Online healthcare platforms serve not just as a medical knowledge-sharing community but also bring about effective interactions between professional physicians and patients. However, it is unclear whether online technology adoption affects such interactions in the same way between traditional Chinese medicine and modern medical departments. By utilizing a large sample of online doctor-patient interaction information from 168,870 doctor-specific interactive webpages recorded in a famous Chinese online healthcare community, this paper studies the differences between 17,513 traditional medicine doctor homepages and 151,357 others from more than 100 different specialty areas. Our chosen platform is representative since it covers about 800,000 physicians working at over 10,000 hospitals across all major provincial regions in China. We document that online medical service users tend to accept and use online health care services. However, patients seeing Chinese medicine doctors exhibit the following unique characteristics. They still prefer choosing doctors according to third-party information and may be reluctant to pay for the current online service price level. This problem is hard to overcome by the platform in the short run. Patients need a long-term process to adapt to the upgraded medical environment gradually. Therefore, establishing a personalized doctor recommendation system has become the most urgent demand presently. As China chooses the urban-centered development route in the early stages of its economic and social growth plan, healthcare services and medical treatments, like other core resources, have experienced large urban-rural differences in distribution. Because of the dearth of quality hospitals, people in need of such care and consulting services are facing a series of problems with insufficient doctor-patient interaction, especially in the field of complementary, traditional, and alternative medicine . In partWith the development of Internet technologies, the online health care (OHC) community represented by the Good Doctor (“Hao Daifu” in Chinese) and the Dr. Clove (“Dingxiang Yisheng” in Chinese) platform has gradually emerged as a rising medical force in China , which sGiven the boom in China's online healthcare services, many people try to visit OHC websites for healthcare information and consultations . The onlIn regard to seeing a doctor online, there are essentially three types of doctor-patient interactive modes on the Internet that have been studied in the extant literature. The first involves making an appointment online and then meeting offline . The secAs one kind of expert service, physicians' service inevitably leads to information asymmetry between doctors and patients . In addiOur study is complementary to the strand of literature on utilizing online technology to deal with the challenges faced by promoting alternative and traditional medicine. On the one hand, several recent studies combine various aspects of Traditional Chinese Medicine (TCM) with new developments in technology, including the Internet tool. For example, Han et al.  considerOn the other hand, quite a few Chinese studies also provided insights. Based on the survey data, Ding et al.  construcWhen OHC became increasingly popular, related laws and regulations were gradually improved, and corresponding review mechanisms were also developed by well-known platforms. OHCs are gradually eliminating the barrier between patients and doctors. For example, the research results of Beaudoin and Tao  showed tFirst, the telemedicine portal provides a wealth of personal information about doctors, but before the user's browsing behavior occurs, the only information source available on the portal is the brief information on the doctor's business card. Can this information fully induce the user's browsing behavior? In other words, is the user's browsing behavior purposeful or random? Based on this, we can judge the direction and extent of the actual effectiveness of Internet medical care. Second, the user's behavior in paying for the OHC platform service can fully show the patient group's preference for a certain type of doctor and enables us to make suggestions for better training of telemedicine service personnel. Third, there are great differences in the ways of interrogation and treatment between traditional Chinese medicine and modern medicine. Modern medicine often relies on high-end medical devices to assist in the completion of interrogation and treatment, while traditional Chinese medicine can often complete the treatment through the intuitive observation of the physiological characteristics of patients. In terms of drug treatment, traditional Chinese medicine should also be more convenient than modern medicine. Traditional Chinese medicine can often be easily purchased in local hospitals. Therefore, is there any difference in the convenience that telemedicine brings to the field of traditional and alternative medicine? In this regard, we start the analysis with the responses of Internet OHC user behavior to doctor information presented and practices delivered online.Among the emerging Chinese OHC platforms, we collect data from the most representative Good Doctor Internet hospitals. This platform was established in 2006 with the brand feature of “user-friendly”. As of June 2022, the platform includes 890,286 doctors from 10,096 hospitals across China. In this study, we used the public data of this platform, including doctors' resumes and their evaluations by Internet patients, since they started an online service, which provided a rich set of data available for our research. In addition, as the most recognized and representative OHC platform in China, the Good Doctor website is chosen by many scholars to study various topics around the theme of OHC, which further reflects the reliability and availability of its data. All variables used in our research are listed and defined in st, 2019 and August 2nd, 2019, including three dimensions of records. First, the basic information on the doctor's business card, including the doctor's name, academic title, clinic title, employer, hospital, and department. Second, personal introduction, including their specialization and personal profile. Third, personal achievements, including page views, number of published articles, number of patients, number of reviews, number of thank letters and gifts received, search heat, recommended star, and the year of starting service. Given the availability of data, we used the data of 168,870 doctors who went online from 2008 to 2019. These doctors come from ten main departments, as shown in The data were collected through web scraping between June 31To compare the differences in online patient behaviors concerning the TCM department and other hospital departments, we employ two commonly used proxies suggested by scholars specializing in Chinese OHC research as our dependent variables. They are doctor web page visits and the number of medical service orders. In particular, we follow Yu et al.'s  researchTurning to our second proxy of the volume of medical service orders, users placing orders and making payments will clearly reflect their preference for doctors as a direct result of browsing. Theoretically speaking, patients mainly use three information sources when selecting doctors: online reviews, comments, or feedback, family and friend recommendations; and doctor referrals . The decStaying in line with the decision-making process in Based on the information received by users when they perform corresponding behaviors on the website, we divided the samples, simulated the decision process, and established models based on the three different evaluation measures to analyze the development status of OHC and the differences between telemedicine in the fields of traditional Chinese medicine and modern medicine.i denotes the doctor's homepage in our sample, and all variables are as defined in We begin by presenting the linear empirical regression of a decision model of page view volume determination. The general process of searching for doctors on the Good Doctor website is to select the target city and target department, and finally, browse the doctor's brief information and decide whether to enter the details page. When deciding whether to browse details, users first receive information about the doctor's name, academic title, clinic title, hospital name, corresponding department, specialized field description, popularity, hot, and online consultation price. It is worth noting that 90% of the online doctors who are good doctors come from lower-ranked hospitals. Therefore, we will mark the hospital level according to whether the city where the hospital is located belongs to the second-tier group of large cities in China instead of using the rankings of the hospitals themselves. In addition, we use the length of the detailed description to reflect the doctor's skills. Academic titles, clinic titles, and their departments are transformed into a series of dummy variables represented by vectors (marked as bold in the following equation).We first present the descriptive statistics of our main variables in We first regress web page visits, a.k.a. page views, on doctor characteristics for making comparisons between TCM and other doctors. The results in However, the behavior of patients' final choices can be significantly explained by the detailed information provided by doctors, especially by evaluative factors. We then replace the previous page view dependent variable with the order volume proxy and incorporate additional potential controls. Wang et al.  also fouWhen comparing TCM with other MM departments, our finding is that when choosing modern medicine doctors on the Internet, users pay more attention to the degree of economic development of the doctor's residence city, while patients browsing TCM online content do not have such concerns. However, concerning placing medical service orders online, patients irrespective of TCM or MM collectively show great concern for regions. This phenomenon may be related to the better medical conditions of modern medicine in large cities. The academic titles of doctors in MM departments matter a lot to patients. However, titles seem to play a lesser role for TCM departments. In terms of goodness of fit, the browsing volume model with more regressors can explain the variations of the dependent variable much better for observations in the TCM department sample than in other departments. Besides, the order volume model also worked better in