To report our recommended methodology for extracting and then confirming research uncertainties – areas where research has failed to answer a research question – derived from previously published literature during a broad scope Priority Setting Partnership (PSP) with the James Lind Alliance (JLA).This process was completed in the UK as part of the PSP for “Common Conditions Affecting the Hand and Wrist”, comprising of health professionals, patients and carers and reports the data (uncertainty) extraction phase of this. The PSP followed the robust methodology dictated by the JLA and sought to identify knowledge gaps, termed “uncertainties” by the JLA. Published Cochrane Systematic Reviews, Guidelines and Protocols, NICE  Guidelines, and SIGN (Scottish Intercollegiate Guidelines Network) Guidelines were screened for documented “uncertainties”. A robust method of screening, internally verifying and then checking uncertainties was adopted. This included independent screening and data extraction by multiple researchers and use of a PRISMA flowchart, alongside steering group consensus processes.Selection of research uncertainties was guided by the scope of the Common Conditions Affecting the Hand and Wrist PSP which focused on “common” hand conditions routinely treated by hand specialists, including hand surgeons and hand therapists limited to identifying questions concerning the results of intervention, and not the basic science or epidemiology behind disease.Of the 2358 records identified  which entered the screening process, 186 records were presented to the PSP steering group for eligibility assessment; 79 were deemed within scope and included for the purpose of research uncertainty extraction . These yielded 89 research uncertainties, which were compared to the stakeholder survey, and added to the longlist where necessary; before derived uncertainties were checked against non-Cochrane published systematic reviews.In carrying out this work, beyond reporting on output of the Common Conditions Affecting the Hand and Wrist PSP, we detail the methodology and processes we hope can inform and facilitate the work of future PSPs and other evidence reviews, especially those with a broader scope beyond a single disease or condition.The online version contains supplementary material available at 10.1186/s12874-022-01777-5. This is a novel and rigorous approach to uncertainty extraction and verification in the setting of a James Lind Alliance Priority Setting Partnership.The detailed methodology provides transparency regarding the extraction and verification of uncertainties.The uncertainty extraction and verification relied upon the HandSRev database – similar resources may not be available for other Priority Setting Partnerships.The James Lind Alliance (JLA)  is a nonIn 2017, The Common Conditions Affecting the Hand and Wrist PSP, funded by the British Society for Surgery of the Hand (BSSH) and managed by a multi-centre, multidisciplinary steering group, reported the top prioritised research uncertainties to map out a framework for future clinical research in common hand conditions. The broader process and results of this PSP are published separately .The current article focuses on principles guiding the identification and verification of uncertainties from the published literature. These were considered in the Partnership longlist alongside the uncertainties directly submitted through the stakeholder survey. Collating these published uncertainties was especially challenging given the huge scope of hand surgery, stretching across both plastic and orthopaedic surgery parent specialties and a wide range of conditions and injuries.Whilst the methods of collating stakeholder uncertainties  are well defined, a reproducible methodology for extracting uncertainties from the published literature, and for the verification of submitted uncertainties, has not yet been proposed by the JLA . The curAs the JLA PSP methodology becomes widely adopted, an increasing number of partnerships focus on broader research areas –9. A lacThis study reports the processes of identifying potential research uncertainties in the published literature in guidelines and Cochrane Reviews, and verifying uncertainties for the Common Conditions Affecting the Hand and Wrist Priority Setting Partnership. In doing so, it aims to formalise a robust and reproducible method of identifying and confirming research priority uncertainties in such a setting.The full PSP methodology for collating submitted research questions is detailed in the full PSP output and executive report .The PSP Steering Group (SG) included five patient representatives with personal experience of treatment for common hand surgery conditions, who helped shape the process throughout, with emphasis on defining the scope and informing the consensus.Selection of research uncertainties for the prioritisation process was guided by the scope of the Common Conditions Affecting the Hand and Wrist PSP, which is detailed in the final report . In summCochrane Systematic ReviewsCochrane Systematic Review ProtocolsNICE  Guidelines andSIGN (Scottish Intercollegiate Guidelines Network) Guidelines.The PSP Steering Group (SG) specified that existing uncertainties in the published literature would be identified via the following sources:http://www.cochranelibrary.com/), using a comprehensive search strategy for hand surgery conditions and terms (developed at the Centre for Evidence Based Hand Surgery at the University of Nottingham) , again using a comprehensive search strategy relevant to hand surgery conditions and terms. The limitation to the length of the search strategy that could be used in NHS Evidence meant that the search had to be split into four separate searches that were run separately. For each search the filter for “Guidance” was applied, combined successively with “National Institute for Health and Care Excellence – NICE” and “Scottish Intercollegiate Guidelines Network – SIGN” from the “Source” option. In the case of guidelines on the same topic generated by both NICE and SIGN, each was considered independently for uncertainly extraction. Withdrawn guidelines were excluded.NICE and SIGN national guidelines relevant to the scope of the PSP were identified using the NHS Evidence search engine (The search date was 12 September 2016. There were no date restrictions applied. Results were combined and duplicates removed.Two members of the SG (AK/DG) independently screened search results first on title and abstract, and where necessary using full text, to identify all guidelines and Cochrane Reviews potentially relevant to conditions affecting the hand and wrist. Reviews/Guidelines focussing on non-interventional, diagnostic or basic science concepts were excluded in line the JLA PSP inclusion criteria. The identified references were collated and grouped into broad categories and presented to the SG for screening and ratification. The SG ratified, via consensus, references as relevant to the scope of the PSP, which pertains to “common conditions affecting the hand and wrist”. Where disagreement existed between steering group members, this was resolved via a two-stage consensus process. The first stage consisted of each of eleven non-lay SG members independently screening identified relevant records for eligibility. The second involved discussion between all SG members for contentious reports in a face-to-face meeting. Consensus for each stage was achieved when percentage agreement between SG members was 75% or more . The proThe Cochrane Reviews, Cochrane Review protocols and NICE and SIGN guidelines determined to be within scope of the PSP by the above process were then distributed amongst the clinical members of the SG for extraction of research uncertainties. Members worked in pairs. The process was piloted, using two example reviews and two reviewers. Reviewers were tasked with forming a research uncertainty from any research recommendations or demonstrable gaps in knowledge highlighted in the identified documents.In identifying uncertainties from Cochrane Reviews, emphasis was placed on the “Authors’ conclusions”, including sections on “Implications for practice” and “Implications for research”. To avoid over-interpretation of the data and encourage transparency, reviewers were asked to focus, wherever possible, on explicit statements of treatment uncertainties and research needs.“Research is required to determine the duration of benefit from local corticosteroid injection and to identify candidates for treatment based on severity and duration of symptoms.”“Local corticosteroid injection should also be compared to, and combined with, other non-surgical and even surgical interventions to determine the optimum management of carpal tunnel syndrome.”Each identified uncertainty was accompanied by an explicit statement(s), extracted verbatim from the text, of whether or not there was particular evidence for a research question (review) and/or if the uncertainty was identified by a guideline group as a research priority (guidelines). Examples of such statements are:Reviewers were advised to look out for phrases such as “there is insufficient evidence”, “the evidence is insufficient”, “there is no evidence that”, etc., as possible clues to uncertainties. Care was taken to distinguish cases where a series of good quality RCTs had shown little or no evidence of the efficacy of a treatment (which implies a certainty of lack of effectiveness rather than an uncertainty about effectiveness) from cases where reliable RCTs were lacking (which implies an uncertainty).Each pair of reviewers identified potential areas of uncertainty independently before discussing their choices as a pair. Once agreement was achieved, a final uncertainty was submitted to the SG. If agreement was not reached, then all versions of the uncertainty were submitted and ratified separately by the SG. In compiling uncertainties, the PICO model was considered whenever applicable, to construct clinical questions: Patient, Population or Problem; Intervention; Comparison; Outcome .Where apparent from the systematic review or guidelines, elements of PICO such as specific patient groups or comparator treatments were built into the uncertainties. For example, a systematic review may have found no evidence concerning effectiveness of a treatment in a specific group of patients or in a particular condition. In these cases, specific uncertainties to match these PICO criteria would be appropriate.For ease, in the title field for each uncertainty, the Intervention (I) was mentioned first, followed by the Population/Patient (IP); for example, Surgery (I) in adults with carpal tunnel syndrome (P). If the uncertainty included comparators and/or specified outcomes, the Intervention was mentioned first, followed by the Comparator (C), followed by the Population/Patient (ICP); for example, surgery (I) compared with splints (C) in adults with carpal tunnel syndrome (P). If outcomes were specified in the uncertainty, these were included [ICPO].Uncertainties extracted by each pair of reviewers were recorded in a table proforma, compatible with the general format of the standard JLA data management Excel spreadsheet . GeneratResearch uncertainty verification was performed by the non-lay members of the SG, working in pairs.The aim of verification was not to repeat the work of Cochrane reviewers or guideline developers by re-assessing the quality of individual studies included in each record. However, to increase transparency, SG members were asked to review the results section and make a judgement as to why each uncertainty