This study examined the relationship between psychological capital (PsyCap) and teacher enjoyment in the context of online teaching and investigated whether the emotion regulation (ER) strategy of reappraisal mediated their relationship. 221 Chinese university teachers were selected as the research sample through snowball sampling in an online survey. After controlling for age, gender, teaching experience, education level, time and energy input during online teaching and online teaching experience, the results showed that PsyCap and reappraisal positively influence the teachers’ online teaching enjoyment (OTE), and reappraisal significantly mediated the relationship between teachers’ PsyCap and OTE, suggesting that optimistic and resilient teachers with more self-efficacy and hope are more likely to find enjoyment during online teaching, and high PsyCap combined with the use of reappraisal leads to greater OTE. The study not only confirms the positive role of reappraisal as an emotion regulation strategy in online teaching, but also provides practical implications for the realization of enjoyable online teaching experience. Over the past few years, online teaching has gained worldwide popularity among students and teachers as a welcoming way which incorporates multimedia resources and technology to maximize learning efficiency . AgainstHowever, when facing the changes of switching the offline teaching mode to online, teachers have experienced various negative emotions such as anxiety , stress Previous research shows that PsyCap is helpful to stimulate an individual’s positive psychological capacities and resources , 2007. PPsychological capital, a core positive construct in positive psychology, has been developed by It is notable that research on the relationship between PsyCap and teacher emotions is still in the initial stage of development. Whereas teachers with positive attitudes and emotions are more likely to create a happy and enjoyable atmosphere in class, those with negative emotions might discourage their students, which is unfavorable to the effectiveness of teaching and learning. It has been found that PsyCap positively predicted the psychological well-being and happiness of university teachers , and helEmotion regulation refers to attempts to influence which emotions individuals have, when they have them, and how they experience and express them . The proOn a daily basis, teachers work in a more emotionally demanding atmosphere than most other professions . TeachinInspired by the development of positive psychology, the study of positive emotions has been attracting constant attention from scholars and practitioners in education . As the Previous studies mainly focus on the teaching enjoyment of teachers from a single discipline. For example, Overall, a review of literature on teaching enjoyment shows that little research has been conducted on teaching enjoyment of either discipline-general teachers or university teachers in an online context. It still remains unclear what makes enjoyable online teaching. Therefore, the current study aims to empirically investigate whether PsyCap predicts OTE and whether reappraisal mediated the relationship between PsyCap and OTE with a sample of Chinese university teachers.As stated above, previous studies have confirmed that there is a positive association between PsyCap and positive emotions such as job satisfaction  and psycHypothesis 1: PsyCap positively predicts online teaching enjoyment.Hypothesis 2: Reappraisal mediates the relationship between PsyCap and online teaching enjoyment.Specifically, in an attempt to explore whether positive psychological state and positive cognitive change relate with a higher level of teacher enjoyment, it is hypothesized that PsyCap (independent variable) is positively correlated with the use of the ER strategy of reappraisal (mediator), which might play a positive and mediating role in the relationship between PsyCap and teacher enjoyment during online teaching (dependent variable).After obtaining ethical approval from the authors’ institution, 221 Chinese university teachers were invited through snowball sampling to participate in this study via WeChat, one of the dominant social networking applications in China. All the respondents participated on a voluntary basis and they were informed in the invitation letter of the purpose of the study and the confidentiality of the survey data.N = 147; 66.5%). Age was between 24 and 60 . Their teaching experience ranged from 0.5 to 42 years . As for education level, almost half of the participants have a Master’s degree , 98 of them (44.3%) have a Ph.D. degree, and only 16 (7.2%) participants hold a Bachelor’s degree. The participants’ online teaching experience ranged from one semester , two semesters , three to four semesters , to five or more than five semesters . A question was also asked as to whether and how the time and energy they put in online teaching had changed compared with the traditional offline teaching. A majority of the participants reported that it had increased , only 18 of them (8.1%) reported a decrease in the time and energy input, and 58 of them (26.2%) claimed that it remained almost unchanged. Further demographic information is presented in A total of 221 Chinese university teachers from different parts of China participated in the study  after receiving an invitation or finding the call for participation on WeChat groups. The majority were female  and OTE . Likewise, reappraisal is positively associated with OTE .The results of the descriptive statistics and correlation analysis of PsyCap, reappraisal, and OTE are displayed in t = 5.71, p < 0.001) and reappraisal , and reappraisal positively predicts OTE . As shown in the mediation model in p < 0.001) to .SPSS macro PROCESS was used in this study to examine the relationships among PsyCap, reappraisal, and OTE and the mediating role of reappraisal between PsyCap and OTE among Chinese university teachers. Mediation model testing was conducted to estimate the parameters of two regression equations: (1) the direct effect of PsyCap on OTE; (2) the indirect effect (mediation effect) of reappraisal on the relationship between PsyCap and OTE. The results of regression analysis are displayed in To further test the reliability of the mediating effect, non-parametric bootstrapping method with 5,000 times of resampling was used. As shown in N = 183; 82.8%) reported that their salary remained unchanged during the period of online teaching, showing that online classroom is a more demanding and stressful job context. Furthermore, it is more difficult for teachers to establish effective and adequate communication with their students and colleagues in the online context, all of which calls more strongly for teachers’ positive emotions. Teachers with high PsyCap are more likely to think in a positive and optimistic way and realize that online teaching not only has distinct advantages but also is the irreversible trend in an increasingly digitalized era. Therefore, based on the survey results, it is expected that teachers engaged with online teaching will be encouraged and trained in teacher training programs to have higher PsyCap, including its four dimensions of efficacy, hope, resilience, and optimism, for PsyCap positively predicts OTE and OTE is beneficial to online teaching and learning.First of all, the results reveal a positive relationship between PsyCap and online teaching enjoyment, which confirms the first hypothesis in this study and is consistent with previous research on the connection between school PsyCap and achievement emotions . PreviouThe study also reveals an important mediating role of reappraisal as an ER strategy in connecting PsyCap with online teaching enjoyment, which confirms the second hypothesis and is a new finding in this field of study. This indicates that teachers with a high level of PsyCap are more likely to reappraise a negative or stressful situation, to reconsider it from a positive perspective, and teachers who use more of the ER strategy of reappraisal tend to have greater enjoyment in online teaching. The findings, in line with previous research on the positive role of reappraisal , are refOnline teaching is enjoying more and more popularity and is playing an increasingly important role among teachers and students worldwide. Hence there is an urgent need at the present time to explore what can help boost online teaching enjoyment and if the use of some emotion regulation strategies can help teachers obtain an enjoyable rather than anxiety-dominated experience when delivering classes online or when organizing online activities for a blended course.Based on The results provided practical implications for finding an effective approach to improve university teachers’ positive emotions in the context of online teaching. As it is necessary during the pandemic and recommendable in the development of a hybrid course to accommodate diversified resources into one course for teachers to engage with online teaching, it is vitally important to seek out ways allowing university teachers to keep a positive emotional state when preparing and delivering their online lectures. To help teachers find more enjoyment in online teaching, colleges and universities should try to strengthen their psychological capital and train them to make better use of the ER strategy of reappraisal, making them more optimistic, confident and resilient. As university teachers face various pressures such as publication and teaching , this stAs one of the initial attempts to explore the relationship between PsyCap, reappraisal, and OTE, this study promoted empirical understanding of their relationship in the context of online teaching, contributing to the literature of teacher psychology. Despite the significance of the study, there are still some limitations. First, the research design was cross-sectional and causal inference cannot be made. Second, the data were collected by using questionnaire survey, which might contain biases. Future studies might adopt a longitudinal or mixed-method research design. Third, this research was restricted to reappraisal as the mediator. Future research might choose more constructs as mediators between PsyCap and OTE. Finally, this survey study used only Chinese teachers as the sample. Future studies might adopt an intercultural perspective by inviting teachers from different countries to participate in the research.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Department of Foreign Languages, Shanghai Maritime University. The patients/participants provided their written informed consent to participate in this study.XZ: research design, data collection, data analysis, and the writing and editing of the article. SZ: research design, data collection, drawing tables and figures, and the writing and editing of the article. Both 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.