explaining the TCM department, which indicates that the online information about the TCM doctors is more efficient and the extent to which patients receive and process these pieces of information is also large. In contrast, the information of interest to Internet users of other medical departments has been, to some extent, hidden in the constant terms of our empirical setup.One last aspect that merits note is that the TCM doctor with more online reviews or comments has a lower volume of web page browsing. However, the number of medical consulting orders placed is positively associated with the number of reviews. This might have something to do with the contents of the reviews. In the TCM field, it is very challenging to evaluate the effectiveness of a TCM treatment. As a result, both positive and negative reviews are more common for TCM doctors. Nevertheless, the number of orders and reviews should have a positive correlation in theory, regardless of good and bad comments. More orders will naturally lead to more views, but how many times a doctor's page has been viewed should be more related to the reputation of the doctor from a third-party perspective. We expect to dig deeper in this regard if detailed textual analysis can be performed on the comments.Although the above empirical analysis preliminarily proves that the information provided by the website can help users make choices and well reflect the logic and preference of users' behavior, it is difficult to convincingly evaluate the acceptance of OHC and users' willingness to pay only by using simple quantitative variables. Moreover, either the number of page views or the number of orders placed for different doctors are not of the same degree of magnitude due to variations in their capability and popularity. Distortions in the estimate are likely to appear because of extreme values. For this reason, we use an alternative but relevant proxy to repeat our previous exercises as a robust test. In particular, we calculate the order conversion ratio to be the ratio of order volume to the number of page views. This is a standardized index, which can give us a unified evaluation standard to evaluate the ability and popularity of doctors with different attributes and more directly reflect the actual applicability of OHC. Compared with the single number of page views or orders, OCR contains more information, allowing us to analyze OHC acceptance and users' willingness to pay for OHC service in more dimensions. On the basis of the second model, we use OCR as the explained variable to establish the following model. Furthermore, because OCR is a positive number less than 1, we adopt the Probit model to analyze our results in addition to the baseline ordinary least squares (OLS) specification. The corresponding results are summarized in When we focus on OCR, the interpretation effect of the information provided by the website is greatly reduced, which may be caused by individual differences in patient behavior. Because the number of views generated by different patients is random, not all browsing behaviors will eventually lead to order placement. However, the previous results are still valid, and the evaluation information about doctors is still the most important factor for users. The significant constant term and low fitting coefficient also show that the ordering behavior and browsing behavior are not unified in most cases, and the users' choice is disturbed by strong external factors.By comparing traditional Chinese medicine with modern medicine, we find that “whether the hospital is located in large cities” is an irrelevant variable for the order conversion ratio of traditional Chinese medicine departments, but it is a significant variable for modern medical departments, which indicates that OHC gives full play to the resources for scheduling medical resources and promotes the redistribution of high-end medical resources to underdeveloped areas. At the same time, nonacademic TCM doctors have been exposed and visited more. In addition, in the process of browsing and placing orders, people who choose traditional Chinese medicine departments do not care about the academic and professional titles of doctors, but people who choose modern medicine will consider the academic title of doctors. This may also be determined by the traditional differences between TCM and modern medicine. Unlike the findings from the two previous models, the OCR determination specification performs less well in TCM than in other departments. Considering that we have far more than usual browsing and query data in TCM, we believe that this result is caused by the presence of excessive invalid browsing in TCM.According to the Department of Health and Human Services, more than 60% of medical institutions and 40% to 50% of hospitals in the United States already use some form of telemedicine . It is wThe latest research points out that the professional ability, integrity, online reputation, and patient group size of psychological counselors have a significant positive impact on patient initial trust. Initial trust and the efforts of psychologists have a significant impact on sustained trust . WhetherThrough the above analysis, it is easy to see that the current information provided by OHC is not enough to support or encourage patients to visit their doctors online, and patients often use third-party information actively or passively to make decisions. However, we are glad to see that users are happy to use the information on the OHC platform as a reference for medical treatment, especially when it is the most frequently browsed department, as represented by traditional Chinese medicine. Among these limited information sources, the factors that directly reflect the ability of doctors, such as the various achievements of doctors on the platform, have become the most recognizable by patients. Interestingly, the academic title is more persuasive in modern medicine than the doctor's clinical title. In addition, whether the hospital where the doctor works is located in a larger city or not turns out not to be a factor to consider. This coincides with the idea that Internet hospitals decrease the importance of geographical factors. On the one hand, it shows that the medical resources of the platform are of sufficient quality to believe, weakening the user's preference for developed cities. On the other hand, it also shows that OHC has overcome the geographical factors to a certain extent and realized the remote redistribution of medical resources by using the Internet.The three proxies all reflect the same problem, that is, although users are gradually trying to accept and use OHC, they still tend to choose doctors according to third-party information and may have a low willingness to pay for the current OHC price level. This problem is difficult to overcome by the platform in the short term. Patients need a long-term process to gradually adapt to the upgraded medical environment.Regarding potential directions for future studies, our findings point out the following aspects. The volume of page views created by patients who want to see a doctor in TCM before selecting an OHC doctor is much larger than that of other departments, but the proportion of patients paying for diagnosis and treatment is much smaller than that of modern medical departments. The status quo of “view but no order” in TCM reflects the following potential problems. First of all, most of the patients who have completed the treatment of online TCM are attracted by the doctors' fame, but they will still actively check the cases and doctors for related information. Second, traditional Chinese medicine is the only alternative for patients. Although browsing occurs, they may eventually choose modern medicine. Third, some patients try to complete self-diagnosis through relevant comments because TCM often does not need CT, X-ray, and other precise examinations. Fourth, the price of online traditional Chinese medicine is relatively high for the low-income group, and patients will give up placing orders for OHC medical treatment. However, due to the purpose and scope of our research, we cannot make a specific conclusion. Future research may allow the analysis of a wider range of data to help identify and improve the development of Internet TCM.


The health research system (HRS) is an important national priority that requires a systematic and functional approach. Evaluating the HRS of Iran as a developing country and identifying its challenges reveals the stewardship-related role in how the whole system is operating well. This study aims to assess the HRS in terms of stewardship functions and highlight the enhancement points.This study was carried out between March 2020 and April 2021 using a systematic review and meta-synthesis of evidence to examine the Iranian HRS stewardship challenges and interview 32 stakeholders, using a critical case sampling and snowballing approach which included both semi-structured and in-depth interviews. The interviewees were selected based on criteria covering policy-makers, managers, research bodies and nongovernmental organizations (NGOs) in health research-related fields like higher education, research, technology, innovation and science. All data were analysed using content analysis to determine eight main groups of findings under three levels: macro, meso, and micro.Analysis of the findings identified eight main themes. The most critical challenges were the lack of an integrated leadership model and a shared vision among different HRS stakeholders. Their scope and activities were often contradictory, and their role was not clarified in a predetermined big picture. The other challenges were legislation, priority-setting, monitoring and evaluation, networking, and using evidence as a decision support base.Stewardship functions are not appropriately performed and are considered the root causes of many other HRS challenges in Iran. Formulating a clear shared vision and a work scope for HRS actors is critical, along with integrating all efforts towards a unified strategy that assists in addressing many challenges of HRS, including developing strategic plans and future-oriented and systematic research, and evaluating performance. Policy-makers and senior managers need to embrace and use evidence, and effective networking and communication mechanisms among stakeholders need to be enhanced. An effective HRS can be achieved by redesigning the processes, regulations and rules to promote transparency and accountability within a well-organized