To obtain the ensemble, we generate payoff matrices at random. Games with a unique pure strategy Nash equilibrium converge to the Nash equilibrium. We then consider a wider class of games that converge under a best-response dynamic, in which each player chooses their optimal pure strategy successively. We show that the frequency of convergent games with a given number of pure Nash equilibria goes to zero as the number of players or the number of strategies goes to infinity. In the 2-player case, we show that for large games with at least 10 strategies, convergent games with multiple pure strategy Nash equilibria are more likely than games with a unique Nash equilibrium. Our novel approach uses an n-partite graph to describe games.We calculate the frequency of games with a unique pure strategy Nash equilibrium in the ensemble of  John Nash showed that any game with a finite number of players and strategies has at least one MSNE . Th. Thpure n-player, m-strategy normal-form game and assume that players choose their optimal strategy  in a clockwork sequence—player 1 goes first, then player 2, etc. until its player 1’s turn again. We call a game convergent, if starting from any initial strategy profile no player changes their strategy under the described dynamic after a sufficiently large number of turns.Consider an n-partite graph with each node corresponding to a pure strategy profile of the strategy choices of all but one player, and each edge corresponding to the optimal strategy choice (best response). A PSNE corresponds to a shortest possible cycle of length n.We describe such games by an Type A: Convergent games with a unique PSNEType B: Convergent games with multiple PSNEsType C: Non-convergent gamesType A games  are very easy to understand and perfectly predictable. They converge to the PSNE. As we may re-arrange the strategies of the players, Type B games are coordination games. An example of a Type C game is Matching Pennies. Type B and Type C games have at least one MSNE.In general, there are three types of games:We will investigate the likelihood of randomly created games that converge (Type A and Type B) in the ensemble of games with a given number of players and a given number of strategies available to each player. The frequencies can provide insights into predictability and stability of equilibria in economic systems. For situations that are conveniently modelled by low-dimensional (e.g. 2-player 2-strategy) games, predictability and stability properties are often obvious. For more complicated biological interactions , 9, biddWe will show that Type A and Type B games become less likely the more complex the game is. Thus, modelling scenarios like climate change or financial market events with Type A or Type B games would lead to misleading results. In spite of the involved difficulty, it would be expedient to employ models that use Type C games.Several papers have considered aspects related to the number of PSNE in games with random payoffs. We briefly consider the papers that dealt with random payoffs that are i.i.d. from a continuous distribution.Goldman  consider Dresher  showed t Dresher  derived  Dresher . McLenna Dresher  obtainedCournot stable; this class of games was studied by Moulin [Alon et al.  studied y Moulin .Concerning the use of best-response structures as a tool to study convergence frequencies, Pangallo et al.  and Pei Finally, random games were studied in the context of theoretical biology, for instance, the authors in  investign-partite graph describing the best responses of a game and use it to obtain the frequency of randomly created games with a unique PSNE in the ensemble of n-player, m-strategy games. These games are perfectly predictable. We then study games with more than one PSNE, that are convergent under best-response dynamics, in which each player successively chooses their optimal pure strategy. We show that convergent games with a smaller number of PSNEs are more common than convergent games with a higher number of PSNEs. We obtain an exact frequency for convergent 2-player games with any given number of PSNEs. We finally highlight that for 2 players and less than 10 strategies, games with a unique PSNE are more common than convergent games with multiple PSNEs, otherwise less common.We introduce an strategy profileenvironment for player i is a set i. A best responsei is a mapping from the set of environments of i to the set of non-empty subsets of i’s strategies and is defined bypure strategy Nash equilibrium (PSNE) if for all non-degenerate, if for each player i and environment mixed strategy Nash equilibrium (MSNE) is a strategy profile in mixed strategies.A game with s to The best-response structure of a game can be represented with a best-response digraph whose vertex set is the set of strategy profiles n-partite graph as an additional representation of the best responses for a given fixed sequence of players. There is a total of n groups, each group corresponding to a player and each node corresponding to an environment of a player. At each node, a player chooses the best response; formally, the edges are constructed as follows: for each pair  of players, where j moves directly after i, and each environment j), place a directed edge from n. Each player chooses among m strategies at each node, thereby the total number of possible arrangements is We now introduce an n-partite graph constructed as above but without the condition  is then given by Figures We have investigated the frequency of games that are convergent under a best-response dynamic, in which each player chooses their optimal pure strategy successively. Such games may either be perfectly predictable, if they have a unique PSNE, or have multiple PSNEs. We analytically computed the frequency of the first type by using a novel graph-theoretic approach for describing games, and showed that if we let the number of players or the number of strategies go to infinity, almost all games do not converge. We also showed that games with a higher number of PSNEs are less common than games with a smaller number of PSNEs. This calls the validity of simple models for complex scenarios into question. If a simple scenario is to be modelled, a Type A game could be the right approach. However, for complex scenarios, models based on Type A or Type B games can lead to misleading results. Instead, techniques from agent-based modelling, network theory, or Bayesian statistics could be employed.For 2-player games, we gave an exact formula for the frequency of games with a given number of PSNEs, and highlight that for less than 10 strategies, games with a unique PSNE are more common than convergent games with multiple PSNEs, otherwise less common.We believe that our graph-theoretic approach can generally be very useful to understand complicated games. Extensions of this work would include finding the analytical frequency of multi-player games with multiple pure Nash equilibria or with mixed Nash equilibria.n-partite graph for an n-player, m-strategy game. We order the nodes in the following way: i and j, if and only if i, n-partite graph by V is the set of vertices and E is the set of edges.Consider the full V| andi. For The Laplacian matrix of a graph m’s on the diagonalS is more irregular, For instance, in the case of 3-player, 2-strategy games, the Laplacian matrix corresponding to Fig. n nodes. Without loss of generality, we choose the nodes where each player chooses their first strategy. We condense these n nodes to a single node representing the PSNE, see Fig where n, we define A by deleting the first row and column.We apply Kirchhoff’s theorem to A is invertible, we haveA by the following algorithm: For a general blockmatrix A can be written asi-th column multiplied by The determinant of the matrix N entries on the upper diagonal, we add the i-th row multiplied bywheren-partite graph and assign k PSNEs, thereby fixing the outgoing edges of kn nodes. We show that the number of possible realizations as a game decreases, when adding another PSNE.Consider a full m, and fixing two nodes of an n-cycle fixes the remaining ones. However, adding a PSNE decreases the number of possible realizations as a game by a factor of n nodes may not form a cycle.The number of ways we can add another PSNE  is bounded from above by Induction over the number of added PSNEs completes the proof.m nodes of each type, where each node has an out-degree one, and with a cycle of length 2k, k vertices on a cycle (It was shown in Austin  that theo et al.  as a rec


IFFAS). Twenty-five normal volunteers were recruited for the current study. To participate, volunteers had to be less than 40 years of age and have a body mass index (BMI) < 30 kg/m2, and be free of medical comorbidity. The proposed model of FFA kinetics was used to analyze the data derived from the insulin-modified FSIGT. Mean fractional standard deviations of the parameter estimates were all less than 20%. Standardized residuals of the fit of the model to the FFA temporal data were randomly distributed, with only one estimated point lying outside the 2-standard deviation range, suggesting an acceptable fit of the model to the FFA data. The current study describes a novel one-compartment non-linear model of FFA kinetics during an FSIGT that provides an FFA metabolism insulin sensitivity parameter (IFFAS). Furthermore, the models suggest a new role of glucose as the modulator of FFA disposal. Estimates of IFFAS confirmed previous findings that FFA metabolism is more sensitive to changes in insulin than glucose metabolism. Novel derived indices of insulin sensitivity of FFA (IFFAS) were correlated with minimal model indices. These associations suggest a cooperative rather than competitive interplay between the two primary nutrients (glucose and FFA) and allude to the FFA acting as the buffer, such that glucose homeostasis is maintained.Glucose and free fatty acids (FFA) are essential nutrients that are both partly regulated by insulin. Impaired insulin secretion and insulin resistance are hallmarks of aberrant glucose disposal, and type 2 diabetes (T2DM). In the current study, a novel model of FFA kinetics is proposed to estimate the role insulin action on FFA lipolysis and oxidation allowing estimation of adipose tissue insulin sensitivity ( Glucose and free fatty acids (FFA) are essential nutrients that are both partly regulated by insulin. While insulin’s role in glucose metabolism promotes disposal in peripheral tissues such as muscle, insulin action in the adipose tissue, mainly suppresses lipolysis. In individuals with obesity or type 2 diabetes suffer from insulin resistance, a state where insulin is inefficient in performing the above outlined roles . Further50) yields the desired index of adipose tissue insulin resistance. However, the complexity and the time involved in performing the multistep pancreatic clamp makes its adaptation difficult (There is no agreement on the best methodology for estimating insulin sensitivity . Previouifficult . Third aIFFAS). Another unique feature of our novel model is that it estimates the contribution of plasma glucose as a regulator of FFA oxidation. Estimates derived from the novel model of FFA kinetics are compared with other model-based approaches and with previously published experimental parameters of FFA metabolism.Previously, several models of FFA kinetics have been proposed that address the bidirectional interaction between insulin and FFA either directly or indirectly –15. ManyThe primary objective was to develop a parsimonious model  that wouFFG(t) is linear interpolation of glucose plasma concentration at time t. FFASis the fractional FFA disposal rate with units 1/min. Parameter α serves dual purpose as a unit conversion and scaling factor for the effect of plasma glucose, FFG(t), on the disposal of FFA with units 1/mmol/l. It is assumed that the FFA plasma concentration at time 0, FFA(0), is equal to the fasting FFA concentration, bFFA.Where FFA(t)) are linked to insulin action on FFA (FFA(t)X) kinetics and glucose homeostasis via equation 1. Insulin action is defined in equation 2, where plasma insulin increment above basal (I(t) – Ib) contributes to insulin action similar to minimal model  is calculated as the ratio between XFCRPand XaP,Plasma FFA kinetics . Insulin concentrations were determined in duplicate by radioimmunoassay using standard commercial kits . Free fatty acids  were measured using colorimetric methods in commercially available kits.Model parameter estimation was performed using WinSAAM , which uses modified Chu-Berman numerical integrator for solving the model equations and a variant of the generalized non-linear weighted least squares version of the Gauss-Newton optimizer . WeightsX and FFAX, t-test was used to assess the similarity between the peaks in the insulin actions. All findings were deemed significant at the level of α=0.05 for the probability of a Type I error.Statistical analysis was performed using