs, and reduced overall quality of life. To accommodate the patient's needs and address the challenges in the COVID-19 pandemic, rehabilitation specialists have devised innovative ways to deliver rehabilitation services for patients and caregivers. Continued research of innovative interventions and remote treatment delivery methods  and government support is needed to inform clinical recommendations and rehabilitation guidelines around the globe. Common findings from the presented success stories from LTCFs demonstrate the importance and effectiveness of a comprehensive approach where health care and rehabilitation are a critical part of one another as well as preparedness and having systems that can reduce the impacts of large-scale unexpected disruption to services, such as the COVID-19 pandemic.The presented stories from high-income developed countries also align with challenges and recommendations from the low-income countries Jordan  and IndiThe unpreparedness to react effectively and promptly to the pandemic was presented as one of the significant public health challenges . Identif


Since the first experiments in 1950s, transmission electron microscopy (TEM) observations of filamentous fungi have contributed extensively to understand their structure and to reveal the mechanisms of apical growth. Additionally, also in combination with the use of affinity techniques (such as the gold complexes), several aspects of plant-fungal interactions were elucidated. Nowadays, after the huge of information obtained from -omics techniques, TEM studies and ultrastructural observations offer the possibility to support these data, considering that the full comprehension of the mechanisms at the basis of fungal morphogenesis and the interaction with other organisms is closely related to a detailed knowledge of the structural features. Here, the contribution of these approaches on fungal biology is illustrated, focusing both on hyphae cell ultrastructure and infection structures of pathogenic and mycorrhizal fungi. Moreover, a concise appendix of methods conventionally used for the study of fungal ultrastructure is provided. Trametes versicolor (L.:Fr.) Pilàt (formerly Polystictus versicolor), a wood decay basidiomycete  Petr. belonging to the Ascomycota and Uromyces caladii Sch. belonging to the Basidiomycota]. At that time, the most used fixative was potassium permanganate (KMnO4), which could easily permeate into fungal walls but did not result in adequate preservation of cell ultrastructure. Later on, fixation with osmium tetroxide, in addition to KMnO4, allowed to better define other organelles, such as ribosomes, endoplasmic reticulum and mitochondrial cristae  that resulted in a much clearer definition of hyphae ultrastructure, i.e., showing various type of apical and subapical vesicles and their connection with the cytoskeleton in different fungal species, such as the Ascomycota Ascodesmis nigricans Tiegh. and the Basidiomycota Armillaria mellea (Vahl.: Fries) , further clarifying the mechanisms of apical growth , before being raised back to room temperature and cryo-sectioned or embedded in conventional plastic resins. Another significant advance in knowledge was the development in the 1980s of immunocytochemical techniques for the detection of macromolecules by TEM  observations of filamentous fungi have been determinant not only for understanding their structure but, even more important, for revealing the mechanisms of apical growth. The first recorded work on the ultrastructure of fungal cells dates back to 1958 and concerned Nowadays knowledge on ultrastructure of fungi achieved by all the above-mentioned techniques and their contributions to improve knowledge in fungal biology are illustrated herewith together with the advancements in sample preparation and TEM observations. Description mainly focuses to the two phyla of Ascomycota and Basidiomycota, the most studied fungi and, besides hyphae cell ultrastructure, infection structures of pathogenic and mycorrhizal fungi are included. Finally, in the Ascodesmis nigricans Tiegh., Neurospora crassa Shear and Dodge, Aspergillus niger Tiegh. and Fusarium oxysporum Schlectendahl as well as in Armillaria mellea Vahl.: Fries belonging to Basidiomycota, and Gilbertella persicaria (E.D. Eddy) Hesselt belonging to Mucoromycotina. Interestingly, they were also present in the hyphae tips of fungal-like organisms, i.e., the Oomycota Pythium aphanidermatum (Edson) Fitzp. and Globisporangium ultimum (Trow) Uzuhashi, Tojo and Kakish   during the different growth stages  and comprising cytoskeletal and endoplasmic reticulum (ER) components , which is upregulated by nutrient starvation as well as during the symbiotic phase, has been localized in the inner cell-wall layer of the ectomycorrhizal fungus Tuber borchii Vittad.  