The application of artificial intelligence (AI) systems is emerging in many fields in recent years, due to the increased computing power available at lower cost. Although its applications in various branches of medicine, such as pediatric oncology, are many and promising, its use is still in an embryonic stage. The aim of this paper is to provide an overview of the state of the art regarding the AI application in pediatric oncology, through a systematic review of systematic reviews, and to analyze current trends in Europe, through a bibliometric analysis of publications written by European authors. Among 330 records found, 25 were included in the systematic review. All papers have been published since 2017, demonstrating only recent attention to this field. The total number of studies included in the selected reviews was 674, with a third including an author with a European affiliation. In bibliometric analysis, 304 out of the 978 records found were included. Similarly, the number of publications began to dramatically increase from 2017. Most explored AI applications regard the use of diagnostic images, particularly radiomics, as well as the group of neoplasms most involved are the central nervous system tumors. No evidence was found regarding the use of AI for process mining, clinical pathway modeling, or computer interpreted guidelines to improve the healthcare process. No robust evidence is yet available in any of the domains investigated by systematic reviews. However, the scientific production in Europe is significant and consistent with the topics covered in systematic reviews at the global level. The use of AI in pediatric oncology is developing rapidly with promising results, but numerous gaps and challenges persist to validate its utilization in clinical practice. An important limitation is the need for large datasets for training algorithms, calling for international collaborative studies. Childhood cancer is one of the priorities of the World Health Organization (WHO) that in 2018 launched the WHO Global Initiative on Childhood Cancer, aiming at achieving 60% survival rate by 2030  was born decades ago , the incAnother promising application of AI regards the improvement of healthcare through process mining which may inform clinical management, and ultimately affect the quality of care . The larAlthough technical solutions for the development of AI applications are largely available, AI algorithms require large amounts of data from interoperable datasets for a widespread application of AI that achieves a high accuracy . MoreoveIn 2021, the European Union (EU) Commission issued the Europe’s Beating Cancer Plan, including the flagship Helping Children with Cancer Initiative, which highlights the value of real word data and artificial intelligence as potential tools for cancer prevention and care . The EU In this scenario of potential rapid development, designing plans and addressing priorities in AI applications for pediatric oncology requires an analysis of the current activities to identify the achievements and the gaps in this field, including clinical and management issues. To this aim, we drew the state of the art in the field of AI applied in pediatric oncology through a systematic review of reviews. In addition, to describe the existing scientific trends in Europe, we performed a bibliometric analysis of publications authored by European authors in the same field.We performed a systematic review of systematic reviews in the field of AI applied on pediatric oncology. To this end, we set up a search query based on a published strategy of the Cochrane Childhood Cancer for PubMed  and a quIn addition, we performed a bibliometric analysis on available publications on AI and pediatric oncology from a search query submitted to the Web of Science platform. We used the same search string adopted for searching the reviews, but we selected the original publications instead. We then manually reviewed the selected records and included the original publications that included quantitative results on AI interventions applied to pediatric cancer. From these publications, we manually extracted information on the disease in which AI was applied, the aim of the work, the data source used for the AI application, and if the performance of the AI algorithm was compared with a natural human. Finally, we extracted information on the funding source in Scopus.The bibliometric analysis of this dataset included the annual volume of scientific publications, the collaboration network based on Authors’ affiliation, and the volume of publications by journal. For this purpose, we used the Biblioshiny platform . DescripWe found 330 unique records from the combination of results from Web of Science and PubMed. We manually selected those reviews which included studies a) with individuals below 18 years of age; b) which focused on tumors typical of pediatric age; c) reporting quantitative results. We excluded the publications on tumors of adulthood even if including some patients < 18. The list of excluded tumors is available in the Supplemental material.Finally, 25 records were eligible to be included in the review Figure 1Although we covered a 20-year time in the search strategy for systematic reviews, none of them was published before 2017, indicating only a recent proliferation of original publications in this field. The included reviews included heterogeneous publications and rarely showed a meta-analysis with a quantitative summary of available evidence. The total number of studies included in the reviews was 674, among them, 224 (33.2%) included an author with a European affiliation.Most available reviews focused on the use of diagnostic images, particularly radiomics. Only 4/25 reviewed the use of data sources other than diagnostic images  for the development of AI applications. While, the use of AI systems to optimize highly repetitive processes (such as image segmentation) was widely investigated, an emerging trend involved the use of radiomic features in predicting the histological and molecular classification of tumors, with the aim to reduce the invasiveness of the diagnostic process.van Kempen et al., Jian et al., and Bhandari et al., the ability to predict the genomic profile of glioblastoma, namely IDH status, MGMT promoter methylation status, and 1p/19q codeletion status, was investigated with promising perspectives  tumors, and seven of them investigated the performance of radiomics. The majority of these reviews were about the performance of AI applications in diagnosis, segmentation and classification, while 4 investigated their prognostic value. Finally, one review focused on the definition of tumor infiltration, and one on quality of radiomics studies. All reviews on CNS tumors concluded for a good performance of AI applications for the specific aim of the review. In particular, in the review by pectives , 25, 29.lleagues . Of notelleagues , 42.Three out of the 25 reviews were on AI applications for bone and soft tissues sarcomas and focused on quality and reproducibility of radiomics. These reviews agreed in concluding that the quality of radiomics studies is still low and that this may hamper their reproducibility and practical clinical application.Two reviews were on lymphomas and focused on radiomics for diagnosis or prediction of outcome. Although the performance of radiomics was good, the quality of the studies was suboptimal and the risk of bias in these studies was moderate or high.Two reviews on head and neck cancers evaluated the performance of radiomics and other AI applications: one on tumor segmentation and classification of tumors showed a high performance of AI applications, the other investigated the prediction of radiation-induced side effects through radiomics and showed the existence of preliminary data only that need validation. Again, although head and neck cancers are rare in childhood, these studies were included because one includes brain tumors, which are relatively frequent in children, while the other focuses on radiation damage, an important issue especially during the developmental stage.The remaining reviews focused on AI applications for predicting prognosis in hematopoietic stem cell transplantation (HSCT) that yielded only weak evidence supporting machine learning (ML) techniques mainly due to small sample size, and AI applications for diagnosis of leukemia  that recommended further validation of the models. None of the reviews focused on AI applications for process analysis of patients with cancer.Almost all the reviews underlined the limitations of the investigated studies due to small data samples for training, heterogeneous methodologies, lack of external validation, and questionable quality of the available papers included in the reviews.We found 978 records, and we selected 304 for the analysis by manual revision applying the same selection criteria used for the reviews. Bibliometric data were extracted from the selected publications and processed to obtain information on temporal trends of publications, most used scientific journals for publication, and geographic trends according to authors’ affiliation. Manually annotated information allowed for the analysis of most frequent diseases, scope, data source, comparison of performance with humans, and funding source.These original papers were published in 172 different journals and had an average number of citations of 32.9. The number of articles regarding AI and pediatric cancer has been modest until 2017, and then sharply raised with a nearly tenfold increase in 2020 compared with 2017 Figure 2Most of the scientific publications in the field of AI and pediatric cancer are available in journals that are not specific for oncology such as Scientific Reports and PLoS One Table 2.Not only the scientific production included in the analysis was scattered through several different scientific journals, but also according to the bibliometric indexes, the number of citations was modest, being higher for those journals that started to host publications on AI in pediatric oncology in early years.The most represented author countries were the UK, Germany and Spain, accounting for 37% of all authors. International collaborations between different countries based on the affiliation of authors is shown in Separate networks including different European countries exist with dense collaboration links. The most evident cluster is between the USA, Germany, several other European countries and Canada  and diagnosis  of pediatric cancer. Much less frequently, the papers focused on AI for planning treatment . Some papers also had multiple scopes (2.0%). We also investigated which data source was used to train the AI intervention in each of the papers under review Table 3.We also explored how frequently the AI application was compared to human capacity in terms of concordance