The treatment of myasthenia gravis (MG) has advanced from steroids and traditional immunosuppressants to targeted immunotherapy. Targeted immunotherapy has been successfully employed in clinical practice in recent years. This study aimed to explore the emerging trend of targeted immunotherapy in MG and summarize the knowledge structure through bibliometric methods.The Web of Science Core Collection database (WoSCC) was chosen to retrieve the literature on targeted immunotherapy for MG. Two bibliometric analysis software, VOSviewer and CiteSpace, and bibliometric online platform were mainly used to evaluate the contributions from countries/regions, institutions, journals, and authors through the construction and visualization of bibliometric networks. By systematically reviewing a knowledge domain, future research developments were determined. The R version 4.1.2 and Microsoft Excel 365 were used for statistical analysis.A total of 562 original articles and 262 reviews relevant to MG targeted immunotherapy were included. The number of publications on targeted immunotherapy for MG exhibited a two-phase advancement. The first stage showed a steady growth trend from 1998 to 2016, with an annual number of no more than 35 publications. The second stage revealed an explosive growth trend from 2017, reaching a peak number of publications in 2020. The United States ranked first in the number of publications, citations, and h-index. The author with the highest citation and h-index was Vincent A. And 28.03% of the articles were published in the top 10 journals. In addition to “myasthenia gravis”, the keyword with the highest consideration was “rituximab”, followed by “double-blind”, which indicate research hotspots gradually from basic research to clinical research over time, especially in the field of targeted immunotherapy. The MG treatment has entered a personalized precision treatment phase. Exploration into new target molecules and conducting high-quality randomized controlled trials on existing biological agents are the further research direction.The current study summarized the global research trends concerning targeted immunotherapy for MG. Research interests gradually advanced from basic research to clinical research. MG treatment has entered a personalized precision treatment phase. Further investigations into new target molecules and high-quality randomized controlled trials on existing biological agents are required urgently to direct future immunotherapy research. Myasthenia gravis (MG) is an acquired autoimmune disease, manifested by disruption of neuromuscular junction (NMJ) transmission caused by autoantibody, cellular immune dependence, and complement . Anti-acBibliometric analysis and data visualization, a well-established bioinformatics tool, are used to analyze a field of research quantitatively and qualitatively, provide evidence for the impact of an area of research, find the emerging area of research, and identify potential research collaborators , 15. DifA team published high-impact articles on targeted immunotherapy for MG. Who are the core authors of these studies? Who are their collaborators? What research topics were they interested in? Which topic received the most attention? What journals were they published in? How did the specific research area develop and evolve? No individual can read all the high-impact articles on a specific area due to limited time and energy . TherefoNo bibliometric studies have been published on targeted immunotherapy for MG thus far. This paper aimed to systematically summarize and visually analyze the literature in the field of targeted immunotherapy for MG based on the Web of Science and using CiteSpace and VOSviewer software to understand the frontiers and emerging trends of research. The outcome can provide more references, novel insights, and directions for future clinical research and guidelines establishments. This bibliometric analysis is the first attempt relevant to this area of research.via the internet, which is the oldest citation database and is currently owned by Clarivate Analytics Company   . The selAmerica) , 26. SecAmerica) . FinallyAmerica) –29.The advanced retrieval function was used to improve the quality of information. The specific retrieval rules were as follows: #1: TS= (myasthenia gravis); #2: TS=(eculizumab) OR TS=(rituximab) OR TS=(RTX) OR TS=(tocilizumab) OR TS=(belimumab) OR TS=(rozanolixizumab) OR TS=(efgartigimod) OR TS=(Zilucoplan) OR TS=  OR TS= (biologic drugs) OR TS= (targeted immunotherapy) OR TS= (targeted immunotherap*) OR TS= (novel therap*) OR TS= (novel treatment strategies); the ultimate dataset: #1 AND #2. Literature in English only were included. The search was limited to systematic reviews and original articles. A truncation symbol “*” was used and the use of truncation searches improved recall and prevented missing inspection. All contents including the titles, authors, abstracts, keywords, and cited references were recorded. A total of 993 records on targeted immunotherapy for MG were searched from 1998 to 2022 . The exclusion materials were 169 records including meeting abstract, editorial material, revision, letters, journalism, and non-English works of literature. Consequentially, 824 valid literatures (562 articles and 262 reviews) were retrieved as the final dataset and exported in the form of “full record and cited references” for further analysis. Subsequently, the text files were renamed as “download∗.txt”, which were recognized by CiteSpace software. The detailed literature screening process is shown in These data were imported into Microsoft Excel 365  for further processing. Two researchers (YS and ZR) performed data extraction and literature selection and analysis to ensure the reliability of the results independently. Any discrepancies between the two researchers were discussed to reach a consensus. The disagreements were resolved through discussion or a third-party consultation (RW and SH). The indicators such as the annual number of publications and citations, countries/regions, journals, institutions, authors, co-cited references, and keywords were primarily focused on. The citation reporting of the WoSCC was used to assess the h-index and citation frequency. The h-index was calculated considering a scientist/country has published h articles, each of which has been cited at least h times . This inThree bibliometric tools, including two software (CiteSpace (5. 8. R3) and VOSviewer (1. 6. 18)) and an online platform were used in this study for a more comprehensive analysis.http://vosviewer.com) is a literature knowledge visualization software that uses the Visualization of Similarities (VOS) technology, which was developed by Professors Eck and Waltman from Leiden University using the Java language. The VOSviewer assesses and visualizes research characteristics from different perspectives, such as co-authors, research institutions, countries/regions, keywords, and co-cited references  is a Java-based computer program designed by professor Chen from Drexel University , plotted the distribution and international collaboration of countries/regions.In addition to the above methods, an online platform for bibliometric analysis and visualization, This study did not involve human or animal subjects and all data used in this manuscript were obtained from public databases. Therefore, ethical approval was not required.Statistical analysis was performed using R version 4.1.2  and Microsoft Excel 365 (Microsoft Corporation). The VOSviewer  and CiteSpace  were used for the analysis of basic metrics.Quantitative analysis of the published papers can reflect the productivity of a given scientific research field over the years and exhibit the trend in development in a specific area. Utilizing the aforementioned search strategies, a total of 993 articles were retrieved. After excluding invalid articles, 824 publications, including 562 original research articles and 262 reviews were included in the final analysis Figure 1A total of 1084 institutions published scientific articles on targeted immunotherapy for MG during the defined study period. As shown in As noted above, the economic foundation contributed the most to scientific development. A summary of the top 10 most active funding agencies in this area is provided in Journal of Neuroimmunology [44 (5.34%)], and Muscle Nerve [41 (4.98%)] ranked second, followed by Annals of the New York Academy of Sciences [27 (3.28%)]. According to the 2020 JCR standards, the IF of the top 10 journals ranged from 3.217 (Muscle Nerve) to 9.91 (Neurology) and was classified as Q1 to Q2 categories. In addition to the number of publications, the impact factor of journals also depends on how often they are co-cited in a particular field of research. As shown in FASEB J had the highest centrality, with a central value of 0.4, followed by the Brain (0.29) and Nat Immunol and J Neurol Neurosur Ps (0.2). Additionally, a dual map overlay of the journals on targeted immunotherapy for MG was constructed . The dual map overlay of journals described the topic distribution of academic journals, and the map of the citing journals was on the left and the map of the cited journals was on the right. Collectively, there were three main citation paths on the current map. The published studies mainly targeted the journals in three fields: i) molecular biology and immunology; ii) medical and clinical areas; and iii) neurology, sports, and ophthalmology whereas the most cited publications originated from the journals of