Abstract
Objectives:
Evidence-based practice (EBP) is a clinical decision-making process combining the best available scientific evidence with clinician expertise and patient preference. While EBP has been associated with a range of benefits, it is recognized that EBP is used suboptimally by a range of health professionals, including naturopathic doctors (NDs). Canadian NDs have expressed a high level of interest in opportunities to improve their EBP skills; however, barriers exist, including those that apply broadly to health professionals, and those that are unique to the naturopathic profession. The objective of the present project was to co-design an EBP continuing education (CE) course tailored to the needs and preferences of Canadian NDs.
Design:
These needs were solicited through the use of focus groups. Groups were stratified based on participants' use of evidence at baseline. The focus groups asked NDs about their definition of EBP, and their interest in an EBP course, including preferred content, and method of delivery. The focus group discussions were transcribed, and thematic analysis was completed.
Subjects:
Twenty-two Canadian NDs participated.
Results:
Participants reported a high level of understanding of EBP, a high level of interest in participating in an EBP course and provided actionable recommendations about course content and delivery. Some of the themes that emerged were consistent across the groups while others differed by stratification.
Conclusions:
The findings of this project will inform the development and evaluation of a future CE course.
Introduction
Within the naturopathic medicine profession, and health care as a whole, there is increasing attention to the use of Evidence-Based Practice (EBP) and Evidence-Based Medicine (EBM). These related terms 1 are often defined as, “the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients,” in conjunction with clinician experience and patient preference. 2 The use of EBP has been associated with an improvement in patient outcomes and a decrease in health care costs. 3 –5 Despite these benefits, concerns have been expressed that health care providers from a range of disciplines use EBP suboptimally. Specific concerns have been expressed about the use of evidence among Naturopathic Doctors (NDs) from both the medical and scientific community and members of the profession. 6 –8
Naturopathic Medicine is a distinct system of health care, which involves the blending of natural and traditional therapies with modern scientific knowledge. 9 The practice of naturopathic medicine is defined by a set of principles. 9 It is considered to be a form of complementary or alternative medicine. 10 Therapeutic modalities used by NDs vary by jurisdiction but may include diet and lifestyle counseling, nutritional supplementation, herbal medicine, acupuncture, homeopathy, physical therapies, and some pharmaceutical prescription. 9 In North America, 4-year, postgraduate naturopathic education programs meet standards for accreditation. 9 Standards for ND education are regulated provincially in Canada. 10 The Canadian College of Naturopathic Medicine academic calendar descries a one-semester course on research and states that one of the program objectives of the Doctor of Naturopathy Degree is the ability to “Appraise and apply research in treating patients”. 11 Additionally, NDs are required to participate in continuing education (CE) activities; in Ontario, for example, the CE requirement is 70 h every 3-year period.
At present, here are no specific requirements for CE related to EBP. 12 A review of the existing literature suggests that NDs' utilization and attitudes toward EBP are relatively positive; however, opportunity for improvement exists. In a recent survey of 235 Canadian NDs, 13 three-quarters of respondents stated that >50% of their clinical decisions were informed by evidence. Skill level was reported to be at a medium-high level among >50% of participants, and most participants reported a largely favorable attitude toward EBP. Notably, a large majority (93%) indicated an interest in learning or improving their EBP skills, suggesting NDs had some insight into their current suboptimal skill level, as well as a high level of interest in addressing these deficiencies. 13
Although qualitative assessments of Canadian ND attitudes toward EBP have not been undertaken, such studies have been conducted in other countries. The results of a recent qualitative study involving American NDs indicate a generally favorable perception of EBP as well as a recent transition “from hesitancy to cautious embrace”. 14 A large diversity of attitudes among professional members was also noted. 14 In a 2011 qualitative study of Australian naturopaths, participants expressed concerns that traditional knowledge could be undermined by scientific evidence. 15 Similarly, in a more recent qualitative study involving Australian and North American ND students and college faculty members, researchers identified a theme of needing to find balance between traditional and scientific knowledge. 16
Naturopathic medicine is guided by a set of unifying principles 17 and additional frameworks such as the Therapeutic Order 18 may be used to guide the delivery of care. Consideration of the role of traditional knowledge as a form of evidence and the unique philosophies related to naturopathic practice are likely to be important in the design of strategies to increase EBP among NDs. Overall, there is evidence of favorable attitudes and moderately high use of evidence among Canadian NDs; however, opportunity and interest to improve these parameters exist.