constituted a persistent research gap by selecting one of five options (A-E) as detailed in Table As most of the included Cochrane Reviews and guidelines were potentially out of date (more than 3 years from publication), each identified uncertainty was further checked against the preceding five years (2011 -2016) of published non-Cochrane systematic reviews, as identified through the HandSRev database . HandSReThe final list of uncertainties derived from the published literature was ratified by the SG.Results of the screening and two-stage consensus process are illustrated in the PRISMA flow chart in Fig. The results of the uncertainty extraction process for this PSP are presented in Supplemental file Cross-referencing allowed assimilation of 81 uncertainties into those already generated by the stakeholder survey. Thus, an additional of 8 uncertainties were added. Two uncertainties covered areas of hand surgery that were novel in the PSP process but extremely common in clinical practice: Local anaesthetic choice, and the treatment of pin site infection. The other uncertainties covered diagnoses that had already been encountered during the PSP but different aspects of these diagnoses, such as the best method for detection of an occult scaphoid fracture, and adjuvant techniques in improving survival following amputation , making its breadth extremely broad. The scope included a very wide range of conditions and intervention types. This made the identification and extraction of uncertainties from the relevant published resources in a systematic and reproducible way challenging.Until recently, most JLA PSPs have focused on a single disease —see While not all PSPs extract uncertainties from published literature and guidelines, all are required to verify that questions submitted via surveys are indeed true uncertainties. This verification process requires the findings from up-to-date systematic reviews, where available. It is hoped that the process described here will help others do this in a more structured, systematic and reproducible way. With such a wide range of conditions and procedures to cover, it is key to have comprehensive search strategies that will find all relevant evidence. The PSP was able to draw on the exhaustive PubMed search strategy developed by the Centre for Evidence Based Hand Surgery for the HandSRev database of systematic reviews relevant to hand surgery practice . This stAs Cochrane reviews and consensus/evidence-based guidelines require methodological rigour and thus take a long time to produce, an unintended consequence is that they can become superseded as new evidence appears. In this work, the HandSRev database , was alshttps://www.epistemonikos.org/), which is a free online database of systematic reviews. Epistemonikos is multilingual database of health evidence which regularly screens multiple electronic databases and other resources, resulting in the largest source of systematic reviews relevant for health-decision making, maintained by a non-profit organisation founded in 2009 [A potential alternative source for PSPs identifying and verifying uncertainties has emerged with the advent of the Epistemonikos database ( in 2009 . HoweverIn carrying out this work, beyond reporting on the details of the output of the Common Conditions Affecting the Hand and Wrist PSP , we deveThe entirety of this work involved patients throughout, in line with the James Lind Alliance objectives.Additional file 1: Supplemental file 1. JLA Cochrane Library search strategy.Additional file 2: Supplementary file 2. Included records, deemed within scope and submitted for research uncertainty extraction.Additional file 3. Low molecular weight heparin for prevention of microvascular occlusion in digital replantation.Additional file 4. Uncertainty long list.


Experts agree that the promotion of  health literacy should be an integral part of the school curriculum. However, promoting  health literacy within the German school system is difficult because  health education is not a mandatory school subject in all the German states. Therefore, experts suggest that  health literacy could be addressed as part of the mandatory framework for digital education and digital literacy in schools developed by the German Conference on Education Ministries and Cultural Affairs (Kultusministerkonferenz).The goal of this study was to evaluate a newly developed e-learning course that was designed to improve  health literacy in school-age children and concurrently to teach skills specified in the mandatory framework for digital education and digital literacy in schools. It was hypothesized that participants’ health literacy and digital health literacy levels would be higher after completing the e-learning course than they were before doing the course. Furthermore, it was hypothesized that after completing the e-learning course, participants’ subjective and objective knowledge in the domain of  health literacy would be higher than it was before doing the course.The pre-post measurement study was conducted online. After participants (N=323) gave their informed consent to participate in the study, they provided demographic information and answered all measures (premeasurement). Following this, participants had 7 days to complete the e-learning course. After finishing the e-learning course, participants answered all the measures again (postmeasurement).t tests (1-sided) were conducted. After completing the e-learning course, participants showed higher health literacy levels. Specifically, they showed higher competency levels in the domains of theoretical knowledge , practical knowledge , critical thinking , self-awareness , and citizenship . Furthermore, participants achieved higher digital health literacy levels. Specifically, they achieved higher competency levels in the domains of information searching , evaluating reliability , and determining relevance . Moreover, participants demonstrated higher subjective  and objective knowledge  in the domain of  health literacy.To test the hypotheses, Bayesian paired samples The newly designed e-learning course provides an easy way for schools and teachers from all German states to integrate  health literacy education into their school curriculums and lessons. The evaluated course is especially attractive because it was designed to improve  health literacy and at the same time to teach skills specified in the mandatory framework for digital education and digital literacy in schools developed by the German Conference on Education Ministries and Cultural Affairs (Kultusministerkonferenz). Health literacy describes people’s ability to evaluate and apply health information in the context of disease prevention and health promotion . Health In Germany, health literacy has decreased since 2014 ,6. A repSuch results are unfortunate because teaching  health literacy to school-age children has the potential to improve various health outcomes later in life ,25. FurtIn line with these suggestions, the independent, nonprofit foundation Stiftung Gesundheitswissen developed the free e-learning platform Gesundweiser.de to teach  health literacy to school-age children. On the platform, visitors can receive information on the topic of  health literacy. Furthermore, they can take part in a free e-learning course. The course was designed to improve  health literacy and at the same time to teach skills specified in the mandatory framework for digital education and digital literacy in schools . Even thHypothesis 1: Participants’ health literacy levels will be higher after completing the e-learning course than they were before completing the e-learning course.Hypothesis 2: Participants’ digital health literacy levels will be higher after completing the e-learning course than they were before completing the e-learning course.Hypothesis 3: Participants’ subjective knowledge in the domain of  health literacy will be higher after completing the e-learning course than it was before completing the e-learning course.Hypothesis 4: Participants’ objective knowledge in the domain of  health literacy will be higher after completing the e-learning course than it was before completing the e-learning course.t tests; statistical test = means: differences between 2 dependent means [matched pairs]; type of power analysis = a priori: compute required sample size – given α, power, and effect size; tail(s)=1; effects size dz=0.2; α err prob=.05; power [1–β err prob]=0.95) =0.95) . To compBefore data collection, the study protocol was submitted to the ethics committee of the Berlin Medical Association (Eth-68/21). The ethics committee had no ethical or professional objections to the study protocol.Data collection took place between December 2021 and January 2022. The pre-post measurement study was conducted online using an online platform for data collection provided by a market research company (SPLENDID RESEARCH GmbH). Prior to the study, participants received detailed information about the context, purpose, and procedures of the study. Furthermore, they were informed that they could opt out of the study at any time. After participants gave their informed consent to participate in the study, they provided demographic information and answered all measures (premeasurement). Following this, participants had 7 days to complete the e-learning course. Because the course was not designed for a specific type of school and subject, it can be used in various contexts. Since the course is self-explanatory and no active supervision is required, it is especially suitable as a homework exercise that can be completed within a set amount of time. To simulate such a homework exercise, participants were given 7 days to complete the course. During this 7-day period, participants could use any device to complete the course and they could start and pause the course as often as they liked. Simulating a homework exercise by giving participants the opportunity to complete the course within 7 days has the advantage that it increases ecological validity. However, it also creates methodological disadvantages that will be discussed in the limitations section.Within the course, participant learned how they could evaluate health information on the internet. The provided material was created by a multiprofessional team, including health and e-learning specialists, and was derived from professional guidelines  . FurtherTo assess health literacy, the Health Literacy for School-Age Children Instrument was used ,40. ThisTo assess digital health literacy, 3 of the 7 subscales of the Digital Health Literacy Instrument were used ,20. The To assess subjective knowledge in the domain of  health literacy, participants indicated their agreement with 5 items ”. The items focused on content covered throughout the e-learning course. Participants rated all items on scales ranging from 1 (strongly disagree) to 6 (strongly agree). A total score was generated by calculating the mean.To assess objective knowledge in the domain of  health literacy, participants answered 15 multiple-choice questions, such as “What does the phrase ‘evidence-based’ mean?” with response options (1) reviewed by experts, (2) based on scientific evidence and proof, (3) based on personal views and experiences, and (4) rated as helpful by a certain number of users. The multiple-choice questions focused on content covered throughout the e-learning course. Depending on the multiple-choice question, 1 to 4 of the responses were correct. For each correctly answered multiple-choice question, participants received 1 point. A total score was generated by adding up all points . The original data set contains further variables that have not been described because they exceed the scope of this study.t tests (1-sided) were conducted with the following specifications: alternative hypothesis (measure 1 < measure 2), Bayes factor (BF10), test (student), missing values (exclude cases per dependent variable), and prior . These specifications imply that the results will report Bayes factors in favor of the alternative hypotheses (measure 1 < measure 2). Following a commonly used classification scheme, Bayes factors above 1 will be interpreted as anecdotal (1-3), moderate (3-10), strong (10-30), very strong (30-100), or extreme (>100) evidence for the alternative hypothesis compared to the null hypothesis in light of the observed data [For all analyses, the statistical software JASP, version 0.16.1 (University of Amsterdam), was used . To testved data . Bayes fved data . Furtherved data -44.A total of 340 participants completed the study; 17 participants were excluded from data analysis because of data collection problems or because they did not finish the e-learning course. Therefore, the final sample contained 323  participants from all German states with an average age of 17.88 (SD 1.22) years. –0=676,000; δ=–0.316), practical knowledge , critical thinking , self-awareness , and citizenship . The corresponding prior and posterior distribution plots, effect sizes, and Bayes factor robustness checks are shown in It was hypothesized that participants’ health literacy levels would be higher after completing the e-learning course than they were before completing the e-learning course. The results show extreme evidence for the hypothesis. After completing the e-learning course, participants reported higher competencies in the fields of theoretical knowledge , evaluating reliability , and determining relevance . The corresponding prior and posterior distribution plots, effect sizes, and Bayes factor robustness checks are shown in It was hypothesized that participants’ digital health literacy levels would be higher after completing the e-learning course than they were before completing the e-learning course. Depending on the measured domains, the results vary from anecdotal to extreme evidence for the hypothesis. After completing the e-learning course, participants reported higher competencies in the fields of information searching  for the hypothesis. The corresponding prior and posterior distribution plot, effect size, and Bayes factor robustness check are shown in It was hypothesized that participants’ subjective knowledge in the domain of  health literacy would be higher after completing the e-learning course than it was before completing the e-learning course. The results show extreme evidence  for the hypothesis. The corresponding prior and posterior distribution plot, effect size, and Bayes factor robustness check are shown in It was hypothesized that participants’ objective knowledge in the domain of  health literacy would be higher after completing the e-learning course than it was before completing the e-learning course. The results show extreme evidence  health literacy in school-age children. It was hypothesized that participants’ health literacy (hypothesis 1) and digital health literacy levels (hypothesis 2) would be higher after completing the e-learning course than they were before completing the e-learning course. Furthermore, it was hypothesized that participants’ subjective (hypothesis 3) and objective knowledge (hypothesis 4) in the domain of  health literacy would be higher after completing the e-learning course than it was before completing the e-learning course. The results support all 4 hypotheses. After completing the e-learning course, participants achieved higher health literacy levels. More specifically, they reached higher competency levels in the domains of theoretical knowledge, practical knowledge, critical thinking, self-awareness, and citizenship. Furthermore, participants achieved higher digital health literacy levels. More specifically, they reached higher competency levels in the domains of information searching, evaluating reliability, and determining relevance. Moreover, participants demonstrated higher subjective and objective knowledge in the domain of  health literacy after completing the e-learning course.There are several reasons why these results are encouraging, and 2 of them seem especially important. First, experts have long argued that  health literacy should be taught to school-age children -28. At tEven though the results of this study show that the e-learning course available in the e-learning platform Gesundweiser.de has the potential to promote  health literacy in school-age children, there are limitations to the generalizability of the results. Three limitations seem especially important. The first limitation concerns the age of the study participants. All study participants were aged 16 to 20 years. Because previous research has shown that age might influence the suggestibility to misinformation, source monitoring, and digital literacy, the results of this study may not be generalized to younger age groups -47. TherThe second limitation concerns the methodological approach that was chosen. This study employed a pre-post measurement study design. This means that study participants answered all measures both before and after completing the e-learning course. One of the main advantages of this methodological approach is that it can reduce random noise. In some circumstances, however, this methodological approach might reveal the aim of the study to the participants. After completing questionnaires about their  health literacy and answering knowledge questions about  health literacy, participants might have guessed that the study was designed to test whether the provided e-learning course has the potential to improve  health literacy. This, in turn, might have induced a demand effect that influenced participants’ evaluations and learning motivation . TherefoThe third limitation concerns the setting in which participants could complete the e-learning course. To simulate a homework exercise, participants were given 7 days to complete the course. During this 7-day period, participants could use any device to complete the course and they could start and pause the course as often as they liked. Simulating a homework exercise by giving participants the opportunity to complete the course within 7 days has the advantage that it increases ecological validity. However, it also creates methodological disadvantages. It cannot be guaranteed, for example, that participants completed the course without any help from parents or friends. Furthermore, learning results might be influenced by the number of times participants started and paused the course and by whether participants completed the optional modules. Following the principle of data parsimony, data collection focused on the variables that were most relevant for hypothesis testing and no data were collected regarding the number of times participants started and paused the course and whether participants completed the optional modules. To ensure that participants complete the course without any external help and to investigate the effects of completing the optional modules and pausing and restarting the course, future studies could repeat this study in a laboratory setting and control for the described variables.


It is of great concern to society that individuals can be vulnerable to problematic mobile phone use (PMPU). However, there are a few studies in the field evaluating associations between behavioral inhibition/activation systems (BIS/BAS) and PMPU, and the results have been inconsistent. This study aimed to explore the relationships between BIS/BAS and PMPU by network analysis.A total of 891 young adults participated in the study. BIS/BAS and PMPU were assessed by using the behavioral inhibition and activation systems scale and smartphone application-based addiction scale, respectively. The structure of the BIS/BAS-PMPU network was characterized using “strength,” “closeness” and “betweenness” as centrality indices. Edge-weight accuracy and centrality stability were tested using a bootstrap procedure.The network analysis showed that “mood modification,” “tolerance” and “withdrawal symptoms” had high centrality. In addition, the positive connection between BIS and “mood modification” or “tolerance” and between BAS-fun seeking and “mood modification” or “conflict” were also shown in the BIS/BAS-PMPU network.These findings shed light on the central and bridge components between the BIS/BAS and PMPU communities, providing new evidence relevant to potential mechanisms that account for how high-BIS or high-BAS individuals develop PMPU, and inspiring component-based PMPU prevention or interventions. Broadly, problematic mobile phone use (PMPU) refers to an inability to regulate individual proper use of the mobile phone, which eventually involves negative consequences in daily life . It sharPrevious studies have indicated that personality traits are associated with PMPU –13. The Drug and behavioral addiction seem to have many commonalities , 23. BasReinforcement sensitivity theory [RST ] attemptThe relationships between BIS/BAS and addiction have been supported by some evidence in the field of drug addiction. It was found that high reward  and low punishment sensitivity  were significantly related to drinking habits  KambouroWith the rapid growth of network technology, problematic internet use behavior is becoming prominent –36. ReseRecently, emerging studies have started to explore the relationships between BIS/BAS and PMPU. However, the number of relevant studies remains insufficient and the results have been mixed. To our knowledge, there are only four studies evaluating the relationship between BIS/BAS and PMPU. Kim et al.  found thAt present, these results are relatively confusing, which may be due to studies used different PMPU scales, and these different scales incorporated different symptoms of addiction. Thus, the BIS/BAS may be linked not only to PMPU, but also to the different symptoms of PMPU. In addition, many studies have not further analyzed the relationship between the dimensions of the BAS and PMPU, and therefore, the relationship between the BAS and PMPU have not been clarified.The method of network analysis involves presenting the characteristics and information of a system in interconnected network form. The system is composed of “nodes” and “edges” , 50. NodSome scholars have carried out research on PMPU by utilizing network analysis, with a focus on three aspects: the symptoms, associated comorbidities, and influencing factors of PMPU. First, regarding the symptoms of PMPU, Huang et al.  exploredPsychopathological network theory portrays mental disorders as causal systems of interacting symptoms . SymptomThrough the above literature review, we identified the following limitations in the current research on the relationships between BIS/BAS and PMPU: First, the results describing the relationship between BIS/BAS and PMPU have been mixed and further clarification is needed. Second, the relationship between BIS/BAS and specific addictive symptoms of PMPU have not been explored. Finally, many studies have used latent variables for these analyses, which ignore the network structure of the relationship between variables. To bridge these gaps, this study attempted to explore the relationship between BIS/BAS and PMPU by using network analysis. We posed the following research questions:R1: Which edges play the role of bridging the BIS/BAS community