and systematic framework.The online version contains supplementary material available at 10.1186/s12961-022-00905-3. Having a systematic approach to health research helps enhance the research system efficiency, integration and practicality.Stewardship needs attention as the essential function of a national health research system (NHRS), especially in a developing country like Iran.The stewardship challenges are the root of many other malfunctions of an HRS such as resource management, knowledge management and capacity-building.The findings presented herein can serve as the basis for further studies and interventions in improving HRS at the policy-making level.A map of an ideal HRS has been imagined to visualize what is needed to achieve a well-organized HRS.Health research efforts have received increasing attention globally over the last two decades, and the adoption of systematic approaches to the issue has also been improved , 2. The The HRS has a critical role in health policy-making by generating evidence  of high Most of the challenges of the HRSs are rooted in the breakdown of stewardship and governance and related sub-functions (as mentioned above), which is the case for most countries, with more intensity in developing ones . The IraOur research team, consisting of the managers of the health research grant bodies and health-related research centre and researchers, is encountering so many challenges in our daily activities that it motivated us to think about the causes and try to find answers to the questions raised from those challenges. The main question is: how much is Iran's HRS melody harmonious? The first answer that comes to mind, as we have experienced, is not so much! Trying to find the exact and specific causes and solutions based on an initial literature review, the answers were not clear and convergent, so each stakeholder blamed the other. Some blamed researchers for their nonpractical research efforts , and othIran has a unique health research and education structure due to the integration of health services and medical education , 23. TheThis study aimed to analyse Iran’s HRS challenges regarding the stewardship function. We wanted to enlist the participation of Iranian HRS stakeholders as interviewees across as wide a group as possible and to systematically review the related evidence to ensure that there were no missing data. We expect to provide a base for further studies, implications and reforms. For this purpose, we tried to adopt a practical approach to analysing the data and presenting suggestions. Acknowledging the importance of knowledge translation (KT) in moving towards a qualified HRS, a conceptual drawing of the main recommendations is also shown in This qualitative, cross-sectional, descriptive situation analysis study uses desk review and expert interviews. A brief overview of the phases is presented in Fig. The study asked the question: “What are the challenges of the Iranian HRS from a stewardship perspective?” The systematic review of qualitative studies and a meta-summary and meta-synthesis were performed based on Sandelowski and Barroso’s guidelines . The resChallenges  from a stewardship perspectiveOne specific challenge  related to stewardship sub-functionsInclusion criteria: English or Persian studies with qualitative research design, aimed at exploring:Exclusion criterion: Studies focusing only on research challenges in non-health-related fields.The Critical Appraisal Skills Programme (CASP) was used for the quality appraisal . The 202Critical appraisal was carried out using the CASP tool. Each item was scored as “yes”, “no” or “unclear” depending on their appropriateness, by assigning a score of 1, 0 or 0.5, respectively. As there is no cutoff point for the CASP tool to exclude records, the researchers agreed to exclude those with a score of less than 5 (less than average). Three peers conducted the data extraction phase independently and checked in pairs to ensure data extraction consistency, and papers were selected using a matrix model .The data, including all records from which they were extracted, supporting the conclusions of this article are included within this article in the results section and the discussion (with citations).An interview approach was employed that included a mixture of semi-structured and in-depth questions, using two types of sampling, critical case and snowball sampling strategies. The interviews were driven by an exploratory approach to capture the challenges in step one. In step two, a group of interviews was carried out using the explanatory method to describe and determine the root causes of the challenges. The interview is reported based on qualitative research reporting standards .The essential HRS subsections and departments (as main stakeholders of the Iranian HRS) were initiated to be the target group of the study. For this purpose, three experts involved in the Iranian health and scientific systems contributed. The selected departments and subsections are government, research centre heads, health innovation system, higher education, science and technology policy-making, senior researchers, HRS, nongovernmental organizations (NGOs), graduate students, and international experts of the Iranian HRS. Participants were identified and selected purposively. After determining the target groups, the strategy was to diversify the participants. The second strategy was to select individual candidates covering more than one category. All the interviewers were asked to propose candidates to be interviewed in parallel with critical case sampling. The interviews continued until they no longer yielded additional information to the data from reviewing the articles.After preparing all expert lists, personal communications with experts were carried out to identify the appropriate time and date for the interviews. One day before the interview, the researcher communicated with experts and sent a summary of the study objectives, consent form and formal invitation. Two methods of structured and in-depth interviews were used for data collection.Senior stakeholders such as policy-makers with insight about HRS due to their executive and managerial experiencesParticipants whose tendency was to point to the issues without structure and based on their conceptual model.The in-depth interview was designed for senior experts and policy-makers to elaborate on more technical and strategic ideas and left it open for them to express their perceptions of Iran’s HRS challenges. The semi-structured interview was used to ask to-the-point questions. The choice of an in-depth approach was based on two main factors:The researcher had a guide in mind to understand the participant's ideas. The researcher attempted to change the direction during the interview, if necessary. Thus, the in-depth interviews helped develop the conceptual map of the Iranian HRS stewardship challenges. In contrast, the structured interviews added more details and implications of the Iranian HRS stewardship challenges. All the explanatory interviews were conducted using the in-depth approach to capture the roots and causes as much as possible.The interviews were conducted virtually using Microsoft Team or Skype, and by phone, and the interviewer was in the Kerman province of Iran. The principal investigator conducted the interviews and transcribed the texts. The interviews were recorded with permission using an AnyMP4 screen recorder for the Skype and Microsoft Team interviews and a call recorder for phone calls.The systematic review and interview results were analysed using the framework analysis method. MAXQDA 2018 software was used for framework analysis. The software helped code the systematic review and qualitative meta-synthesis and interviews. After the framework analysis, all the codes related to the stewardship were reanalysed to develop a conceptual model of the Iranian HRS from the stewardship perspective. The approach was content analysis, and the results of both steps are reported based on consolidated criteria for reporting qualitative research (COREQ) .The following steps were taken to avoid misleading, reporting bias or any other kind of unconscious bias:The transcribed text of the interviews was checked by a peer in the research team before the qualitative analysis step to ensure the quality and validity of the results.After the qualitative analysis, a national virtual session was held by the participants involved. The preliminary results of the qualitative analysis of the interviews in alignment with the review results were presented to receive stakeholder feedback and comments. More codes were also mentioned in the session by the participants' debate. The session helped the research team avoid biases, improve the themes and codes, sensitize the stakeholders on results, and let them know about the study progress they have been involved in.The results are sourced from two phases of the systematic review and interviews. After eliminating the duplicates, 149 records were investigated through the selected databases, yielding 42 copies. Three records were also added after asking the experts in the interview phase. After title and abstract screening, 35 records entered the next step, and peers screened 28 full texts to enter the data extraction phase. The other record entered the data extraction by the interview. This record was proposed by senior experts of the Iranian HRS and was not available through database search. Nineteen papers were excluded in the critical appraisal step (their score was less than 5 based on the CASP checklist), and finally, 10 records entered the data extraction. Figure A total of 32 interviews were carried out in this study. Twenty-two interviews were structured, and 10 were in-depth. The structured interviews took 45 minutes on average, varying between 30 and 60 minutes, with the in-depth interviews taking 60 minutes on average, and ranging from 45 to 75 minutes. Eleven participants were female and 21 were male; age ranged from 31 to 65 years. Additional information about the participants is presented in Table The organizations, sectors and individuals identified as the study's target are presented in Table The results obtained from both the review and interview are presented after the content analysis. The use of both data collection instruments helped us articulate a map of the challenges and their potential and active relations. The data mentioned here as the study results were obtained from the qualitative analysis of both data sources (desk review and interview) using