and accuracy for external validation. The total number of papers including such a comparison with a human counterpart was 31/304 papers (10.2%). Finally, information regarding the use of any research funding was available in 294/304 papers; among them, 173 (58.8%) acknowledged a funding source for the research activity and 40 of them (13.6%) reported a European funding source, while the remaining 121 (41.2%) we not supported by any research fund. European funding supporting the work reported in these publications were from the FP6, FP7, Horizon 2020, ERDF, and ESF Programmes.We searched for existing evidence and the trends in publications regarding the application of AI in pediatric tumors. Our work, which combined a systematic review of systematic reviews and a bibliometric analysis, applied a detailed search string to find the existing contributions in the domain of AI and pediatric tumors screening the existing publications over a long period of time. Although the inclusion of other publication sources than Web of Science and PubMed databases may have increased the number of publications in this field, our analysis has captured the vast majority of existing scientific production in the field of AI and pediatric oncology.Our review focused on Europe, showed that AI in pediatric oncology is still in its infancy and, although many publications on this topic have been issued, the available evidence is still poor and mostly limited to proof-of-concept studies. No robust evidence is available yet in any of the clinical domains investigated in the available systematic reviews. On the other hand, the scientific production generated in Europe is significant and consistent with the topics covered in systematic reviews at the global level. Most of the literature generated in Europe is on AI applications for imaging in brain cancer. Radiomics, the most developed area of research, still suffers from a low degree of reproducibility and repeatability due to the paucity of existing studies and the rarity of multicentric initiatives in this field . HoweverAlthough the scientific production on AI and pediatric cancer significantly increased in the last years, still most of published works remain proofs of concept. Indeed, most studies used datasets from single centers, with a small sample size, and did not perform any external validation of their model, limiting their applicability and generalizability. Data-sharing privacy concerns and several other barriers preventing data linkage and multicentric collaborations result in low inter- and intra-observer variability of AI algorithms and ultimately decrease their generalizability. Moreover, ensuring external validation through comparison of AI algorithms with humans, remains essential.Our focus on Europe showed a very active network of collaborating centers across countries in Europe and other continents. According to our bibliometric analysis, Germany and the UK, two among the most represented countries in the field investigated in this review, have strong collaborations with the US and China that co-authored several published papers. Finally, almost half of the publications from European authors included in this review did not acknowledge any funding source for their research suggesting that many of these studies are based on single center initiatives. Although authors may have missed to report a funding source, only 13% of these studies acknowledged funding from research projects of the EU Commission. The recent Horizon Europe research programme already includes several calls for proposals on AI and pediatric cancer, which hopefully will be instrumental to fill in the existing gaps in this field and to explore the existing opportunities. Several topics in this respect deserve attention.Cancer in children may result from genetic changes that are currently unknown, linked either to inherited genetic changes or exposure to diagnostic or therapeutic radiation . In esseIn terms of diagnostic strategies, minimally invasive diagnostic tools with a broadened spectrum should be developed integrating different biometric data . MoreoveAI can also improve the understanding of tumor spread by comparing molecular/anatomical features of primary tumors and metastases or by comparing multiple metastases in the same person and explore genetic, molecular and physiological factors associated with spontaneous tumor regression.The development of new treatments and drug repurposing is also an important issue . InteresAdditional opportunities of AI in pediatric oncology are in supporting and accelerating randomized clinical trials for novel therapies, and integrating data from wearable sensors, patient reported outcomes and data from electronic health records.To achieve these objectives, an acceleration of research efforts is required in the implementation of AI in pediatric oncology at all levels. Most importantly, this effort cannot be pursued in limited geographic areas, but has to be developed at a global scale to take advantage of a collective scientific effort and the largest possible amount of data. The strong international research activities in this field that Europe has been conducting with other continents represent an excellent starting point in this respect.Additionally, with the exception of some work aimed at applying AI for diagnostic image segmentation, we did not find publications investigating the use of AI to analyze and improve healthcare processes, although we applied a comprehensive search strategy in our review. This observation is in line with the scarce maturity of research in the field of AI in pediatric oncology while future applications may certainly include stratification of patients undergoing invasive procedures and actions that may speed up the patient journey with an impact on quality of care, patient satisfaction, and costs.Finally, the ethical dimensions of AI in pediatric cancer are of paramount importance not only because of the intrinsic issues of AI, but also because such a technology should be applied in a vulnerable population affected by rare diseases, as cancers in this age group are, severe and potentially fatal, and where genetic information may play an important role. The vast majority of the published literature on AI for pediatric cancer does not address the specificity of these circumstances yet. Notably, a systematic effort on achieving models for a trustworthy AI is ongoing in many international projects . It mustAI has the potential to represent an efficient solution for many unmet needs in pediatric oncology. The work presented in this review shows several potential areas of development and improvement that can match these needs. One central issue for achieving this goal regards the availability of large datasets that should be continuously updated. The future progress of AI in pediatric oncology, as in other fields, will greatly depend on the development of technical solutions that will allow streamline data sharing across different stakeholders while preserving privacy.AT and AM conceptualized the manuscript, coordinated the work, and wrote the manuscript; FF, VD, and EC reviewed the papers included in the analysis, extracted the data, interpreted them, and wrote the results of the review; ME drafted and reviewed the work, and contributed to interpretation of results; IC managed the data analysis and reviewed the results and their interpretation. All authors contributed to the article and approved the submitted version.This paper has been developed with support of the EU4CHILD project that has received funding from the European Union’s Call for Pilot Projects and Preparatory Actions (PPPA) under grant agreement No 101018783.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.


Since 1990 there has been a decline in the stroke-related incidence and mortality in the high-income countries (HIC). On the contrary, in low and middle-income countries (LMIC) the incidence and mortality rates of stroke have not shown a tangible improvement and their absolute numbers have increased. Currently, LMIC account for >75% of global stroke related deaths and >80% of disability-adjusted life-years (DALY)  revealed younger age of stroke onset (median age 62 years) and higher proportion of cerebral hemorrhage (around 30%) in their subjects compared to those from the Western countries. The age-standardized incidence rate of stroke, as derived from the Zanzibar study was much higher than that from HIC. The study also underscores the urgent need for enhancing public awareness in taking regular medications for hypertension and diabetes mellitus, the two common risk factors of stroke.Data derived from the African nations, namely, Ethiopia and Zanzibar .Many countries have 2-tier healthcare system: one that is government-provided universal healthcare and is essentially free for all; the other privately-funded for those who can afford. In several middle- income countries (MIC), some privately funded healthcare provides very advanced quality of treatment on a par with the best in the world but for that the beneficiary has to pay a substantial amount from their own pocket. This results in clear disparity in terms of medical outcome between the two tiers. The government should aim to close this gap in order to deliver universal good quality healthcare. In a study from Brazil, stroke outcomes were compared between those treated in a good quality large public medical facility and those managed in a private hospital. Although appropriate medical treatment including intravenous thrombolysis were administered to the patients in both the hospitals, worse outcome was demonstrated in the former group. Among other factors, paucity of post-stroke rehabilitation program in public hospital is responsible . On the other hand, opium dependence is an important risk factor for stroke in Iran. This is because opium abuse in Iran and Afghanistan is 3 times higher than global average. Opium leads to atherogenesis and also enhances the propensity for diabetes and hypertension.Earlier, the INTERSTROKE study did show that the principal risk factors for stroke include hypertension, diabetes mellitus, smoking and physical inactivity . Data frDas et al.). Prevalence of posterior circulation MMA in India was found to be 2 times higher than the other Asian countries and 6 times higher than the Western countries.Moya-Moya angiopathy (MMA) is a rare cause of stroke, more often seen in pediatric population. It is far more common among the Orientals than among Whites. So far there had been no large clinical series on MMA from India. The interesting study from Kolkata, the Eastern Indian metropolis, presented the largest series of angiographically proven MMA (The author confirms being the sole contributor of this work and has approved it for publication.The author declares 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.