Stata 15MP . All descriptive statistics of the observed data are shown as mean ± SEM unless otherwise stated. Normality testing was used to assess the skweness of the data. Correlation analysis was performed using Spearman rank correlation. In order to establish equivalence between FFAX). Analogues to insulin action, FFAX arises as a result of changes in plasma FFA concentration alone and regulates the suppression of lipolysis, via the suppression of FFA disposal.It was initially assumed that insulin action (X(t)) was identical for both glucose and FFA and a model was constructed incorporating this feature XFFA. AnaloguResults for the analysis of the FSIGT data on the 25 health volunteers using the final model of FFA kinetics is shown in IS from the minimal model was moderately correlated with IFFAS  estimated by the minimal model and IFFAS . No additional significant correlations were observed between minimal model indices and parameters of our novel FFA model.The associations between parameter estimates from the proposed FFA model and metabolic indices from the traditional minimal model were assessed Table 3 FFAX and X are analogues to their model specification, FFAX) at approximately 4 min post challenge. Endogenous glucose insulin action averaged . The profile of FFAX closely resembled the profile of plasma Insulin in the first 10 minutes.While Since the seminal work by Randle et al. , there hRecently it has been recognized that impaired FFA disposal may be as important in the accumulation of fat in non-adipose tissue increased FFA uptake . By contvia a time delay before it exerts its action on FFA lipolysis. This “remote” compartment is considered to be either a proxy for the action of insulin on lipolysis or the direct effect of elevated glucose levels in the “remote” compartment on the rate of lipolysis (IFFAS).The FSIGT is a widely-accepted approach for assessing glucose homeostasis that does not require the use of tracers. The purpose of the novel FFA model was to extend the usability of the FSIGT experimental approach so it provides a more comprehensive metabolic picture. Recently, the insulin-modified FSIGT has been used to study the kinetics of plasma FFA . The curipolysis . Thus, tvia HSL is extremely sensitive to insulin . Estimates of IFFAS confirmed previous findings that FFA metabolism is more sensitive to changes in insulin than glucose metabolism. Novel derived indices of insulin sensitivity of FFA (IFFAS) were correlated with previous Bergman’s minimal model indices. These associations propose a cooperative rather than competitive relationship between the two primary nutrients (glucose and FFA) and allude to the FFA acting as the buffer, such that glucose homeostasis is maintained. The new model proposed in this study is likely to shed useful insights into the changes in FFA metabolism during development of insulin resistance and type 2 diabetes.In conclusion, the current study describes a novel one-compartment non-linear model of FFA kinetics during an FSIGT that, for the first time, provides an FFA metabolism insulin sensitivity parameter  for this work.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.


Improving the public’s awareness of and engagement with sustainable practices is essential for transitioning from a linear to a circular economy (CE). This task is not trivial; however, research into new ways of effectively supporting awareness and engagement, especially in view of digitalization trends, is still missing. In this study, we investigate the ability of augmented reality (AR) technology to improve awareness of CE practices and to engage citizens, inclusively, in the CE approach. Specifically, we report on the development of a novel AR engagement tool and present the results of two studies undertaken using this tool to assess the reliability and validity of this engagement practice. The first study focuses on the citizens of a municipality in Greece, and the second focuses on the general public outside the municipality boundaries. Attributes related to user engagement, such as novelty, aesthetics, perceived usability, endurability, focused attention, self-efficacy, perceived learning, and interest in the topic, were assessed, as were factors affecting these attributes related to the participants’ knowledge of CE principles and exposure to similar technologies. The two studies indicate that the AR engagement tool increased social inclusion and community cohesion and was able to successfully bring CE principles and benefits to the public’s attention. Higher engagement levels were observed in participants who had limited exposure to the concept of CE prior to using the AR tool, and its use was found to improve their confidence and interest in CE. This study aspires to contribute to the ongoing discourse on the use of mobile AR and to support further evidence-based development of digital tools for public awareness and engagement.The online version contains supplementary material available at 10.1007/s43615-021-00137-7. It is understood that to progress towards sustainable living effectively, citizens in all their diversity must be tightly engaged , , 2. TowaAn effective citizen engagement process should include the voices and needs of all participants and increase their knowledge about a public issue, encouraging them to apply that knowledge and finally what they learned to improve their quality of life and the community , 6. CreaNew technologies and digital transformation play an essential role in the process of citizen engagement and active participation, helping to reconfigure social relations and empower citizens, connect individuals, and facilitate knowledge exchange across ever-widening specificities . SeveralOver the past decade, media, technologies, software, and cultural practices that change how we experience and interact with the environment have emerged. Various Information and Communication Technologies (ICT) tools, including websites, mobile solutions, social media, and platforms, have been proposed to improve the understanding of public matters and engage citizens in a great variety of topics . NeverthRegarding the overall usability of ICT-based engagement practices for societal issues, Mukhtarov et al.  providedEurope’s communities are in many ways uniquely placed to transition to a CE model that aims to improve citizen’s life quality in many environmental, social, and economic aspects, and citizens — of all ages and skills — need to be positioned in the center of this process . NeverthGiven the immersive nature of AR technology, the extended use of smartphones and the internet on the go, and the ability to couple them together with advanced location and camera settings, AR can be part of the citizen participatory process. AR has been reported to be achieving a turning point for large-scale adoption, while vast expansion is expected in the upcoming years . Having Given the adaptable nature of the technology, mobile AR can comfort the limitations that other engagement tools face. Immersive technologies have demonstrated a significant effect in educating end-users  and offeIn the present study, we contribute further to the discourse of citizen engagement tools by developing and exploiting a user-friendly mobile application to engage citizens in CE principles and empower a sense of action towards this change. Our motivation is to effectively apply an AR-based tool to motivate and educate citizens around the notions of a CE model. Using an AR application to foster engagement, we exposed a municipality’s citizens to digital content related to a CE approach. A web survey was utilized to recruit the citizens and collect the required data. We recruited 127 citizens of a municipality in Greece to investigate which attributes and factors affect their engagement and self-efficacy. Concurrently, we collected data from a second sample (of 101 participants) outside this municipality to investigate the validity of our questions and extract preliminary results to an extent more significant than that of one municipality. This paper presents the results of this study and tries to draw some conclusions in the primary research hypothesis that the use of AR can prove a valuable tool for a mental shift towards CE approaches at a citizen level in an inclusive, accessible, and educative manner.The paper is organized as follows: in the following section, we discuss research on user engagement and explore the attributes and factors associated with engagement. We proceed by describing our research methodology and substantiating our analytical approach. The AR system is described then to demonstrate the features that affected engagement and assist future development efforts. We continue in our final section with a report of the results from the two research studies and conclude with a discussion section of how our findings relate to the improvement in citizen engagement and self-efficacy in CE, while we describe our limitations and provide suggestions for future research.User engagement is the emotional, cognitive, and behavioral connection that exists, at any point in time and possibly over time, between a user and a resource . User enThe engagement process involves several stages, starting from initiation, continuing with a period of engagement, then disengagement, and reengagement. Several attributes are present in each stage and define the engagement process . The engOne of the attributes affecting user engagement is the aesthetic appeal, which refers to the app’s visual elements. An aesthetically appealing ICT tool gives more pleasure and enjoyment, leading to a higher probability of using it. A significant component contributing to a mobile app’s aesthetic appeal is the user interface (UI), which refers to the flow of experience when users navigate an app, and whether performing tasks is user-friendly and convenient. According to Tang , it is eFocusing on AR tools, attention improves when the AR content is multimodal, and users can interact. The immersive capabilities of AR help users maintain high levels of attention and interest in the learning content, positively impacting users’ attention and engagement .Novelty reflects the software or tool’s view as new, attractive, and identifiably different from others used or understood at the time of the introduction . NoveltyOther attributes affecting user engagement are often associated with the interest, value, affect, and conscious awareness of motivation towards a particular activity or situation . IndividIn our approach, and following the aforementioned analysis, we posit a model that examines nine attributes affecting user engagement, notably (i) perceived usability, (ii) felt involvement, (iii) focused attention, (iv) novelty, (v) aesthetics, (vi) endurability, (vii) interest in the topic of CE, (viii) perceived learning, and (ix) self-efficacy. The first six attributes affect user experiences with technology and define user’s intentions. The last three attributes affect the user’s motivation towards a specific topic or content . The model’s reliability and validity are evaluated in the context of citizen engagement in CE in the following sections.The User Engagement Scale (UES) was introduced by O’Brien and Toms , as meanIs citizen engagement through AR technology inclusive for participants with low CE literacy and confidence on this topic?Is citizen engagement through AR technology inclusive for participants of all age groups, educational levels, and genders?Is citizen engagement through AR technology inclusive for participants who have never been exposed to similar technologies?To address the limitations of previous efforts, we built an AR engagement tool aiming to improve social cohesion by considering factors such as age, disability, low income, low education, cultural or language differences, and geographical or social isolation . A guidiAnswers to these questions are important as more extensive knowledge concerning citizen engagement may assist in designing inclusive and adaptive engagement tools with educative character and ultimately impact the adoption of CE principles. We also sought to provide insights that would help transform citizens of all ages from passive audiences to interactors regardless of their tech-savviness and prior exposure to technology.In our study, we exposed 127 citizens of a municipality and 101 citizens outside this municipality to the AR engagement tool and investigated at first the impact of specific attributes on user engagement and, ultimately, how specific factors affected them. The nine attributes that affect citizens’ engagement, as described above, and three factors affecting these attributes  were assessed.The AR mobile application (CirculAR) used in this study aims to improve citizen awareness and engagement towards CE principles. The app was developed using ARCore and Mapbox for the Unity game engine. RestAPI was used for server communication. CirculAR is compatible with Android