molecular biology and genetics.In total, the retrieval article was published in 323 journals in this research field. The top 10 active journals that published 231 papers on targeted immunotherapy for MG, accounted for 28.03% of all 824 publications. The number of research papers published by an author may translate the contribution to the research in the field. A total of 200 researchers authored 824 articles. The top 10 most productive authors in the field are presented in The top 10 original articles relevant to targeted immunotherapy for MG with the most citations are summarized in In addition to references, keywords can offer readers information about the research topics and methodologies of the publications, and analysis of keywords co-occurrence is often employed to detect the research hotspots and directions in the research field. The network visualization map was generated for keywords with the value of co-occurrence greater than 20 times. As shown in The CiteSpace was used to detect burst keywords to determine the hotspots and research frontiers over time. The burst keywords are terms cited frequently over a period. The top 25 keywords with the strongest citation bursts are presented in The current study was the first to use bibliometric methods to measure research trends on targeted immunotherapy for MG from 1998 to 2022. Unlike systematic reviews and scoping reviews, bibliometric analysis has become a powerful tool for summarizing the current status of knowledge and predicting future trends , 42. BasFrom 1998 to 2022, the total number of publications on MG was 7672, and the total number of publications on targeted immunotherapy for MG was 824, which accounting for 10.74%. In recent years, targeted immunotherapy has gradually entered the view of neuroimmunology specialists. The research on targeted immunotherapy for autoimmune diseases has also increased over time, including NMOSD (neuromyelitis optica spectrum disorders), MS (multiple sclerosis), MG, etc. We searched the publications on targeted immunotherapy for NMOSD and MS. Comparing the number of publications on targeted immunotherapy for NMOSD, MS and MG, they all show an increasing trend, but each disease has its own unique increasing trend. This is because the pathogenesis, the time of significant breakthrough was achieved and investment in different diseases are different. For example, MS is mediated by cellular immunity, while NMOSD and MG are caused by humoral immunity and the production of AQP4 antibody and AChR antibody respectively. In conclusion, the MG has a special growth trend compared with other diseases.A general upward trend was found in the number of targeted immunotherapies for MG-related publications, indicating that this field was actively researched in recent years. Two phases, including a slow growth period (1998-2016) and a rapid growth period (2017-2022) were noticed. The number of publications exhibited a stable increasing trend from 1998 to 2016, but the increase was not apparent because the average annual publication volume did not exceed 35 articles. After 2017, the annual publication output dramatically increased which peaked in 2020, and this stage accounted for 47% of the total publications. The growth trend of citations was consistent with the publications. This phenomenon may have been connected to the significant events in this field, Firstly, REGAIN study entitled “Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory myasthenia gravis: a phase 3, randomized, double-blind, placebo-controlled, multicenter study”  was publThe distribution of contributing countries/regions and institutions showed some characteristics. As shown in Journal of Neuroimmunology (IF=3.478), followed by Muscle Nerve (IF=3.217) and Annals of the New York Academy of Sciences (IF=5.691). Due to the rare nature of MG, the option for journals is narrow. Although the impact factor of the top 3 journals was not high, Muscle Nerve is a professional journal in the MG field and all other journals are comprehensive in immunology or neurology. Researchers can focus on these journals to know about research trends and frontiers in targeted immunotherapy for MG. In addition, when submitting manuscripts, researchers can find the most suitable journals for timely processing, avoiding delays in time of the study. An analysis of journals and co-cited journals can provide a wealth of information for researchers to choose the best journal to submit their manuscripts , 53. TheIn our analysis, Vincent A scored the highest citations and h-index. Further, Vincent A and his research team had the highest research strength and influence. They published important findings in this field when compared to others.The more frequently an article is cited, the more important it is perceived in a specific field. Therefore, the most cited publications or influential literature can be regarded as a knowledge base in a particular field . As showLancet in 2001. This article summarized the epidemiology, clinical characteristics, classification, pathophysiological parameters, treatment, diagnosis, and differential diagnosis of MG. As a high-quality review in the field of MG, it served as a very important reference value for the targeted immunotherapies for MG. The third co-cited paper “Imbalance of regulatory T cells in human autoimmune diseases” was published by Christian Dejaco  (Tregs). In autoimmune diseases, altered Tregs and insufficient suppression of inflammation were thought to be critical factors for disease development and persistence.The 4 reviews published in the early phase mainly described the pathogenesis, diagnosis, and treatment of MG, and these reviews played a landmark role in elucidating the mechanism of pathogenesis and diagnosis of MG. The article titled “Rituximab, an anti-CD20 monoclonal antibody: History and mechanism of action” was published by Pescovitz MD , which wn Dejaco . This arNeurology in 2012  completed phase III clinical trials and was approved by the FDA for the treatment of anti-AChR positive GMG  and an online platform. Despite the above‐mentioned strengths, several limitations are unavoidable, First, there are diverse factors that can affect the number of publications, both known and unknown. It is very difficult to obtain the overall funds data in different countries from the WoSCC database (the specific amount of fund support is not available from the WoSCC database). Moreover, many countries lack national epidemiological data in MG field, which may cause statistics bias. Therefore, our study adopted bibliometric analysis methodology, we only compared the number of publications in different countries, and through this important indicator to reflect the research status of different countries. This method has many limitations obviously, but it is also a feasible method at present. Second, the database selection bias was that all literatures included in this study were downloaded from the WoSCC. The relevant studies deposited in other databases might have been missed. Finally, our literature search was only dependent on the English language, hence our analysis may have excluded articles reported in non-English.Taken together, the current study summarized the global research trends concerning the targeted immunotherapy for MG. The outcome of the study demonstrated that the USA is leading ahead in both the sum of publications, total citation frequency, and funding in this field. Along with improving life quality of MG patients, high efficiency, rapid onset, less side effects and good compliance have become new treatment needs. The MG treatment has entered a personalized precision treatment phase. Further exploration into new target molecules and conducting high-quality randomized controlled trials on existing biological agents are urgently needed to guide the future directions of immunotherapy research. Consequently, it is not difficult to predict that this field is likely to advance rapidly and more studies will be published in the future. Meanwhile, there are also multiple challenges for MG targeted immunotherapy in the future, such as the long-term effectiveness, safety, accessibility, and cost of biological agents. We should focus on providing precise treatment schemes for patients with different subtypes, which will help patients achieved the treatment goal rapidly, reduce the treatment burden and provide convenience for patients to the greatest extent.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.TC conceptualized the study, secured funding, and designed uniform procedures for data collection across the study centers. TC, ZL, YS, ZR, RW and SH contributed to the study design. YS, ZR, RW and SH contributed to collect and analyzing data. TC, YS, ZR, RW and SH contributed to the drafting of the manuscript. YT, XH and TG contributed to collecting data. All authors contributed to the critical revision of the manuscript for important intellectual content and provided approval of the final manuscript for submission.The authors disclosed receipt of the following financial support for the research, authorship, and publication of this article: This work was supported by the discipline innovation and development plan of Tangdu Hospital-major program of clinical research (Grant No. 2021LCYJ002), Key Research and Development Projects of Shaanxi Province (Grant No. 2021ZDLSF02-01).The authors greatly acknowledge Yafei Qin for the revision of the article and Liang Wang provided methodological support.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.