To support the increased use of EBP, attention to barriers is warranted, of which several have been identified. In the most recent Canadian survey of NDs, participants frequently cited the following barriers to EBP: lack of time (67.1%), lack of naturopathic medicine-related clinical evidence (67.1%), and patient preference for specific treatment approaches (61.9%). 13 Moderate barriers included lack of resources (46.2%), and insufficient skills in locating (47.1%), interpreting (53.4%), and appraising (54.7%) research. Enabling factors reported by at least 60% of survey respondents included access to online databases and full-text journal articles, access to educational materials related to EBP, access to critical reviews of relevant research, and access to tools to assist in critical appraisal. These barriers were consistent with those reported in a systematic review of the barriers to EBP in medicine; although additional obstacles were evident, including lack of leadership and support, financial barriers, lack of incentive, low priority, and clinician attitudes. 19 While there are known barriers to EBP, many of these obstacles can be overcome through intentional efforts to develop skills and increase access to resources.
To date, no coordinated efforts have been made to mobilize knowledge and support EBP among NDs in Canada. 20 While slow uptake of new evidence has been documented throughout health care, 21 the process of evidence utilization in naturopathic medicine is complicated by the added challenge of balancing traditional knowledge, with the naturopathic principles and naturopathic philosophy 22 ; however, these barriers do not preclude successful uptake. Instead, these factors necessitate a tailored approach. The present project aimed to address the EBP skill needs of Canadian NDs in a way that was interactive, cooperative, aligned with the principles of naturopathic medicine, and designed to address the barriers and facilitators to EBP uptake to maximize the likelihood of acceptability and engagement. There are presently no known CE courses on EBP that have been explicitly tailored to the needs of Canadian NDs.
The primary objective of the overarching project was to assess the feasibility and acceptability of a pilot EBP CE course. This report describes the first phase of this work, the process of assessing the EBP educational needs and preferences of the Canadian Naturopathic profession to subsequently guide the design of a CE course on the topic of EBP.
Methods
To guide the co-design of an EBP CE course tailored to the needs of Canadian NDs, we conducted focus groups with members of this population. The project used a qualitative descriptive design as it sought to describe participant experiences and perceptions, drive quality improvement in clinical practice and inform the development of new interventions. 23 Focus groups were chosen as a method because they are considered to be effective at understanding the characteristics of groups of people, capturing insights on behaviors, and guiding program and service development. 24
Study participants
We applied the following participant inclusion criteria: (1) ND maintaining an active license to practice in one of the following Canadian provinces: British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, or Nova Scotia; (2) willing to provide informed consent; and (3) ability to communicate in English.
Sample size
Guidance on sample size calculation was informed by Malterud et al.,
25
who highlight five items impacting “information power”: Narrow/broad focus: This study is narrowly focused on the question of EBP knowledge needs among Canadian NDs. Sample specificity: Participants are homogeneous in their profession, scope of practice, and geographic location. Established theory: There is limited theoretical background related to the EBP educational needs of NDs. Quality of dialog: NDs are likely to communicate clearly about their EBP needs. Analysis strategy: Qualitative thematic analysis will be used.
Considering these factors, we aimed to recruit 18 to 24 participants to run 3 focus groups, each comprising 6 to 8 participants. A previously conducted qualitative assessment of attitudes toward scientific and traditional evidence among NDs included 28 participants. 16 Our population of interest was limited to NDs maintaining an active license in a province where naturopathic medicine is regulated to minimize variability in training and issues that relate to scope of practice.
Recruitment
We recruited participants using social media posts published on a closed ND virtual community of practice. An invitation was also circulated in the monthly electronic newsletters of the Canadian Association of Naturopathic Doctors, the Ontario Association of Naturopathic Doctors (OAND), and Canadian College of Naturopathic Medicine (CCNM). Recruitment took place between July and August 2021.
Study procedure
When individuals responded to the recruitment materials, they completed a brief screening questionnaire to assess their eligibility and their present use of evidence in clinical practice. The latter information was used to categorize participants as relatively high (“Group 1”), moderate (“Group 2”), or low (“Group 3”) users of evidence. These three groups completed the focus group sessions separately to minimize tension related to differing views on the role of evidence in naturopathic medicine. The focus groups aimed to be inclusive and respectful so that all participants felt comfortable voicing their opinions.