smartphones and requires Global Positioning System (GPS) tracking as it supports both marker and location-based applications to overlay the digital data. Marker-based experiences are enabled after scanning a unique QR code for the digital media. The digital data consist of single image and video reveal, image gallery and multiple videos, and static three-dimensional 3D) models. More information regarding the system design and architecture of the AR application can be found in Katika et al. . Figure D models.The user of CirculAR can utilize finger gestures for object manipulation (both rotation and positioning) on the touch-based display of their smartphone . A virtuThe digital media were positioned via a web-based content management tool . This toThe first part aimed to assess the factors affecting engagement. More specifically, the technological profile  and the users’ demographic data were collected. In this part, ten questions aimed to assess the participant’s overall understanding and confidence towards the CE principles.The second part of the survey included a video demonstrating the AR application’s use, features, and content. The overall video lasted 3 min, and the users were unable to proceed to the third part of the survey unless having watched the video. This part exposed the users to the media and functionalities of the AR engagement tool.In the third part of the survey, changes in the user’s perceived comprehension of the CE principles and confidence towards such an economic approach upon exposure to the AR engagement tool were assessed. At the same part of the survey, the nine attributes affecting engagement were also assessed.For the period that the present study was conducted, in situ tests were not allowed due to the COVID-19 restrictions in the country. Therefore, virtual material and consultation, as well as online distribution were the sole means to expose participants to our AR engagement tool. To assess the information required regarding the attributes and factors affecting engagement, and to inform users about the AR engagement tool, we conducted an extended web survey, which consisted of three parts:To ensure the UES’s robustness and that the attributes adequately capture our proposed construct, we prepared a questionnaire as part of the third part of the web survey, based on relevant work by O’Brien and Toms . Using tThe web survey was distributed to the citizens of Karditsa, Greece. Karditsa is an evolving peripheral town that belongs to the Municipality of Karditsa, Region of Thessaly — Central Greece. The survey was translated to the native language of the citizens (Greek) to avoid any language barriers or bias. The city of Karditsa was selected primarily due to the sectors, related objectives, and priority axes set in the public space strategic management plan . The citTo ensure proper web survey methodology, we followed the core web survey process proposed by Callegaro et al. . The proTo support the model suggested to the municipality, we distributed our web survey through open channels to address citizens outside of the municipality, as part of a general population. The survey was distributed in English. To ensure that many interested stakeholders participated in our study, we recruited users via groups related to AR and CE on popular social platforms, such as Facebook and LinkedIn. Thus, this was a purposive sample with individuals chosen based on their interaction with the applications of interest to this study. The survey was posted online for 2 weeks . For the first 5 days, we collected feedback from 20 participants to optimize the survey and correct any technical issues. These responses were discarded by the analysis.The questions in the web survey assessing the engagement and factors affecting engagement used the Likert scale to demonstrate the agreement of the participant with statements. We used both positive and negative frames in the statements to ensure the participants are not biased towards agreeing with all of them to show themselves in a positive light and that the participants’ responses are reliable and consistent. The questionnaire consisted of 67 items that requested participants to indicate their agreement level, from “strongly agree” to “strongly disagree” .We chose four maturity levels for the Likert scale to enable the user to form a clear opinion on each statement. As we made sure that all questions apply to our AR application user, we concluded a specific user opinion is essential. We chose a unipolar scale to measure the attribute of agreement in each statement that was treated as interval level. Overall, we used descriptive statistics to summarize the data we collected, but we also analyzed single Likert-type questions for deeper insights into specific attributes presented in the discussion. Since we kept participation in the survey relatively high and acquired an adequate sample size where the data are normally distributed, parametric tests were used with Likert scale ordinal data . Since tIn total, 127 valid responses were collected by the web survey distributed to the citizens of Karditsa, Greece. All participants of the municipality viewed the demo of the AR application and answered all the mandatory questions in the survey. In parallel, 101 valid responses were collected via the web survey addressed to the general population outside the municipality. Table The low participation in the web survey, outside of the municipality of Karditsa, did not qualify for a reliable analysis of the data extracted. Trends in the factors will be extracted in the following sections to demonstrate any correlation with our case study within the municipality (city of Karditsa) outcomes. Therefore, all paragraphs therein refer to the engagement attributes assessed by the survey contacted with the citizens of Karditsa.The User Engagement Scale’s reliability and validity of the survey has been evaluated with six attributes  applied in online shopping . To ensuUsing IBM SPSS Statistics 21, we aimed to understand whether the attributes of the User Engagement Scale load together to capture the user’s engagement. A similar approach was followed for the attributes of motivational engagement. Felt involvement was removed by the hypothesized model since the a-determinant was significantly lower due to this attribute. Our preliminary assumption is that users are not able to experience felt involvement of a mobile app through a video.For all remaining attributes of engagement assessed via the web survey in the municipality, we determined Cronbach’s alpha as a measure of internal consistency reflecting how closely related a set of items are as a group. Values of the parameter from 0.7 to 0.9 were considered “respectable” to “very good,” and values above 0.9 were considered “excellent” . Table 2Principal component analysis (PCA) was then run with all items to ensure that a single factor did not emerge. Correlations for the measures used in the study were calculated Table . Upon reAccording to Wolf et al. , a minimThe fitness of the questionnaire’s internal structure was evaluated with confirmatory factor analysis, employing SPSS AMOS 26. The model suggested that endurability was predicted by perceived usability and focused attention. Aesthetics predicted perceived usability and focused attention; novelty predicted focused attention and perceived usability; and the structural model becomes as shown in Figure β) and significance (p) are presented in Table Following the CFA’s goodness of fit and satisfying the subsequent tests, the structural equation model was then estimated. We performed multiple analyses, and we excluded all values below 0.2. The final structural equation model is presented in Figure In each case, the following indices of fit were calculated: root mean square error of approximation (RMSEA), goodness of fit (GFI), normed fit (NFI), and comparative fit (CFI). The proposed values for excellent fit are described in Hooper et al.  as the fχ2 = 51, df = 11, p < 0.01, CFI = 0.938, NFI = 0.923, GFI = 0.947, TLI = 0.945, and RMSEA = 0.103.As expected, given the low number of participants, the resulting model did not have an ideal fit, but since our results are in close agreement, we proceeded with further analysis. For the 127 participants, we determined To perform descriptive statistics with the Likert scale results, we assumed the difference between each point in the scale to be evenly spaced . Table 5In our survey, we extracted several factors to investigate their effect on the engagement attributes. These factors included the CE literacy, tech-savviness, and demographics of the 127 participants from the citizens of the municipality of Karditsa.Starting with the participants’ exposure to technologies, such as smartphones, AR features, mobile games, cameras, and search engines, we established that more than 90% of the participants use a smartphone, perform web searches, and use their smartphone to take photos. Therefore, only exposure to AR and mobile games should determine how tech-savviness affects engagement attributes. As for the CE literacy, the variation in all assessed factors allowed us to proceed with the correlation analysis. Figure Figure While investigating the engagement attributes separately, one of the factors that demonstrated the highest variance comes from end-users who claimed that CE already holds their attention before exposure to AR, most likely, demonstrating highest CE literacy and confidence. These users resulted in 10–15% lower in all engagement attributes Figure . They alOn the same note, users who were already confident to practice the CE practices or to explain the CE principles to their friends appear to miss out on the AR app’s perceived usability to a degree of 20 to 30% Fig. . ParticiThe same trend is followed by another factor; users who already wanted to contribute to CE found the AR engagement tool almost 30% less useful than users who had not expressed their interest to contribute to CE Figure . ConfideDespite the difference in the participation between males and females, no significant differences are seen in all engagement attributes Figure . DiffereAge appears to affect many engagement attributes as seen in Figure To investigate the validity of our questions and extract preliminary results to an extent more significant than that of the municipality in Greece, we performed a similar analysis with the independent sample that answered the global survey. We collected most answers from the capitals of Greece, Denmark, and the Netherlands. Even though the response rate was low, we proceeded by investigating the most determining factors of the overall engagement from the previous analysis, the CE literacy and tech-savviness. Similar trends are observed regarding the CE literacy in both surveys and validated our initial results. CE-proficient participants scored lower in all engagement attributes. Figure Guided by the research questions, our study suggests that AR, acting as an engagement tool, can increase end-users’ perceived interest and engagement in CE concepts. At the same time, it can help narrow the gap between public authorities and citizens, which has been found to impact CE adoption , 48. ResAnswering the first research question, one of this study’s main findings is that our AR tool had a more pronounced effect on the engagement of participants who have low CE literacy on the topic. It should be noted that general public exposure to CE principles is relatively low and new, providing confidence in our tool’s relevance . The abiA very promising finding, revealing the relevance of the second research question, is that the gender of the end-users is not affecting the engagement and interest in the topic we convey via AR. A thorough investigation on the motivational factors regarding the climate change mitigation performed by Brink and Wamsler  demonstrUpon exposure to the AR engagement tool, more than 75% of all users in this survey reported a high interest in CE, and more than 83% of all participants demonstrated high self-efficacy and perceived learning in the same topic. The results are higher for users who do not have higher education, agreeing with Billinghurst and Duenser  who demoTo further support the AR engagement practice’s inclusivity and answer the third research question, the citizens of the municipality demonstrated high self-efficacy regardless of any exposure to similar technology. Self-efficacy is a significant predictor of success associated with the ability to complete tasks, and was not affected by the low prior exposure to AR . Nearly The citizens of Karditsa have articulated their need to follow a more circular approach by expressing their dissatisfaction due to the lack of effective waste management processes in the town center and with their access to information that affects public matters . They haYounger age groups in the municipality of Karditsa demonstrated high dissatisfaction in terms of environmental