This study unveils the effects of stressors on employees' task performance through the mediating role of thriving at work (TAW) and a moderating role of resilience (RES) grounding on conservation of resources (COR) theory. The analysis of collected data from 331 supervisor-employee dyads in the hospitality sector of China explicates that the role conflict (RC) and perceived workload have a negative influence on TAW, and thriving has a positive relationship with task performance. The results corroborate the mediating role of TAW between RC, perceived workload, and task performance. Furthermore, the RES suppressed the negative relationship between RC, perceived workload, and TAW. Moreover, our study underscores the theoretical and practical contributions regarding the negative influence of stressors on TAW by exhibiting the importance of the COR mechanism for employees' behavioral outcomes. Organizations are operating in a competitive era that urges them to be competitive in the global environment  theory Hobfoll,  as the uRole conflict is defined as when there is a contradiction between authorities, messages, and responsibilities , which cause in loss of resources  RC, (b) PWL, and task performance.Along with thriving, we posed that individuals' ability to cope with stressors, such as RC and perceived workload, is contingent on their level of RES  RC, (b) PWL}, and thriving, such that these negative relationships will be weaker at higher levels of RES (vs. low).The participants are the front-line hotel workers in the Chinese hotel industry. A simple random sampling technique was used for data collection from 3-star and above hotels. Front-line employees are considered to be in a more advantageous position to have information about customers' preferences  and the main variables of this study. To avoid the common method variance , age , education , and tenure .This study uses a mature scale and takes great care while designing the survey ensuring the quality of the study. We used the back-translation method Brislin,  because We measured the concept of RC through 8-items and perceived workload through 4-items by Allen et al. . The samWe measured the level of RES as employees' coping strategy through 6-items borrowed from Smith et al. . The samWe measured employees' sense of learning and vitality through 10-items borrowed from Porath et al. . The samWe measured the effectiveness of employees' task performance through supervisor-rated 4-items adapted from Eisenberger et al. . The samr = −0.372, p < 0.001) and PWL  were negatively related with thriving. TAW was positively related with TP .2 = 579.832, df = 454, χ2/df = 1.277, SRMR = 0.055, TLI = 0.977, CFI = 0.979, and RMSEA = 0.029. The composite reliability (CR) showed the values 0.819–0.937 which are >0.70 , , and   due to its ability to examine the multiple variables at the same time. As the first step, we tested the multicollinearity among variables through the value of (VIF = 1.237-1.464). < 0.001) .RC→TAW→TP) = −0.137, , and  RC, (b) PWL, and TAW. We employed the bias-corrected method with 5,000 bootstrap samples at a 95% confidence interval (CI) Hayes, . The res effects . The resRES X RC → TAW = 0.367, , p < 0.001) and , thus supports H5a and H5b , we used PROCESS macro 3.3 model 1 (H5a and H5b) with 5,000 bootstrap samples at 95% CI Hayes, . For RC  and H5b . The resThis study discusses in what way the job stressors affect individuals' thriving based on the COR theory, which suggests that individuals need resources for the accomplishment of their tasks, and the absence of which can be resulted in a loss in a spiral of resources. The results showed that RC and perceived workload have a negative relation with TAW. It shows a consistency with previous literature which shows that RC was negatively related to employees' behavioral outcomes, such as work engagement, job satisfaction, and organizational commitment   anxiety and thriving.This research was aimed at exploring a framework that can provide useful insights to understand the concept of TAW in connection to stressors. This study has contributed to the existing pool of research from different perspectives: first, by offering different insights about job stressors and TAW; second, by explicating the effects of thriving on task performance; third, by offering useful insights and theoretical support for COR theory; and fourth, by testing the proposed theoretical model in the hospitality industry of China which reveals key insights into the working environment and employees' behaviors.To start with, the results of this study through the structural equation model showed that factors, such as RC and perceived workload affect TAW, negatively based on COR theory. More closely, we examined the effects of RC and perceived workload and observed that PWL has a slightly higher negative association with TAW which shows that work overload is a greater cause of loss in individuals' resources, which do not let them experience TAW. It suggests that hospitality managers should clarify the role of employees to avoid the collision, and most importantly, lowering the workload of employees will make them in a better position to gain the spiral of resources and to experience TAW.This study has examined the important relationships between thriving and task performance. We observed that thriving has a positive relationship with task performance. Moreover, the crucial mediating role of thriving bears high importance which links RC, perceived workload, and task performance. The results suggest that RC and perceived workload cause the loss in individuals' resources, which reduces their thriving, leading to lower task performance. This study also entails the crucial moderating role of RES between RC, perceived workload, and TAW. The results showed that resilient individuals are in a better position to cope with the negative consequences of RC and perceived workload on their level of thriving.hassaanfarid3@gmail.com.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Requests to access these datasets should be directed to HF, ZH conceived the idea and developed the theoretical framework. HF adopted the methodology and calculated the results. WA and XL completed interoperation and discussions based on statistically analysis. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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.


Employment outcomes after liver transplant (LT) over the past decade have not been described.LT recipients ages 18–65 from 2010-2018 were identified in Organ Procurement and Transplantation Network data. Employment within two years post-transplant was assessed.Of 35,340 LT recipients, 34.2% were employed post-LT, including 70.4% who were working pre-transplant, compared to only 18.2% not working preLT. Younger age, male sex, educational attainment, and functional status were associated with returning to employment.Returning to employment is an important goal for many LT candidates and recipients, and these findings can be used to guide their expectations. Returning to work after liver transplantation (LT) is a common goal of transplant candidates.We performed this study using data from the Organ Procurement and Transplantation Network after 2009 to characterize employment post-LT and to identify factors associated with posttransplant employment. We identified first-time, non-status 1, single organ LT recipients of ages 18–65 from 2010 to 2018 with at least 6 months of follow-up. Demographic and clinical variables were assessed at the time of transplant, and employment information was evaluated at the time of listing, transplant, and posttransplant. Working pre-LT was defined as employment at the time of listing or transplant. The primary outcome was employment posttransplant, which was defined as the employment within 2 years post-LT and was evaluated separately for individuals working and not working before transplant. Impaired functional status was defined as needing any assistance or a Karnofsky performance status <80%. Two time periods were defined, the first from 2010 to 2014 and the second from 2015 to 2018, each containing ~half of the total LTs in the cohort.p<0.10 were entered in the multivariable models and retained at a p<0.05 level of significance using a backward selection process. The time period was included in all models. This study was exempted from the institutional review board review.Demographic and clinical characteristics of LT recipients were compared by pretransplant and posttransplant employment status using Chi-square tests for categorical variables and Wilcoxon rank sum tests for continuous variables. Multivariable logistic regression was performed to identify predictors of an individual returning to employment posttransplant. Peri-transplant demographic and clinical characteristics were evaluated in univariable models and the predictors with http://links.lww.com/HC9/A160). Overall, 34.2% of recipients were employed post-LT, and the majority had been employed pretransplant (62.7%). Among individuals working before transplant, 70.4% were working posttransplant, while only 18.2% of the individuals were not working in pre-LT achieved employment . Recipients who returned to employment were more likely to be younger, male, with greater educational attainment, and privately insured, and were less likely to be Hispanic, with diabetes and impaired functional status and in the intensive care unit (ICU) at transplant (Table A total of 35,340 LT recipients were included; 3023 were excluded due to missing pre-LT and post-LT employment information (Supplemental Figure; Supplemental Table 1, Our study shows that post-LT employment in this contemporary cohort has improved overall compared with the previously reported 24% from 2002 to 2008.The factors associated with returning to employment were overall similar to prior studies and included younger age, male sex, and greater educational attainment.While the use of the Organ Procurement and Transplantation Network data allowed for an updated national assessment of posttransplant employment over the last decade, there are also inherent limitations associated with a retrospective review of the administrative databases, including missing, incomplete, or potentially inaccurate data. Employment data was not available on all transplant recipients, and we were also limited by the lack of additional information, such as whether post-LT employment was desired, the barriers when it was not achieved, and other factors that may be relevant that should be evaluated in future studies. Local job conditions are also likely important, and the changes in the job landscape as a result of the COVID-19 pandemic and the rise in remote work may impact the transplant recipients as well and will be important to assess in the future.In conclusion, in a contemporary transplant population, overall employment post-LT has improved, and 70% of the recipients with employment pretransplant returned to work within 2 years. New employment in the recipients not working before transplant is much less common, however. Both sociodemographic and clinical characteristics are associated with regaining employment after LT. Returning to work is an important goal for many LT candidates and recipients, and these findings can be used to guide their expectations.