The focus groups took place virtually using the licensed version of Zoom. The focus groups were conducted using a semistructured qualitative interview methodology. 26 Supplementary Table S1 includes the list of questions used in the focus groups. The sessions were audio recorded and Zoom's transcribe function was used to generate a draft transcript. The audio recording and transcript draft were reviewed to ensure accuracy and corrected where required.
Data analysis
We analyzed the focus group transcripts by thematic analysis 27 using two approaches. Direct question analysis was completed to assess for themes or responses emerging from specific questions. Additionally, general thematic analysis was used to identify any themes that emerged from the entire dataset.
Ethics approval
This study was reviewed by the Research Ethics Board of the Canadian College of Naturopathic Medicine. All participants provided written, informed consent.
Results
Participants
Table 1 summarizes the number of participants who provided informed consent, and attended a focus group. A large proportion of the individuals who expressed an interest to participate in the study reported a high use of evidence. As a result, participants in this focus group were recruited quickly. Many additional inquiries were received from individuals reporting a high use of evidence; thus, it was decided that an additional focus group with high-use participants would take place to proportionately represent the participants enquiring. No additional data were obtained from the second focus group involving Group 1 participants indicating that data saturation had been achieved.
Summary of Participant Recruitment by Level of Evidence Use
Focus group responses and themes
A summary of the responses to the focus group questions is presented in Table 2. An overview of the themes that emerged in the general thematic analysis is presented in Figure 1. Participants expressed interest in improving core EBP skills such as searching for, appraising, and applying evidence. There was also interest among participants to balance scientific evidence with other factors. Some of these factors are relevant to health care more broadly, while others are specific to naturopathic practice.

Overview of the themes that emerged in the general thematic analysis. EBP, evidence-based practice.
Summary of the Direct Question Analysis
EBM, evidence-based medicine; EBP, evidence-based practice; ND, naturopathic doctor; RCT, randomized controlled trial.
Defining EBP
With respect to a definition of EBP, each of the groups mentioned the EBM triad (i.e., best evidence, clinician expertise, and patient values and preference), and also highlighted that EBP involves the integration of multiple sources of evidence. However, the evidence sources that were emphasized by each group differed. Participants in Group 1 described the prioritization of scientific evidence in clinical decision making.
“For me evidence-based practice means that the recommendations that I make to patients, in fact, mostly everything that I say to patients in terms of their health, is actually backed by research.” Group 1, participant 4.
There were many comments from group 1 participants about the importance of patient education in EBP, including the need to provide information to support the informed consent process, the need to correct misinformation that patients obtained from internet sources, the desire to present patients with options and empower their own decision making, and the role of the clinician in helping the patient to interpret and understand research results and their clinical implications.
Participants in Group 2 also defined EBP as the use of evidence to guide treatment decisions; however, there was more discussion about the EBP triad, and the importance of clinical experience. Participants highlighted that the best available evidence on a topic may not be from a randomized controlled trial (RCT) and that discounting non-RCT evidence was not part of the definition. Participants in this group also mentioned the limits of RCTs, such as the challenge of applying findings to real-world situations, and the limitations of studying whole systems of care such as naturopathic medicine. One participant also emphasized that within the context of EBP, any evidence should be tailored to the needs of an individual.
“Basically, using the best available evidence […] RCTs are showing if a therapy or treatment works in general, [but] it's not necessarily specific to a patient so keeping that in mind, and not discounting everything else.” Group 2, participant 9.
Group 3 participants highlighted the need to assess and integrate many forms of evidence in their clinical decision making, as well as the need to understand the root cause of illness to guide the application of evidence. This perspective seemed to suggest that the principles and philosophy of naturopathic medicine were an integral component of EBP for these participants.
Terminology
Participants from all groups expressed dissatisfaction with the term “Evidence-Based Medicine” (EBM). One participant described a visual model of “Evidence-Informed Decision Making” as being more consistent with their beliefs, while another reported a preference for the term “Evidence-Informed Practice” as it suggested “less pressure” to base treatment recommendations strictly on evidence. One participant in Group 3 suggested that there was a lot of negative association with the term EBM. Participants suggested that EBM implied the use of “biomedical or mechanistic” thinking that it excluded people who did not adhere to this ideology, and that it imposed limitations on practice. Participants indicated that in their experience, individuals with more restrictive views on evidence seem to use the term EBM, while people who are open to a wider range of sources of evidence use EIP, “[EIP] strikes me as being closer to that ideal that everyone's reaching for.” Group 3, participant 4.