content analysis to determine the main themes and codes. The results were classified into eight characteristic groups and three levels of macro, meso and micro, combining the content of interviews with the findings from the desk review. The micro level includes research bodies (research centres and universities) and researchers (e.g. faculty members and postgraduate students). The meso level is considered within the MOHME authority, and its education and research deputies are the main structures related to health research. The macro level is considered beyond the MOHME authority. At the national level, the key stakeholders include the Supreme Council of the Cultural Revolution and the Expediency Discernment Council of the System; the MOHME is not the only stakeholder. The results of the review and interviews are presented in Table The eight groups are as follows: (1) leadership; 2) vision; (3) priority-setting; (4) structure; (5) regulation; (6) monitoring and evaluation M&E); (7) communication, networking and collaboration (CNC); and (8) evidence-based/informed decision-making. Table  vision; Complexity and lack of collective leadership are the main concerns at the macro level. Multiple stakeholders are not harmonized, with many overlapping and/or contradictions in their scope . This is why CNC mechanisms are limited among key stakeholders of this scale. Concerning the vision as an essential function of HRS stewardship, a lack of shared vision among stakeholders was identified, so despite defined long-term plans at the macro level, leadership and legal obligation to persuade stakeholders of all roles to follow its advice are not embedded in the HRS structure. The priority-setting process is not well defined, transparent, participatory, systematic, future-oriented or efficient. No research M&E system has been defined at the macro level of HRS. The regulations regarding HRS are inefficient regarding incentives, intellectual property, capacity-building and public–private partnership matters, with many contradictions. The development of the research structure has been inefficient. Finally, there is no clear evidence showing a linkage of research to action and policy. Research is not prioritized for potential clients, policy-makers and decision-makers.The lack of collective leadership was also highlighted at the meso level. The is no defined vision aligned with the macro level. The MOHME authority's priority-setting mechanism has the same malfunction as the macro level, not being well defined, transparent, participatory, systematic, future-oriented and efficient. The priorities of the meso level are not matched with national development needs, so the preferences of the research bodies and researchers are not aligned with upper national ones.Conflict of interest (COI) management is also important, and the structure of health research is centralized, bureaucratic and influenced by political dominance. The policy dominance also exists at the meso level, leading to the unsustainability of the HRS. The HRS is not aligned with the education system, which is related to the challenge of separating two functions of education and research at both the ministry and its underlying units (e.g. universities and research bodies). Education and research are not the main priority of the MOHME and medical universities . RegulatThe leadership challenges in the previous levels are also transferred to this level. The lack of shared vision among stakeholders results in the misalignment of the health research activities at the micro level with the overall strategic direction of HRS in the country. Furthermore, most research institutions have no vision that manages, regulates or monitors the research. The structure at the micro level is not uniform and varies among cases (in different research bodies). The system of research bodies is dependent on the centralized design at the meso level and is mainly supported by a fixed governmental budget. The design of HRS is not agile enough on all three levels and has not been updated based on new requirements, context and research environment. The rules and regulations are fairly inefficient in motivating research and performance improvement, with challenges in performance M&E at this level. The CNC among research bodies and individual researchers is not well defined, with lower efficiency. The research bodies also could not respond to required evidence with expected quality at the right time, leading to less motivation and trust of both research clients and research bodies.We conducted a relatively comprehensive study in Iran involving many stakeholders in our in-depth interviews and desk reviews of published and unpublished documents. Like many other developing countries, Iran’s HRS challenges are primarily stewardship and governance , 32, eveHealth leadership is an international issue [The top challenge at this level is national health research leadership. Others are structure, legislation and use of evidence in decision-making. The leadership-related challenges are not limited to HRS or to Iran. al issue , 35 in cal issue –36 and dal issue , medicalal issue  and HRS al issue –42. Specal issue , 43. At al issue , 42–44. al issue , 45–47 sal issue , 48.Next are structural issues: political dominance, COI management, centralization, bureaucracy and lack of sustainability and agility in the HRS. The authority of power and policies is not specific to Iran or any other country, but is a global public health issue . The parThe third challenge includes laws, legislation and regulations that constitute the initial basis of the health sector and its underlying subsystems on a national and international scale. Legislation and laws related to the Iranian HRS have some malfunctions regarding intellectual property, capacity-building, public–private partnership, research process transparency, motivation and performance improvement. WHO also mentions the restrictive financial and administrative regulations of the Iranian HRS as a primary challenge . One exaTransparency in research is another issue with some main dimensions including transparency in legislation and performance monitoring, data transparency, open data resources , and traAt this level, challenges that need to be addressed are priority-setting, M&E and the use of evidence as the basis for decision-making. Priority-setting is not transparent, participatory, systematic or efficient , 50. RevM&E frameworks aid in the achievement of policy goals and targets. They also make it possible to track stakeholder performance, estimate the effectiveness of the policies and design subsystems. A well-developed M&E framework provides data collection, analysis and sharing . Iran’s The use of evidence in Iran's health policy and decision-making is not well established and not systematic , 24. At Two issues with more weight at the micro level are promotion law and CNC. The promotion law for faculty members is a clear example of the effects of regulation on capacity-building, performance evaluation and motivation of HRS human resources. It emphasizes quantity instead of research quality and output effectiveness and destroys motivation after receipt of a master's degree . This laThe CNC challenges in the Iranian HRS can be classified into three main categories. The first is the CNC of research bodies. There is no networking and data-sharing mechanism among researchers and research centres active in the Iranian HRS, which is the main barrier to knowledge sharing and networking . The secAdopting a systematic approach to health research activities is binding in some aspects—most notably, establishing vision and targets, determining the components, and defining the relations, processes and rules. Achieving all those features requires effective stewardship of the NHRS. Following up on the roots and causes shows that despite other functional challenges of the Iranian HRS, stewardship issues are more heavily weighted and more fundamental than other HRS weaknesses. The research question stated a challenge that this study investigator encountered every day in their management and research tasks and for which they were trying to find the answers. The Iranian HRS has started its improvement, but there is still work to do. It has missed a potential synergy among critical stakeholders so that improving focal leadership seems essential. This can lead to a vision that mobilizes the research efforts comprehensively and harmoniously, providing a big picture perspective where all resources are mobilized to complete the puzzle. This enhancement will spread to any individual active in HRS as well. Reviewing rules and regulations, strengthening cross-sectoral and intrasectoral links, restructuring the priority-setting, incorporating evidence-based decision-making, increasing transparency and effectiveness in research processes at all three macro, meso and micro levels, and finally strengthening the networking among stakeholders are other solutions that will help enhance the research of the health system from a stewardship perspective. The authors have drawn a conceptual symbolic image of the recommendation to show the systematized recommendations presented in Fig Considering the nature of the stewardship scale, we hope to draw the attention of national policy-makers in Iran and related intergovernmental organizations like WHO that can make a difference or at least start the journey to reforms for Iran or any other developing country in improving their HRS through a systematic and framework-based approach. Each sub-function-related recommendation needs attention at the policy-making and leadership level, such as developing practical planning in separate studies. This study had some limitations, such as lack of access to some top policy-makers. If possible, providing a mechanism for the participation of all stakeholder in finding and making sense of the challenges can help improve this study's results and, more importantly, achieve consensus on issues and solutions among stakeholders. This requires the will of top managers and motivation of other stakeholders to participate. We wanted to present the NGO perspective in this study as the community representative, but engaging the community on a broader scale can help as well. As to the methodological aspect, a quantitative analysis assessing the NHRS based on quantitative measures and indexes can complement this study.Additional file 1: Standards for Reporting Qualitative Research (SRQR)a.Additional file 2: Main findings extracted from included studies.