and PMPU community?R2: Which symptoms are central in the BIS/BAS-PMPU network?SD = 1.27; range: 16–24 years).The ethics of all procedures in the research were approved by the ethics committee of the authors' research institution. A total of 914 university students from two provinces in China participated in the study by utilizing convenience sampling from December 2019 to January 2020 (before the COVID-19 epidemic). The survey was conducted by using the WeChat-based Wenjuanxing program. All participants received instructions and were told that their participation was voluntary and they could withdraw from the study at any time for any reason. To encourage honest responses, the anonymity of the survey was emphasized. Participants who met the following criteria were included: (1) ability to understand Chinese; (2) consent to participate in the study; and (3) owned a mobile phone. We eliminated twenty-three participants who (1) completed the surveys, but indicated they did not respond at the appropriate times or (2) responded improperly or randomly on some of the essential study variables. The final sample was 891 students. Across the entire sample, 218 of the participants were men (24.47%), and 673 were women (75.53%); 485 were from rural areas (54.43%), and 406 were from urban areas (45.57%). The mean age of the participants was 19.09 years  is the most recently developed scale for assessing PMPU . The ChiThe BIS/BAS scale was utilized to assess sensitivity to punishment and rewards . The Chid and network analysis were conducted by using JASP (Jeffrey's Amazing Statistics Program). Edge-weight accuracy and centrality stability were tested by using R (Version 4.1.2).Descriptive statistics, Pearson correlations, and Cronbach's α were performed by using SPSS 25. Cohen's z-scores).A visualized network analysis was performed in the present study. A graphical LASSO [glasso ] estimatCS-coefficient), which was suggested to preferably be above 0.5 and should not be below 0.25 for interpretability and stability . Bootstrapped 95% confidence intervals were utilized for estimating the accuracy of edge-weight  and fewer overlaps indicated higher stability/accuracy. The stability of node attributes was estimated by using the case-dropping bootstrap procedure. If most samples can be excluded from the dataset without observing significant changes in the centrality index of the node, the network is considered to be stable. Centrality stability is represented graphically and quantified by calculating the correlation stability coefficient  and BAS-F  scores. Similarly, the six components of PMPU were all significantly positively associated with BIS and BAS-F scores and the correlations among them ranged from small to medium. In addition, BAS-R scores were significantly positively associated with salience  and mood modification  scores.Descriptive statistics and correlation analyses for the study variables are shown in r = 0.34 for each). In addition, nodes BIS and BAS-F had positive associations with mood modification and tolerance scores. In addition, edge weights' accuracy was relatively high and reliable based on the results of the bootstrapped network analysis , followed by the connection between node BIS4 (“I feel pretty worried or upset when I think or know somebody is angry at me”) and node PMPU4 . In addition, edge weights' accuracy was relatively accurate and reliable based on the results of the bootstrapped network analysis , indicating that 67% of the sample could be dropped without the network structure changing a significant extent compared to the original structure (CS-coefficient ≥ 0.5).tructure . The cenCS-coefficient for strength = 0.75), indicating that 75% of the sample could be dropped without the network structure changing to a significant extent compared to the original structure (CS-coefficient ≥ 0.5).In the item-level network, the item PMPU3 [“Preoccupying myself with my smartphone is a way of changing my mood ”] had higher levels of betweenness, closeness, and strength  in PMPU. Item BIS4 (“I feel pretty worried or upset when I think or know somebody is angry at me”) had a higher level of strength (strength = 0.70) in BIS, and item BIS5 (“I feel worried when I think I have done poorly at something. I have very few fears compared to my friends”) had higher levels of betweenness and closeness  in BIS. Item BAS-R5  had higher levels of betweenness and closeness  in BAS-R, and item BAS-R2  had a higher level of strength (strength = 1.96) in BAS-R. Item BAS-D3  had higher levels of betweenness and closeness  in BAS-D, and item BAS-D1  had a higher level of strength (strength = 1.03) in BAS-D. Moreover, item BAS-F3  had higher levels of betweenness, closeness, and strength  in BAS-F . We alsotructure . The cenTo the best of our knowledge, this is the first study to use network analysis to explore relationships between BIS/BAS and PMPU. First, this study clarified which specific symptoms of PMPU are related to BIS/BAS and identified which dimension of the BAS is related to PMPU. Second, this study also revealed core symptoms of PMPU among the components of the BIS/BAS-PMPU network. The network perspective adds novel characteristics about which symptoms of PMPU are most related to BIS/BAS and how specific symptoms interconnect with each other in the specific network, which may help in the better design of precise and effective interventions.The domain-level network showed connections between mood modification, tolerance, and BIS. The item-level network further revealed a more detailed relationship, in which BIS4 (“I feel pretty worried or upset when I think or know somebody is angry at me”) was connected with PMPU4 . These findings are consistent with some previous studies that reported that individuals with high BIS are more likely to be addicted to mobile phones , 48.The results indicated that individuals who were sensitive to punishment or termination of rewards were susceptible to become addicted to mobile phone. This may be because they are more prone to develop specific addictive symptoms such as mood modification and tolerance. A possible explanation for these results may be that those who score highly on BIS would be more likely to experience negative emotions , and atThe current study found that BAS-F has a relatively strong connection with mood modification and conflict in the domain-level network. The item-level network further revealed a more detailed relationship, in which BAS-F4 (“I often act on the spur of the moment”) and PMPU2 (“Conflicts have arisen between me and my family (or friends) because of my smartphone use”) had a positive connection. These findings are in line with the findings that fun seeking has been reported to be the only BAS subscale associated with IA , 38–40.The results indicated that individuals who were sensitive to rewards or termination of punishment, especially the desire for novel rewarding experiences , more easily develop addictive symptoms such as mood modification and conflict. A possible explanation for the association between BAS-F and mood modification might be that BAS-F is associated with immediate gratification  and actiThe positive connection between BAS-F and conflict may partly be explained by the impulsive characteristics of BAS-F individuals. Gray  suggesteA homeostatic network of mental disorders  might be developed by interactions of symptoms that are no longer independent of each other. Among such homeostatic networks, central symptoms are more likely to activate other symptoms. Thus, central symptoms are thought to play a major role in causing the onset and/or maintenance of mental disorders . Our reOur results are different from Huang et al.,  and 52)52), who The present study has several limitations that should be considered. One of the main limitations is the use of cross-sectional data and presentation of a static network, which unfortunately fails to provide dynamic information and causal relationships between variables. Therefore, it is important to explore the dynamic development of PMPU symptoms caused by BIS/BAS based on time series data. When a node in the symptom network is activated by BIS/BAS, it may further activate other symptoms “adjacent” to it in the network.Moreover, the network analysis in this study incorporated only personality variables, ignoring the role of environment, cognition, and emotion [which are thought to play an important role in the development and maintenance of IA ], and maThird, after the update of RST , differeLast, this study did not specifically examine the content of mobile phone use. Previous studies have called for PMPU to investigate the specific contents of mobile phone use , which wThe aforementioned findings contribute to PMPU research both theoretically and practically. Regarding to theoretical contributions, first, to our knowledge, our study is one of the first works to show the network of the relationships between BIS/BAS and PMPU. Emerging evidence that the BIS and BAS-F are connected with tolerance and mood modification, which are the core symptoms of PMPU, in the BIS/BAS-PMPU network, has been provided. Second, these findings might help us identify new ways in which PMPU forms and gain a better understanding of the components model of addiction. The traditional SEM/latent variable analysis approach focuses on the relationship between individual factors and PMPU e.g., –48], whi, whi48)]The current research also provides important practical contributions concerning the object and content of prevention. Regarding the object of prevention, our findings highlight the importance of centering on individuals with a high BIS or high BAS-F when formulating PMPU prevention for vulnerable individuals. Regarding the content of prevention, our findings suggest that when intervening in the addictive behavior of specific individuals with a high BIS or high BAS-F, it is necessary to intervene not only in their behaviors but also in their behavioral motivations, especially their motivation for emotion regulation. Inventions could replace PMPU by guiding these individuals to adopt appropriate emotional regulation methods (e.g., mindfulness-based cognitive-behavioral intervention . In turnThe relationship between BIS/BAS and PMPU were examined by using network analysis. These results indicated that mood modification, tolerance, and withdrawal symptoms are central symptoms in the BIS/BAS-PMPU network. In addition, edges between mood modification, tolerance, and BIS and edge between mood modification, conflicts, and BAS-F bridge the BIS/BAS community and PMPU community. Furthermore, a new perspective on PMPU prevention is suggested by these findings. More specifically, practitioners developing interventions to overcome PMPU should consider aspects focusing on individuals who are sensitive to punishment and fun and their behavioral motivation.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 Ethics Committee of Institutional Review Board of School of Psychology, Central China Normal University. Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.LG executed the study and wrote the paper. HC and WL collaborated with the design. XC and WZ collaborated in the writing and editing of the final manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Digital health interventions are efficient and flexible methods for enhancing the prevention and management of cardiovascular disease and type 2 diabetes. However, little is known about the characteristics associated with eHealth literacy in the Canadian South Asian population.The aim of this study is to describe perceived eHealth literacy and explore the extent to which it is associated with sociodemographic, health status, and technology use variables in a subset of South Asian Canadians.We analyzed data from the e-Patient Project survey, a mixed-mode cross-sectional survey that occurred in 2014. The eHealth Literacy Scale (eHEALS) was used to measure eHealth literacy in a convenience sample of 511 English- or Punjabi-speaking South Asian adults recruited from a community pharmacy, a family physician office, and community events in Edmonton, Alberta. Multivariable quantile regression was used to explore variables associated with eHealth literacy.The analysis was restricted to 301 internet users  who provided responses to all 8 eHEALS questions and complete demographic information. The mean overall eHEALS score was 29.3 (SD 6.8) out of 40, and 71.4% (215/301) agreed to at least 5 out of the 8 eHEALS items. The eHEALS item with the lowest level of agreement was “I can tell high-quality health resources from low-quality health resources on the internet” . Although there were statistically significant differences in eHEALS scores according to age, educational achievement, language preference, and the presence of chronic medical conditions, multivariable regression analysis indicated that language preference was the only variable independently associated with eHealth literacy .In our sample of South Asian Canadian internet users, preference for written health information in languages other than English was associated with lower eHealth literacy. Opportunities exist to improve eHealth literacy using culturally and linguistically tailored interventions. Digitally engaged patients are those who have taken up new digital media technologies in their own medical care and preventative health efforts . These einfodemic of medical misinformation [To optimally engage with and have equitable access to a digital health care environment, health care consumers must have an understanding of their condition as well as the skills to effectively use electronic resources -17. Thisormation ,21. Asseormation -25. eHeaormation ,26,27.South Asian Canadians are a large visible minority group  who faceWhether South Asian Canadians have adequate eHealth literacy to effectively use eHealth to improve their health is uncertain as are the demographic and technology use determinants of eHealth literacy in this community. Although eHealth strategies may support improving both the prevention and management of cardiovascular disease and type 2 diabetes, a systematic review of eHealth literacy suggests that underserved populations may have lower levels of competence in the 6 core domains of eHealth literacy, decreased access to health infrastructure, and technology . For exaOwing to a lack of information on digital device use and eHealth literacy in South Asian Canadians, we conducted the South Asian e-Patient Project, a survey conducted in a convenience sample of 831 South Asian Canadians in Edmonton, Alberta in 2014 . We prevThe design as well as the results on the prevalence and variables associated with internet and digital device use for health purposes from the e-Patient Project survey have been published previously . BrieflyA subset of the survey participants was invited to complete the eHealth literacy assessment. Owing to the time required to complete the survey, this subset included all individuals recruited in person at the participating community pharmacy, family physician practice, a large community event, and 1 community center, as well as those who completed the survey via the web. Individuals recruited at faith-based gatherings were excluded from the eHealth literacy assessment.Potential respondents were notified about the study via personal invitations by pharmacy or clinic staff, announcements at community events, and posters. We recruited consecutive attendees from the community pharmacy and family physician office sites. Individuals were then approached by trained, bilingual English- and Punjabi-speaking research assistants or community volunteers. They were presented with the e-Patient Project survey information letter and were asked if they would like to participate. The agreement and completion of the survey implied participants’ consent.Research staff administered the survey, including the eHealth literacy assessment, via computer-assisted personal interviews in English or Punjabi, according to respondent preferences. One-on-one interviews using paper surveys were conducted at the community event before the tablet computers became available. A web-based version was also offered to those who preferred to complete the survey on their own time. Respondents who completed the survey were offered a reusable shopping bag and the opportunity to enter a draw for a tablet computer or various gift cards as incentives.eHealth literacy was measured using the 8-item eHEALS scale, which is the most commonly used validated measure of eHealth literacy ,46. The α=.950, and principal components analysis produced a single factor solution with factor loadings from 0.68 to 0.80 among the 8 items, with eigenvalue=5.95 and 74.4% of the variance explained  was used to compute descriptive statistics for the demographic characteristics, technology use variables, and eHEALS scores. Summary eHEALS scores were calculated by summing the responses to 8 eHEALS questions. We also explored the proportion of individuals who agreed to at least five out of the eight eHEALS items, an indicator of adequate eHealth literacy , and theropriate -57. StatP values reported were based on bootstrap SEs with 1000 repetitions.Multivariable quantile regression was performed using R  to assess the effect of each demographic variable on the eHEALS score while controlling for the effect of others. This analysis was restricted to internet users and explored both demographic and internet use predictors. Quantile regression through the median was performed instead of mean regression  because The Health Research Ethics Board at the University of Alberta (Pro00038210) approved this study.A total of 511 individuals were invited to complete the eHealth Literacy Assessment. Although we originally invited both internet users and noninternet users to complete the eHEALS assessment, given that it is more meaningful to investigate eHealth literacy in internet users, in this paper, we focus on reporting the results in the n=301 internet users who provided data for all 8 HEALS items and demographic characteristics. . Finding. The mean age was 39.9 (SD 14.8) years and just over half of the respondents were female . Most respondents were married ; had college, university, or higher education ; and self-identified as Sikh . A total of 29.2% (88/301) lived in Canada for <5 years. Most respondents  indicated that English was their preferred language for written health information. Overall, 81.8% (246/301) indicated that their health was at least good, 53.2% (160/301) had at least 1 of the 8 chronic health conditions we inquired about, and only 1.7% (5/301) reported not being confident at all in filling out medical forms by themselves. Most respondents  were recruited from the participating community pharmacy and family physician office.I can tell high-quality health resources from low-quality health resources on the internet  and I feel confident in using information from the internet to make health decisions .Total scores on the eHEALS ranged from 8 to 40 and were negatively skewed with a mean of 29.27 (SD 6.84), median of 31, and IQR of 27 to 32. A total of 2.3% (7/301) participants had the worst possible score, whereas 4.7% (14/301) of participants had the best possible score. Over three quarters of respondents  felt it is important to be able to access health resources on the internet and that the internet is useful in helping make decisions about their health . The proportion of respondents who agreed with each eHEALS item is shown in P=.01), and age was negatively correlated with eHEALS scores . Further, there were statistically significant higher mean eHEALS scores in those with college or university education versus high school education , and those who preferred to receive written health information in English versus language other than English  of participants used the internet several times per day, 71.4% (215/301) of participants sought web-based health information, and 31.6% (94/297) of smartphone or tablet owners used health and fitness apps. Of the internet users, 84.4% (254/301) were interested in future eHealth interventions. As shown in The results of the multivariable quantile regression using demographic, health status, and technology use variables for internet users are shown in Among our sample of primarily Sikh, highly educated internet users recruited from community pharmacies and family physician offices, the mean overall eHEALS score was 29.3 (SD 6.8) out of 40, suggesting high levels of eHealth literacy. Almost three quarters of the respondents agreed to at least 5 out of 8 eHEALS items and were categorized as having adequate eHealth literacy . A largeMost comparable with our study, is a case study conducted by Zibrik et al , which uOur results compare favorably to existing studies that looked at measures of eHealth literacy among internet users in the general population, reporting mean overall eHEALS scores ranging between 24 and 30 out of 40 ,49,61-63In other studies focusing on eHealth literacy among internet users, as in our study, overall mean eHEALS scores ranged from 16.1 (SD 4.25) to 30.34 (SD 5.30), depending on the population studied ,50,64-68Several studies have explored variables associated with eHealth literacy ,50,62,65By contrast, we found that language preference was the only variable independently associated with eHealth literacy. This could be a proxy for acculturation, as years living in Canada were not an independent predictor in our model. Limited English proficiency is a widely cited barrier in studies examining health care and eHealth access in immigrant or minority populations . HoweverFirst, although our results suggest that a large proportion of South Asian internet users have adequate eHealth literacy, there remains a sizable minority in our study group whose eHealth literacy can be strengthened. Understanding levels of eHealth literacy is even more important in 2022 than in 2014, as the COVID-19 pandemic has globally increased the remote internet-based delivery of health care . TraininOur study suggests several areas for future research. First, further work with representative samples should compare levels of health and eHealth literacy using newly available tools among recent and established Canadian immigrants and nonimmigrants similar to that of Neter et al . Second,At the time the survey was conducted in 2014, our work was unique, and to our knowledge, there are only 2 other published studies exploring eHealth literacy in members of the South Asian community in Canada ,60. DespThis cross-sectional study in a subset of e-Patient Project survey respondents provides insights for clinicians and researchers on the levels and variables associated with eHealth literacy in a sample of South Asian adults living in a major Canadian city. Preferring written health information in languages other than English was the only independent variable associated with reduced eHealth literacy in our sample. Our results suggest that respondents may still benefit from interventions targeting skills to evaluate web-based health resources and that linguistically and culturally appropriate interventions are required to improve eHealth literacy.