This cross-sectional study was conducted in patients with BC, stage 0-III, and receiving therapy for BC; the women were recruited at the Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy. A control group with similar age and BMI was selected from the internal database. Anthropometry, bioimpedance analysis (BIA) and hand grip strength (HGS) were measured to detect sarcopenia. A total of 122 patients  and 80 healthy controls were analyzed. Sarcopenia was found in 13.9% patients with BC, while none of the subjects in the control group was sarcopenic. By comparing BC patients with and without sarcopenia and the control group, the fat-free mass of sarcopenic BC patients were significantly lower than those of both non-sarcopenic BC patients and the control (p < 0.05). The phase angle was also significantly lower in sarcopenic patients  than in the control group. Considering the prevalence of sarcopenia in patients with BC, our findings suggest the usefulness of body composition and HGS evaluation for early screening of sarcopenia to reduce the risk of associated complications.Sarcopenia is a common finding in patients with cancer and potentially influences the patient’s outcome. The aim of this study was to evaluate the prevalence of sarcopenia, according to the European Working Group on Sarcopenia in Older People, in a sample of women with breast cancer (BC) and a BMI lower than 30 kg/m Breast cancer (BC) is the most frequently diagnosed carcinoma and the second leading cause of cancer death among females worldwide . AccordiSarcopenia is a syndrome characterized by the progressive reduction in both muscle mass and muscle strength, which is accompanied by a reduction in the quality of life and an increased risk of adverse outcomes . DespiteIn 2010, the European consensus [Recently, the European Working Group on Sarcopenia in Older People (EWGSOP2) published a revised consensus on the definition and diagnosis of sarcopenia, by focusing on low muscle strength, also called dynapenia, as a key characteristic of sarcopenia that is measured by hand grip strength (HGS) ,11,12. IDifferent techniques can be used for the evaluation of muscle mass, such as dual X-ray absorptiometry (DXA) , computeTherefore, it is crucial to evaluate the presence of sarcopenia before starting cancer treatment in all patients, since it is strongly associated with chemotherapy-induced toxicity, post-operative complications and poor survival . Indeed,2.To our knowledge, there are only a few studies in the literature that have specifically screened the presence of sarcopenia in Italian women with BC, according to the EWGSOP2. Thus, the objective of this study was to evaluate the prevalence of sarcopenia in a sample of Italian women with BC and a BMI lower than 30 kg/mThis is a cross-sectional study of baseline data collected from an ongoing randomized controlled trial in pre-and postmenopausal Italian women with stage 0-III BC, candidates for surgery and adjuvant/neoadjuvant therapy. Patients were consecutively recruited at the Oncology Unit, Department of Clinical Medicine and Surgery, Federico II University, Naples Italy, from September 2018 to June 2021.2 and available past medical history. Patients with metastatic cancer, BMI ≥ 30 kg/m2 and severe clinical conditions were excluded. In addition, a control group with similar age and BMI was selected from our database  with anthropometric and body composition data from the last two years.Caucasian patients were consecutively included according to the following criteria: women, age ≥ 18 years, 18.5 ≤ BMI < 30 kg/mThe study was conducted in accordance with the Declaration of Helsinki, and it was approved by the local Ethics Committee of Federico II University (prot. n. 280/17). All patients gave their informed consent to participate in the study.Body weight and stature were measured according to standardized methods. Body weight was measured to the nearest 0.1 kg using a platform beam scale and stature to the nearest 0.5 cm using a stadiometer . Body weight and stature were used to calculate BMI (weight in kilograms divided by stature in meters squared).Body composition was evaluated by the BIA method. BIA was performed using Human Im Plus II  at a room temperature of 22–25 °C in the 12 h fasted state after voiding the bladder and cleaning the surface of the skin to adhere the electrodes. Participants were asked to remain in the supine position for at least 10–15 min before starting the measurement, with lower limbs and upper limbs slightly abducted at 45° and 30°, respectively, to avoid any contact between the extremities and the trunk.Resistance (R) and reactance (Xc) were measured at 50 kHz; PhA (degrees) = arctan (Xc/R) × (180/π) was calculated. Body composition assessment, namely, FFM and FM, was estimated using the Sun BIA equation . ASM wasMuscle strength was assessed by HGS, measured in both the dominant and nondominant hands with a Jamar dynamometer .Patients performed the test standing with their upper limbs by their sides, and they were instructed to squeeze a dynamometer at maximal voluntary isometric contraction. The measurement was repeated three times alternately on both sides (dominant and nondominant hand), with 1 min apart to avoid fatigue, and the dominant hand was determined by asking subjects if they were right- or left-handed. The mean value was recorded in kilograms .Sarcopenia was diagnosed according to the EWSGOP2 criteria. This new revised consensus suggests that the first parameter of sarcopenia is dynapenia evaluated with the HGS method (recorded in kilograms). The diagnosis of sarcopenia is confirmed by reduced ASM in addition to dynapenia and/or low physical performance. According to the cutoff points of Dodds RM et al. , dynapenp < 0.05. Differences between two groups (patients with BC and control group) were assessed by unpaired t-tests, while data were compared between four groups  by using non-parametric analysis (Mann–Whitney test); the false discovery rate approach was performed to account for the multiple comparisons, and significant level (p < 0.05) was adjusted according to Benjamini and Hochberg [The data obtained were analyzed by the SPSS  software. Results are presented as the mean ± standard deviation (SD), and statistical significance was defined as Hochberg . HGS andA total of 142 patients with BC participated in this study, but 20 were ruled out for the following reasons: 3 subjects did not meet the inclusion criteria and 17 left for personal reasons.2, while 56 (46%) had a BMI range from 25 to 30 kg/m2. Additionally, as reported above, a control group with similar age and BMI to the patients was selected. In detail, healthy women aged between 35 and 75 years, with a body weight between 46 and 89 kg, of whom 45 (56.2%) were normal weight and 35 (43.8%) were overweight , while none of the subjects in the control group had sarcopenia. In addition, among patients with BC, 31.1% (38/122) were pre-sarcopenic due to the presence of either HGS value < 16 kg or ASM < 15 kg. The remaining 54.9% (67/122) of patients were classified as non-sarcopenic, having both values in the normal ranges.Data concerning anthropometry, body composition, PhA, muscle mass and strength between sarcopenic, pre-sarcopenic, non-sarcopenic BC patients and controls are shown in By comparing the results among the four groups, we found that sarcopenic patients with BC were older than non-sarcopenic and control group patients and had significantly lower body weight than in the other groups .p = 0.045 and −0.5 degrees, p = 0.048), respectively.Regarding body composition, differences were observed between sarcopenic BC patients compared to non-sarcopenic BC patients and control group in terms of both quantitative (FFM) and qualitative muscle parameters (PhA); in detail, the differences of PhA in sarcopenic BC patients compared to non- sarcopenic BC patients and control group were .Instead, the FM expressed in kilograms was significantly lower in sarcopenic BC patients than in non-sarcopenic BC  and control group , respectively.As in patients with sarcopenia, the group with pre-sarcopenia had both lower FFM and ASM than non-sarcopenic patients  and fat-free mass (FFM) in clinical settings ,32,33,34The compromised conditions of our patients with BC are also confirmed by the lower PhA values than in the controls.Given its non-invasivity, BIA can be performed whenever necessary, without the limitations of other exams using radiation, such as DXA or CT scan, thus allowing a strict monitoring of the patient body composition. On the other hand, abdominal CT scan is not recommended for early stages of BC . For thiThe prevalence of sarcopenia in patients with BC was assessed according to the EWGSOP2 criteria. Sarcopenia was found in 13.9% of patients with BC and was absent in the control group. Moreover, a considerable number (31.1%) of patients with BC were pre-sarcopenic, showing similar characteristics to sarcopenic patients. These prevalence data are not irrelevant if we consider that the evaluated patients are relatively young, normal or overweight and with early-stage BC. The influencing factors, such as tumor stage, breast surgery, physical activity, may play a significant role .Based on a recent systematic review , the preTo our knowledge, the presence of sarcopenia according to the new EWGSOP2 guidelines in Italian patients with early-stage BC was evaluated only in one study by Bellieni et al. . The stuPreviously, Oflazoglu et al. evaluated the prevalence of sarcopenia using the BIA method in a Turkish population with different types of cancers: breast, colorectal, pancreaticobiliary, genitourinary, lung, and head and neck . The preBased on these controversial results and considering the widespread use of the previous guidelines for diagnosing sarcopenia, we analyzed our data according to the EWGSOP criteria as well ; sarcopeLess is known about the body composition of women with early-stage BC, probably because the absolute recurrence and mortality rate in this population, to date, remains extremely low .Considering the prevalence of sarcopenia observed in our patients, in our view, it is important to define the nutritional needs and physical activity programs to improve skeletal quality and strength . Body composition and the levels of physical activity should be assessed at baseline and periodically re-evaluated during the entire course of the treatment and over time, in the long-term follow-up, to suggest specific strategies , which have been shown to reverse sarcopenia and were associated with improved quality of life ,52,53,54Our study had some limitations. Firstly, this is a cross-sectional study, thus only baseline results are reported; follow-up data are ongoing and will be shortly available.Secondly, although BIA is a valid and reliable tool for body composition analysis in clinical practice , it is n2 were excluded according to the study protocol, and the control group was retrospectively obtained from our dataset, and these may be considered further limitations.Finally, patients BC with BMI ≥ 30 kg/mIn conclusion, we found that the overall proportion of sarcopenic and pre-sarcopenic patients in our population was somewhat higher than expected in a healthy population of women . The use