These preferences suggest that EBP training should give due consideration to a profession's ideology, but also emphasize the need to balance the best available evidence with other factors impacting the clinical decision-making process.
Trusted sources of evidence
The focus group participants reported using a range of evidence sources to inform their practice. Although the use of scientific evidence was consistently cited across all three groups, additional sources of evidence varied between groups. Participants in all groups reported using evidence from RCTs and clinical experience to inform their practice. Group 1 participants reported the use of many more presynthesized evidence sources (such as guidelines, CE courses, and various databases) relative to other groups, while Group 2 participants reported a relatively balanced use of scientific evidence and clinical experience. Group 3, on the other hand, reported the use of other sources of evidence such as traditional knowledge, elders, and patient expertise.
Using synthesized evidence
Participants reported an interest in synthesized evidence sources, but some also recognized the inherent limitations and challenges of using such evidence. Groups 1 and 2 both expressed an interest in learning how to access synthesized evidence.
“Although being able to appraise is absolutely very important, I'm not going to spend hours of my week doing it, I don't have time, so for me, learning some of those really good resources that would be more trustworthy.” Group 1, participant 3.
However, comments from Group 2 pointed to concerns that guidelines could compromise the level of individualization that happens in naturopathic practice as well as potentially introducing a source of bias. Participants in Group 3 were highly concerned about the use of guidelines in the naturopathic profession for a number of reasons. For instance, they were concerned that guidelines resulted in a loss of individualization, a loss of naturopathic philosophy, and that application of protocols resulted in less effective care than individualized treatment plans, “My fear with evidence-based practice is we're looking for treatment protocols and treatment protocols will destroy the profession.” Group 3, participant 1.
Overall, there was interest in using synthesized evidence to support clinical decision making, but caution from group 3 participants about the implications of using such sources.
Participants in all groups commented on the relative lack of evidence generated by NDs, which was considered necessary for implementing EBP. One participant in Group 1 described NDs as “second-hand users of evidence” (Group 1, participant 6). Participants in Groups 2 and 3 suggested that EBP training should include content related to case report writing to encourage more NDs to participate in the generation of written evidence that is reflective of naturopathic practice. Participants in group 3 expressed significant concern about the deficiency of naturopathic research and its subsequent utility for practice, “[…] when you don't have research that follows that philosophy, when you don't have naturopathic research that maintains integrity to the principles and the way that we practice, it's not beneficial.” Group 3, participant 1.
The eagerness among all participant groups for more evidence to be created by NDs further emphasizes the desire to engage in EBP in a way that is consistent with naturopathic medicine philosophy and practice.
Searching and appraising evidence
With respect to the skills that participants were interested in improving, searching for evidence and critically appraising scientific evidence were key themes that emerged in all three groups.
“I want to know how to do it [EBP] efficiently so that I wouldn't be spending so many hours.” Group 2, participant 7.
“I really loved the research class at [institution name] but I really forgot a lot of the key points from that class, and I wish I could go back and refresh myself on some of those things.” Group 1, participant 4.
All participants were particularly interested in becoming more skilled at navigating PubMed and learning about additional databases and search tools. There was an interest in identifying trustworthy or “go-to” sources of evidence as well as resources and websites to which they could refer.
Applying evidence to practice
Groups 1 and 2 also expressed an interest in learning about communicating and applying evidence in their practice. These groups were interested in learning to better navigate situations where the available evidence was generated in a population that was different from their patient. Additionally, participants in Group 2 were interested in learning how to approach a lack of scientific evidence on a particular topic
“A lot of the medicines that we use haven't been researched in terms of the high level on the hierarchy. There's lots of evidence, in sort of traditional sources, and so, how do practitioners discern… if this is the best available evidence […] Because our medicine is generally under-researched, [and] under-represented in the whole pool of literature, are there appropriate strategies that can be used to extrapolate the evidence?” Group 2, participant 10.