Evidence mapping of systematic reviews (SRs) systematically and comprehensively identifies, organizes, and summarizes the distribution of scientific evidence in a field. The aim of this evidence map is to provide a synopsis of the best clinical practices and interventions in stroke rehabilitative care and to identify areas with a paucity of evidence to guide future research. PubMed, EMBASE, CDSR, six Korean databases, and two Chinese databases were searched for SRs evaluating the effectiveness of any stroke rehabilitation intervention through October 2021. The quality of the SRs was assessed using AMSTAR 2. A bubble plot was used to graphically display clinical topics, the number of articles, the number of patients included, confidence, and effectiveness. In total, ninety-five SRs were identified; however, after methodological analysis, only 48 had sufficient quality to be included. In total, forty-eight SRs were included in the evidence mapping. The overall search identified SRs from 2015 to 2021. A total of four SRs focused on post-stroke cognitive impairment, whereas the other forty-four SRs focused on post-stroke motor function. In total, nineteen different traditional Chinese medicine (TCM) intervention modalities were included. Acupuncture was the most commonly used treatment. Overall, the quality of the included SRs was low or very low. Most SRs concluded that TCM interventions may have potential benefits in stroke rehabilitation. The results were more promising when acupuncture was used for shoulder–hand syndrome. However, the identified reviews cautioned that firm conclusions cannot be drawn. The evidence map provides a visual overview of the research volume and content involving TCM interventions in stroke rehabilitation. Evidence mapping can facilitate the process of knowledge translation from scientific findings to researchers and policymakers and possibly reduce waste in research. Stroke is the second leading cause of death and long-term disability worldwide . DespiteTCM has been used for centuries in the treatment of stroke. Because of fewer side effects, TCM has often been sought to provide intervention therapies for the prevention of and rehabilitation from a stroke in China and Korea. Furthermore, TCM is popular not only in other parts of Asia but also in some Western countries, including USA and Australia. TCM mainly includes herbal medications, acupuncture, moxibustion, cupping, and tuina. More than 100 kinds of TCM interventions have been used to prevent and treat stroke . AcupuncThere is a vast amount of scientific literature proposing treatment approaches for stroke rehabilitation. Systematic reviews (SRs) are one of the options used to organize and critically assess published studies and summarize the results of the evidence from healthcare-related primary studies to answer specific research questions. Evidence mapping of SRs systematically and comprehensively identifies, organizes, and summarizes the distribution of scientific evidence in a field, aiming to identify gaps in knowledge and future research needs. This evidence mapping aims to provide a synopsis of the best clinical practices and interventions in stroke rehabilitative care and identify areas with a paucity of evidence to guide future research.Evidence mapping is not associated with an official standardized method . The appSRs were searched in 11 databases, including PubMed, EMBASE, and the Cochrane Database of Systematic Reviews (CDSR), and also six Korean databases  and two Chinese databases [the China National Knowledge Infrastructure (CNKI) and Wang Fang], from database inception through October 2021. In addition, the reference lists of potentially eligible articles were searched manually to identify additional relevant articles.The search terms used were based on the text words “systematic review” or “meta-analysis.” and “stroke rehabilitation,” and database-specific filters for SRs were used to develop the search strategy with no language restrictions .Only SRs focusing on TCM interventions in stroke rehabilitation and summarizing primary research studies for all the clinical indications were included. In this study, we considered SRs containing at least one randomized controlled trial (RCT), which addressed the use of TCM in stroke rehabilitation.We examined trials, including adults (aged over 18 years) with a clinical diagnosis of stroke , paresis of the upper, lower, or both sets of limbs (motor function), and confirmed cognitive impairment as specified in each trial .All types of TCM interventions were considered, including but not limited to the following: acupuncture, electroacupuncture (EA), Chinese herbal medicine (CHM), moxibustion, tai chi, qigong, Chinese herbal bath, and tuina. Combination therapies incorporating TCM interventions were also included. Comparators included non-treatment, sham treatment, placebo treatment, and routine treatments (rehabilitation and positive interventions).SRs reporting on patients' health outcomes were eligible for inclusion. SRs focused on provider outcomes, study design, or intervention features that did not report patient health outcomes were excluded.All scoping, rapid, critical, and narrative reviews were excluded. Two reviewers (T-YC and JJ) independently screened all the titles and abstracts and selected full-text articles to exclude irrelevant SRs. Disagreements were resolved through discussion and consensus, and an additional reviewer (MSL) was consulted. Where originals and updates of SRs by the same author group were available, only the most recent version was considered, and multiple publications of the same review were counted as one review, although data were extracted from all the available publications. If multiple reviews of similar clinical topics were identified, the most pertinent and best-performing SR was used for inclusion in evidence maps and was selected based on the results of the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR 2) assessment.All the articles were read by two independent reviewers (T-YC and JHJ), data were extracted from the articles based on predefined criteria, and a methodological quality assessment was conducted. Disagreements were resolved by consensus, and when necessary, an additional reviewer (MSL) participated in the discussion. Information on PICO , the number of RCTs included in each SR, summary effect estimates for main outcomes, overall risk of bias (ROB), publication bias, and conclusions  were extracted from the included SRs.The AMSTAR 2 tool was used to critically appraise the quality of reporting for each included SR. A validated 16-item instrument for critically appraising SRs that assesses the quality and bias using ratings of “yes,” “partial yes,” or “no” . OverallWe used the topics of the identified SRs to categorize the reviews. We presented the evidence mapping in tables describing the characteristics of the included SRs and a graphic display of the mapping based on bubble plots. Each bubble in the chart represents one included SR. The SR grouping into the clinical topics was drafted by one reviewer and discussed among the review team.The chart displays information in four dimensions:1) X-axis: stroke rehabilitative symptoms.Stroke rehabilitative symptoms were classified. The studies were categorized into those assessing cognitive function and those assessing motor function.2) Y-axis: AMSTAR 2 assessment/strength of findings/Confidence was decided based on the results of the AMSTAR 2 assessment, and the reviews were classified into four categories as follows: “high,” “moderate,” “low,” or “critically low.”3) Bubble size: number of primary studies included in the SR.Each SR bubble size is proportional to the number of primary studies included in the SR evaluating the effects of a particular intervention.4) Circle color: effect estimate.The clinical effectiveness of the rating of the authors' conclusions and overall ROB are described in the selected SR. Clinical effectiveness was categorized as a green circle if “effective” , a blue circle if “potentially effective” , or a yellow circle if “unclear” .The database search identified 847 potentially relevant studies. The research yielded 432 articles after removing duplicates. After title and abstract screening, 146 articles were obtained for the final full-text review. In total, ninety-five SRs were identified for potential inclusion; however, after methodological analysis, only 48 had sufficient quality to be included . Among tThe forty-eight SRs –59 inclun = 10) being the most frequent among them, followed by shoulder pain (n = 4), hand spasm (n = 1), strephenopodia (n = 1), motor dysfunction (n = 5), spasticity (n = 5), spastic hemiplegia (n = 9), hemiplegia (n = 8), and thalamic pain (n = 1).This article is based on multiple SRs. Four SRs focused on post-stroke cognitive impairment , whereasn = 11), EA (n = 5), eye acupuncture (n = 1), floating acupuncture (n = 2), fire-needle acupuncture (n = 2), Jin's three-needle acupuncture (n = 2), scalp acupuncture (n = 1), warm-needle acupuncture (n = 3), appoint catgut embedding (n = 1), bee venom acupuncture (n = 1), needle knife acupuncture (n = 1), moxibustion (n = 2), CHM (n = 5), herbal fumigation (n = 2), herbal socking (n = 1), taichi (n = 2), baduanjin (n = 1), daoyin (n = 1), and tuina (n = 4). Descriptions of the TCM interventions are described in In total, nineteen different TCM intervention modalities were included: acupuncture  and based on a substantial number of research studies, included findings with acupuncture for shoulder–hand syndrome  and based on a substantial number of research studies, included acupuncture for cognitive impairment  that provided evidence of the potential lack of effectiveness of TCM interventions in stroke rehabilitation for clinical indications across more than one included study: scalp acupuncture for cognitive impairment , in combination with conventional interventions, could improve cognitive and motor function. The results of this evidence map showed that in-line with available evidence, there is a sparsity