In recent years, soft robotics has developed considerably, especially since the year 2018 when it became a hot field among current research topics. The attention that this field receives from researchers and the public is marked by the substantial increase in both the quantity and the quality of scientific publications. In this review, in order to create a relevant and comprehensive picture of this field both quantitatively and qualitatively, the paper approaches two directions. The first direction is centered on a bibliometric analysis focused on the period 2008–2022 with the exact expression that best characterizes this field, which is “Soft Robotics”, and the data were taken from a series of multidisciplinary databases and a specialized journal. The second direction focuses on the analysis of bibliographic references that were rigorously selected following a clear methodology based on a series of inclusion and exclusion criteria. After the selection of bibliographic sources, 111 papers were part of the final analysis, which have been analyzed in detail considering three different perspectives: one related to the design principle , one related to functionality (closed/open-loop control), and one from a biomedical applications perspective. Soft robots are primarily composed of easily deformable matter such as fluids, gels, and elastomers that match the elastic and rheological properties of biological tissue and organs.” . I. I76]. ISoft Robotics” were searched, resulting in a total number of 7646 articles. From the graph analyzing the evolution of the field  and a specialized journal titled “he field , the nums et al.  had the The qualitative analysis was the second component addressed in this paper and was based on a total of 111 research and review articles in the 2018–July 2022 timeframe. The articles were identified from four international databases and a peer-reviewed journal based on the search phrase “Soft Robotics”, which resulted in a total of 6400 articles. Due to the large number of articles identified, the selection of articles was conducted in two stages to increase the relevance of this study. The selection of articles was based on a set of clear criteria for inclusion in each selection stage. It is a certainty that the field of soft robotics is in continuous development given the number of publications and previous reviews, including the present one. According to the present review, the field of soft actuators has developed considerably, especially their operation and properties, and there is a wide range of actuation methods. The most common actuators encountered in the analysis were fluidic actuators of various types, configurations, and reinforcements, which were most often actuated by pressurization and less often by vacuum (or both simultaneously). Use of a specific type of actuator was determined by the specific application. Other common actuation methods included electrically actuated actuators, such as dielectric elastomers (DEA), and shape memory alloy (SMA)-based actuators. Each of these actuation methods has advantages and disadvantages and the choice of an actuator variant requires identification of the optimal characteristics concerning the specific application. The problems found in the analysis are still related to limited force output and limited lifetime.Concerning the sensors currently used in soft robotics, sensors with a direct role in capturing information from the soft robot by being integrated into the robot’s structure and deforming with the robot structure are predominantly used. These are specifically liquid metal-based sensors (EGaIn) and flexible bending sensors. Regarding sensors with an indirect role , pressure, force, current, voltage, laser, ultrasonic, and video camera sensors are most often found. Direct role sensors (the flexible ones) do not offer many options for applications and face various limitations in terms of accuracy, sensing range, and sensor linearity.Concerning the manufacturing methods of soft robots, the methods most often identified in this review and other similar works are molding methods that use molds and 3D printing. Casting technology offers advantages in terms of part complexity; however, manufacturing time is longer. In the case of 3D printing, future research directions identified in the literature are related to the transition from the 3D printing of molds to full 3D printing of soft robots; however, this requires the realization of new soft materials, simultaneous printing with different materials, and solutions to issues related to their behavior and adhesion. Steps have been made towards full 3D printing with soft materials and 3D printing processes that realize soft structures, such as soft lithography or magnetic field stereolithography (M-PSL), these being some of the new manufacturing technologies identified that may offer new opportunities for the realization of soft robots.From the perspective of materials used in soft robots, there is a considerable variety available. In the present analysis, most of the materials used were elastomer-based materials, and in this category we identified Ecoflex and DragonSkin bi-component silicone materials from Smooth-On being used in the molding process. Common materials identified in the analysis of 3D printing included acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA), which were used for making the molds and various semi-rigid components of the robotic structure. The analysis identified certain materials that react to various stimuli that have high potential in terms of the manufacture of medical or non-medical equipment and devices, such as drug delivery, surgery, and rehabilitation devices. These materials also have potential for assistive applications as they are similar to the structures and tissues of living organisms. These materials, such as magneto/electro-responsive polymers (MERPs), hybrid robots with 2DLMs  or liquid crystals, hydrogel-based robots, liquid metal -based robots, and graphene- or textile-based robots, have great potential in the medical and non-medical field but have several limitations, which has led to them being seen as “stuck” in the testing stages. Magneto/electro-responsive polymers have great potential in drug delivery but, to move beyond the test approach and into real-world applications, additional testing and analysis 3in in-vivo and in-vitro environments is required to accurately determine their behavior in the presence of stimuli ,65. AddiThere are manifold directions in soft robotics that mainly aim to increase the autonomy and integrability of soft robots so as to achieve the performance of biological organisms, thus exhibiting “natural life artificially” . The keyDue to the non-linear behavior of elastic materials in the soft robot structure, the modeling methods most often used and identified in the analysis are numerical and experimental modeling methods, while analytical methods are less frequently used. The numerical finite element modeling programs most often used in the analysis were Abaqus (Dassault Systèmes) and Ansys, which offer the possibility of simulating and visualizing the results of analysis. There are also other approaches identified depending on the specifics of the applications, for example, in the case of modular reconfigurable robots, there is a need for a 3D simulation and visualization platform of the behavior of the modules that can shorten design time, reduce costs, and verify the effectiveness of algorithms. Based on the present analysis, some future research directions have been identified to improve the future characteristics of soft robots so that they may reach characteristics comparable to those of biological beings while also being feasible in industry or commercially available devices. These directions relate to autonomy, integrability, material capabilities to withstand various environmental stresses, controllability, flexible sensors, actuation methods, and manufacturing methods adapted to soft robots. The first area where further research is needed is related to the autonomy of soft robots, which is currently severely limited by the connection to external power supplies as this strongly affects the robot workspace and negatively influences the behavior of the soft robot. With a focus on achieving these characteristics, there are some limitations related to the miniaturization of the components to be integrated, especially in terms of meeting the dimensional criteria corresponding to biological organisms.Another direction that implicitly also leads to increased autonomy and requires new approaches in research is related to the closed-loop control or feedback control of soft robots. The use of feedback in the control of soft robots is based on the use of flexible sensors within the external structure of the soft robot that transmit data related to the position and deformation of the robot structure. A limiting factor in the use of closed-loop control is closely related to the flexible sensors used, which offer a limited range of available options and also have important limitations. Another limitation that can hamper control is related to the use of a large number of flexible sensors for the satisfaction of control requirements, thus transmitting a multitude of data that makes it difficult to implement the control algorithm.Another future research direction is related to the development and improvement of 3D additive manufacturing processes that offer the possibility of making soft robots entirely out of more soft materials, as well as the possibility of making soft robots with integrated internal structures such as sensors. One possible way to realize these robots is through 3D printing methods such as soft lithography or magnetic field stereolithography (M-PSL). To achieve the performance of biological beings in terms of autonomy, integrability, adaptability, and efficient locomotion, soft robots still have many aspects that need to be improved or developed in order to achieve these goals, especially if they are to be used in industrial or commercial applications. These limitations and challenges have been identified and addressed above, while this entire paper has aimed to create an overview of the evolution and current state of research in the field of soft robotics while at the same time highlighting research directions in the field.


The COVID-19 pandemic, associated with confinement and social isolation, seems to have impacted the course of many mental disorders in children and adolescents. An increase in hospital admission rates for juvenile anorexia nervosa (AN) has been documented in many regions of the world. However, data from Europe are scarce.We asked clinicians in specialized eating disorder units in hospitals of maximum care in France, Germany, Italy, Spain, Sweden, and the Netherlands to report on (i) overall (inpatient and outpatient) and (ii) inpatient admission rates for adolescents with AN during 2019 and 2020. Additionally, a modified version of the COVID Isolation Eating Scale (CIES) was used to assess the child and adolescent psychiatrists’ estimations of a possible increase in symptom severity in children and adolescents with AN during the COVID-19 pandemic and to (iii) inquire about the contributing factors perceived by the caring professionals.Four out of six representatives of European hospitals described a higher rate of overall admissions during the pandemic. Three hospitals out of six reported an increase in inpatient admissions, and two centres had constant high numbers of admissions of both outpatients and inpatients. The clinicians perceived a higher symptom severity in 2020 than in 2019, especially involving more frequent use of social media, longer duration of exercising, and more restrictive eating. They supposed an increase in social media consumption, a perceived “loss of control”, and a lack of in-person assessments and weight controls as the main contributing factors for the deterioration in AN numbers and symptomatology.The COVID-19 pandemic seems to have had a deep impact on symptom severity in AN, which is mirrored by a large increase in admission rates across Europe. An increase in exercise, social media consumption, a perceived “loss of control”, and a lack of face-to-face health care seem to have contributed to this development. Further investigation is required to identify which factors may lead to the increase in incidence and deterioration of childhood and adolescent AN. Possible preventive means for the future could include educating paediatricians and health care workers about AN, regular weight assessment, and home-based treatments. The COVID-19 pandemic has contributed to an increase in the mental health problems of children and adolescents worldwide . An impoIn addition to an increase in prevalence, young patients with AN seem to be more severely ill than before the pandemic. In a cohort study comparing adolescents admitted with AN in 2020 to those admitted in 2019, the former had a lower body weight and higher rates of self-reported functional impairment as a result of ED symptoms and were more likely to be medically unstable . ReadmisThe reasons for the increase in prevalence and/or severity of child and