issues, which appear to be their preferences on prioritization of local resource distribution for meeting citizens’ expectations . Such a Upon exposure to our AR engagement tool, the citizens of Karditsa agreed that an AR app would positively affect their understanding of CE principles and their ability to apply them in real life to a degree of 88%. Such a promise is fundamental to improve the use of the city resources since the citizens of Karditsa are not committed to an inclusive, sustainable, city- and citizen-specific, strategic public space management and regeneration plan, and their perception of it as a “common good” is relatively poor . There iThis study investigated whether an AR app can increase citizen engagement in CE-related topics. Due to AR’s infancy as an engagement tool, a limited number of apps utilize AR to its fullest potential. Additionally, since not many societies have adopted CE, there is a limited number of interested (or well-informed) users. Given the promising nature of our results, in terms of inclusivity, relevance, accessibility, and educative means, other municipalities can use the example of the city of Karditsa to improve their citizen participatory practices. The municipality is planning an in situ activity upon seizing the COVID-19 restrictions to investigate the impact of this initiative on the citizens. The AR engagement tool will be distributed to the citizens, and surveys and questionnaires will assess the before and after changes in their behavior and mindset as an effect of the actionable and timely information available on their mobile devices. The citizens will report changes in performance and other initiatives to reflect whether the AR engagement tool contributed to more sustainable lifestyle choices.The inability to correlate felt involvement with engagement , despite suggestions from other research studies that claimed to be one of the determining attributes of engagement, reflects the need for future research to explore this attribute as well as assess its effectiveness. Future research should expose the participants directly to the AR engagement tool via in situ tests  to ensure better insights into such an attribute. An experiment-based research design may allow researchers to gain further insight into the unique AR attributes influencing citizen engagement towards CE adoption.In the case studies reported in this paper, we examined how age, gender, tech-savviness, prior exposure to related content, and education level affect such an adoption. A future study should consider additional vital dimensions such as disabilities, income, cultural or language differences, and geographical or social isolation of the participants.Lastly, a limitation of this work lies in its use of an online survey as a data collection method. To ensure that the participants had a great understanding of the AR app, they watched a lengthy video demonstrating the AR app’s content, features, and capabilities. Plus, to assess all user engagement attributes and all factors affecting these attributes, the users had to respond to 44 questions. Therefore, our response rate was low.In this work, we reported on the development of a novel, inclusive, accessible, and portable citizen engagement tool that utilizes AR technology. We assessed its ability to improve the attributes that the literature suggests to predict engagement, along with the factors that affect these attributes. The research was conducted both in a closed urban environment, the municipality of Karditsa, and globally.The study demonstrated significant improvement in context-specific citizen engagement. Specifically, both the municipality citizens and a global sample of participants demonstrated high motivation towards CE and an enhanced self-efficacy in the same topic. Overall, all attributes demonstrated a good correlation with end-user engagement.With regard to inclusivity requirements, the tool was found to be more useful to citizens with low CE literacy and confidence than to CE-proficient participants. The tool’s usability also increased with the dissatisfaction with the current city initiatives towards a more sustainable environment. Upon exposure to the AR engagement tool, citizens who did not have higher education feel more confident towards CE and are more likely to recommend the experience to their friends. Such an outcome points towards the ability of AR-driven engagement to make information that affects public matters accessible to everyone.We conclude that in communities aiming to change their participatory approaches and governance schemes towards climatic and economic issues, such an AR engagement tool supports sustainable change and adoption, providing an inclusive and democratic engagement platform appropriate for citizens of all ages, education levels, tech-savviness, and genders Tables , 3, 4, 5Supplementary file1 (DOCX 17 KB)Below is the link to the electronic supplementary material.


T) was isolated from a peat bog in northern Minnesota. On the basis of 16S rRNA gene sequence similarity (99.8 % identity with Mycolicibacterium septicum and 98 % with Mycolicibacterium peregrinum) and chemotaxonomic data (fatty acid content), strain DL90T represents a member of the genus Mycolicibacterium. Physiological tests  and biochemical analysis (arylsulfatase activity and fatty acid profiles) distinguish DL90T from its closest relative M. septicum. Phylogenomic reconstruction of the ‘Fortuitium–Vaccae’ clade, digital DNA–DNA hybridization (DDH) values of 61 %, and average nucleotide identity (ANI) values of approximately 95 % indicate that DL90T is likely to be diverged from M. septicum. Thus, we propose that DL90T represents a novel species, given the name Mycolicibacterium nivoides with the type strain being isolate DL90T (=JCM 32796T=NCCB 100660T).A fast-growing, non-chromogenic, acid-fast-staining bacterium (DL90 FAME, fatty acid methyl esters.Mycobacterium contains over 188 species and has recently been subdivided into four novel genera, including the fast-growing ‘Fortuitium–Vaccae’ clade for which species are designated with the new genus name Mycolicibacterium [rpoB, dnaJ and hsp65. Isolates with unique banding patterns were pooled and their PCR products sequenced for reconstruction of concatenated sequences (rpoB–dnaJ–hsp65) to produce phylogenetic trees for comparison with known species. From this initial screen a potential novel species was chosen for further characterization and is referred to here as strain DL90T.The genus acterium . Given tacterium . Severalacterium . CandidaT was grown using tryptic soy broth (TSB) or agar (TSA), Middlebrook 7H10 agar supplemented with oleic acid, bovine albumin, sodium chloride, dextrose and catalase (OADC), or Middlebrook 7H9 broth supplemented with albumin dextrose and catalase (ADC). Tween 80 was added to both TSB and 7H9 liquid cultures during growth curve experiments to compare with other characterized mycobacterial isolates obtained from the American Tissue Culture Collection. No Tween 80 was added for experiments testing biofilm formation. fatty acid methyl ester (FAME) analysis was performed by Microbial ID Inc  using DL90T cells grown on TSA, as previously described [Isolate DL90escribed .T genome, DNA was isolated from liquid-grown cultures (7H9 supplemented with ADC) using NucleoSpin Tissue Extraction kits (Macherey–Nagel). The DNA sequencing library was prepared using a Nextera XT kit (Illumina) and sequenced on the MiSeq platform with 2×300bp v3. Assembly of the genome was done using the Galaxy web platform. Prior to assembly, reads were trimmed using Trimmomatic [https://www.bioinformatics.babraham.ac.uk/projects/fastqc/). A de novo assembly was performed using Unicycler [T genome, we compared DL90T to previously characterized mycobacteria, as previously described [clustalx and a maximum likelihood phylogenetic tree was reconstructed with mega7 [T is closely related to the species Mycolicibacterium septicum, which was also determined by blast sequence analysis [To sequence the DL90mmomatic  and qualnicycler . The finanalysis .T genome , hence this was excluded from the alignment. Phylogenetic placement using the concatenated protein tree indicates, as expected, that the DL90T genome is highly similar to the M. septicum DSM 44393T genome and belongs to a larger clade with M. setense, M. neworleansense, M. fortuitum and M. peregrinum , which has a different implementation of ANI than fastANI, indicated that the two genomes were 94.97 % similar [M. porcinum, M. vulneris, M. conceptionense, M. farcinogenes and M. senegalense). This would indicate that either these isolates have a high degree of phenotypic divergence or that they should be reclassified as strains of a single species.Comparison of the 16S rRNA gene sequences of DL90isolates  indicate similar . InteresT to M. septicum DSM 44393T revealed that their genomes are similar in size  with the DL90T genome slightly larger and containing approximately 80 more genes (Table S2). Although their genome sizes are similar, and DL90T and M. septicum DSM 44393T share 5234 orthologous genes, this homology constitutes only 81 % of their genomes. This indicates their genomes have gained and/or lost genes as they have diverged. For comparison, the genome content of DL90T  varies across the larger clade of closely related genomes (Table S2) and indicates that the life history of these organisms is complicated. Amino acid identity (AAI) values were slightly higher than ANI values at 95.93 similarity (Table S2), however, there are currently no recommended or accepted AAI values to delineate novel species [T and M. septicum DSM 44393T which is below the <70 % threshold of hybridization between members of the same species [T with other isolates show very low DDH values (<40 %), which is consistent with our other analyses (Table S2). Nonetheless, these indicate that DL90T is potentially sufficiently diverged at the genomic level from M. septicum DSM 44393T to be considered to represent a novel species.Further genomic comparisons of DL90 species . Digital species . CompariT and M. septicum colonies have similar smooth circumferences on 7H10 agar supplemented with OADC , but there are numerous differences between the two strains. When grown on tryptic soy agar, DL90T is much more scalloped compared with M. septicum . While M. septicum is fully susceptible to kanamycin (20 μg ml−1) on TSA, DL90T is completely resistant. When standing liquid cultures were compared, M. septicum biofilm was much thicker and adhered more strongly to glass surfaces than DL90T . Permissible growth temperature ranges were similar for DL90T and M. septicum, however, DL90T grows much faster growth than M. septicum in aerated liquid cultures . Both M. septicum and DL90T showed resistance to heat killing in a water bath although DL90T was much more resistant to heat killing at the two temperatures tested . Arylsufatase activity was detected at 3 days for DL90T while M. septicum DSM 44393T was negative. Lastly, the fatty acid methyl esters (FAMEs) profile of DL90T is distinct from that of M. septicum  Specifically, DL90T contains four fatty acids  that are not detected in M. septicum. Overall, these genetic, biochemical, morphological and physiological features of isolate DL90T distinguish it as representing a novel species that is given then name Mycolicibacterium nivoides.Both DL90septicum  , resembling, similar; N.L. neut. adj. nivoides snow-like).M. septicum DSM 44393T, but ANI values indicate that this is a novel species. The fatty acid methyl ester (FAME) profile is distinct from that of M. septicum.Cells are small, Gram-reaction-variable, acid-fast-positive, non-spore-forming, non-motile straight rods. Colonies are dry, rough, flat, non-chromogenic with undulated/scalloped edges on tryptic soy agar. Colonies bind tightly to agar surfaces, and the isolate forms a flocculent, white biofilm on the surface of liquid media with some attachment to glass surfaces. Colonies appear within 3 days of growth on tryptic soy broth with 1.5 % (w/v) agar, with relatively slower growth on 7H10 agar enriched with OADC. Growth is observed at 25–37 °C with optimal growth at 28 °C. No growth is observed at 42 °C although cultures can survive up to a week at 42 °C on agar before resuming growth at lower temperatures. The isolate cannot survive on agar at 45 °C for a week. Modest growth with 5 % (w/v) NaCl. Positive reaction in enzymatic tests for 68 °C catalase, semi-quantitative catalase, urease, 3- and 14-day arylsulfatase activity and 10-day tellurite reduction. Negative reactions for Tween 80 hydrolysis, nitrate reduction, and 3-day tellurite reduction. The 16S rRNA gene is most similar to that of T (=JCM 32796T=NCCB 100660T) and was isolated from a sphagnum peat bog in northern Minnesota, USA. GenBank accession numbers for the 16S rRNA and the genome of the type strain are MH290160 and CP034072.1, respectively.The type strain is DL90Click here for additional data file.