Bri. & Cav., carried out by O'Connell and co-authors in 1980s, also with the pioneering use of high pressure freezing followed by freeze substitution and immunolabelling with antibodies or lectins to recognize specific fungal macromolecules  Speer, by its many specialized races infect almost all cereals, Podosphaera fuliginea (Schltdl.) U. Braun & S. Takam  affects cucurbits and Erysiphe necator Schwein  causes one of the main fungal diseases in the vineyards  Link, and zoospores of some fungal-like Oomycotes, i.e., Plasmopara viticola (Berk. & M. A. Curtis) Berl. & De Toni, penetrate through stomata and form haustoria in mesophyll cells (Chong and Harder, Puccinia hemerocallidis Thüm haustoria, coupled with the use of gold-conjugated wheat germ agglutinin for labeling of chitin, revealed that the electron-dense material present in the extrahaustorial matrix were not part of the haustorial wall, but likely of the host. At this regard, the EHM showed points of continuity with electron-dense tubular elements present in the host cytoplasm nearby the haustorium, as well as with flattened cisternae, possibly as a consequence of the host endomembrane rearrangement in the form of smooth endoplasmic reticulum (Mims et al., Contrary to powdery mildew, which penetrates the epidermal cells forming haustoria inside them, some Basidiomycota, i.e., urediniospores of the rust fungi omics techniques on fungi belonging to diverse groups, ultrastructural studies offer the possibility to support the molecular data. Although in the last years, mainly thanks to the data obtained in the frame of fungal genome projects, several novel information has been obtained. The full comprehension of the mechanisms at the basis of the fungal growth and the interaction with other organisms, is in fact closely related to a detailed knowledge of the structural features.In conclusion, ultrastructure analyses have extensively contributed to highlight fungal features correlated to cell organization and growth. The potential of transmission electron microscopy to study the fungal ultrastructure has been accompanied by development of more advanced techniques, such as freeze-fracturing, microautoradiography and the application of affinity techniques using lectins or antibodies in conjugation with colloidal gold particles against defined cell-wall epitopes. More recently, TEM observations might advantage or may represent a support for next-wave single cell analyses that provide highly resolved structural and compositional features of biological specimens at micro- and nano-resolution. Thanks to detailed works at TEM and the use of affinity techniques, information on plant-fungal interactions has been also provided. If in the past the spread of the molecular biology approaches allowed to explain what was observed, nowadays, after the huge of information obtained from diverse FF and RB conceived and wrote the manuscript. AF performed high pressure freezing experiments on truffle mycelium and ectomycorrhizae. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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Musculoskeletal disorders are a growing burden on the health care system in the United States. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to assist in the management of mild-to moderate musculoskeletal pain. After the withdrawal of rofecoxib because of cardiovascular toxicity, the safety of these agents became a topic of controversy and confusion. Recent evidence is facilitating a better understanding of the risks and mechanisms by which NSAIDs cause injury. In an effort to raise awareness, this review addresses the current challenges, recent progress, and novel strategies for improving tolerability. With new data to help guide decision making and the anticipated increase in pharmacological options for managing musculoskeletal pain, the role of the managed care professional is particularly important in this evolving field.To review recommendations for the appropriate use of NSAIDs, incorporate risk/benefit analysis into decision making, and evaluate the efficacy and safety of recently approved and emerging NSAID formulations.Musculoskeletal-related conditions are a major public health burden. NSAIDs are among the most commonly used medications for musculoskeletal conditions. Since the introduction of selective cyclooxygenease-2 (COX-2) inhibitors (or coxibs), there has been ongoing discussion and debate about the safety of all NSAIDs. Current available evidence suggests both traditional NSAIDs and coxibs increase the risk of gastrointestinal and cardiovascular toxicity; however, with proper risk assessment, these dangers can be limited. Moreover, new and emerging NSAID formulations and delivery systems aim to enhance the effectiveness and reduce the toxicity associated with these anti-inflammatory agents.