Large-scale natural disasters have a significant effect on residents’ mental health. The Miyagi Disaster Mental Health Care Center (DMHCC) was established as a long-term mental health care center in response to the 2011 Great East Japan Earthquake and Tsunami (GEJE). Although six DMHCCs have been established in Japan, their exact role and functioning are still unclear. This study aimed to explore which population used the center in each recovery phase. Logistic regression was performed to identify the residents’ characteristics according to the consultation pathways using the data collected by the Miyagi DMHCC. These data included personal information of the residents who were supported by the center from 2013 to 2018. The working-age unemployed men sought help by themselves, and the isolated older females were supported by home visits through the health survey. Long-term mental health care centers should observe community recovery and provide appropriate support. The implications of this result and future research directions are discussed. Natural disasters such as floods, earthquakes, hurricanes, and fires have significant effects on human beings’ health. Studies report that major disasters have significant negative effects on survivors’ socio-emotional functioning and mental health ,2,3. AltIn the aftermath of a large-scale natural disaster, the psychological needs of a community change with each recovery stage . McFarlaPost-disaster mental health services have been established in many cases and various types of mental health support have been provided after many disasters around the world; these include the 2004 tsunami in the Maldives , HurricaFirst, the history of the emergency mental support system in Japan should be reviewed. The emergency mental health support system and the long-term mental health support system were established after two major disasters in Japan: the 1995 Hanshin-Awaji earthquake  and the 2011 GEJE . Prior In Japan, local governments and public health centers play an important role in supporting communities in their long-term recovery, in the wake of disasters. However, these facilities could not sufficiently support communities, as the scale of the disaster was overwhelming. The Japanese government and the affected municipalities, therefore, established new organizations, such as the Disaster Mental Health Care Centers (DMHCC), which specialized in reconstructing local mental health systems. For example, the Hyogo DMHCC was established in 1995 in response to the Hanshin-Awaji earthquake, while the Niigata DMHCC was established in 2004 in response to the Niigata-Chuetsu earthquake ,25. SimiMiyagi is the largest prefecture in the Tohoku region, with a population of 2,323,224 people in 2011. The Tohoku region is a relatively rural area in Japan and the mental health indicators among its residents are worse than those of other regions. In 2011, the Tohoku region had a suicide rate of 27.1 per 100,000 people . AlthougOn 11 March 2011, an earthquake with a magnitude of 9.0 and a tsunami hit the eastern part of Japan; 19,630 people died, and 6230 were injured. A further 2569 people were reported missing  and apprAlthough some existing works reviewed the activities of the DMHCC ,29, therThis study was based on the residents’ data who were supported by the Miyagi DMHCC from 2013 to 2018. Since no informed consent was obtained from any individual, personal information was not included in this study. The statement of opting-out was developed on the webpage of the Miyagi DMHCC and procedures as to how to opt-out were also displayed on the webpage. The Miyagi DMHCC developed a brief database in 2013 and recorded its support activities in the form of digital data. The workers of the center confirmed and recorded the residents’ information, including gender, age, area of residence, medical history, and other disaster status. The experiences that could be a psychological burden were confirmed: they had lost loved ones (Yes/No), had been injured (Yes/No), had near-death experiences (Yes/No), lost their community (Yes/No), loss of property other than the house (Yes/No), forced evacuation from home (Yes/No), or lost their jobs (Yes/No). The consultation pathway was considered: whether patients visited by themselves, or were referred by family members, by neighbors, by workplace, through a health survey by local municipalities and public health care centers, by temporary housing supporters, by medical resources, or by welfare facilities, among others. This study was approved by the Miyagi DMHCC Ethics Committee .n = 43) and age (n = 658) were unavailable were excluded from the analysis. Furthermore, the residents whose information of experiences in the disaster and their environmental changes after the disaster was incomplete were also excluded (n = 1143). Thus, 9756 residents were eligible for analysis .We performed chi-squared tests and two multivariate logistic regression models to examine the characteristics of residents in two significant pathways and to identify the odds ratios (OR) and the corresponding 95% confidence intervals (CI). We focused on two major pathways  to understand the trend of the residents. Two multivariate logistic regressions were performed: the dependent factor was visiting the center to seek help by themselves (Yes/No) in the first analysis  and was The total number of residents who needed support was 9756 in six years, from 2013 to 2018 . There was no significant difference among residents based on gender: the number of males and females were 4326 (44.3%) and 5430 (55.7%), respectively. There was no significant difference in the mean age of males  and females , those age range was from one to 97. The chi-squared test of independence revealed significant differences according to gender in terms of the annual number of individuals supported by the center. Furthermore, the chi-squared test of independence revealed significant differences between individuals who experienced a psychological burden and those who did not. The test also demonstrated significant differences among each of the experiences.Residents were connected to the Miyagi DMHCC through various pathways. After the GEJE disaster, an increase in the demand for mental health services was expected, as a vast number of residents experienced psychological trauma due to the disaster. Owing to the lack of mental health resources in the disaster-affected area in the aftermath of the 2011 earthquake, local municipalities and public health centers faced difficulties in providing residents with adequate treatment. The number of residents who needed mental health support dramatically increased after the 2011 disaster, and the Miyagi DMHCC continuously followed up on additional residents . A reporThe residents who visited the center and sought help by themselves were not a large percentage compared to the overall support activities of the center. In our study, males, a relatively younger age group (20–40 years old), who had lost their jobs had a significant association with help-seeking behavior. There is a possibility that some men, especially those of working age, struggled to reconstruct their life because they lost their job, and therefore started seeking mental health support by themselves. The number of completely unemployed individuals was estimated to be approximately 150,000 to 200,000 in several years following the disaster, and the largest population was the primary industry such as fishing and agriculture; approximately 40% of them became unemployed . This reIn our study, the younger residents did not receive home visits, and the residents who lived alone and lost their community were highly associated with receiving home visits. There was a possibility that isolated older females were likely to be found at higher psychological risk by the health survey and were provided with support in the first several years following the disaster. Evidence from a previous health survey indicates that many older individuals lead an isolated life in temporary housing, which is a major issue that needs to be addressed . These rThe residents who experienced visiting psychiatric facilities were significantly associated with seeking help by themselves and did not tend to receive home visits in this study. Since some major disasters make it difficult to access mental health resources and routine treatment is interrupted ,35, the The number of residents who needed mental health support increased after the 2011 earthquake, and the Miyagi DMHCC was established in response to the disaster to provide long-term community support. Working-age men sought help by themselves due to unemployment or economic status, and isolated older females who were evaluated to be at high risk through the survey were supported by home visits. In addition, residents with pre-existing mental disorders were supported by the emergency support team and connected to the Miyagi DMHCC smoothly.As post-disaster reconstruction efforts change phases, community residents face diverse issues and need specialized mental health support. It is necessary to observe these changes and provide appropriate support at the correct time. Further research regarding the increase in specific mental illnesses and budget allocation for mental health is needed. Despite its clear contributions, this article has several limitations. First, since the subjects we analyzed included only the residents who were connected to the center, they were not representative of the communities. Therefore, the study was only an explanatory analysis of the residents who were supported by the center and is limited generalizability. Second, since any standardized psychological rating scales were not used in this study, the data might not correctly reflect the psychological status of the residents. Third, because the Miyagi DMHCC is not a medical organization, it mainly connected the residents with pre-existing community resources. As a result, the researchers were unable to ensure that all the individuals seeking support recovered and could not analyze the extent to which their efforts contributed to the individuals’ recovery. Finally, the residents on whom long-term mental health care centers should focus may differ, depending on the structure of the communities before disasters. The problems faced by communities may be different from those explored in this study if the main industry of the region is urbanized, the residents are younger, and the employment rate of the females is higher. The characteristics of the Japanese society, the aging population, and the low female employment rate might have affected this study’s results.