Background: In contrast to studies in patients, an association between obesity and blood coagulation factors has not been established in the population. If confirmed it could become a target for primary prevention. Objective: To investigate the relationship between Body Mass Index (BMI) and waist circumference (WC) with plasma concentrations of antithrombin III, D-dimers, fibrinogen D, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value, and international normalized ratio (INR) in the general population. Materials and Methods: Participants of the Cooperative Health Research in the Region of Augsburg (KORA) S4 study who took part in the KORA Fit follow-up  examination were eligible. Citrate plasma samples were collected in fasted participants. After the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men) with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the association between BMI or WC with hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the prevalence of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol, and serum triglycerides. Results: In the multivariable models , significant positive associations with BMI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein S, and quick value, while INR and antithrombin III were inversely associated. Similar to BMI, WC was significantly associated with all hemostatic factors, except for aPTT. Conclusion: In this population-based study, both increasing BMI and WC affect the blood coagulation system. Thus, modification of a prothrombotic coagulation profile emerged as a potential target for primary prevention in obese subjects. The WHO declared obesity an epidemic as it became a worldwide health threat affecting people of all ages, sex, and various socioeconomic status . AccordiThus, the present study investigated whether Body Mass Index (BMI), a measure of relative body weight also used to classify overweight and obesity, is related to parameters of the blood coagulation system. In addition, waist circumference (WC) as a measure of visceral body fat accumulation was examined. For the analyses, data from the population-based KORA  Fit study were utilized.KORA is a research platform established in 1996 for population-based surveys. It is the continuation and development of the MONICA (monitoring trends and determinants in cardiovascular disease) studies, which were conducted in the study region of Augsburg from 1984 to 1995 [The KORA S1–S4 studies consist of around 18,000 participants and include a random sample of the inhabitants of the study region between the ages of 25 and 74 years. Since recruitment, all participants are being followed up by questionnaires to assess incident diseases and changes in exposure factors. In the KORA Fit follow-up study (2018–2019), MONICA/KORA study participants born between 1945 to 1964 were re-invited to the study centre for interviews and physical examination. For the present analysis, all participants of KORA S4 who took part in KORA Fit and for which citrate plasma could be collected were considered, leaving 805 study participants. After the exclusion of those with anticoagulative treatment, 776 participants (420 women and 356 men) with analytic data on hemostatic parameters measured in citrate plasma were included in the present analysis. All study participants gave written informed consent. The study protocol was approved by the Ethics Committee of the Bavarian Chamber of Physicians and conducted according to data protection requirements. The investigations were conducted in accordance with the Declaration of Helsinki.The KORA Fit study consists of an interview and self-administered questionnaires, on, for example, health conditions, and physical measurements.2), normal weight (BMI ≥ 18.5–<25 kg/m2), overweight (BMI ≥ 25–<30 kg/m2), and obese (BMI ≥ 30 kg/m2) [Anthropometric measurements were performed with the subjects in light clothing and without shoes, according to the World Health Organization MONICA protocol . Body Ma0 kg/m2) . Waist c0 kg/m2) . HabituaDetailed information on the data collection procedures and examinations in the KORA studies has been described elsewhere .Hemostatic factors were analyzed in citrate plasma samples collected after an overnight fast. Plasma samples were centrifuged (10 min. at 15°) immediately after collection and then aliquoted and stored at −80 °C. The separation of plasma from the other blood components was completed after 30 min. at the latest. The following hemostatic factors were analyzed: antithrombin III, D-dimers, factor VIII, fibrinogen, protein S, partial thromboplastin time (aPTT), quick value, and international normalized ratio (INR).2, SCS Cleaner). Fibrinogen  was measured photometrically and turbidimetrically . INR  was calculated from the prothrombin ratio  by dividing the thromboplastin time of the subject by that of normal plasma squared with International Sensitivity Index (ISI) as defined by the World Health Organization [Antithrombin III  was determined by chromogenic activity assay . D-dimers  were measured by means of a particle-enhanced immunoturbidimetric assay . Factor VIII activity  was measured photometrically , as well as quick value , aPTT , and protein S  was used. The Kolmogorov–Smirnov and Shapiro-Wilk tests were used to test for the normal distribution of data. Normally distributed variables were presented as arithmetic mean and standard deviation. None of the blood coagulation markers were normally distributed and thus described by the median and interquartile range (25–75% percentile). Non-parametric tests were used to test for differences between two (Mann–Whitney U) or more  independent samples. A Linear regression models with BMI or WC as independent variables were created. The models included the blood coagulation markers described above as dependent variables. The models were first adjusted for age (continuous), alcohol consumption (continuous), sex , education , smoking status , physical activity  no physical activity), and in a second model further adjusted for prevalent stroke (yes/no), hypertension (yes/no), myocardial infarction (yes/no), serum non-HDL cholesterol, and triglycerides (continuous).2 as compared to women with 27.39 ± 5.18 kg/m2, leaving more men than women in the overweight and obese categories.The baseline characteristics of the study population are given in The median concentrations of hemostatic parameters differed between men and women, except for D-dimers, factor VIII, and fibrinogen . Median The results of the linear regression models that explored the association between BMI and each of the blood coagulation factors are shown in This population-based study identified significant associations between nearly all analyzed blood coagulation markers and BMI as well as WC. Increased BMI or WC were related to higher concentrations of D-dimers, factor VIII, fibrinogen, protein S, and quick value and decreased values of antithrombin III and INR.Many studies confirmed a higher risk of early mortality for people with a high body fat mass (often expressed as BMI)  but dataThe basis for the correct interpretation of our findings is the physiologic role each hemostatic factor has in the complex blood coagulation system. D-dimers reflect both activations of fibrinolysis and thrombin production . It is cA few other investigations have also confirmed positive associations of coagulation markers with rising BMI as observed in our study. Hörber et al.  investigClotting tests used in clinical practice to describe failures in the intrinsic or extrinsic pathway are aPTT, INR, and quick value. They mostly depend on partial thromboplastin time. Quick and INR are inversely proportional to each other, meaning that a rise in one causes a decrease in the other. This was also confirmed in the present study. While Quick and INR detect influences on extrinsic blood coagulation, aPTT detects those in the intrinsic system. To the best of our knowledge, the influence of BMI or WC on the results of clotting tests has not been reported so far.Since, in our study, BMI- and WC-based analyses indicated similar associations with markers of coagulation, it appears to be the extent of body fat in general—and not limited to visceral fat—that affects the coagulation system. In a review article, De Pergola et al.  describeThe strengths of our study are a large sample size, the population-based design, the availability of standardized data on cardiovascular risk factors, and standardized anthropometric and laboratory measurements. However, several limitations of the study also need to be considered. The lack of measurement of other important coagulation factors like thrombin, von Willebrand factor, and plasminogen activator inhibitor limits the significance of the study. Furthermore, follow-up studies need to consider the distribution of subcutaneous fat and visceral fat by bioelectrical impedance analysis (BIA) dual-energy X-ray absorptiometry (DEXA), or magnetic resonance imaging (MRI) measurements. Finally, the results may not be transferable to persons of other ethnicity or other ages, since only participants in the Augsburg region ranging in age from 53 to 74 years were considered.Overall, our results in this population-based study indicated that an increase in BMI and WC impacts the blood coagulation system in a sense that the balance between coagulation and fibrinolysis is shifted towards a more prothrombotic constellation, which is confirmed by the increase in pro-coagulative factors and the result of clotting tests in our study. As an additional mechanism to explain the effect of obesity on the development of selected chronic diseases, the coagulation system could be considered a target for the primary prevention of thrombotic events.