Cardiovascular disease (CVD) and cancer are increasingly recognized as two intimately interconnected conditions, with one predisposing to the other, with a continuous interplay. It is now well established that cancer patients have significantly higher cardiovascular mortality risk than the general population, mostly because of the cardiotoxic side effects of anticancer treatments. In this regard, understanding and tackling cancer therapy-related cardiotoxicity (CTRC) represents the major goal of the branch of cardiology known as cardio-oncology .Montisci et al. provided an overview of the CV complications of the most feared oncological treatments, i.e., those requiring admission to the intensive care unit, including but not limited to anthracyclines and anti-HER2 monoclonal antibodies. The review article by Madonna extended this summary by discussing the CV side effects of proteasome inhibitors and tyrosine kinase inhibitors (TKIs), two highly effective treatments for hematological malignancies. Notably, the CV toxicity of these therapies renders these tumor types difficult to treat in the elderly with CV comorbidities, requiring either discontinuation or reduction of drug dosage, with increased likelihood of tumor relapse. The authors then elaborated on the mechanistic basis of the CV side effects of TKIs, suggesting that these drugs could negatively impact the reparative and regenerative properties of the different cell types of the CV system.CTRC remains nowadays a highly relevant Research Topic as treatments with established cardiotoxicity, but also high efficacy, are still widely used, and new anticancer therapies with potential cardiovascular (CV) side effects are continuously introduced in clinical practice. In this Research Topic, the review article by Robinson et al. further dissected the molecular basis underlying the late and long-lasting cardiotoxicity that can ensue from a short-termed treatment with anthracyclines. RNA-sequencing of human endomyocardial biopsies, mass spectrometry of genomic DNA and proof-of concept in vitro experiments revealed loss of DNA methylation. The authors thus concluded that long-lasting epigenetic modifications resulting from anthracycline treatment are key determinants of late-onset cardiotoxicity. Whether changes in DNA methylation could be associated with a biomarker or used to pinpoint patients at risk for early or late cardiotoxicity remains to be determined by future studies.If earlier studies proposed a similar mechanism to explain anthracycline cardiotoxicity, the current notion is that the CV side effects of this class of anticancer therapeutics is multi-factorial . In thisYang et al. performed a meta-analysis of 41 studies investigating the relationship between genetic variations and CTRC, with a primary focus on anthracycline-based and HER2-targeted therapies. Out of 14 single nucleotide polymorphisms that were consistently detected in the 41 studies, 6 variants were strongly associated with the increased risk for CTRC. Of note, these variants were anticipated to affect the activity of drug transporters, thus being responsible for drug accumulation and/or excessive reactive oxygen species generation, leading to exaggerated cardiotoxicity. Nevertheless, the pathogenic and mechanistic roles of these variants in mediating cardiotoxicity warrant further investigations.Conversely, growing evidence suggests a role of germline genetic variants in mediating the risk of CTRC and the possibility of leveraging these variants to identify patients at risk for CTRC and to guide treatment decisions as well as monitoring and management strategies. In this respect, Guha et al. highlighted a further layer of complexity in the interplay between risk factors, CVD, and cancer, proposing socio-economic disparity and ancestry as mediators of obesity-driven higher predisposition to CVD and cancer in African Americans (AA) compared to Caucasians. On the one hand, socio-economic disparity hinders access to a healthy lifestyle among AA while, on the other hand, polymorphisms of two genes, APOL1 and ACKR1, were found more frequent in AA than in other ethnicities, suggesting the existence of genetic determinants. Although ACKR1 is a strong attractant of monocytes and could account for enhanced monocyte mobilization and activation in AA, further studies are required to clarify its clinical relevance.While acknowledging the importance of CV toxicity of anticancer therapies, contemporary cardio-oncology has widened its focus, since mounting evidence indicates that CVD and cancer are linked to one another at multiple levels . The nasBanerjee et al. discussed how the conventional concept of senescence as the mediator of cell cycle arrest has been progressively replaced by the view according to which senescent cells can remain metabolically active and secrete pro-inflammatory mediators known as senescence-associated secretory phenotype (SASP). The article provided an overview of recent evidence suggesting that SASP can be at the intersection of CVD and cancer, suggesting the use of senolytics as an approach for the treatment of both diseases.Another cellular process strictly intertwined with inflammation and that could underlie the occurrence of both cancer and CVD is senescence. The review article by Bracun et al. now reported that 6 tumor biomarkers also predicted CVD and CV mortality in more than 8,000 subjects enrolled in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study, which was originally conducted to assess renal disease and CVD in a large cohort sample in Netherlands. The strongest associations were for CEA and CYFRA 21-1 and, interestingly, differences were observed between males and females, which are worth of additional investigation.Irrespective of common underlying pathways, the interrelation between CVD and cancer is confirmed by the prognostic value that biomarkers classically associated with one condition also play in the other one. While it was previously shown that increased concentrations of established markers of CVD portend a higher risk of cancer incidence and mortality , Bracun In conclusion, this Research Topic highlights that CVD and cancer are interlinked by shared genetic and non-genetic risk factors, and common mechanistic basis, like inflammation and senescence. Interestingly, anticancer therapies may exacerbate CVD in cancer patients by impinging on the same molecular processes, which could thus represent actionable targets to prevent CTRC.