Aortic stiffness is an important clinical parameter for predicting cardiovascular events. Carotid–femoral pulse wave velocity (cf-PWV) has been proposed for performing this evaluation non-invasively; however, it requires dedicated equipment and experienced operators. We explored the possibility of measuring aortic stiffness using ultrasound scans of the abdominal aorta coupled with the Bramwell–Hill equation. Healthy subjects were investigated; measurements of cf-PWV were taken by arterial tonometry and aortic systo-diastolic pressure difference was estimated using a validated model. Pulsatility of an abdominal tract of aorta was assessed by automated processing of ultrasound scans. Through a Bland–Altmann analysis, we found large biases when estimating each parameter by applying the Bramwell–Hill equation to the measured values of the other two paramters . These results indicate that the two measures are not interchangeable, and that a large part of the bias is attributable to blood pressure estimation. Further studies are needed to identify the possible sources of bias between cf-PWV and aortic pulsatility. The loss of the cushioning function of large arteries leads to the development of arterial stiffness, which occurs with aging and various pathological states . The stiMeasuring the stiffness  of an artery non-invasively has been a technical issue for a long time . EvaluatThe Bramwell-Hill equation  providesUltrasounds are commonly used to explore arterial morphology in the clinical setting. Arterial cross-sectional area changes, i.e., from systole to diastole, are considered in order to calculate local PWV values, especially in the carotid ,10 and fThe aim of our study was to investigate this problem, focusing on measurements of aortic stiffness, PWV, and blood pressure and their relationship as provided by the Bramwell–Hill equation. Pulsatility in the abdominal aorta was obtained by ultrasound evaluation, cf-PWV was measured with arterial tonometers, and blood pressure was computed by validated models. Then, these values were determined using the Bramwell–Hill equation applied to each pair of variables to estimate the third, and possible sources of bias between the measurements and the estimations were investigated.Carotid–femoral PWV (cf-PWV) was measured non-invasively by tonometry with the foot to foot method, which represents the gold standard. The foot of the curve corresponds to the end-diastole point as identified by the tangent method .Two different instruments were used to measure the delay , and Lisendo 880®, Hitachi (Pisa group).A long axis section of the abdominal aorta was visualized by subcostal view, following current recommendations . The bort) as the mean of five diameters uniformly distributed in the region of interest and placed orthogonally to the midline of the blood vessel [After the two borders of the aorta were obtained, the software computed the mean diameter, d vessel . From thA is the mean area during the same time interval. Different heartbeats were included in the ultrasound scans (which lasted about 10 s) in order to obtain different measurements of pulsatility (one for each beat), which were taken and then averaged.Pulsatility was then measured from the computed area of the region of interest. Specifically, the dilation of the vessel during systole depends on its elasticity, which is predominantly determined by the elastin/collagen ratio. Pulsatility is a parameter that measures this dilation. It was computed as The pressure in the aorta is different from the values of systolic and diastolic pressure, which can be easily measured from the upper arm using a sphygmomanometer. Indeed, the pressure wave propagating from the center to the periphery (direct wave) encounters the pressure wave generated at sites of bifurcations of arteries and terminal arterioles (reflected wave) and overlaps with it. This phenomenon, known as amplification, makes the pressure variation in the aorta lower than that measured at the brachial site .In the absence of direct invasive measurement of the local pulse pressure in the abdominal aorta, an estimate of the central pressure was obtained by tonometry for subsequent use.Using the PulsePen, the central pressure was derived from carotid pressure waves, which have been shown to be similar to those recorded in the ascending aorta .With the SphygmoCor, tonometry was performed at the level of the radial artery and aortic pressure was derived using a validated transfer function ,22.Different calibrations of the pressure curve were performed depending on the instrument used: A is the mean area of the blood vessel;The Bramwell–Hill equation provides the relationship between PWV, pulsatility, and pressure variation :(3)PWVesFor the blood density, we considered , recruited seven subjects, two males and five females, with ages varying between 27 to 30 years , taking two measurements of PWV for each with the PulsePen. The University of Pisa  investigated fourteen subjects, nine males and five females, with ages within a range 25 to 63 years, , taking a single measurement for each using the SphygmoCor. Each subject was monitored once by taking an ultrasound scan of 10 s duration with the system indicated in All subjects were healthy volunteers selected among the medical and paramedical staff of the clinical units.Statistical analyses and all processing were performed using MATLAB® version 9.9.0.1467703, R2020b; Natick, Massachusetts, The MathWorks Inc. .In order to compare data obtained by direct and indirect measurement techniques, scatter and Bland–Altman plots were used. The Bland–Altman plots allowed us to evaluate whether two different measurement methods were interchangeable. It was applied for the comparison of measured and estimated values of PWV, pulsatility, and greement .A few examples of experimental data are shown in 1.carotid–femoral pulse wave velocity (cf-PWV);2.pulsatility  excluded.A further observation is that cf-PWV accounts for the average velocity of pulses along a portion of aorta, whereas the ultrasound scan was localized in a specific cross-section. Previous studies have documented that local and regional measures of PWV are not interchangeable, and that aortic PWV seems to decrease along the aortic path . In geneHowever, previous studies failed to identify the reasons for this discrepancy, which may be attributable to multiple factors, such as the measurements  of cf-PWV, evident mistakes in the pressure jump, and poor reliability of the Bramwell–Hill equation due to the many approximations involved.The evaluation of aortic stiffness is a relevant clinical parameter that has been widely validated as an independent predictor of cardiovascular events . AlthougWe have already mentioned factors that may affect the comparison between cf-PWV and local aortic PWV, namely, possible indeterminacy in the measurements or physiological variations of cf-PWV, evident mistakes in the pressure jump, and poor reliability of the Bramwell–Hill equation due to the many approximations involved. Moreover, cf-PWV and local aortic PWV are an integral and a local measurement, respectively, as the first depends on the average velocity of the pulse along an entire portion of aorta, while the second accounts for only a specific section visualized by the ultrasound scan. In addition, in the present investigation we used two different tools to measure cf-PWV and to estimate aortic PWV (Sphygmocor and PulsePen devices), which may have introduced a further methodological discrepancy. Moreover, the limited number of observations, which were conducted only in healthy subjects, may limit the generalization of our results to the overt pathological states that are the main outcome for the clinical use of arterial stiffness measurements. Furthermore, there are patients for whom the investigation of abdominal aorta by ultrasound could be critical , in which case the generalization of our approach could be difficult.While cf-PWV has been widely validated in several studies, further methodological improvements are required for the estimation of aortic PWV using the Bramwell–Hill equation. On the one hand, the automation of image processing for the correct quantification of areas and pulsatility is a mandatory step for implementation of this method with the current ultrasound devices. On the other hand, large studies to establish reference values for local aortic PWV as well as clinical validation of the effect of this method on health outcomes are both needed before it can be applied in clinical practice.Our study compared two methods (cf-PWV and ultrasound-derived aortic PWV) which are notably correlated by the Bramwell–Hill equation, identified several relevant discrepancies, and quantified the possible sources of bias inherent to the equation. Our results suggest that these two measures should not be considered merely interchangeable, and that the bias between them is mainly attributable to issues in blood pressure estimation. It is possible that measuring cf-PWV by tonometry and aorta pulsatility by ultrasound scan could be important in further improving the clinical picture.Additional studies are needed in order to identify the relationship between cf-PWV and ultrasound-derived aortic PWV in both healthy and pathological states. The identification and possible correction of the sources of bias identified in this study may lead to methodological improvements and the validation of easily accessible tools for cardiovascular medicine that are reliably applicable in patient care.


They all completed self-report questionnaires: Ladder of Life, BSI-18 and Cognitive problems. Paired t test evidenced significant differences between survivors  and controls  in perceptions of quality of life regarding 5 years before the current time , with a lower level for childhood cancer survivors. Specifically, Hierarchical regression  identified a shorter time since the completion of treatment  and a trend of stem cell transplantation experience  as factors associated with negative perception of precedent quality of life. The AYA cancer survivors reported lower cognitive difficulties (Mean = 1.46) than controls (Mean = 1.56) : in memory  , in concentration   and in mental organization skills  , even if they had a lower educational attainment [Xp = 0.001]. They showed similar satisfaction with their psychological well-being and their lives as healthy counterparts, except for past life perceptions associated with the cancer period. Important recommendations for future research and clinical suggestions could be given.The majority of the studies underlined how adolescent and young adult (AYA) Cancer Survivors had no significant differences in their well-being and quality of life compared with a control group of healthy counterparts, although  An analysis of the most recent literature presents conflicting results on studies investigating psychological well-being in adolescent and young adult (AYA) cancer survivors.Some studies, in fact, showed that the quality of life perceived by cancer survivors was good for most of them . In a grIn fact, there are many studies that emphasized the positive consequences on psychological well-being of having childhood cancer, especially highlighting the perceived benefits and personal growth that hospitalization experience could offer during adolescence , also inA second line of studies has a more “pessimistic” view of the psychosocial well-being of these childhood cancer survivors, reporting a preponderance of negative outcomes related to the disease.Although many surviving patients reported high levels of perceived well-being and satisfaction with their lives, in some situations there were difficulties in accepting and coping with the experience of illness. To confirm these results, the research of In the study of An interesting fact, that emerged from studies on quality of life, was linked to age