Interest in interactive virtual reality (IVR) is increasing due to its potential for embodied learning and group-led teaching. However, few studies have investigated the internal mechanism by which IVR technology features and learning experiences affect learning outcomes in terms of psychological and emotional value. Based on media technology models and the control value theory of achievement emotions (CVTAE), this study uses structural equation modeling (SEM) to investigate the correlations among the internal elements of IVR technology features, learning experiences, and learning outcomes. It also emphasizes the role played by emotional experience in this context.The sample referenced by this study consisted of 480 college students  who were simultaneously engaged in guided inquiry and learning in an IVR-based COVID-19 pandemic science museum in groups of 10.The findings suggest that presence and perceived enjoyment have a key mediating effect on the relationship between virtual reality (VR) features and perceived learning outcomes in an IVR-based learning simulation. In addition, the results indicate that presence is more strongly correlated with perceived learning effects, while enjoyment is more strongly correlated with learning satisfaction.These findings provide intellectual support and theoretical backing for VR-based instructional design and environmental development. Moreover, this study has practical value with regard to the future large-scale application of IVR to experiential teaching, group-led teaching, and the promotion of the digital transformation and intelligence upgrading in education. VR has At present, the application of IVR in education remains in its early stages , and theIVR can support embodied learning because it offers a highly interactive environment that enables learners to gain embodied experience through the interactions among the body, its sensory motor system and the environment, thus allowing individuals to produce positive and relatively lasting changes in their behavior or behavioral potential. This process is known as “experiential learning involving feeling, perception, mind–body interaction and reaction” . This invia the learning experience  more transparent , thus resulting in important implications and insights.Based on this conceptual framework, a hypothesized model for evaluating the ways in which IVR can improve learning outcomes is developed, as shown in via emotional experiences (perceived enjoyment and presence)?”The relationship predicted in the previous model is given in H1: Immediacy of control is significantly associated with interactivity.H2: Immediacy of control is significantly associated with presence.H3: Immediacy of control is significantly associated with perceived enjoyment.H4: Interactivity is significantly associated with presence.H5: Interactivity is significantly associated with perceived enjoyment.H6: Presence is significantly associated with learning satisfaction.H7: Presence is significantly associated with perceived learning effect.H8: Perceived enjoyment is significantly associated with learning satisfaction.H9: Perceived enjoyment is significantly associated with perceived learning effect.4.4.1.With regard to the COVID-19 pandemic, the novel coronavirus exhibits high infectivity, rapid diffusion, a long incubation period, strong concealment, and a tendency toward easy variation; in addition, knowledge of pandemic prevention and control exhibits the characteristics of abstractness, complexity, and negligence. As a result, most people’s knowledge in this context lacks a scientific and systematic basis, and so they cannot cooperate scientifically with pandemic prevention and control measures, especially in densely populated places, such as schools. Therefore, during the spring semester of 2022, China West Normal University offered a popular science course on pandemic prevention and control knowledge that included an IVR-based COVID-19 pandemic science museum. Simultaneously, an empirical survey was conducted to investigate the associated learning outcomes and processes. This approach can greatly enhance the scientificity and effectiveness of pandemic prevention and control.4.2.The sample referenced by this study comprised 480 typical college students from a Chinese university, including 193 males and 287 females between the ages of 18 and 25 years. The students learned about pandemic prevention and control by visiting the IVR-based COVID-19 pandemic science museum. Each session of the learning activity was attended by 10 learners and one teacher simultaneously, and students in each group were required to wear VR glasses. Students in each group were shown the glasses and guided by a teacher wearing the main-view VR glasses. Each learning activity lasted approximately half an hour. Throughout the learning experience, first, the teachers wore the main-view glasses to demonstrate and guided the operation of the VR controller and the main-view glasses, as well as how to visit; then, the students chose to wear the main-view glasses in turn for experiential learning according to their individual learning needs; at the same time, group members could communicate the learning content and discuss their progress with each other. Subsequently, each member participated in the following questionnaire survey, which focused on input (VR function), process (learning experience), and output (learning outcomes). That is, the variables included immediacy of control and interactivity, presence and perceived enjoyment, and learning satisfaction and perceived learning effect. In the experiment, the students were informed of the nature of the study and participated voluntarily.4.3.4.3.1.The questionnaire included independent variable associated with VR function (immediacy of control and interactivity); mediating variables pertaining to learning experience (presence and perceived enjoyment); and dependent variables focused on learning outcomes (learning satisfaction and perceived learning effect). The complete list of items and the sources of the scales used are included in Appendix A.Immediacy of control was measured using 4 items adapted from Interactivity was measured using 4 items adapted from Presence was measured using 4 items adapted from Perceived enjoyment was measured using 3 items adapted from Learning satisfaction was measured using 5 items adapted from Perceived learning effects were measured using 4 items adapted from All items were rated on a 5-point Likert scale ranging from strongly disagree to strongly agree.4.3.2.The IVR-based COVID-19 pandemic science museum was customized by China West Normal University for Shanghai ManHeng Digital Technology Co., Ltd., and used as learning material. The scenes and activities associated with this museum are shown in The IVR system consists of IQ-Tracker tracking, an LED display, a graphics workstation, a sound system, 11 VR glasses (1 main-view) and a VR controller. Both the main-view VR glasses and the VR controller have a signal transmitting ball, which can be used to locate their own position with the tracker. When the VR controller points to the LED display, the program generates an indicator line on the screen that the operator can use to point to a text, a picture, or a detail of a model in the museum. In the COVID-19 pandemic science museum, 2D video windows are embedded in 3D scenes, and while each section of the pandemic prevention and popular science documentary is played, learners can control the playback progress. Simultaneously, the simulation features an exhibition of COVID-19 pandemic knowledge using graphics, images and text, and an interactive intelligent robot is included in the simulation to broadcast and explain this information. Learners can touch and manipulate learning objects directly or indirectly using bodily movements or third-party media. For example, learners wearing main viewing glasses can change the size and position of the VR viewing angle by rotating their head or moving their body; learners can achieve the five operational requirements of movement, steering, pointing, selection and menu navigation through the VR controller. Learners communicate with the learning environment system mainly by dialog and control. For example, learners can point to learning content and get intelligent broadcasts or answer preset window questions and receive timely feedback; learners can determine the progress and order of learning plots through control. That is, multichannel perceptions, direct control, and real-time responses facilitate interaction, thus allowing learners to complete the relevant learning experience in the VR science museum.The simulation experience begins with the display of a 2D documentary regarding the pandemic at the Science Center. Subsequently, learners advance interactively through the simulation and visit a circular science popularization corridor. Relevant pandemic prevention and control knowledge and 3D objects are displayed in the air and on the walls on both sides of the corridor. Finally, learners choose whether to initiate the answer mode, according to which a simple test including 10 questions measures users’ mastery of basic knowledge regarding COVID-19 prevention and control. Throughout the whole process of the simulation experience, self-pacing and guided learning principles are adopted to enhance perceived learning outcomes.4.4.It takes about 15 min for each subject to fill out the questionnaire. The data referenced by this study were collected in January 2022. First, the questionnaire was uploaded to WJX.5.5.1.In this study, the means, standard deviations, CR (Composite Reliability), AVE (Average Variance Extracted), and Pearson correlation coefficients of VR features , the learning experience emotion factor , and learning outcomes  were analyzed .r = 0.60, p < 0.01; r = 0.64, p < 0.01) and the learning experience emotion factor . Learning satisfaction was positively linked with VR features  and the learning experience emotion factor . Perceived enjoyment was positively linked with VR features  and presence . Presence was positively linked with VR features . Immediacy of control was positively linked with interactive feedback .The average variance extracted (AVE) is higher than 0.5, but we can accept 0.4. Because Fornell and Larcker said that if AVE is less than 0.5 but composite reliability is higher than 0.6, the convergent validity of the construct is still adequate . All six5.2.2 value by the degrees of freedom (χ2/df), standardized residual mean root (SRMR), and root mean square error of approximation (RMSEA), comparative fit index (CFI), and Tucker–Lewis index (TLI) to evaluate the fit index for this study. This study takes the VR characteristics as independent variables, emotional variables as intermediary variables, and result variables as dependent variables to construct a mediating model. This model uses the χIn social science studies, common method variance is normal due to the data collection procedures. We run the Harman one-factor test to evaluate the effect of common method variance on the constructs of the study . The res5.3.a priori model shown in A confirmatory factor analysis was conducted to test the fit of the hypothesized relationships among the constructs in the 5.3.1.