Metastatic prostate cancer is the most common cancer in males and the fifth cause of cancer mortality worldwide. Despite the major progress in this field, leading to the approval of novel anti-androgens, the prognosis is still poor. A significant number of patients acquire an androgen receptor splice variant 7 (AR-V7), which is constitutively activated and lacks the ligand-binding domain (LBD) while maintaining the nuclear localization signal and DNA-binding domain (DBD). This conformational change, even in the absence of the ligand, allows its retention within the nucleus, where it acts as a transcription factor repressing crucial tumor suppressor genes. AR-V7 is an important oncogenic driver and plays a role as an early diagnostic and prognostic marker, as well as a therapeutic target for antagonists such as niclosamide and TAS3681. Anti-AR-V7 drugs have shown promise in recent clinical investigations on this subset of patients. This mini-review focuses on the relevance of AR-V7 in the clinical manifestations of castration-resistant prostate cancer (CRPC) and summarizes redemptive therapeutic strategies. Prostate cancer is the second most common cancer in men and the fifth cause of mortality worldwide, accounting for 33,330 deaths in the United States in 2020 . AndrogeIn order to overcome castration resistance, the United States Food and Drug Administration (FDA) has approved the use of second-generation ADT agents targeting androgen synthesis (abiraterone acetate) and androgen receptor  following favorable Phase III trial results ,9. CabazData from the Phase III ALSYMPCA trial show that radium-dichloride (radium-223), an alpha emitter selectively targeting bone metastases with alpha particles , increasOver the past decades, preclinical and clinical research on tumor samples from CRPC patients has uncovered diverse resistance mechanisms leading to persistent androgen receptor addiction . Indeed,Several androgen receptor splice variants have been identified in PCa cell lines and xenograft tumors at the mRNA level ,26. In 2This mini-review focuses on how the structure of AR-V7 impacts its own function, leading to prostate cancer cell proliferation and resistance to second-generation hormonal therapies. In the era of precision oncology, better knowledge of AR biology, including AR splice variants, will help select mCRPC patients likely to derive little clinical benefit from potent drugs such as abiraterone and enzalutamide and offer them more effective treatment leading to a paradigm shift in mCRPC management.Various clinical markers  are generally used to predict prognosis in advanced prostate cancer ,31. In aThe Gleason grading system, originally proposed by Donald Gleason in 1966, has undergone several important changes, which have been incorporated into the 2016 World Health Organization (WHO) Classification of Tumors of the Urinary System and Male Genital Organs blue book . AlongsiImaging techniques are commonly employed to assess the extent of prostate cancer spread and play a pivotal role in therapeutic decision-making . Over thFor many years, the cornerstone treatment of advanced prostate cancer has been traditional androgen deprivation therapy (ADT), accomplished with surgical castration or chronic administration of gonadotropin-releasing hormone analogs. This regimen is highly effective in patients with biochemical recurrence following radiation or surgical procedure for localized prostate cancer ; howeverNo consensus has been reached on the best treatment sequencing for mCRPC patients, nor do current clinical data support unambiguous guidance concerning the best second-line treatment. Many physicians routinely prescribe taxanes in this setting, although a substantial subgroup of patients may still benefit from oral, less toxic, and better tolerated ARS inhibitors. In addition, an empiric sequencing approach could result in toxicity, higher treatment costs, and delays in patients administered with potentially more effective regimens ,47.In recent years, AR-V7 genomic alterations have been associated with progression to mCRPC, patients with detectable AR-V7 in liquid biopsies usually manifesting more aggressive disease and shorter survival . EmerginBoth preclinical and clinical studies have demonstrated a correlation between abiraterone or enzalutamide resistance and AR-V7 expression, as well as decreased OS in CRPC patients ,51,52. IThe canonical AR gene, located on the X chromosome (Xq11-12), exceeds 90 kb and contains eight exons encoding the AR protein, a ligand-dependent nuclear transcription factor and member of the steroid hormone receptor family . AR is aAR-V7 mRNA retains the first three canonical exons, followed by variant-specific cryptic exon 3 (CE3) within intron 3 ,64,65. ANumerous molecular alterations are reported to be associated with AR Axis-Targeted Therapy (AATT) resistance . AlthougOf paramount importance is the ability of AR-V7 to repress the transcription of tumor suppressor genes . Unlike p = 0.03) and higher OS than AR-V7 positive patients .The expression of AR-V7 has been extensively investigated in both normal and neoplastic prostate tissue. Using a recombinant rabbit monoclonal antibody validated for immunohistochemistry, Sharp et al. demonstrated that AR-V7 is rarely observed in primary prostate tumor specimens (<1%) but is frequent in metastatic biopsy specimens after ADT (>75%), suggesting that AR-V7 increases under the selective pressure of hormonal treatment . AR-V7 pSeveral studies comparing outcomes of mCRPC patients administered second- and third-line therapies have identified AR-V7 in CTCs by means of qRT-PCR and immunohistochemistry. Antonarakis et al. were the first to show that the presence of AR-V7 transcripts in CTCs from mCRPC patients is correlated with second-line AATT resistance . Of 31 ep < 0.001). During AATT, OS and PFS were significantly shorter in AR-V7-positive than in AR-V7-negative patients. In AR-V7-positive patients, multivariate analysis revealed that HR for death was lower in those treated with taxanes compared with those treated with AATT . This study concluded that: (1) AR-V7 positivity increases with the number of treatment lines; (2) AR-V7 positive CTCs can predict a lack in clinical AATT benefit and (3) AR-V7 positive CTCs in men with mCRPC can predict resistance to ARS inhibitors but not to taxanes , differently from conventional therapies targeting the ligand-binding domain. For this reason, EPI-001 was initially considered useful for mCRPC treatment. The successor to EPI-001, EPI-506, a prodrug of ralaniten (EPI-002), was investigated in a Phase I study on mCRPC, but was discontinued after showing only minor PSA decline. Though well tolerated, it proved ineffective probably on account of its high metabolization rate, indeed, 19 metabolites were detected in patient plasma . AR-V7 antagonists, niclosamide and TAS3681, and possibly PROTAC ARV-110, therefore remain the most promising drugs for mCRPC patients progressing under second-generation androgen-depriving therapeutics. Despite recent therapeutic advances, CRPC still remains a lethal disease. AR-V7 is a constitutively active AR isoform that does not require ligand binding and is difficult to treat with commercial androgen-depriving second-generation drugs. AR-V7-positive CTCs have been associated with poor clinical outcome and AATT resistance, thus making AR-V7 a valid biomarker to estimate patient prognosis. Novel drugs such as niclosamide and TAS3681, capable of targeting this variant, have been developed. Future randomized and large clinical trials testing these molecules in patients with AR-V7 positive CRPC are warranted.