at the time of diagnosis: those who were older at the time of diagnosis later reported more depressive symptoms and higher levels of stress , while yN = 167) with a control group of peers (N = 170) who had never experienced hospitalization, highlighted how survivors perceived themselves as less competent than healthy counterparts in terms of health knowledge: in particular, with respect to their perception of health, with respect to the cognitive skills related to the health topic, and the autonomy they were able to gain from parents. These results could be explained by the negative impact that anticancer treatments and prolonged hospitalization had on cognitive abilities  and on ideas about the future of cancer survivors, who experienced it as more uncertain.Another study  comparinIn a study on the frequency of absences and the school performance of survivors with respect to the perceived quality of life, it emerged that only the perception of one’s physical functioning  was linked to worse school performance and more frequent absences from school. In fact, these patients declared that they feel more fatigued even when performing daily activities related to domestic tasks or free time . FurtherA recent comprehensive population-based study on long-term survivors of AYA cancer  evidenceThe literature highlighted how, at present, the results of studies on the quality of life of patients who survived cancer were contradictory, especially if AYA cancer survivors underwent hematopoietic stem cell transplantation (HSCT) . It was There is a lack of studies on the life perceptions and hopes in AYA cancer survivors and also on their cognitive functioning perceptions that could be independent from their real academic performance.In Italy there are limited studies conducted on this topic and that adopted control groups of healthy peers. To the best of our knowledge, there is only one Italian study  aimed toThe first group of hypotheses aims to determine if there are significant differences in well-being, life satisfaction, and cognitive functioning in AYA cancer survivors based on sociodemographic and disease parameters. We expected a lower well-being and life satisfaction in females, in older adolescents, those with fewer years off therapy, and experience of stem cell transplantation.The second group of hypotheses aims to verify whether there are statistically significant differences between the two groups in terms of psychological well-being, life perceptions, cognitive functioning and higher educational level obtained. Based on the existing literature, we expected to find a similar trend in the two groups for psychological well-being and life perceptions. Regarding achieving higher educational qualifications and cognitive functioning perceptions, we hypothesized a worse trend for the AYA cancer survivors.All eligible survivors who attended the Pediatric Hematology-Oncology Clinic of the University of Padua in the period 2015–19 were asked to participate in this project. Eligibility criteria included being treated for cancer before the age of 18, at least 5 years having passed since the last day of therapy, and being currently 15–25 years old. We excluded survivors treated for central nervous system tumors, those with learning or sensory problems or genetic syndromes, and those who were unable to complete the questionnaires independently.n = 205) met the following eligibility criteria: no history of life-threatening or chronic illness or injury and absence of learning or sensory problems and other pathological aspects. The healthy peers in the control group of were enrolled in secondary schools, youth groups, and university faculties in the same region as the patients .The participants in the control group , date of stopping therapy, years from stop therapy, relapses (yes/no and when) and surgical intervention (yes/no and when).Most of the instruments used for this investigation were derived from the Childhood Cancer Survivor Study (CCSS), a cohort of 27 centers in the United States and Canada that assembled survivor samples that were sufficiently large and diverse enough to allow investigators to investigate delayed effects of treatment.Participants had to evaluate, using a 1–10-point scale, the quality of their current life (Current life score), the quality of their life 5 years before their disease (Past life score), and how satisfied their life will be in the future (5 years after the child’s diagnosis) (Future life score). There were no cut-offs available that could be used to interpret the scores, but the scale could be easily interpreted using the following rule: an insufficient score was identified in the range 1–5; a sufficient score corresponded to 6–7; and a good score was 8–10. With this instrument, we could obtain information about individual perception of the past, the present, and the future. It had been administered to 118 Italian mothers of patients with cancer, demonstrating good global internal consistency  .The Brief Symptom Inventory 18 (BSI-18) consisted of 18 items grouped into three dimensions of six items, serving as a screening for depression, somatization, and anxiety. Respondents were asked to comment on how they felt in the last 7 days, and each item was rated on a 5-point Likert scale from 0  to 4 (extremely) . BSI-18 This is a 25-item questionnaire, used in another Italian study  that invEach participant filled out a sociodemographic questionnaire with questions about their highest year of schooling, their mother’s and father’s education, their perceived economic situation, their type of home situation, their romantic relationship, and their type of employment.t-test. We ran preliminary Pearson bivariate correlations and hierarchical regression analyses to find the possible significant associations/predictions between the examined variables. Statistical significance was evaluated at the nominal level of p = 0.05, with adjustments for multiple comparisons, after controlling the normal distribution of the test scores.A chi-squared test in crosstabs was used to estimate the possible sociodemographic differences between the two samples and to better understand the comparability of the samples. The two groups were matched according to gender and age, and a file was created with the matched clinic and control pairs. Descriptive measures of central tendency and variability were calculated for all relevant variables and comparisons were made between the two groups. Inferential comparisons were made between cancer survivors and control samples using a paired sample Altogether, 230 of the 325 eligible survivors were informed about the study and contacted by telephone, prior to a follow-up visit. The 95 eligible survivors who the researchers did not reach in the study had changed phone number, moved from their original residential location, had no check-ups during the research period, or had no more follow-ups in the clinic. Informed consent and completed questionnaires were received from 222 individuals (response rate = 96.5%). We have no data from the eight patients who refused to participate, so any comparison between the two groups was not possible. Of these 222 survivors, 205 were matched with participants in the control group. All patients were Caucasian with a mean age of 18.96 (SD = 3.08). We matched only 205 patients with the control group because only 205 patient–healthy peer pairs with the same gender and year of birth were possible. Comparative analyses of the different areas measured by the questionnaires used in the study were carried out on the final sample made up of 205 AYA out-of-therapy and healthy peer pairs. AYAs were paired considering gender and current age: It was possible to form 79 pairs of women and 126 pairs of men, whose average age was 18.96 years (SD = 3.08).p = 0.0001]  = 29.939; p = 0.02]. As can be seen from Regarding the family characteristics of the two groups , they art(202) = −2.51; p = 0.01; d = 0.43; CI 95%: −0.29/−0.12] of the Problem Scale questionnaire in which women  scored higher than men . This indicated that women have more mood-related problems, which limited them in managing daily problems.There were no statistically significant gender differences compared to the other variables in the scores obtained in the BSI-18 and Ladder of Life instruments. A statistically significant difference appeared on the mood subscale  , the means that were statistically significant in comparison between the two groups are the following:From the analyses carried out (–t(204) = −3.410; p = 0.001], for which the highest scores were detected for the control group  compared to the group out-of-therapy ;Difficulty in solving general problems , in which the control group  scored higher than the group of Recovered young people ;Disorganization  for which higher scores are recorded for the control group  compared to off-therapy group ;Difficulty concentrating  in which the non-therapy group  scored lower than the control group .Memory difficulty [The main purposes of this study were to investigate the psychological well-being, cognitive problems, and life perceptions of AYA childhood cancer survivors, and to identify the illness or sociodemographic factors associated with these outcomes.We intended to compare the self-reported quality of life and experiences between survivors and matched controls. The main findings of this study are: (1) the lower educational attainment reported by AYA cancer survivors and by their parents comparing with healthy peers, even if recovered patients recognized less cognitive problems; (2) a good current and future quality of life perceptions in AYA cancer survivors compared with healthy peers, even if they reported a worse quality of life in the 5 years before the current time; (3) a good psychological well-being in recovered patients comparable with that of healthy peers; (4) the identification of risk factors for cognitive and psychological difficulties such as female gender, experience of HSCT, less years off therapy.Cancer survivors had significantly lower educational attainment than controls. Our results were in line with the international literature, according to which a large proportion of patients out of therapy tended to terminate their studies earlier than their healthy pairs . The difHowever, regarding cognitive functioning, AYA in the out-of-therapy group surprisingly perceived themselves in a more positive light, in both domains, than their peers in the control group. Higher scores corresponded to more cognitive problems. These findings did not support our original hypothesis which presumed that survivors of cancer might perceive more cognitive problems than peers. In fact, the collected data showed that they perceived themselves better than the adolescents and young adults in the control group. On the one hand, compared to healthy pairs, they declared that they have less cognitive difficulties, specifically in terms of concentration and memory, and related to mental disorganization. These data could be explained, in part, by considering the results that emerged from the comparison of the sociodemographic variables of the two groups. The out-of-therapy group had a lower educational qualification than the control group: among survivors, fewer young people had a university degree and more were already in full-time jobs. Perceiving oneself as having less difficulty in cognitive functioning could perhaps be explained by the fact that the AYA cancer survivors, whose studies had been interrupted encountered fewer cognitive problems compared to their peers in the control group, who were more committed in their education and, consequently, more concerned about this area. Another possible confirmation of what has been said so far comes from the results of the analysis of the sociodemographic variables of the families of the two groups. Parental couple of the off-therapy group had lower