adolescent AN during the COVID-19 pandemic are not yet clear. Several contributing factors have been reported, such as school closures, social isolation, exacerbated comorbidities, and a cessation of face-to-face appointments . A disruThe goal of this study was to obtain data about the total number of patients admitted for AN and, more specifically, rates of inpatient admissions for AN across several European countries. Additionally, the study obtained qualitative data from mental health clinical experts using a modified standardized instrument to gather impressions about ED symptom severity.We asked well-known European researchers in the field of AN to designate representative specialized ED units for children and adolescents of hospitals of maximum care in their respective countries. In addition to our own unit, we asked six departments of child and adolescent psychiatry with specialized ED units in France, Italy, Sweden, and the Netherlands to participate. Data were collected by the administrative institution of the hospital regarding the total number of patients presenting with typical and atypical AN according to the DSM-5  as well Furthermore, we requested ten mental health clinicians across the various European hospitals to give a subjective global impression of a possible change in symptom severity of the ED in the entire patient group they treated during the COVID-19 pandemic as well as their explanation for this change. The survey data were collected between March and May 2021.There were two centres from Italy participating, but as we were not able to obtain exact patient numbers from the department of the University of Padua, we only used clinicians’ symptom severity estimation from the hospital of Padua as well as their evaluation of contributing factors.We modified the Isolation Eating Scale (CIES)  to ask tFurthermore, we listed seven possible explanations for an increase in prevalence and symptom severity of EDs  and let the clinicians rate their significance .Finally, we asked the clinicians to provide their subjective rating of which of the national lockdowns contributed to the highest increase in AN admissions.As explained above, the clinicians rated their qualitative impression of the total group of patients they treated, not of individual patients.Symptom severity was assessed by eight medical doctors , one clinical psychologist (ALS), and one family therapist and social worker (GPK).We plotted the absolute number of admissions for AN provided by the respective centres for 2019 and 2020, depicting the total number of admissions and the number of inpatient admissions, respectively. In addition, we reported the indicated mean age of the total number of admissions for AN for each single treatment centre in 2019 and 2020.The total number of weeks in lockdown and of school closure were summed up. However, the exact dates of lockdowns and school closures varied even between different regions of an individual country. Moreover, there were different stages of restrictions within the single lockdowns, and school closures differed regarding stages of intensity as well as different age groups, e.g., in some countries, the school closures were limited to children or younger adolescents. Therefore, the given time spans are only approximations.The clinicians’ subjective assessment of the ED-associated increase in symptom severity was summarized for all countries and averaged for each respective item.Finally, we plotted the impact of possible contributing factors based on the estimation of the participating clinicians.In four out of six ED centres, there was an increase in total (outpatient and inpatient) admissions. There was also a substantial increase in inpatient admissions in three out of six centres see Fig. .Fig. 1NuThe Dutch centre had only an overall increase in admissions, whereas the number of inpatients remained stable. The Swedish and the German centres had an approximately unchanged number of patients, both in terms of total patients and inpatients.All ED departments witnessed the greatest increase in admissions at the beginning of the second lockdown. Between the time before and during the lockdowns, there was no significant change in age at the time of admission in any participating department.With the exception of the Netherlands, waiting times for hospital admissions increased in five out of six centres . In the Netherlands, waiting time during the lockdowns was even shorter because the respective department started a “crisis management” to care for the most acute patients. Five out of seven centres had a longer average length of stay. The departments in Germany and Sweden reported no change in the duration of hospital treatment.Apart from Sweden, there were two lockdowns in all countries included in this study until May 2021. Except for the Netherlands, the periods of the lockdowns and the school closures corresponded in all selected countries. In the Netherlands, lockdowns and school closures lasted approximately 8 to 10 weeks longer than in the other European regions  is only based on the subjective impression of the clinicians during the pandemic. Most likely, there was also a discrepancy in illness severity of the admitted patients in the European hospitals enumerated above, which makes a comparison between countries very difficult. Third, we assessed only the number of cases admitted for AN and not the number of persons. Therefore, in our study, we could not determine whether the pandemic contributed to a higher new occurrence of AN or whether it was associated with a higher rate of relapse.In conclusion, the COVID-19 pandemic seems to have had a deep impact on the burden of AN, which is mirrored by a mostly large increase in admission rates across Europe. In comparison to other mental disorders, symptom worsening was stated most frequently by patients with AN . They ar


The IVR intervention was feasible, with no adverse effects being reported , no dropouts, high adherence, and good post-gaming usability . The EG showed significant improvements: Tinetti scores for balance , gait , total score , and handgrip  (pre–post assessment). The CG showed significantly worsened compared to the EG: Five times sit-to-stand test, Tinetti scores for balance, gait, and total score, and the Timed Up and Go test total score (post-assessment). The findings show that the IVR intervention is a feasible method to approach a personalized exercise program and an effective way by which to improve physical function in the target population.One of the pillars which underpins active aging is found in the performance of physical activity. While adherence to physical activity programs has traditionally been low in older people, immersive virtual reality (IVR) could provide an alternative and complementary training mode. A randomized clinical trial was conducted to explore the feasibility and effects of a 10-week IVR exergame program on physical functions of 24 institutionalized older adults who were allocated to an experimental group (EG  Life expectancy is rapidly increasing and is expected to rise in the years to come, thereby giving rise to an aging population. However, a significant proportion of older people may develop frailty, multi-morbidity, and disability, causing a significant impact both on their quality of life and also on health care and social costs ,2.Aging is associated with physiological changes and systemic alterations . These mOne of the keys to active aging lies in the practice of physical activity and exercise on a regular basis . These hIt should be noted that the risk of falls increases progressively when strength and balance levels decrease . FortunaTherefore, it is advisable that strength and balance exercises are present in neuromuscular training aimed at reducing falls and, in turn, should include different tasks that progressively increase in difficulty. Moreover, it is possible that the ideal multicomponent exercise addressed to reducing falls is a combination of training in cognitive abilities (attention and decision making), perceptive abilities, neuromuscular performance (trunk and lower and upper limbs), and cardiovascular endurance .A tool that could be useful to collaborate with active aging strategies is virtual reality (VR), where older people could find the motivation to carry out their physical therapies .VR can be divided into three main categories and each category can be ranked by the sense of immersion, or degree of presence it provides. These categories include non-immersive systems (desktop), semi-immersive projection systems (large screen monitor), and fully immersive systems  ,13.Immersive virtual reality (IVR) allows users to view content in all directions, providing a first-person perspective and a higher level of immersion based on multisensory approaches .Taking into account that the adherence to physical activity programs has traditionally been low in the senior population , this imBesides, if this technology can expand resources for physical and functional rehabilitation programs (multisensory stimulation and greater sensorimotor integration), it is logical to think that IVR could help in the development of neuromuscular programs aimed at preserving physical functions and prevent falls in frail older people .Some current systematic reviews have reported that IVR has been a solution used to support psychological rehabilitation  and cognitive rehabilitation . However, the evidence regarding its use in physical and functional rehabilitation of older adults (with and without pathologies) is limited.For all the above, our hypothesis is based on the fact that an IVR exergaming program could achieve greater benefits than a traditional exercise program since it could achieve more complete and more attractive neuromuscular programs, increasing the levels of motivation and adherence of the participants.In light of this, the purpose of this study was to conduct a randomized control trial to analyze the effects of an IVR exergaming program on physical function, quality of life, and parameters related to IVR exposure training across a sample of institutionalized older adults.clinicaltrials.gov (NCT04336670).A randomized clinical trial study was conducted at a senior center in Pontevedra, Spain. The study design was registered on n = 11) or the experimental group . Allocation was done by computer. This study was announced in the senior center chosen. A total of 41 participants applied, all of whom underwent a screening process. All people >65 years old and residents of the senior center were included in the enrollment. Those who had medical conditions that discouraged the practice of physical exercise or who had a physical or cognitive disability that prevented them from standing without aids or understanding the intervention protocol were excluded. In addition, those that presented severe visual impairment, vertigo, epilepsy, or psychosis and that could interfere with the normal performance of the IVR tasks were excluded for caution. Finally, and following the exclusion criteria, 24 out of 41 subjects were recruited. After agreeing to be part of the study, the subjects signed the informed consent and were then randomly assigned to either the control group  Ethics Committee (Ref. 2020/078), and in compliance with national legislation and the Declaration of Helsinki. Participants were required to agree to all aspects of the study and were able to leave the study at any time.TheBlue and Steam VR Home, whose features are described below:Three weeks prior to the intervention, the IVR equipment was installed in the center’s gymnasium room and training sessions were scheduled for the center’s staff in charge of supervising the sessions. In addition, they were taught how to troubleshoot minor technical issues that might arise with the software and hardware. During this time, therapists and center users could experience various games (mountain landscape or seabed scenarios), and receive instructions on handling. The most commonly used environments were TheBlue: This is a game based on the observation of the seabed. There are three possible scenarios: one located in a coral reef, another in a sunken ship, and the last one in the abyssal depths of the ocean. This last scenario was discarded because it was considered a claustrophobic and unsuitable scenario. In the coral reef setting, participants could observe and interact with fish, anemones, and jellyfish. In the shipwreck scenario, they could also interact with small fish, and observe manta rays and a large whale. User feedback on these scenarios was very positive.Steam VR Home: This portrays an environment located in a house in the mountains. It allows greater freedom of movement than in the previous game and a greater degree and variety of options in the tasks to be undertaken . It is a very pleasant setting. In particular, the participants very much enjoyed the possibility of butterflies landing on their hands, or simply observing the mountain views on a clear day.In order to verify the presence and immersion in both experiences, the staff in charge of supervising the VR sessions was who guided, proposed different actions to carry out in the virtual experiences, and asked various questions