Type 2 diabetes mellitus causes left ventricular (LV) remodeling and increases the risk of aortic regurgitation (AR), which causes further heart damage. This study aimed to investigate whether AR aggravates LV deformation dysfunction and to identify independent factors affecting the global peak strain (PS) of LV remodeling in patients with type 2 diabetes mellitus (T2DM) who presented with AR and those without T2DM.In total, 215 patients with T2DM and 83 age- and sex-matched healthy controls who underwent cardiac magnetic resonance examination were included. Based on the echocardiogram findings, T2DM patients with AR were divided into three groups . LV function and global strain parameters were compared, and multivariate analysis was performed to identify the independent indicators of LV PS.The T2DM patients with AR had a lower LV global PS, peak systolic strain rate (PSSR), and peak diastolic strain rate (PDSR) in three directions than those without AR and non-T2DM controls. Patients without AR had a lower PS  and PDSR in three directions and higher PSSR  than healthy controls. Further, regurgitation degree was an independent factor of LV global radial, circumferential, and longitudinal PS.AR may aggravate LV stiffness in patients with T2DM, resulting in lower LV strain and function. Regurgitation degree and sex were independently correlated with LV global PS in patients with T2DM and AR.The online version contains supplementary material available at 10.1186/s12933-022-01471-2. Type 2 diabetes mellitus (T2DM) and its related cardiovascular diseases are causing increasing burden in terms of morbidity and mortality. T2DM is characterized by insufficient or non-effective utilization of insulin, resulting in chronic hyperglycemia , 2. AortCardiac magnetic resonance (CMR) tissue-tracking technology, which is based on the post-processing of standard steady-state free precession cine images, has become a well-accepted imaging tool for quantifying diabetes-related cardiac deformation dysfunction –8. CMR cThis study was approved by the Biomedical Research Ethics Committee of our hospital and conducted in accordance with the Declaration of Helsinki (2013 Edition). Due to the retrospective nature of the research, the need for informed consent was waived.2, respectively. Among them, 66 (37.6%) presented with AR , whereas 149 (62.4%) did not. Concurrently, 83 individuals with sex, age, and BMI distribution similar to those of our patients were included in the control group. All patients and controls underwent the same CMR examination.This research included 432 individuals with T2DM who were clinically diagnosed based on the current American Diabetes Association guidelines and who underwent CMR examinations at our hospital between April 2012 and April 2021  vs. [60.7 ± 11.4 g/m2]), but there existed no significant difference. Patients with T2DM who presented with AR had a lower LV global PS, PSSR, and PDSR in the three directions than patients without AR and healthy controls . The patients without AR had a lower PS  and PDSR in the three directions and a higher PSSR  than healthy controls .Tables In the T2DM (AR +) group, 28 43.9%) patients presented with mild, 21 (30.3%) with moderate, and 17 (25.8%) with severe AR. Table .9% patieThe mild AR group had lower PS , PSSR , and PDSR  than the healthy control group . The moderate group had lower PS, PSSR, and PDSR in the three directions than the healthy control group . Compared with patients with mild AR, those with moderate and severe AR had a lower PS , PDSR , and PSSR  . The severe AR group had significantly lower PS, PSSR, and PDSR in the three directions than the healthy control and mild AR groups .There was a negative correlation between the AR degree and LV global radial PS , circumferential PS , and longitudinal PS  in patients with T2DM who presented with AR. In addition, fasting plasma glucose level was negatively correlated with LV global radial PS  and longitudinal PS , but not circumferential PS  in patients with T2DM who presented with AR Table . Figure After adjusting for age, sex, BMI, systolic blood pressure, and resting heart rate, the multiple linear regression analysis further showed that the regurgitation degree was an independent factor of LV global radial (β =  − 0.577), circumferential (β = − 0.662), and longitudinal (β = − 0.621) PS . Sex was found to be an independent factor of LV global radial (β = − 0.158), circumferential (β = − 0.181), and longitudinal (β = − 0.163) PS in patients with T2DM who presented with AR Table .The intragroup correlation coefficient analysis revealed that the CMR tissue-tracking technique for measuring LV strain parameters had good intra- and interobserver consistency  and PDSR  even without AR. Second, patients with T2DM who presented with AR had a significantly lower LV strain parameters in the three directions, and there was a decrease in LVEF and increase in LV mass. Third, along with the aggravation of regurgitation, the LV strain of patients with T2DM who presented with AR decreased progressively. Meanwhile, early diastolic dysfunction was observed in the mild AR group and further impairment in systolic function in the moderate and severe groups. Fourth, AR degree was independently correlated with LV PS .Previous studies have shown the importance of CMR-derived global longitudinal PS in patients with T2DM. Habek et al. and Vukomanovic et al. revealed that strain in the longitudinal direction and in the diastolic period is initially impaired at the early stage , 20–22. Patients with T2DM (AR +) had a higher LV mass, LVEDV, and LVESV and a significantly lower LVEF than healthy controls and patients with T2DM (AR −). Moreover, the T2DM (AR +) group had a remarkedly lower LV global PS, PSSR, and PDSR in the three directions. Therefore, AR has an additive effect on LV deformation in patients with T2DM, particularly LV function impairment. A series of studies about nondiabetic AR have shown that global longitudinal strain decreases early in the course of the disease and is a marker of AR severity , 30, 31.Based on the systolic and diastolic data, compared with the healthy control group, the T2DM (AR −) group experienced a significant decrease in PDSR in the three directions, and PSSR  but not PSSR . Patients with T2DM without AR first developed LV diastolic dysfunction due to subendocardial fiber damage. However, their systolic function remained within normal range at the early stages. Combined with AR, the systolic function of the left ventricle will significantly reduce. Then, LV dysfunction and heart failure may eventually develop. Therefore, AR can not only further aggravate LV diastolic dysfunction but also cause severe LV systolic dysfunction. Therefore, the development of AR must also be considered in the management of patients with diabetes due to these negative superimposed effects , 5, 34.The different regurgitation degrees of patients with T2DM were compared. The results showed that the mild, moderate, and severe AR groups experienced a progressive decrease in LV global PS. The diastolic function of the mild AR group was impaired. Meanwhile, the systolic function of the moderate and severe groups decreased. A previous study revealed that damage in the LV caused by AR starts from diastolic function. With the aggravation of regurgitation, there was evident systolic dysfunction –37. TherThe current study had several limitations. First, although the sample size was large enough to confirm the additive effect of AR on LV impairment in patients with T2DM, this was a single-center study. Second, long-term follow-up data were not available, and there were limitations due to the cross-sectional nature of the study. Third, only patients with diabetes who presented with AR were assessed, and individuals with AR alone were not included. However, previous studies have assessed the effects of AR alone. Nevertheless, a comparative study including patients with AR alone should be performed.AR may aggravate LV stiffness and cause decreased LV strain and cardiac dysfunction in patients with T2DM. Regurgitation and sex were independently correlated with LV PS in patients with T2DM who presented with AR. The evaluation of LV strain may help clinicians monitor the progression of myocardial stiffness and use additional strategies to delay LV dysfunction in patients with T2DM who present with AR.Additional file 1: Figure S1. Analysis of left ventricular volume and function by cardiac magnetic resonance cine images. The left ventricular endocardium (red) and epicardium (green) were outlined on the left ventricular short axis images of end diastolic (A) and end systolic (B) according to the reference line (C), two-chamber long axis (D) and four-chamber long axis (E) images of end diastolic. The blue T-line defines the mitral plane and apex. (F) shows the 3D volume tissue tracking model of left ventricle automatically established.Additional file 2: Figure S2. Ratio of the aortic jet width (diameter) to left ventricular outflow tract (LVOT) diameter. The diameter of the color jet is measured immediately beneath the aortic valve is a semi-quantitative index of aortic regurgitation severity. Parasternal short axis view (A); Parasternal long axis view (B).Additional file 3: Table S1. Reproducibility about intragroup correlation coefficient of LV strains via CMR tissue-tracking technique.