educational attainment than that of the control group. Probably this variable could also have influenced the choice to stop studies earlier in the young survivors, choosing to follow the parental model.A further explanation could be due to the fact that the tools used were self-report questionnaires that detect not so much the actual cognitive abilities, but the personal perception that one has of them. It is possible that as a result of the difficult past, cancer survivors out of therapy were led to see themselves in a more positive light, sometimes overestimating their skills.The presence of significant differences between the two groups could be expected: Life perception could be worse in the AYA cancer survivors’ group due to the possible long-term consequences of the disease, which is particularly burdensome. However, a good current life perception was shown in the clinic group despite the past traumatic experiences in childhood.Perhaps, it was possible to advance the hypothesis that these cancer survivors continually compare their current state of health with their difficult past, so much so that they recognized a clear improvement over past years. For this reason, they tended to declare themselves satisfied with their life and cognitive functioning, even overestimating themselves. These results are in line with some studies conducted internationally , accordiConfirming the consistency of these results, a significant difference emerged between the two groups in the area of satisfaction with the last five-years of life. Patients out of therapy declared themselves less satisfied when looking back on past experiences than healthy counterparts. These results were likely to be in line with the painful experience of illness experienced by the young people out of therapy in their past, which probably marked them compared to their peers who had never experienced with this traumatic past.In fact, this particular group of adolescents in the past had faced challenges that left them very debilitated, and this is undoubtedly a differentiating element.However, despite the memory of the disease still present, these AYA probably aspired to look at their present and future with positivity. Our data seemed to go more in the direction of other research , accordiRegarding mental health status, in some studies a more negative profile emerged in AYA childhood cancer survivors, who declared themselves more tired in their cognitive tasks and as having self-esteem difficulties , having However, the results obtained from the comparison between the two samples of the present research were encouraging and not in line with that part of the literature that described AYA cancer survivors as less satisfied with their lives and as having more limitations than their healthy counterparts.From the point of view of psychological functioning, no significant differences emerged between the two groups that do not perceive themselves as different with respect to anxiety levels, physical problems, and the presence of possible depressive symptoms. A similar result was also obtained in preadolescents and adolescents during the acute therapy phase .Both groups were equally satisfied with their current and future life perceptions: these data were comforting since it would seem that the history of illness, undoubtedly painful and difficult to process, had not left negative marks on the lives of these young people who were preparing to face their future with optimism.Some studies highlighted the presence of gender differences among young people out of therapy in terms of perception of their health. In particular, recovered women report higher depressive and emotional symptoms . Our resWorse perceptions of life in the precedent 5 years were influenced by fewer years off therapy and the presence of hematopoietic stem cell transplantation. All these disease parameters could be identified as risk factors in determining negative life perception during the treatment period.This study has some merits, but also some limitations.We would like to highlight a few strengths of this study. First, we included age- and sex- matched peers as the comparative group. Both survivors and peers were asked if they had any previous hospitalization due to a serious illness before participating in the study. Second, the size and the relative homogeneity of the sample of who participated in the research were really good. Even when controlled for, the medical variables appear to have a limited association with aspects related to the psychosocial well-being of recovered patients and adolescents. Third, both groups received the same complete set of questionnaires that investigated the concept of psychological well-being and life perceptions in a multidimensional way, making it possible to develop complex health profiles.The study has also some limitations. First, our obtained results were not always homogeneous and coherent with the literature on this topic. Probably, this non-homogeneity could be explained by the fact that, very often, in cancer studies is not usual to find a distinction between different types of cancer in pediatric age, or because uneven control groups were used  that did not always reflect the socio-demographic characteristics of AYA childhood cancer survivors. Second, the fact that the data were collected exclusively in a region of Northern Italy makes it difficult to generalize the data to the entire national context, due to social and environmental variables that could significantly affect the results collected. Third, the exclusive use of self-report questionnaires allows the rapid collection of a large quantity of information, but which risks being negatively influenced by some variables that are difficult to control, such as social desirability, with the result that collected data do not always reflect reality.Highlighting the most problematic areas could help health professionals to propose psychological and/or psychotherapeutic interventions to those patients and their families found to be most at risk and to those who explicitly request it. For example, a clinical suggestion could be to strengthen the schooling activities during the cancer treatment and in the off-therapy time to improve AYA cancer survivors’ educational attainment. It could be useful also to set up cognitive and psychological interventions especially for women, or for those that had a HSCT experience and that were nearer to the stop therapy time. The worse quality of life perceptions related to the experience of the cancer disease could be ameliorated by adopting more recreational, social and educative activities for children and adolescents during the cancer therapies.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 Hospital of Padua Committee. The patients/participants provided their written informed consent to participate in this study.MT and SB: conceptualization and methodology. MT and LT: formal analysis. MT: investigation, data curation, and writing—original draft preparation. AB: resources. LT and SB: writing—review and editing. MP and AB: visualization. SB and MP: supervision. SB: project administration. All authors have read and agreed to the published version of the manuscript.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.


Wastewater is one of the most common by-products of almost every industrial process. Treatment of wastewater alone, before disposal, necessitates an excess of energy. Environmental concerns over the use of fossil fuels as a source of energy have prompted a surge in demand for alternative energy sources and the development of sophisticated procedures to extract energy from unconventional sources. Treatment of municipal and industrial wastewater alone accounts for about 3% of global electricity use while the amount of energy embedded in the waste is at least 2–4 times greater than the energy required to treat the same effluent. The microbial electrolysis cell (MEC) is one of the most efficient technologies for waste-to-product conversion that uses electrochemically active bacteria to convert organic matter into hydrogen or a variety of by-products without polluting the environment. This paper highlights existing obstacles and future potential in the integration of Microbial Electrolysis Cell with other processes like anaerobic digestion coupled system, anaerobic membrane bioreactor and thermoelectric micro converter.  The different sources of wastewater can be domestic wastewater, landfill wastewater, industrial wastewater, refinery wastewater, livestock, and dairy wastewater to name a few . Electrochemical techniques and anaerobic digestion can be merged for improved productivity, with stillage from a certain process utilized as feedstock in the earlier and energy retrieved from the earlier utilized in the latter . Recently, the scaling-up of MECs from bench to pilot-scale for production of hydrogen was described. Even though the electric energy recovery was greater than 70%, the Coulomb efficiency and the rate of hydrogen were much lower than the maximum value reported in lab-scale research, emphasizing the need for future tuning. Additionally, several MEC applications, like pollutant removal, chemical synthesis, and recovery of metal, have yet to be scaled up from a lab scale ,130.8.2Scaling up raises two important economic challenges: the materials of the electrode and reactor design. Efforts should be aimed toward the development of low-cost reactors capable of competing with a variety of different energy-generating and wastewater-treatment technologies. This, in turn, will have the additional benefit of supporting the phenomena of cost reduction with increasing manufacturing units, thus enhancing the practicability of this technology and favoring the development of more efficient MEC reactors. Cost-effective anode materials capable of efficient electron transfer from bacteria to the electrode in Microbial Fuel Cells, such as carbon fibre brush or activated carbon, might be a suitable alternative for anodes of MECs. Similarly, as a cathode catalyst, biocathode may be a promising alternative to noble metals. This is due to its low cost, excellent stability, and ecologically sound qualities. However, the effectiveness of the biocathode in pilot-scale activity remains unknown ,131.8.3Process control and monitoring is another significant area that has received little attention but it does have the ability to propel this technique forward on its path to practical use . To atta9.Microbial Electrolysis Cells show great potential in not only reducing the pollution quotient in the wastewater stream of the industry but also helping in aiding in the resource recovery from the industrial wastewater. This system not only helps in reducing biodegradable matter in the stream but also helps in generating electricity and hydrogen which is used as a clean fuel due to its nonpolluting properties. Due to its increased demand globally, the use of MEC has proved to be an efficient source of hydrogen generation. This system is energy positive and carbon negative and its integration with traditional technologies leads to higher output and refined processes. However, there are certain shortcomings in this process as well like the competition amongst the microbes, structural shortcomings, etc. and an extensive study and research needs to be directed in this regard to increase the efficiency of the process and maximize the yield produced in the process. Efforts to enhance reactor design and substrate selection can be done to maximize the efficiency of the setup. The MEC technology can prove to be a great asset for energy generation and resource recovery and can significantly help in reducing the dependence on conventional sources of energy like fossil fuels which are also polluting in nature. This technology can therefore pave a new way for energy generation and help meet the global energy requirement.