of SRs evaluating TCM interventions in the context of stroke rehabilitation (cognitive and motor function). Furthermore, acupuncture can be more effective and safer than rehabilitation training in the treatment of post-stroke shoulder–hand syndrome –36. On tThis evidence map describes the research foci that were reported in the existing SRs and displays the gaps in evidence so that areas that should be prioritized in future research can be identified. However, this evidence map is unable to answer more refined questions, such as what the best TCM interventions for specific applications and the differences between health services are. To advance our evidence-based knowledge of TCM, we should collect more data on the effectiveness of TCM for rehabilitating stroke symptoms and patient populations through meta-analyses across primary studies. In addition, the large number of treatments that were classified as having potential effectiveness warrants additional primary studies. More studies have been published in some of the areas of interest included in the unclear evidence category, and the currently available SRs must be updated. As there might be other efficient ways of drawing evidence maps, further research should also include developing evidence maps of other research designs.The evidence map has several limitations. First, most publications are from mainland China and are written in Chinese, which eliminated their inclusion in this mapping of available evidence published in any other language. The generalization of these results to other countries might be limited. Second, the analysis was based on published SRs, and primary studies contributed to more than one included SR. Furthermore, individual review conclusions may have been limited by the quality of the primary studies and susceptible to publication and outcome reporting bias. There may be clinical trials that were included in more than one SR that might have an impact on the synthesized findings. Third, we attempted to retrieve possible eligible studies through comprehensive searches of numerous databases regardless of publication language, but there may have been missed trials related to this topic. Finally, the methodological quality of most included SRs scored “low” and “critically low.” More high-quality RCTs and SRs are needed to support clinical decision-making about the use of TCM interventions in stroke rehabilitation regimens. These findings highlight the need to conduct future research focusing on new treatments and addressing knowledge gaps in this field, and increased efforts are required to improve the methodological quality and reporting process of SRs on treatments to be used in stroke rehabilitation.Stroke prevention and treatment remain a challenge worldwide. In China and Korea, many stroke patients are treated using traditional medicine, and there have been reports on their functional recovery , 61. MosThis evidence map summarized, organized, and provided a visual overview of the currently available research volume and content related to TCM interventions during stroke rehabilitation involving cognitive function and motor function. This visualization facilitates an easy and engaging overview and suggests evidence mapping as a useful tool for a large array of stakeholders and for informing policy and clinical decision-makers. Our results provide policy and clinical decision-makers guidance regarding the interpretation of the current state of evidence regarding the effectiveness of TCM interventions in stroke rehabilitation.The original contributions presented in the study are included in the article/T-YC and MSL conceptualized the study and wrote the original draft. T-YC, JHJ, and MSL contributed to methodology. T-YC and J-MY contributed to the software and resources. HWL and MCJ validated the study and investigated the study. T-YC and JHJ contributed to formal analysis. JHJ and HWL contributed to data curation. JHJ, HWL, J-MY, and MCJ contributed to writing, reviewing, and editing the manuscript. T-YC visualized the study. MCJ and MSL contributed to supervision and funding acquisition. HWL contributed to project administration. All the authors read and approved the final manuscript.This study was supported by the Korea Health Industry Promotion Agency's Health and Medical Technology R&D Project (Grant No. HI20C1951) and the Korea Institute of Oriental Medicine (KSN2021210 and NHT2012480). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation 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.


Therefore, we chose laying hens as model animals, as their diet usually does not contain much fat, to expand the study of BAs. BAs were investigated in vitro for emulsification, simulated intestinal digestion, and release rate of fat-soluble vitamins. Subsequently, a total of 450 healthy 45-week-old Hy-Line Gray laying hens were chosen for an 84-day feeding trial. They were divided into five treatments, feeding diets supplemented with 0, 30, 60, 90, and 120 mg/kg BAs, respectively. No extra fat was added to the basic diet (crude fat was 3.23%). In vitro, BAs effectively emulsified the water-oil interface. Moreover, BAs promoted the hydrolysis of fat by lipase to release more fatty acids. Although BAs increased the release rates of vitamins A, D, and E from vegetable oils, BAs improved for the digestion of vitamin A more effectively. Dietary supplementation of 60 mg/kg BAs in laying hens markedly improved the laying performance. The total number of follicles in ovaries increased in 30 and 60 mg/kg BAs groups. Both the crude fat and total energy utilization rates of BAs groups were improved. Lipase and lipoprotein lipase activities were enhanced in the small intestine in 60, 90, and 120 mg/kg BAs groups. Furthermore, we observed an increase in vitamin A content in the liver and serum of laying hens in the 60, 90, and 120 mg/kg BAs groups. The serum IgA content in the 90 and 120 mg/kg BAs groups was significantly improved. A decrease in serum malondialdehyde levels and an increase in glutathione peroxidase activity were also observed in BAs groups. The present study concluded that BAs promoted the absorption of vitamin A by promoting the absorption of fat even under low-fat diets, thereupon improving the reproduction and health of model animals.Fat-soluble vitamin malabsorption may occur due to low dietary fat content, even in the presence of an adequate supply of fat-soluble vitamins. Bile acids (BAs) have been confirmed as emulsifiers to promote fat absorption in high-fat diets. However, there are no direct evidence of exogenous BAs promoting the utilization of fat-soluble vitamins associated with fat absorption  Fat-soluble vitamin deficiency is plaguing millions of people in low-income countries, especially among women and children . The absIn vitro studies have shown that BAs can not only emulsify fat, but also promote the hydrolysis of fat by lipase (The absorption of fat is inseparable from bile acids (BAs). BAs are the general term for a series of cholanoic acids, mainly found in the bile of animals. BAs are the major products of cholesterol catabolism and play a crucial role in lipid absorption and metabolism . Structuy lipase –13. Prevy lipase . Many rey lipase . In animy lipase .Although there have been some studies on the promotion of fat absorption by BAs in animals under high-fat diets –18, direin vitro and in vivo experiments were all from Shandong Longchang Co., Ltd . The porcine BAs are composed of the following components: 7.99% of hyocholic acid, 19.65% of chenodeoxycholic acid, and 70.88% of hyodeoxycholic acid. The lipase used in the in vitro experiment was from porcine pancreas . The vitamin A used in this study was in the form of retinol . And the vitamin D used in this study was in the form of ergocalciferol . The vitamin E used in this study was in the form of α-tocopherol .The porcine BAs used in the A total of 10 g of soybean oil was weighed and placed in beakers, and 0, 400, and 800 mg of BAs were added, respectively. Then, 100 mL of PBS was added to the beakers of each treatment group. After stirring in a magnetic stirrer for 10 min, the liquid was left to stand for 3 min to observe the stratification of the liquid level.We selected two main kinds of plant oil, soybean oil and corn oil, which often contained in laying hen diets, to measure the lipase-boosting effect of BAs. Since fat is hydrolyzed into fatty acids and glycerol by lipase, we used acid value to measure the fat hydrolysis. A total of 5 g of soybean oil or corn oil was weighed and placed in conical flasks. Then, 300 mg of lipase, 25 mL of PBS, 0, 5, 10, 15, 20, 25, 30, 35, 40, and 45 mg of BAs were added to the conical flasks, respectively. The pH of the solution was adjusted to 6.8 with hydrochloric acid, and then placed in a shaking water bath (180 rpm) to react at 40°C for 3.5 h. After cooling to room temperature, we added 2∼3 drops of phenolphthalein indicator solution in the mixed solution and then titrated with the potassium hydroxide (KOH) standard titration solution (0.05 mol/L), until it appeared reddish and did not fade within 30 s as the end point. To differentiate single BAs and the combined effects of BAs and lipase, we also established lipase-free groups. Three parallel experiments were performed in each group. The calculation formula of acid value is as follows:V is the volume of KOH standard titration solution consumed by the sample, mL; c is the actual concentration of KOH standard titration solution, mol/L; m is the mass of the sample, g; 56.11 is the mass of KOH equivalent to 1.0 mL of KOH standard titration solution [c(KOH) = 1.00 mol/L], mg.Where: Firstly, quantitative amounts of vitamins A, D, and E were dissolved in soybean oil or corn oil. Subsequently, lipolysis experiment was carried out according to the aforementioned method. After the lipolysis, the solution was placed in a separatory funnel and left to stand until the layers were separated, and the aqueous layers was separated. The contents of vitamin A, D, and E in the aqueous phase were determined by high