The second volume of the special issues dedicated to the involvement of blood-brain barrier (BBB), neurovascular coupling, and angiogenesis in the regulation of brain functions contains four original articles, two reviews, and one perspective to complete the overview of the complexity of the neurovascular unit and its functions. The articles are more focused on astrocytes' participation in neurovascular coupling and on alteration after subarachnoid hemorrhage or in murine Alzheimer's disease models.Toro-Fernández et al.). This transplantation, inducing remodeling of astrocyte shape and modification of calcium signaling, affects the expression of synaptic proteins such as PSD95 or synapsin, suggesting the modification of neuronal activity in the hippocampus. These results should be taken into consideration for further investigation as a potential tool for cell transplantation to restore brain function after brain injuries.In this issue, the control of the neurovascular unit by astrocytes is discussed in two articles. Firstly, the astrocyte expression of CDK5, known to participate in protecting the neurovascular unit during glutamate-induced excitotoxicity, regulates functional interaction between astrocytes and neurons as shown by the transplantation of CDK5 knock-out astrocytes in the hippocampus  is focused on component 8 gamma (C8γ), known to inhibit neuroinflammation. The study specifies that C8γ is expressed by astrocytes of the neurovascular unit and antagonizes the sphingosine-1-phosphate receptor 2 (S1PR2) expressed on endothelial cells. Knockdown of C8γ enhances BBB permeability, whereas recombinant C8γ reduces neuroinflammation-induced BBB damage, thus confirming the crucial role of interactions between astrocytes and endothelial cells in neuroinflammation pathophysiology.The second study , the increase of cerebral blood flow due to Shaffer collaterals stimulation is drastically reduced compared to those observed in wild type, and the properties of neuronal activity are altered in hippocampus slices. At the same time, gliovascular coupling is impaired as shown though alteration of vascular reactivity and both calcium and reactive oxygen species' signals in perivascular astrocytes as observed in hippocampus slices by two-photon microscopy.The hypothesis indicating that neurovascular coupling is affected in Alzheimer's disease is now well established in several animal models. However, the mechanisms altered in the different mouse models remain to be elucidated. In the APP mouse model . This method allows for evaluation and validation of preclinical approaches to restore cerebral vascular autoregulation, which is impaired by several cardiovascular or cerebrovascular pathologies.Finally, subarachnoid hemorrhage (SAH) represents a severe form of stroke that induces neurological deficits long after the ictus and considerably alters the life of the patient. Koide and collaborators, through modeling of SAH in mice, investigate how SAH impacts cerebral autoregulation required to maintain brain perfusion. They have developed elegant new technics to calibrate Eltanahy et al.) perfectly completes the one published in the first volume of this special issue regarding pericytes , the authors remind us of the specificity of the endothelial cells of the cerebral microvessels, their polarity through their specific equipment in transporters and proteins of junctions, and their specific interactions with the pericytes and astrocytes to form the neurovascular unit. They analyze the advantages and disadvantages of the three main techniques of three-dimensional reproduction of intracerebral vascular networks in context of the challenge of stable perfusion of the network, the implementation of cellular interactions while preserving the vascular complexity, and allowing the expression of neuronal activity. They also insist on the importance of the shear stress and force applied on the 3D reconstructed vascular network and on the choice of the cell lineage to reproduce the diversity of situations observed in brain vasculature.The review entitled “Pericytes: Intrinsic Transportation Engineers of the CNS Microcirculation”  evokes the “geographic heterogeneity” of neurovascular units in the brain. Since the cell composition along the vascular tree is heterogenous, they argue that regional specificity of neurovascular unit compounds should be considered to propose new research pathways and be able to develop more acute therapeutic targets. In fact, the specific alteration of the white matter in small cerebrovascular diseases suggest vascular specificities of white matter as detailed in sections concerning each cell type of the neurovascular unit. They also point out differences between endothelial cells of the cortex and subcortical areas such as the hippocampus, the pericyte density in cortex layers, and differences in shapes and interactions between astrocyte and endothelial cells. These differences could explain the vulnerability of vascular function in specific regions. The last part of the review compares the in vivo methods to appreciate the dynamics of neurovascular unit function .The last review  and Centre National des études spatiales (CNES). DC received grants from the Italian Ministry of Health (MOH) for the Ricerca Corrente program.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. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Cardiomyocyte-specific targeting of α2-AR would provide cardiac muscle-delimited stress control and enhance the efficacy of cardiac malfunction treatments. However, little is known about the specific contribution of the α2-AR subtypes in modulating cardiomyocyte functions. Herein, we analyzed the expression profile of α2A, α2B and α2C subtypes in mouse ventricle and conducted electrophysiological antagonist assay evaluating the contribution of these isoforms to the suppression of L-type Ca2+ current (ICaL). Patch-clamp electro-pharmacological studies revealed that the α2-agonist-induced suppression of ICaL involves mainly the α2C, to a lesser extent the α2B, and not the α2A isoforms. RT-qPCR evaluation revealed the presence of adra2b and adra2c , but was unable to identify the expression of adra2a (α2A isoform gene) in the mouse left ventricle. Immunoblotting confirmed the presence only of the α2B and the α2C proteins in this tissue. The identified α2-AR isoform-linked regulation of ICaL in the mouse ventricle provides an important molecular substrate for the cardioprotective targeting.Sarcolemmal α2 adrenoceptors (α2-AR), represented by α2A, α2B and α2C isoforms, can safeguard cardiac muscle under sympathoadrenergic surge by governing Ca Primers  used for the assay are listed in Total RNA was extracted from left ventricular walls (~100 mg) isolated from isofluorane (2%)-anesthetized mice. Tissue samples were stored and homogenized in 1 mL of ExtractRNA reagent . RNA isolation was performed according to the manufacturer recommendations. At the final step, RNA was precipitated by 3 volumes of 96% ethanol. The pellet, following washing in cold 75% ethanol and air-drying, was resuspended in 100 µL of deionized water. RNA preps were treated with DNAse I (04716728001 Roche) for 1 h at 37 °C, followed by DNAse inactivation for 10 min at 70 °C, to reduce genomic DNA contamination. The quality of RNA isolation was controlled spectrophotometrically, using the NanoDrop 2000c . Synthesis of cDNA was carried out with the commercially available reverse transcription MMLV RT kit  using an oliogo(dT)Proteins were separated in 10% SDS-PAGE, transferred to nitrocellulose membranes  and probed with antibodies against α2A , α2B  and α2C  diluted to 1:100. Counterstain was performed with horseradish peroxidase (HRP)-conjugated anti-rabbit  secondary antibodies. HRP signals were detected by using 3,3′-diaminobenzidine tetrahydrochloride (DAB) substrate . All expression assays were performed in triplicate in at least two independent experiments.The stock solutions (10–20 mM) of the α2-AR agonist guanabenz acetate , non-selective antagonist yohimbine dihydrochloride (Sigma) and selective antagonists BRL44408 maleate (α2A-AR), ARC239 dihydrochloride (α2B-AR) and JP1302 dihydrochloride (α2C-AR), all from Tocris, were prepared in deionized water.50IC is the half-inhibition constant, c is the concentration and h is the Hill coefficient.The averaged data are presented as mean ±SEM. Inhibition profiles of measured membrane currents in dose-response experiments were presented relative to the control current values measured before drag application and fitted with corresponding Hill’s equations:


AR/VR technology can fuse the clinical imaging data and information to build an anatomical environment combining virtual and real, which is helpful to improve the interest of teaching and the learning initiative of medical students, and then improve the effect of clinical teaching. This paper studies the application and learning effect of the VR/AR system in human anatomy surgery teaching. This paper first shows the learning environment and platform of the VR/AR system, then explains the interface and operation of the system, and evaluates the teaching situation. This paper takes the VR/AR operation simulation system of an Irish company as an example and evaluates the learning effect of 41 students in our hospital. Research shows that the introduction of the feature reweighting module in the VR/AR surgery simulation system improves the accuracy of bone structure segmentation . For real human ultrasound image data, the IOU value increases from 80.21% to 82.23% after the feature reweighting module is introduced. Therefore, the dense convolution module and feature reweighting module improve the learning ability of the network for bone structure features in ultrasound images from two aspects of feature connection and importance understanding and effectively improve the performance of bone structure segmentation. At present, AR/VR technology has been applied in various fields, but its application in the medical field is still in the exploratory stage. With the rapid development of the digital era, the combination of AR/VR technology and medicine has unlimited prospects. It is believed that VR technology will bring disruptive changes in medical training, disease diagnosis, doctor-patient communication, clinical diagnosis, and treatment in the future. This paper reviews the application of AR/VR technology in medicine.VR technology has applied research in clinical medicine, for example, the use of VR technology to perform CT angiography (CTA) on patients and establish a patient's heart model to diagnose congenital heart disease (CHD). Another example is to select 36 children with heart disease and use AR/VR technology to diagnose the clinical manifestations of their arterial heart disease. The diagnosis of arterial heart disease is highly valued in the experience of AR/VR technology. AR/VR technology has significant advantages in anatomical identification and diagnosis . Chabaa Jacob et al. have created a set of educational tools for lateral ventricular puncture using AR/VR technology. It is used for trainee lateral ventricular puncture training. The anatomical structure of orthopedics is complex, and it is difficult to convert a 2D image into a 3D model with only spatial imagination . Shaikh This paper studies the application and learning effect of the VR/AR system in the teaching of human anatomy surgery. This paper first demonstrates the learning environment and platform of the VR/AR system, then explains the interface and operation of the system, and evaluates the teaching situation. In order to break through the limitations of terminal types and enrich the interaction mode, this paper proposes a lightweight multiperson multiterminal cooperation mechanism, which ensures the collaborative effect and has the characteristics of simple application. In short, the system in this paper is highly practical, interesting, and interactive, which provides a new way for scientific display of big data on the Earth and a new means for exploring the mysteries of the Earth. The proposed multiperson multiterminal cooperation technology has strong practicability and scalability.The core value of VR/AR technology can be summarized from its system form, application direction, and main characteristics, which can be summarized as immersion, desktop, and enhanced and distributed system forms . The immB-ultrasound, and accurate diagnosis often requires years of clinical experience and high spatial imagination ability [Traditional imaging examinations mainly include X-ray, CT, magnetic resonance imaging (MRI), and  ability . However ability . At the  ability . AR/VR t ability . At the  ability . Based o ability .Physicians use AR/VR technology to gain a deeper understanding of surgical risks and surgical plans, reduce differences in patient-patient understanding, and reduce physician-patient inconsistencies caused by unequal medical knowledge and information . As showOne of the problems in current VR surgery simulation research is that researchers only consider the temporal characteristics of VR/AR surgery, but ignore the spatial correlation between regions. In addition, there will be short-term and long-term repetitive patterns in VR/AR surgery, which will lead to nonlinear periodic data and linear trend data in VR/AR surgery. Considering these factors in the process of VR/AR surgery prediction will help to improve the accuracy of prediction . In ordeThe neural network model is composed of the convolutional neural network and long-term and short-term memory network. CNN is used to obtain the short-term local dependence pattern of variables, which solves the problem of ignoring the spatial correlation between regions in the current VR/AR surgery prediction model. It is used to capture the long-term development trend of data. The historical data connection component adds the past data into the prediction process to improve the accuracy of VR/AR surgery prediction:The autoregressive model is used to deal with the linear part of VR/AR surgery and enhance the robustness of the hybrid model to VR/AR surgery with the variable input scale. There is a certain periodicity in the real VR/AR operation data, so we can use the characteristics of VR/AR operation data to improve the prediction accuracy. For example, when you want to predict the VR/AR operation value at 5pm on that day, a classic method is to take the recent data records into account and also apply the VR/AR