Naturopathic philosophy and principles
Participants had varied views on the role of naturopathic philosophy or naturopathic principles in EBP training. Group 1 participants were particularly divided. Some participants felt that the naturopathic principles were not relevant to a course on EBP. Others felt the principles should not be separated from EBP, or that the principles created a framework that guides evidence-based clinical practice, even if not explicitly addressed in the course content. The usefulness of whole systems research, and the challenge of studying complex naturopathic interventions were also emphasized by Group 1 participants, indicating an understanding of some of the challenges of incorporating EBP with naturopathic medicine philosophy.
Group 2 participants were open to the idea of including some component of naturopathic philosophy within a course on EBP. Group 3 participants felt very strongly that the principles of naturopathic medicine should be embedded in a course on EBP. Most participants were interested in learning how to interpret research within a naturopathic framework and applying research findings in a way that was consistent with naturopathic principles. All groups were also interested in learning how to integrate scientific evidence with the therapeutic order, a naturopathic framework used to guide clinical care. 18
“If you think about the therapeutic order, it would be a really neat juxtaposition of what kinds of studies are appropriate for different levels of the therapeutic order so if we're talking about optimizing conditions, we're talking about supporting the health of vulnerable or weakened organ systems. To me that requires a different kind of study design than treating a symptom or disease-oriented study with a particular medicine.” Group 2, participant 10.
One participant (group 2) commented that the principles of naturopathic medicine make it distinct from other forms of clinical practice in that they influence the unique evidence needs of the profession. Similarly, there was a desire to balance the best available evidence with the principles of naturopathic medicine, rather than “hammering down the hierarchy of evidence” (Group 2, participant 10). One participant from Group 3 also suggested that the art and science of naturopathic medicine had become divorced in the naturopathic curriculum and that there was a need to integrate these. Another suggested that much of the controversy around EBP in the naturopathic profession comes from miscommunication and misunderstanding that practices cannot be guided by both scientific evidence and naturopathic principles, and that this should be addressed in a course on EBP, “So it's this whole dance all the time and for me it's… we have to find how everything fits together versus, we have to decide what we're throwing out or what we're keeping. And what gets us into trouble, as too often the discussion has been, in order to advance the profession, we need to move to evidence based practice. But they word it in such a way that…you lose your principles—you can't do both and it doesn't work that way.” Group 3, participant 1.
While groups had different perspectives on the role of naturopathic philosophy and/or naturopathic principles in EBP training, all participants expressed some degree of support for integrating naturopathic philosophy into a course on EBP.
Discussion
This project examined, for the first time, Canadian NDs' needs and preferences related to an EBP CE course. The themes that emerged from the focus groups highlighted a high level of understanding of the EBP framework, largely favorable attitudes toward EBP and a high level of interest in the proposed EBP course. Participant descriptions of the components of EBP, including perceived strengths and limitations, were consistent with generally accepted or established ideas about the concept. 2 Participants valued scientific evidence but also recognized the importance of clinical experience, the role of patient preference and the importance of informed consent. Although not specifically queried, participants in Groups 1 and 2 expressed relatively positive attitudes toward EBP and the proposed CE course, while participants in Group 3 expressed more cautious views.
Overall, focus group participants had a reasonably strong level of understanding of the EBP framework, which may have been related to their relatively favorable views of the framework. When North American NDs were asked to define EBM in a 2017 study, NDs who described it more broadly (such as including numerous sources of evidence) expressed less “hostile” views toward EBP. 14 Conversely, critics of EBP tended to demonstrate a limited understanding of the EBP framework, and were inclined to place undue emphasis on evidence from RCTs. 28 The relatively positive view of EBP among most of the study participants may be related to their accurate understanding of EBP.