β = 0.86, p < 0.001).H1 was supported. As expected, immediacy of control is a significant antecedent of immediacy .5.3.4.β = 0.78, p < 0.001).H4 was supported. As expected, according to this study, a change in interactivity is significantly related to a change in presence .H6 was supported. As expected, presence is positively correlated with learning satisfaction .H7 was supported. The results of this study indicate that presence is positively correlated with perceived learning effect .H8 was supported. Perceived enjoyment is positively correlated with learning satisfaction .H9 was supported. The results indicate that perceived enjoyment is positively correlated with perceived learning effect  should be emphasized. Specifically, the degree to which learners have a psychological sense of “being there” in the VR environment is related to their perceived learning outcomes, and the degree to which learners find the VR environment to be pleasant, fun, and enjoyable is also related to their perceived learning outcomes. In other words, learners with high levels of presence and enjoyment exhibit greater improvement in terms of learning satisfaction and perceived learning effect. Therefore, we can ensure a high level of emotional experience in two ways in activity design. The first way is to facilitate presence by offering scenarios that are more closely related to real life and emphasizing the scientific, artistic, educational, and technical principles of VR activities. Another way is to enhance perceived enjoyment. For example, according to the primacy effect, a novel and unique theme should be established to ensure that learners receive a deep first impression. Likewise, based on the tailing effect, learners’ enjoyment and memory can be improved by summarizing and reflecting at the end of the activity, such as taking pictures. In addition, in the context of learning activities, a reasonable reward mechanism can be implemented to drive game-based teaching.via presence, and we can control learning satisfaction more effectively via learners’ perceived enjoyment. Therefore, when developing targeted interventions, our practitioners can design teaching plans or experiments based on different significant paths. This approach can help us develop a data-driven comprehensive evaluation of education more effectively.Third, the data results show that when designing learning outcome interventions, presence and enjoyment are two relevant emotional variables. Specifically, in the learning experience, the correlation between the level of presence and the learning effect is significantly greater than the correlation with learning satisfaction, while the correlation between the level of enjoyment and learning satisfaction is significantly greater than the correlation with the learning effect. In other words, we can control learners’ perceived learning effect more effectively 7.This study faced three limitations. First, the effect of individual differences in terms of the relevant variables on learners’ perceived learning outcomes was not assessed. Certain individual variable-related differences can moderate the impact of the technical learning interventions discussed in this study, including vertigo, spatial ability, cognitive style, learning motivation, self-efficacy, and learning attitude . To ensuBased on the current research findings and the remaining limitations, we propose the following research directions that can be pursued in the future:The impact of individual differences in terms of variables on learning experiences in an IVR-based environment represent an important direction for future research.The impact of social cues, such as textual cues or visual cues, on the interactive VR-based learning process is an important direction for future research . AccordiFuture research should investigate whether the model framework constructed in this study can be generalized to other learner samples and different learning topic scenarios.8.via learning experience based on media technology models and the CVTAE. Unlike previous studies, we focused on IVR environments and emphasized the interactive effect of VR features and learning experience on learning outcomes from the perspective of psychological and emotional value. By using SEM, the key mediating effect of emotional experience (presence and perceived enjoyment) on the relationship between IVR features and perceived learning outcomes was explored, which facilitated the development of a preliminary theoretical model of the emotional factors that influence learning outcomes in an IVR learning environment. In addition, by reference to the data thus analyzed, we highlighted the different effects of presence and enjoyment on learning satisfaction and perceived learning effect in the IVR learning experience.In this study, we explored the internal mechanism by which IVR features affect learning outcomes Practitioners and educators can benefit from this study because, first, these results can provide intellectual and theoretical support for VR teaching design and VR environment development for educational purposes, such as by helping to develop a training platform for educational virtual simulation experiments. Second, this study expands the applicability of embodied learning theory to different scenarios, and the research results thus have practical value for the large-scale application of IVR in the future with the aim of providing experiential and group-led teaching and promoting the digital transformation and intelligence upgrading in education. Third, this study proposes a preliminary theoretical model of the emotional factors that influence learning outcomes in the context of IVR learning experience, which can help scholars in this field conduct further related research on this basis.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the Ethics Committee of China West Normal University. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.HY and YD: research design, methodology, and funding acquisition. RL and LL: material preparation, data collection, and reference management. HY and MC: data analysis and critical manuscript revisions. QX: writing – review, editing, and manuscript revision. All authors contributed to the article and approved the final draft submitted.This study was supported by the General Project of Teaching Reform of Sichuan Education Department (JG2021-947), the Doctoral Project of China West Normal University (21E007), the Projects of Industry-University Collaborative Education of the Ministry of Education (202102464026), the Project of High-quality Development of Sichuan compulsory Education (YWZDWT-2022-02), and the Project of Nanchong Social Science Planning (NC2020B227).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.https://www.frontiersin.org/articles/10.3389/fpsyg.2022.1081372/full#supplementary-materialThe Supplementary material for this article can be found online at: Click here for additional data file.


The disease burden trend of lung cancer that is attributable to occupational carcinogens in China remains unclear. We used the data from the Global Burden of Disease (GBD) study in 2019 to investigate the related disease burden from 1990 to 2019 and to project the disease burden for the next 25 years. The results indicate that the disease burden of lung cancer that can be attributed to occupational carcinogens significantly increased from 1990 to 2019 in China, and the absolute burden will continue to increase in the next 25 years.Background: Little is known about trends in the lung cancer burden from the disease that can be attributed to occupational carcinogens in China. Methods: Data regarding the lung cancer burden that can be attributed to occupational carcinogens in China were extracted from the Global Burden of Disease (GBD) study in 2019. Joinpoint regression analysis and an age-period-cohort (APC) analysis were conducted to estimate the trend of lung cancer burden as a result of occupational carcinogens from 1990 to 2019. A Bayesian APC model was used to predict the disease burden until 2044. Results: The average annual percentage changes of age-standardized summary exposure values (SEVs) of occupational lung carcinogens, as well as the age-standardized population attributable fraction (PAF) of lung cancer due to occupational carcinogens, were 0.5% : 0.4–0.5%) and 0.1% (95% CI: 0–0.2%), respectively. In addition, both the joinpoint regression analysis and APC analysis demonstrated significantly increased trends of age-standardized lung cancer mortality (ASMR) and age-standardized disability-adjusted life years (ASDR) as a result of occupational carcinogens. Asbestos and silica accounted for the two most important occupational lung carcinogens in China. The absolute burden is expected to increase, mainly due to population aging and the age-specific rate of illness. Conclusions: The lung cancer burden that could be attributed to occupational carcinogens significantly increased from 1990 to 2019 in China, and the absolute burden will continue to increase in the next 25 years. Lung cancer is the most common cancer and is the leading cause of cancer deaths globally, with an estimated 2.1 million new lung cancer cases and 1.8 million deaths in 2018 . HoweverLung cancer is the most common occupation-related cancer, which accounts for 89.0% of attributable cancer deaths . Among tChina is a rapidly developing country that has experienced marked socio-economic changes. However, this has led to a high disease burden that is attributable to occupational risks . In our The GBD study estimates a variety of metrics of diseases recorded annually, dating back to 1990. This provides a unique opportunity to assess the long-term trends of the disease burden in relation to various risk factors. Based on the GBD data, several studies investigated the disease burden attributable to occupational risks for cancer in China or worldwide ,13. Howehttps://ghdx.healthdata.org/gbd-results-tool, accessed date: 20 April 2022). As a secondary analysis of publicly available data, no ethical approval from an institutional review board was required for this study.Data regarding the disease burden of lung cancer that can be attributed to occupational carcinogens in China were derived from the GBD 2019 . The GBDA total of 13 work-environment carcinogens associated with 7 cancer types were assessed in GBD 2019. In this study, we focused on the disease burden of lung cancer that can be attributed to 9 occupational carcinogens, including arsenic, asbestos, beryllium, cadmium, chromium, diesel engine exhaust, nickel, polycyclic aromatic hydrocarbons, and silica. The individual and combined age-standardized SEVs for occupational carcinogens that are associated with lung cancer were obtained. A SEV was developed for GBD 2015, in terms of the relative risk-weighted prevalence of exposure. The SEV ranged from zero, when no excess risk exists in a population, to one, when the population is at the greatest risk.Data on the annual number of lung cancer-related deaths, DALYs, ASMR, ASDR, population attributable fraction (PAF), and age-standardized PAF that were attributable to occupational carcinogens from 1990 to 2019 were obtained. Attributable deaths and DALYs were estimated using the total resulting death rate or DALYs, multiplied by the PAF for the risk-outcome pair for each age, sex, cause, and location. The detailed computation process of PAF was described in a previous study . The ageThe uncertainty estimation interval (UI) was calculated to address the possible heterogeneity issue from both the sampling error and non-sampling variance for GBD 2019. The 95% UI was calculated by taking 1000 samples from the posterior distribution of the respective step in the modeling process and was reported as the 2.5th and 97.5th values for each estimate. The UIs for SEV and the number/rate/PAF of lung cancer incidences attributable to occupational carcinogens were also obtained directly from the Global Health Data Exchange website.Descriptive analyses were conducted on lung cancer cases that were attributable to occupational carcinogens between the years of 1990 and 1999 in China. The percentage change was calculated to describe the trend of the measures. The trends of age-standardized SEV, ASMR, ASDR, and age-standardized PAF were further assessed using joinpoint regression analysis on a log scale, since these measures followed a Poisson distribution . JoinpoiFurthermore, we used an APC model to analyze the effects of age, period, and cohort on mortality and the DALYs of lung cancer cases attributable to occupational carcinogens. The APC model was based on a log-linear model for the rate, with additive effects from age, calendar period, and birth cohort, as shown in the formula below :Logλij =i refers to the age effects, βj refers to the period effects, and γk refers to the cohort.In the above model, μ refers to the intercept term, αhttp://analysistools.nci.nih.gov/apc/, accessed date: 20 April 2022) [We performed the APC analysis with a freely available web tool , assuming the inverse gamma prior distribution of age, period, and cohort effects and applying a second-order random walk (RW2) to adjust for excessive dispersion . The estp-value of less than 0.05.In addition, we used a newly developed decomposition method to attribute changes in the total number of lung cancer deaths and DALYs, from occupational carcinogens to population growth, population aging, and age-specific changes between 1990 and each subsequent year from 1991 to 2044 ,23. The In 2019, among 67,264 deaths and 1,639,492 DALYs from occupational carcinogen-attributable cancer, 93.5%  deaths and 92.1%  DALYs were from lung cancer. The estimated number, all-age and age-standardized PAF, mortality, and the DALYs of lung cancer due to occupational carcinogens in 1990 and 2019 are presented in According to the results of the joinpoint regression model, the average annual percentage change of the age-standardized SEV of occupational carcinogens, taken collectively, was 0.5% (95% CI: 0.4–0.5%). Furthermore, the average annual percentage changes for ASMR, ASDR, the age-standardized PAF for death rates and age-standardized PAF for DALYs were 0.9% (95% CI: 0.7–1.1%), 0.4% (95% CI: 0.2–0.7%), 0.1% (95% CI: 0–0.3%), and 0.1% (95% CI: 0–0.2%), respectively. All of them demonstrated a significantly increased trend. However, these trends fluctuated in different segments. As shown in The trends of age-standardized SEVs, PAF and ASMR, and the ASDR of lung cancer cases that were attributed to individual occupational carcinogens are shown in The estimated period and cohort RRs for lung cancer deaths attributable to occupational carcinogens are displayed in The effects of age, time period, and cohort on the death rates and DALYs of lung cancer that can be attributed to individual occupational carcinogens are shown in Finally, we conducted a Bayesian APC analysis to project the future trends of the ASMR and ASDR of lung cancer that can be attributable to occupational carcinogens from 2020 to 2044 in China. The age-specific rates of death and DALYs were shown in In this study, based on data from the GBD 2019, we found that the lung cancer burden that is attributable to occupational carcinogens still increased in terms of ASMR, ASDR, and age-standardized PAF in China. However, these trends fluctuated in different time segments from 1990 to 2019. After adjusting for the age and cohort effects with the APC model, similar trends were also observed for ASMR and ASDR. Although both the ASMR and the ASDR will decline in the coming 25 years, the numbers of both deaths and DALYs will continue to increase.The significantly increased trend of ASMR and ASDR for lung cancer that can be attributed to occupational carcinogens might mainly result from the high prevalence of occupational exposure, which was a reflection of the rapid economic development and increased industrialization processes in China in previous decades. This finding can be supported by the significant increase in the SEVs of occupational lung carcinogens from 1990 to 2019 seen in our study. A previous study also reported the elevated trend of SEVs of the most common occupational risks in China from 1990 to 2017 .However, the above analysis could not eliminate the confounding effects of age and cohort, and the results may have some limitations . TherefoResults from the joinpoint analysis demonstrated that from 2011 to 2016, a significant reduction in ASMR and ASDR for lung cancer could be attributed to occupational carcinogens. Similarly, in the APC model, time-period RRs also showed a downward trend since 2012, after adjusting for the confounding effects of age and cohort. Furthermore, we found that the local drift values were lower than 0, while both the period RRs after 2015 and the cohort RRs in those born after 1960 demonstrated decreased trends. These results might be due to the long-term continued efforts regarding the control and prevention of occupational exposure to carcinogens in China, which included policy-making and legislation, occupational supervision, occupational surveillance, labor protection, etc. ,26. FurtMore advanced age is associated with lung cancer. In this study, the rates of both deaths and DALYs regarding occupational carcinogens that can be associated with lung cancer are low during their youth and increase with age, reaching a peak among the 85–90-year age group, which might be due to both age-related biological factors and the increased level of occupational exposure. Consequently, the rapid aging process, the rising life expectancy, and longer exposure to occupational carcinogens in China might be the main reasons for the continuing increased number of deaths and DALYs of occupational carcinogen-attributable lung cancer predicted by the Bayesian APC model ,28,29, wPrevious studies found that asbestos was responsible for the largest number of lung cancer deaths and DALYs globally. However, its attributable rates of death and DALYs have decreased significantly since 1990 ,32. ThisOccupational exposure to silica is very common in certain industries, such as metal or coal mining, construction, painting, glass production, and foundries. Silica exposure has consistently been associated with lung cancer . It is eThis is the first study to investigate the impacts of age and time period on cohorts regarding the temporal trends of lung cancer burden caused by occupational carcinogens in China. The predicted increase in the absolute lung cancer burden due to occupational carcinogens emphasizes the importance of improving occupational health in China. Because lung cancer was the most common cancer type affected by occupational carcinogens, a comprehensive strategy integrating significant resources from governments, employers, workers, and other stakeholders to prevent and control occupational lung cancer should be developed. In particular, the prevention and control of asbestos and silicon use should be strengthened.The global burden of lung cancers due to occupational carcinogens is decreasing ,37. HoweSome limitations, as highlighted in earlier GBD study reports, should be addressed ,39. FirsThe lung cancer burden due to occupational carcinogens still increased from 1990 to 2019 in China. Although the predicted ASMR and ASDR of lung cancer that was attributable to occupational carcinogens showed a significant declining trend, the absolute number will still increase in the next 25 years due to the rapid population aging seen in China. This study provides guidance for prevention and control programs for occupational lung carcinogens, especially in the case of asbestos and silica.