performance liquid chromatography with reference to the previous method . The vitCt is vitamin concentration in aqueous phase; C∞ is the theoretical maximum concentration of vitamin released in micelles.Where: ad libitum.The protocol of the animal experiment was permitted by the Institutional Animal Care and Use Committee of China Agricultural University . A total of 450 healthy 45-week-old Hy-Line Gray laying hens were raised in cages. Before the experiment, the hens were reared 7 days in advance to adapt to the experimental environment. Temperature (26°C), humidity (65%), and light (16L: 8D) were accurately controlled throughout the experiment, and hens were allowed to eat and drink Hens were randomly divided into five treatment groups with six replicates of 15 birds per replicate. The five treatment groups were fed with: corn soybean meal diets supplemented with 0, 30, 60, 90, and 120 mg/kg porcine BAs, respectively. No extra fat was added to the basic diet (crude fat was 3.23%). The whole experimental period was 84 days, and the pre-feeding period was 7 days. The diet is formulated according to Nutrition Requirement of Chicken in China (NY/T 33-2004) to meet the nutritional requirements. See The number and weight of eggs produced in each replicate were recorded at a fixed time every day, and the egg production (%) and average egg weight were calculated. Feed consumption was recorded weekly and average daily feed intake (ADFI) was calculated. Feed conversion ratio (FCR) was calculated weekly based on egg mass and feed intake, expressed as feed-to-egg ratio.g for 15 min at 4°C in a centrifuge. After blood collection, euthanasia was performed, and the liver, duodenum, jejunum, and ileum mucosa were collected, quick-frozen in liquid nitrogen, and stored at –80°C. Intact ovaries were removed for follicle sorting and counting. On the last day of the experiment, six eggs were collected from each treatment group, and the yolks were separated and stored at –20°C.Fecal samples were collected every 24 h during the last three consecutive day at the end of the experiment. Samples were dried at 65°C for 48 h, then exposed to air at room temperature for 24 h to prepare air-dried samples. Air-dried samples were ground through a 425 μm sieve for analysis. On the last day of the experiment, six hens from each treatment group were randomly selected for sample collection. After a 12-h fast, sub-wing vein blood was collected into blood collection tubes. After standing at room temperature for stratification, the serum was separated by centrifugation at 1,500 × Acid-insoluble ash (AIA) was used as an endogenous indicator to determine the total tract nutrients apparent utilization according to the method previously described . Crude fNdigesta is the nutrients concentration of the digesta; AIAdiet is the acid-insoluble ash concentration of the diets; Ndiet is the nutrients concentration of the diets; AIAdigesta is the acid-insoluble ash concentration of the digesta.Where: The immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), vitamin A, vitamin D, and vitamin E in the serum were determined by assay kits. All the kits were purchased from Nanjing Jiancheng Bioengineering Institute .After saponification and extraction, the contents of fat-soluble vitamins A, D, and E in liver and yolk were determined by high performance liquid chromatography .Follicles were classified as large yellow follicles , small yellow follicles , large white follicles , and small white follicles  according their size. All types of follicles were counting after the classification.The activities of lipase (LPS), lipoprotein lipase (LPL) and content of hormone-sensitive lipase (HSL) in duodenum, jejunum and ileum mucosa were measured by assay kits .P-values were given. Multiple comparisons among different treatment groups were tested by Tukey’s test. The difference at P ≤ 0.05 was considered statistically significant. The replicate served as the experimental unit for all analysis in this experiment.IBM SPSS Statistics 19.0 program  was used to process the analysis. GLM procedure was used to analyze variance. The most suitable regression equation was selected based on the curve fit, and the linear or quadratic We observed the stratification of the liquid surface after the mixing of water, oil, and BAs . In the P < 0.001). According to the regression equation, it can be known that when the BAs dose is 42.65 and 38.69 mg, the curve of acid value change has an inflection point .With the increase of BAs content, the acid value of soybean oil digestive juice increased evidently, and it leveled off until 30 mg of BAs . SimilarP < 0.05), while it leveled off in the 25 mg BAs group. Compared with the control group, the release rate of vitamin A in the 25 mg BAs group in soybean oil and corn oil increased by 24.62 and 33.05%, respectively. Similarly, vitamin D and vitamin E also had the same growth trend, but these two vitamins leveled off in the 35 mg BAs group. The vitamin A release rate at the highest value was higher than the other two vitamins in the dosage range of the present study. That is, in soybean oil, the highest release rate of vitamin A (80.20%) was 48.24 and 121.79% higher than that of vitamin D (54.10%) and vitamin E (36.16%), respectively. In corn oil, the maximum release rate of vitamin A (89.26%) was 55.34 and 263.73% higher than that of vitamin D (57.46%) and vitamin E (24.54%), respectively. It seems to suggest that in the presence of BAs, vitamin A is more likely to be released from the oil. Then we carried out curve fitting and found that the cubic regression was more suitable for the change trend of the release rate of these three kinds of fat-soluble vitamins (P < 0.001). The release rates of the measured vitamins were monotonically increasing in the range of BAs from 0 to 45 mg.Considering that BAs have both emulsifier properties and the effect of promoting the hydrolysis of fat by lipase, we investigated the release rate of fat-soluble vitamins from oil under the action of BAs. The release rates of the three fat-soluble vitamins increased with the increase of BAs content in both soybean oil and corn oil . The infP < 0.05), while other treatments have no obvious changes. Dietary supplementation of 120 mg/kg of BAs in laying hens reduced average egg weight (P < 0.05). However, BAs supplementation had no significant effect on ADFI (P > 0.05). This resulted in a significant improvement in the feed conversion ratio of laying hens in the 60 mg/kg BAs group (P < 0.05). In view of the significant quadratic regression relationship between laying performance and BAs dose, we calculated the optimal BAs dose according to the regression equation. According to the regression equation of egg production  and FCR , the optimal amount of BAs supplementation was 65 mg/kg to 75 mg/kg.There was no significant difference in the initial production performance of laying hens among the treatment groups . It can P < 0.01; P < 0.05), but not in the 120 mg/kg BAs group (P > 0.05).Crude fat utilization was increased when bile acids were supplemented in the diets of laying hens, with the 60, 90, and 120 mg/kg BAs groups reaching extremely significant levels , but did not affect LPS activity in jejunum and ileum , and the change of LPL activity in ileum was not obvious (P > 0.05). As for the content of HSL, it was obviously decreased in the duodenal mucosa of 90 and 120 mg/kg BAs groups (P < 0.05), but not changed observably in the jejunum and ileum mucosa (P > 0.05).Dietary supplementation of 60, 90, and 120 mg/kg BAs enhanced LPS activity in duodenal mucosa . Dietary supplementation of 60, 90, and 120 mg/kg of BAs in laying hens increased the vitamin A content in the liver by 76.61, 62.95, and 73.27%, respectively. This increasing trend is consistent with the results of our in vitro experiments, but the growth rate is much higher than that in the in vitro experiments. According to the curve estimation, there were significant linear and quadratic relationships between liver vitamin A content and BAs supplementation. Comparing the R2 values of the two regression equations, it can be judged that this change rule was more suitable for quadratic regression. The regression equation is y = 142.027 + 2.139x-0.009x2 (R2 = 0.544), when x = 118.83, ymax = 269.12. The content of vitamin D and vitamin E was not affected by BAs supplementation (P > 0.05). Similarly, we observed that dietary supplementation with 60 mg/kg BAs increased serum vitamin A levels , but had no significant effect on IgG and IgM content , but the activity of T-SOD was not affected.Supplementation of 90 and 120 mg/kg BAs in laying hens’ diets increased serum IgA content  synthase is down-regulated, and the synthesis of glutathione in the body decreases, which leads to liver cell damage, and this symptom can be alleviated by ursodeoxycholic acid treatment . This raThe present study reinforced the study of BAs, namely that BAs have both emulsifying and lipase-promoting effects. This combined effect improved the body’s absorption of dietary fat and promoted the absorption of vitamin A even under low-fat diets. Due to the improved absorption of vitamin A, the immunity and antioxidant capacity of the model animals were also enhanced. These evidences are sufficient to suggest that BAs supplementation in low-fat diets can be used as an effective means of nutritional regulation to improve the absorption of fat-soluble vitamins and help alleviate vitamin A deficiency in underdeveloped areas.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The animal study was reviewed and approved by Institutional Animal Care and Use Committee of China Agricultural University .QM, AC, SH, NY, and BY designed the study. BY performed the experiments and drafted the manuscript. BY and SH carried out the statistical analysis. QM, SH, NY, AC, LZ, JZ, and GZ helped the revision of this manuscript. NY, QM, and GZ contributed to the funding acquisition, project supervision, and guidance of the present study. All authors read and approved the final manuscript to the published.