about the virtual environment . At all times they were warned that they should stop the session if they experienced discomfort or dizziness, although none occurred, and the scenarios were mostly described as pleasant and calm . These tDuring the study period and the previous acclimatization sessions, approximately 450 IVR sessions were conducted. A total of 30 IVR sessions of an exergame over a period of 10 weeks was programmed for each participant in the EG. Three sessions were held every week and each IVR training session lasted for 6 min. At the same time, both the CG and the EG participated in the usual care programs of the center . Some sessions were rescheduled if justifiable absences occurred due to illness, doctor’s appointments, etc.2 play areas were delimited within this room). The hardware selected was: HTC Vive ProTM, consisting of an HMD equipped with a wireless adapter, two base stations, and two controllers; desktop computer ; and a LED monitor. Support software was obtained from Viveport .The place chosen to conduct this study was the center´s gym room .For the choice of the exergame, we looked for an immersive experience that was close to the general exercise recommendations for older people . StartinBOX VR is able to place the user in a virtual gym with a very large training area and allows them to choose up to four different environments. The challenge consists of achieving a quick motor response to different stimuli based on boxing practice. During the game, the participant stands with one foot in front of the other, and different colored balls are presented to be hit with one or the other hand. Some of them incorporate an arrow that guides the movement to be performed . In addition to the balls, other stimuli are presented: a diamond that involves blocking with both hands and lateral and/or perpendicular bars to the ground with the intention of moving the trunk, head and lower limbs to vary their position. This game also offers the possibility of working on another important component, such as hand-eye coordination or cardiovascular training.At the same time, the game is also useful as cognitive stimulation since the random appearance of unexpected stimuli further aids the participants´ work by adding attentional mechanisms, improving concentration on the task and providing greater sensorimotor integration .As mentioned above, the proposed exergame is based on the continuous movement of the body, focused on improving joint ranges, strength, endurance, and muscle power. These objectives are a fundamental part of conventional physiotherapy sessions in older people . In addiEven so, each participant received individual guided and supervised sessions . Three tPhysical function was assessed by balance and gait, mobility, lower limb function and handgrip strength. The balance and gait were evaluated by the Tinetti test . FunctioQuality of life (QoL) was assessed by the 12-Item Short Form Survey (SF-12), Spanish version 2 . These dBOX VR sessions completed and their scores. These data were collected in the EG in intermediate and post evaluations.Parameters related to IVR exposure training were assessed for cybersickness, usability, post-gaming experiences, and VR sessions. Cybersickness was evaluated by the Simulator Sickness Questionnaire (SSQ), translated into and adapted for Spanish ,31,32, uDemographic characteristics were collected by trained researchers before the intervention. The experimental protocol involved a set of pre/post- and follow-up evaluations . Furthermore, one set of extra evaluations was carried out four weeks after the initial evaluation to ensure VR exposure adequacy (intermediate assessment only included parameters related to IVR exposure training). The following parameters were collected in three blocks .In addition to these assessment, two extra safety control measures were established: Administration of the SSQ at the end of the first 6 sessions to check the tolerability of the proposed exergame and heart rate monitoring and perceived exertion  throughp > 0.05) was used. As the outcomes were not normally distributed, non-parametric tests  were conducted to assess the effect of the program between the groups  and in the three moments . To assess the differences between the two groups (EG and GG) on the FTSTS, Tinetti test, HGS, TUG, and SF-12 over time (post–pre and post–follow), we conducted a multivariate analysis of variance (MANOVA), with “group” as the between-subject factor.Descriptive statistics  were used to represent the demographic characteristics of the sample. For the normal distribution analysis, the sample Shapiro–Wilk test  for MAC version 26.0. The level of significance was set at <0.05.The IVR intervention was feasible, with no adverse effects being reported (across 100% of the sample), no dropouts, and a high adherence . Only one participant did not complete all the sessions, and his absence for two weeks had just cause (absence due to quarantine for COVID-19 infection and close contact). No significant differences were observed at the baseline between the groups .The main outcomes are summarized in p < 0.001), gait , total score  and handgrip  (post–pre assessment).The CG shows significantly worsened compared to the EG: FTSTS test, Tinetti test scores for balance, gait, and total score, and TUG test total score (post assessment) and Tinetti test scores for balance, gait, and total score (follow-up assessment). At the same time, the EG showed significant improvements in Tinetti scores for balance  nor dropouts associated with the proposed program. The high number of successful sessions carried out backs up our proposal, with high adherence . This success was made possible by being systematic and rigorous, and following the constraints outlined by Davis et al. , which iFurthermore, IVR provides an artificial interactive environment closely representing reality. Older adults with different conditions can experience varying sensory stimulation in a comfortable and safe virtually simulated environment, which may lead to a boost in motivation and adherence rates to physical exercise programs .The chosen game was safe (no symptoms of cybersickness) and makes significant demands on the physical capacities of the participants, ensuring a multicomponent workout . At the same time, it also achieves cognitive stimulation, since it requires attentional strategies to respond to unexpected stimuli that require different motor responses. We used the multitasking paradigm as an element for cognitive training.Other interventions with IVR that have sought to improve cognitive aspects have succeeded in improving physical aspects in elderly people with mild cognitive impairment ,41,42, sIt should be stressed that IVR has several requirements for motor and cognitive rehabilitation interventions: repetitive practice, feedback about performance, multimodal stimulation, and controlled, safe, and ecologically valid environments .Similarly, recent studies have shown that the combination of physical and cognitive factors is the key to improving response times , a very Regarding the effects of our intervention on physical function, the incorporation of the exergaming program to the usual therapies of the center has enabled the EG to avoid the significantly lower values that were recorded by the CG for FTSTS, Tinetti  and TUG test . The HGS scores were also lower, although not significantly so. Furthermore, in the intragroup comparison, the EG achieved improvements in FTSTS times and significant improvements in Tinetti  and HGS. For the TUG test times, the results were slightly worse , although to a lesser extent than the loss shown in the CG for the same variable . It is possible that the discrete results obtained by the CG in the TUG test are related to the fact that the tasks in the proposed exergaming differ significantly from activities such as “turning” or “stand to sit” (items where there was a greater increase in TUG times).Nevertheless, from our point of view, the maintenance of functional capacities in this population  can be considered a good indicator, especially when compared with the results obtained in this same variable by the CG.These results are in line with other studies in which exercise programs undertaken with IVR have improved aspects related to balance ,41.As expected, the follow-up did not show statistically significant intragroup differences since both groups continued to maintain the usual therapies carried out in the center. Nevertheless, in general, it could be said that the physical functions between both groups were equal, maintaining only significant intergroup differences for the Tinetti test scores.Regarding QoL, the CG obtained significant improvements when compared to the EG in the physical score. However, both groups improved their mental scores. These results coincide with those reported in previous studies , althougThe results shown in the domain related to IVR exposure were satisfactory. First, the experience was feasible and safe. In line with previous research ,25, the Secondly, usability was considered good in the two controls carried out  with values that exceeded 73/100 points. These results are also congruent with other studies that have used this device with similar objectives and in a senior population ,21,48,49Third, post-gaming experiences and satisfaction corroborated the appropriateness of the selected task. The GEQ post-gaming values were residual in the items rating negative experiences (range 0.15–0.37/4), and the satisfaction questionnaire showed that the whole sample considered the experience good (100%), that there was nothing they did not like (72.73%), that they would recommend the experience (81.82%), and also that they considered it useful for people their age (81.82%)—generally because it encouraged them to do exercise. These results are in line with other studies ,50,51,52In our trial, the participants showed a high level of tolerability to the proposed virtual program. We have successfully incorporated cognitive strategies combined with physical exercise to achieve comprehensive training proposals aimed at older people.Do you think this could be useful for people of your age? Why? in Relating to the overall post-gaming experience, the participants highlighted how fun the sessions were, with a good musical rhythm that helped them to carry out the tasks and a very spacious and comfortable training area . In particular, the participants showed very positive opinions linked to the physical exercise performed and the benefits for people like them, as can be seen in the responses to question, These findings show that bodily movement and individual sessions are undertaken in a group mode are an engaging factor for older adults, and one which can motivate them to prolong exercise training.Our study has several limitations: (1) The sample size limits the ability to generalize our results. It is possible that the pandemic situation meant that the initial number of subjects likely to participate was lower than expected due to fear of COVID-19. (2) Possible drawbacks of the chosen statistical analysis technique could influence the interpretation of the results. (3) We compared the EG with the CG where both received a common intervention . Therefore, with the methodology used, it is not possible to know with certainty which of the improvements shown are attributable to the IVR program (which ones are to the exercise program or which ones are to the VR exposure) and which to the influence of the usual center therapies. More research is needed where these groups are compared. (4) Another limitation could be the duration of the program. It is possible that establishing a similarity with medium- and long-term benefits that exercise programs achieve in older people, a longer intervention could achieve better results in physical and functional domains and could have influenced our TUG test scores. (5) Following our previous findings, we set the difficulty of the game at an intermediate level. Although the profiles were quite homogeneous, it is possible that in some participants this level was below their actual abilities and as a result they could have experienced less intense and challenging training. If this is so, it is likely to result in fewer training benefits. Since this could have an impact on the benefits of training physical and functional abilities, future research should explore how the level of challenge in the VR game could be tailored to the capacity of each participant without diminishing their sense of autonomy.In summary, outcomes show that our 10-week IVR exercise program was feasible and had positive effects on physical functionality in institutionalized older adults, particularly in aspects related to gait, balance, and handgrip strength. Although cognitive function and mood were not direct objectives of this study, the physical and cognitive stimulation of the selected exergame, the results of the mental dimension of quality of life and the satisfaction responses obtained all support the idea that future studies with IVR exercise programs may be considered as a multidisciplinary evaluation offering the holistic assessment of the health of institutionalized older adults.