In addition to understanding the EBP conceptual framework, focus group participants also demonstrated an understanding of the skills needed for engaging with EBP. When participants were asked about educational topics to be included in the CE course, participants identified a list of EBP skills that was well aligned with those previously established through expert consensus as necessary for health care providers. 29,30 Participants expressed a high level of interest in improving skills related to the acquisition of scientific evidence as well as interest in critical appraisal, and the application and communication of research findings to clinical care. These skills, such as learning to efficiently search for evidence using free or low-cost strategies, and address knowledge gaps and barriers to EBP, have been frequently cited by other health professions. 13,19 Participant interest in the inclusion of experiential components and opportunities to practice the skills being taught is consistent with existing priorities from many professions to make the teaching of EBP interactive, engaging, and case based. 31 –34
Although the degree varied significantly by group, most participants agreed about the need to design the course in a way that was consistent with naturopathic philosophy and principles. Other professions have sought to combine EBP with other philosophical considerations in a way that meets the needs of professional members. 35,36
One unexpected finding in this study was that despite their high level of evidence use at baseline, participants in Group 1 expressed the highest level of interest in increasing their use of evidence. This finding could potentially be explained by the Dunning–Kruger effect, which suggests that a cognitive bias may cause an individual to inaccurately estimate their knowledge on a particular topic. 37 Individuals with lower knowledge may be overly confident in their knowledge while those with higher levels of knowledge may be more aware of their limitations and deficits. Previous studies have proposed this phenomenon as a possible explanation for lower confidence among health professional students with greater experience and knowledge. 38,39 This phenomenon may explain some of the variable level of interest in EBP education between the different groups. This project had a number of strengths. The focus group methodology is well suited for use in the early stages of research on a topic assessing needs, understanding participant views, and guiding the development of programs or services. 24
Focus groups are particularly useful in eliciting issues that are relevant to participants to guide the design of subsequent studies. 40 In our study, we used a co-design approach to engage relevant stakeholders in an effort to design a course that would be relevant to their needs and interests. It has been acknowledged that needs assessment is a commonly omitted step in the development of continuing professional education. 41 The focus group participants were all members of the naturopathic profession who would be eligible to participate in the proposed CE course. Additionally, several focus group participants represented other stakeholder groups such as educators or professional association leaders.
Significant effort was also made to reach all Canadian NDs through the use of various recruitment methods. Stratifying participants by level of scientific evidence use served to facilitate the open sharing of views and mitigate hostility within focus groups. This was important, given that opinions on the role of evidence in naturopathic medicine can vary widely and sometimes be considered controversial. 8,42 This strategy minimized the risk of participant discomfort related to expressing significantly different opinions with their colleagues. Within Group 1, participants acknowledged that the full range of views from the profession were not being represented, demonstrating that members of the profession have an understanding of the diversity that exists and a level of concern that all voices be heard. Lastly, similarities and nuances between groups were also able to be captured as data from each group were analyzed separately.
Despite these strengths, some limitations did exist. These include the inherent limitations of focus groups, such as the potential for one or more members to dominate the discussion 40 or the possibility that participants may provide inaccurate information based on how they wish to portray themselves. 24 One limitation of our project was that the views expressed by participants may not have been representative of the entire profession within Canada. For example, the high level of interest in this project may have been driven by an interest in taking part in a future EBP CE course; this might suggest the presence of selection bias. While we achieved data saturation from participants assigned to the high evidence use group (Group 1), it was difficult to recruit participants to take part in the moderate- and low-use groups; from previous work we know that such individuals exist within the profession. 13 It is possible that reluctance of these individuals to participate resulted in incomplete or underrepresentation of their views in the data collected.
Conclusions
This project has identified a high level of interest among Canadian NDs in undertaking EBP CE. The project also uncovered important insights into the professions' needs and interests regarding EBP education. These findings will be combined with the best evidence on EBP competencies to create an EBP CE course that will be delivered and evaluated in a future phase of this research. The findings from the current study, and subsequent phases of this research, will be used to inform larger-scale studies to facilitate the implementation of EBP training for Canadian and/or international NDs, with a view to improving the quality of care received by individuals accessing naturopathic services.
Footnotes
Acknowledgments
The authors wish to acknowledge the contributions of Sasha Monterio for transcript review. The authors thank the focus group participants for their time, interest, and participation.
Authors' Contributions
Conceptualization: M.A. and G.N.; Methodology: M.A., G.N., and M.L.; Investigation: M.A.; Data Curation: M.A.; Project Administration: M.A.; Formal Analysis: M.A., G.N., K.C., and M.L.; Writing—original draft: M.A.; Writing—review and editing: G.N., M.L., and K.C.
Author Disclosure Statement
No competing financial interests exist.
Funding Information
Funding for this project was provided by the Canadian CAM Research Fund.
Supplementary Material
Supplementary Table S1
References
Supplementary Material
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