operation at 5pm in the past historical period to the prediction. Therefore, in the nonlinear part of the model, a historical data connection component is added innovatively, which connects the current hidden units with the hidden units in the same historical period in the adjacent time period and takes the VR/AR operation data in the historical period into account in the prediction process, which can make the VR/AR operation prediction more accurate:By combining the advantages of CNN and LSTM, the short-term and long-term dependence patterns of VR/AR surgery data were obtained, and the temporal characteristics and spatial correlation of VR/AR surgery were considered:The historical link component is added to introduce historical data into the prediction, and the autoregressive model is used to process the linear part of the data. Combined with the output of the linear and nonlinear parts, the final prediction result is obtained, which makes the hybrid model perform well in the VR/AR surgery prediction task. By designing a manual assembly task to install precision connectors, the precise installation relationship between the connector and socket is mainly expressed by the following ar instruction design:Logic constraint is an organic combination of user cognition and precision assembly at the information level. It transforms the assembly relationship between the pin of the connector and the pinhole of the socket into the distance constraint between two cross marks and obtains an output feature map. Its calculation process is shown in the following equation:e is the excitation function, which represents the memory of LSTM and completes its own update by forgetting the old memory and adding new memory. The first step is to determine the information to be discarded in the cell state, which is mainly realized through the forgetting gate. It chooses whether to forget the cell state of the upper layer according to a certain probability. The calculation process can be represented by the following equation:m is the weight matrix and D is the value of the bias term of the forgetting gate. This step is completed in two steps: the first step is to use the function to determine which computer to update the 5-point value, and the second step is to create a new cell value through the function and add it to the state. The modification process can be expressed as follows:In the above equation, It integrates the old memory through the forgetting gate and the new memory through the input gate. The update process is shown in the following equation:The final step is to determine the output, which will be based on the cell state. First, an original output value is obtained by a sigmoid function. Then, the unit state is calculated and scaled to a value between −1 and 1. Then, the output value of LSTM is obtained by multiplying the original output value pair by pair. The output results are  and 7)::7):(17)Yx at each time point before, to predict the value of the current time point. The autoregressive model is derived from linear regression in regression analysis, and it is modified. In linear regression, X is used to predict y, while in the autoregressive model, X is used to predict x, so it is called autoregressive. It has the characteristics of stationary, normal, and zero mean, and the value at t time can be expressed linearly by its previous n-step value. According to the idea of multiple linear regression, AR can be predicted. The model can be defined as follows:P and R are orders and coefficients, respectively, and E1ij represents the white noise sequence; then, the autoregressive model can be simply understood as a linear combination of one or more past values of x plus a random error. The use of the autoregressive model can solve this problem well. In order to prevent the gradient from disappearing and accelerate the convergence of the network, the maximum and minimum normalization is used to preprocess the data:Commonly used in the processing of time series, its basic idea is to use the value of the same variable k is the number of data, y is the actual value of the data, and u is the predicted value of the model.The SAE model uses a logistic regression layer to complete the prediction task. Using the collected VR/AR data to complete the training and testing of LSTM, Gru, SAE models and the proposed CNN-LSTM + AR model and according to the prediction results to compare their model performance; among them, the test values of MSE, RMSE, and Mae are smaller; is as follows:This paper studies the application and learning effect of the VR/AR system in human anatomy surgery teaching. This paper first shows the learning environment and platform of the VR/AR system, then explains the interface and operation of the system, and evaluates the teaching situation. This paper takes the VR/AR operation simulation system of an Irish company as an example and evaluates the learning effect of 41 students in our hospital.The traditional preoperative planning and discussion mainly rely on two-dimensional imaging information, such as X-ray, CT, and MRI, and then present the three-dimensional effect in the brain, which depends on the operator's mastery of anatomical knowledge and spatial imagination ability. Due to the differences in these two aspects, it is very likely that different surgeons will have different understanding of the patient's condition, resulting in different surgical options. In addition, due to the anatomical variation, the information is not accurate, which will also affect the formulation of precise treatment plan, leading to the increase of surgical risk. In this paper, AR/VR technology is used to implement accurate puncture and accurate positioning of the lesion area for patients, so as to achieve accurate personalized treatment of human disease location. Based on sufficient preoperative preparation and planning, the conventional preoperative discussion is to make the choice of operation mode and the development of operation process accurate, smooth, and practical. The application of AR/VR technology in preoperative preparation and planning not only adds a very professional “imaging” expert but also visually shows the operator's simulation of the operation process before operation, which further increases the accuracy and rationality of the operation.41 questionnaires were sent to the education reform group, and the recovery rate was 100%. The questionnaire survey shows that 98.9% of the students are interested in the two-way feedback method (VR/AR surgery teaching of human anatomy), 95.6% of the students think that the teaching time of VR/AR surgery teaching of human anatomy is appropriate, 93.4% of the students think that VR/AR surgery teaching of human anatomy is appropriate, 91.3% of the students think that teachers can provide them with specific suggestions on how to improve their academic performance, 92.3% of the students think that VR/AR surgery teaching of human anatomy can improve their self-evaluation ability, 94.5% of the students think that VR/AR surgery teaching of human anatomy can improve their autonomous learning ability, 93.4% of the students think that VR/AR surgery teaching of human anatomy can improve their self-evaluation ability and VR/AR teaching of human anatomy can stimulate students' learning interest and self-confidence. 86.9% of the students are willing to discuss teaching methods with teachers in an open way, and 90.2% of the students think that VR/AR teaching of human anatomy is conducive to understanding and mastering anatomical knowledge. The students' opinions in the group discussion also support the above results.As shown in As shown in As shown in As shown in As shown in As shown in As shown in u-net model, two improvements of the dense convolution module and feature reweighting module are added to the bone structure segmentation model. These two points are important to improve the performance of bone segmentation.As shown in The comparison of bone structure segmentation performance under different experimental settings is shown in As shown in As shown in As shown in As shown in Different vision of VR device wearers will also cause the difference between the model and the real world. As shown in AR/VR technology is a new type of holographic imaging technology after AR, VR, 3D printing, and other modern technologies. It combines the advantages of AR and VR technology. In addition, VR model is more realistic. It can be removed and replaced by coloring, transparency, or at will to get the desired model, which is more practical than the traditional printing model. Through the use of virtual simulation technology to build clinical scenarios and the unique comparative teaching method of clinical differential diagnosis experts, each case is divided into history collection, physical examination, auxiliary examination, examination results, differential diagnosis, treatment plan, and other functional modules, and through a large amount of clinical data collection, the data of diagnosis and treatment process are exchanged by text, sound, image, and other multimedia. The virtual clinical operation technology is integrated into the case, and the clinical skills and clinical thinking ability of medical students are comprehensively improved by using the online assessment and evaluation function of the system. AR/VR technology can meet the training of this skill and has repeatability. In the process of real-time teaching, the difficulty of real-time data processing can be solved. Some scholars have established a virtual three-dimensional reduction model of distal radius extension fracture, which further strengthens the promotion of bone setting manipulation and the mechanism research of manipulation effect. In the process of manipulation operation, we can clearly see that bone setting manipulation effect improves the displacement of the fracture end. Orthopedic surgery requires high aseptic conditions, so medical students will be limited in the operation observation. Although endoscopic technology is widely used, but the camera picture lacks a sense of orientation and space and can only see the anatomical structure in the picture, but can not observe the operator's operation method of surgical instruments, resulting in medical students to lose interest in learning surgery, and orthopedic surgery gradually tends to be minimally invasive; it is difficult for medical students to further learn surgical operation skills. With the help of virtual technology, the above problems can be effectively solved by online live broadcast of surgery. AR/VR technology is a new type of holographic imaging technology that has emerged after modern technologies such as AR, VR, and 3D printing. It combines the advantages of AR and VR technology. In addition, the VR model is more realistic and can be obtained by coloring, transparent or arbitrary removal, and replacement. The desired model is more practical than the traditional printing model. Through the use of virtual simulation technology to construct clinical scenarios and the unique comparative teaching method of clinical differential diagnosis experts, each case is divided into multiple functional modules such as medical history collection, physical examination, auxiliary examination, examination results, differential diagnosis, and treatment plan. Through a large amount of clinical data collection, the information of the diagnosis and treatment process is displayed to learners in the form of text, sound, image, and other multimedia interaction, and virtual clinical operation technology is integrated into the case, and further, through the online assessment and evaluation comparison in the application system function, the clinical skills and clinical thinking ability of medical students are comprehensively improved. AR/VR technology can meet the training of this skill, and it is repetitive. A new solid fracture model can be developed by analyzing the solid fracture model combined with data processing technology. During the manual reduction process, the synchronization of the manual effect information is completed in real time, which solves the practical difficulties of manual reduction teaching. Some scholars have established a virtual three-dimensional reduction model of the distal radius extension fracture, which has further strengthened the promotion of the orthopedic technique and the study of the mechanism of the maneuver effect. During the manipulation, the effect of the orthopedic technique can be clearly seen to improve the fracture end and the displacement situation. Orthopedic surgery requires high aseptic conditions, and medical students will be restricted when performing surgical observations. Although laparoscopic technology is widely used, the camera images lack a sense of orientation and space and can only see the anatomical structure in the image, but cannot observe the operation method of the surgeon's surgical instruments, causing medical students to lose interest in learning surgery; moreover, orthopedic surgery is gradually becoming more minimally invasive, and it is difficult for medical students to further learn surgical techniques. With the help of virtual technology, the abovementioned problems can be effectively solved through online live broadcast of surgery.It will realize the preoperative planning, the choice of the surgical path, the coincidence of the model and human body, the display of the virtual needle path, etc., which are still not well applied in clinic, but the emergence of AR/VR technology can well complete the above application. Although the application of AR/VR technology in the medical field is just in the beginning, it has unlimited prospects. On the basis of previous research results, we can look forward to the bright future of AR/VR technology in surgery. First of all, we should continue to use VR as a surgical training tool, and at the same time, we should use more advanced technology to detect the surgeon's technology or reduce the difference between the virtual environment and the real surgical environment. In addition, the wide clinical application of AR/VR technology in surgery will accelerate the development of remote surgery. With the rapid evolution of 5G, we believe this intelligent surgical environment will come soon. In the future, AR/VR technology may bring disruptive changes in medical training, disease diagnosis, doctor-patient communication, clinical diagnosis, and treatment and promote the rapid development of medicine.