Despite the lack of high-quality evidence regarding its long-term effectiveness, intravenous corticosteroid therapy is recommended as the standard treatment of acute multiple sclerosis relapses in Germany. High financial expenses and the equivalent effectiveness of oral corticosteroid therapy contrast with this trend. There is an urgent need to provide patients with evidence-based and comprehensible information on relapse management and to actively involve patients in relapse treatment decisions. Web-based decision support on relapse management could be an effective measure to empower people with multiple sclerosis making informed treatment decisions.To develop a web-based programme on relapse management for people with multiple sclerosis and evaluate the feasibility and acceptability of the intervention.The study followed the first two phases of the UK Medical Research Council Framework for complex interventions. The first phase involved the development of an interactive web-based programme on relapse management. The second phase focused on the feasibility and pilot testing of the programme with people with multiple sclerosis and experts with a professional background in multiple sclerosis. Data was obtained using questionnaires with closed- and open-ended questions as well as qualitative semi-structured telephone interviews. Quantitative data was analyzed descriptively, whereas qualitative data was clustered by topic.Feasibility of the intervention programme was tested with 10 people with multiple sclerosis and 10 experts. Feasibility testing indicated good practicability and acceptance of the content. After revision, the programme was piloted with seven people with multiple sclerosis and three experts. The results showed good acceptance in both groups. Based on the feedback, a final revision was performed.ClinicalTrials.gov: NCT04233970). It is expected that the programme will have a positive impact on patients' relapse management and strengthen their autonomy and participation.Feasibility and pilot testing indicated good user-friendliness, acceptance, and practicability of the programme. The programme is currently evaluated in a randomized controlled trial (Registration Number on  Multiple sclerosis (MS) is a neurological disorder that is substantially accompanied by uncertainties and impairment in quality of life for those affected . Even thAn earlier randomized controlled trial (RCT) with 150 PwMS showed that an EBPI and group training programme on relapse management led to a significant increase in informed decision-making and reduction of IV corticosteroid therapies . In the ClinicalTrials.gov: NCT04233970, date of registration: 17.01.2020). Detailed information on this RCT and the accompanying process evaluation is provided in the study protocols  with 160 PwMS  on developing and evaluating complex interventions, a systematic development process, as well as an assessment of feasibility and piloting, are vital preparatory steps before an intervention can be evaluated and implemented . FollowiThe development, feasibility, and pilot testing of the web-based programme ABouts was guided by the UK MRC framework on developing and evaluating complex interventions and comprises the first two stages of the framework .After the development of the intervention and the modelling of outcome measures in the first phase, the feasibility of the intervention components was tested as part of the second phase . After rThe first phase included the development of the intervention programme as well as the development and adaptation of outcome measures. The detailed concept of the intervention and outcome measures are outlined in the main study protocol . The intThe development of the complex intervention programme ABouts, including an interactive, web-based EBPI programme on relapse management, a webinar and an online chat room, started in 2018. All three components, presented in ®, which has already been successfully used for other patient support systems  . To rate systems , 37.Development of the platform, transfer and adaptation of the information was performed by GAIA, a public health company that specializes in the development and research of digital therapeutics . To ensuA nurse-led webinar, which constitutes the second component of the complex intervention ABouts, aims to provide a structured online exchange for participants and to clarify questions patients might have . To ensuThe third intervention component, an online chat room, was set up as a private, protected group chat on the platform “MS Connect,” operated by the German Multiple Sclerosis Society (DMSG) . The chaTo assess the primary and secondary endpoints of the main trial (RCT), different questionnaires are used in the course of the study . The devAssessment of feasibility included testing of comprehensibility and acceptability of the EBPI programme and the webinar with PwMS and experts, who are professionally involved in MS  . A conveBased on the results of the feasibility testing, the intervention was revised and further developed. The subsequent pilot testing was intended to gather information on the usability, accessibility and acceptance of the EBPI programme, the webinar and the chat . PwMS weData from the feasibility and pilot testing as well as the testing of the outcome measures was analysed separately. The quantitative data extracted from the evaluation forms was analysed descriptively using IBM SPSS Statistics version 26.0 and Microsoft Excel (Microsoft Office 365). Instead of using thematic analysis, we clustered the feedback from the audio-recordings of the interviews and the notes taken during the interviews according to themes. This allowed us to provide prompt feedback to the platform developers. All results and necessary changes were discussed and agreed upon in advance by the researchers AR, CH, SK and LW. The results guided the revisions in an iterative process.Concerning the update of the EBPI programme and the systematic literature searches conducted, a variety of systematic reviews and cohort studies were identified and included. The initial search with regard to the research question “What is the effect of corticosteroids in the treatment of relapses in MS?” retrieved 1,671 citations. Of these, eight systematic reviews were included in the update of the programme. The search concerning the research question “What are the triggering factors of relapses in PwMS?” resulted in 707 citations for systematic reviews and 2,484 for cohort studies, of which three systematic reviews and 14 cohort studies were included. Applying the research question “What is the prognostic relevance of relapses in MS?” resulted in 1,085 citations for systematic reviews and 1,592 for cohort studies, of which two systematic reviews and six cohort studies were included . After dBased on the GRADE rating tool, all RCTs included in module three were categorized using a four-point scale, indicating the certainty of evidence from very low to high . The ratTo enable individual processing of modules, the programme is dialogue-based and provides PwMS with tailored information depending on the level of knowledge and interest of the participants . ModulesThe respective studies building the basis of the EBPI programme are available as brief abstracts written in lay language, which can be displayed on request by users. In addition, participants have the opportunity to obtain additional information through the provision of various web links. Module three, which covers the topic of corticosteroid therapy, is the central element of the programme. The literature update and critical appraisal of studies dealing with corticosteroid therapy resulted in the development and embedding of two figures illustrating the effects see  and sideDue to the sequential activation of the modules, the EBPI programme takes about 4 to 5 weeks to complete (active usage at least once a week for 1 to 1.5 h), including a knowledge quiz on corticosteroid therapy, which is embedded after module five . After sTesting of outcome measures, which had to be adapted to the present study, confirmed feasibility and comprehensibility. Two questionnaires, the RKQ (manuscript in preparation) and the adapted version of the PBMS, required minimal adjustments. The validation study of the PBMS indicated the construct validity of the instrument and demonstrated that the tool is useful for explaining and predicting relapse treatment decision-making in PwMS . ConcernFeasibility testing was conducted between July and August 2019. Fifteen PwMS with a relapsing-remitting disease course and ten MS experts (patient representatives and neurologists) were selected, of whom five PwMS either declined to take part in the study or did not respond to the invitation email. In total, ten PwMS and ten experts were included in the study. PwMS included seven women and three men with a median age of 51 years (range 24–62). Although we initially planned to include only participants with a clinically isolated syndrome (CIS) or definite RRMS, one participant reported having secondary progressive MS (SPMS). The participants had a median disease duration of 16 years (range 5–37) and all PwMS stated that they had a history of high-dose corticosteroid therapy. Concerning the degree of disability, assessed with the PDDS questionnaire, the participants indicated minor to moderate impairment with a median of 2 (range 0–3) .The group of experts participating in the testing comprised four patient representatives, one nurse and five neurologists. Two neurologists worked in a private practice and three worked at a university hospital. All experts stated that they were either experts or very competent in the field of MS. The detailed characteristics of all participants are summarised in n = 9), and experts of 1.8 (n = 10) (1 = very good – 6 = unsatisfactory). PwMS expressed that they were generally very satisfied with the programme and thought that the programme provided a good orientation on different relapse treatment options. However, some PwMS considered the programme to be better suitable for people with early MS and reported a lack of information on treatment options other than corticosteroids . Furthermore, PwMS stated that the programme, especially module 3, was partly very text-heavy, and they wished for more key summary points and less repetition. Several PwMS and experts stated that they would prefer more self-determined processing of the individual modules rather than predetermined time intervals after which the individual modules are activated. However, the experts' feedback primarily requested a more balanced presentation of different treatment options for an acute relapse, with the comment, particularly from the neurologists, that other treatment options (such as symptomatic treatments) are not equivalent options to corticosteroids. Also, the experts raised the concern that the neurologists' role in relapse treatment decision-making was not adequately addressed. Concerning the understandability of the EBPI programme, some experts suggested simplifying the texts to be understandable for all levels of education. The detailed results of the feasibility testing are presented in All PwMS and experts stated that they had reviewed all five modules and the decision aid for an acute relapse. For the overall quality of the programme, PwMS gave a mean rating of 2.33 (The feedback led to the following revisions in the EBPI programme: (1) The programme settings were changed so that modules one and two were activated at the same time and could be processed consecutively if desired. (2) Practical examples of how to deal with stress were added to the chapter on stress as a triggering factor of relapses. (3) An optional break was integrated to module three. (4) References to neurologists' roles in relapse treatment decision-making and consultation were added in some sections . (5) Response options of the dialogue-based programme were revised. (6) The decision aid, presenting the various options for action in case of an acute relapse, was slightly modified. (7) Minor formal changes, simplifications of chapters and text reductions were made.Between September and December 2019, the entire intervention was pilot-tested. In total, thirteen PwMS were contacted via email. Six PwMS did not respond, did not meet the inclusion criteria or declined to take part due to timing issues. Therefore, the final sample consisted of seven PwMS, two men and five women with a median age of 37 years (range 28–57). Due to the generally positive feedback in the feasibility testing, the sample of PwMS included was sufficient.Three male experts also took part in the testing, two of whom had already taken part in the feasibility testing. The group included two patient representatives and one neurologist working at a university hospital. For more information on participants' characteristics see n = 6) stated that they would recommend the programme to people with early MS immediately after diagnosis or up to 4 years after diagnosis since most questions arise at the beginning of the disease. Only one participant recommended the programme to PwMS at later stages. One expert each stated that he or she would recommend the programme to people with early MS, to PwMS 1 to 4 years after diagnosis or to PwMS 5 to 9 years after diagnosis.Asked to judge the overall quality of the programme, PwMS provided a mean rating of 1.57, and experts of 1.67 (1 = very good – 6 = unsatisfactory). The majority of PwMS  Parts of the text were shortened, especially in the third module. Some text passages were replaced by bullet points. (2) In several parts of the texts, more attention was paid to neurologists' roles in relapse treatment decision-making and the consultation. (3) Typographical and spelling errors were corrected.This paper outlines the development, feasibility testing and piloting of an interactive web-based complex intervention on relapse management for PwMS, following the MRC guidance . The resOur feasibility and pilot study add to the literature on patient empowerment in relapse-treatment decision-making. Trials show favourable results for telerehabilitation interventions as an alternative method of service delivery for PwMS concerning short-term physical ability and symptoms such as fatigue. However, there is limited evidence to verify what type of intervention is effective . Further® and resulted in a significant decrease in fatigue.Regarding the EBPI programme used for our intervention, Pöttgen et al. tested an interactive online fatigue management programme with PwMS with self-reported fatigue . SimilarIt was not possible to address the wishes of many PwMS to provide more information on alternative and complementary treatment options in our programme. Although there seems to be a great need, there is hardly any evidence regarding such treatments in the context of relapse management. Thus, the EBPI programme includes an explanation of why these possible treatment options are not equivalent options and thus cannot yet be addressed in an evidence-based tool for PwMS. Furthermore, the experts' wish to emphasise the neurologists' role in relapse treatment decision-making could only partially be addressed, as this would contradict the programme's underlying principle of patient empowerment and autonomous relapse treatment decision-making. However, due to the experts' feedback it was pointed out in several parts of the text, that in case of severe symptoms consultation with the neurologist should take place.This project demonstrates the benefits of the mixed methods data collection and analysis and the iterative user feedback process in the development of the intervention. The design allows generating insights and an in-depth understanding of the context, impact on different target groups and behavioral barriers to implementing a complex health intervention. A further strength of this study is the systematic, theory-based development process, feasibility testing and piloting of the intervention, involving relevant target groups from different fields of expertise.Despite these strengths, our study also has some limitations. Due to limited resources and ensuring quick feedback to the platform developers, we clustered the feedback rather than using a systematic, formal analytic approach conducted by independent researchers. However, all results were discussed in team meetings, where different researchers' perspectives were negotiated until reaching a consensus. Furthermore, the study sample was rather small, so that the results cannot easily be generalized. Nevertheless, the sample size was appropriate for the study design and the development of the underlying intervention as this study does not aim to assess clinical impact of the programme. Even though we tried to sample according to educational background, most PwMS who participated in the feasibility and pilot testing had a high level of education. Therefore, we cannot be certain whether PwMS with lower levels of education are also adequately addressed by the intervention. However, we simplified the texts and adapted them to the reading level of secondary school students to make the intervention more understandable for these groups. In addition, the interactive nature of the programme enables the possibility of obtaining in-depth information if needed. Concerning the pilot testing of the online chat room on the platform MS Connect, the usefulness and usability of the platform could not be fully evaluated. Three participants registered for the online chat room, however, no exchange occurred via the chat during the pilot testing.The programme development, feasibility and pilot testing described in this paper are part of the POWER@MS2 project, which focuses on the development and evaluation of the intervention programme ABouts . The intWe developed a web-based programme on relapse management that is feasible in terms of PwMS' and experts' acceptance of the programme and its applicability in relapse treatment decision-making. The innovative approach may be a low-barrier and cost-effective option to support patients and physicians and facilitate the decision-making process. The intervention is currently evaluated in an RCT with an accompanying cost and process evaluation. If the RCT demonstrates a benefit of the intervention, the intervention could be made accessible to all PwMS in Germany and similar platforms could be developed with focus on, for example, rheumatic diseases or chronic infectious diseases. Furthermore, the intervention could be adapted by other countries.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of the University of Lübeck, Ratzeburger Allee 160, Building 21, 23562 Lübeck. The patients/participants provided their written informed consent to participate in this study.AR, CH, and SK are principal investigators of the POWER@MS2 study and planned the conceptualization, methodology, design, and development of the intervention. LW, AR, CH, and SK discussed and continuously revised the design and planning of the feasibility and pilot study. LW conducted the interviews and performed the data analysis. LW drafted the manuscript with contribution from AR, CH, and SK. JP conducted the systematic literature searches supervised by AR and contributed to the critical appraisal and evaluation of studies as well as data extraction. KG contributed as expert, EF and JS as patient experts in testing and revising the content of the intervention programme. FT and BM contributed to the design and development of the EBPI programme. All authors read, reviewed, and approved the final manuscript.The POWER@MS2 trial, including the development, feasibility and pilot testing of the complex intervention, is funded by the German Innovation Fund of the Federal Joint Committee (GBA), grant number 01VSF17015. The funding body has no influence on the content or the implementation of the study.Author CH has received research grants, speaker honoraria, and travel grants from Biogen, Celgene, Genzyme, Roche, and Merck. Authors FT and BM are employed at GAIA AG, the company that developed and operates the intervention described in this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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