Abstract
Background
Methods
Results
Conclusion
Zusammenfassung
Hintergrund
Methoden
Ergebnisse
Schlussfolgerung
Abbreviations:
EBHI (Evidence-based health information), GRADE (Grading of Recommendations Assessment, Development and Evaluation), RCT (Randomized controlled trial), SDM (Shared decision-making), UKMRC (United Kingdom Medical Research Council)Keywords
Schlüsselwörter
Introduction
Australian Goverment, National Health and Medical Research Council. General guidelines for medical practitioners on providing information to patients. 2004. https://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/e57_guidelines_gps_information_to_patients_150722.pdf (accessed 21 July 2017).
National Health Service. Brand guidelines. Patient information introduction. 2010. http://www.nhsidentity.nhs.uk/tools-and-resources/patient-information (accessed 2 June 2016).
Barmer GEK. Osteoporose verstehen – Knochenbrüchen vorbeugen. Informationen für bessere Entscheidungen [Understand osteoporosis – prevent bone fractures. Information to make better decisions]. 2011. https://www.gesundheit.uni-hamburg.de/pdfs/osteoporose-web-finale-version-200911.pdf (accessed 13 Dec 2017).
- Lühnen J.
- Albrecht M.
- Hanssen K.
- Hildebrandt J.
- Steckelberg A.
Lühnen J., Albrecht M., Mühlhauser I., Steckelberg A. Leitlinie evidenzbasierte Gesundheitsinformation [Guideline evidence-based health information]. Hamburg 2017. http://www.leitlinie-gesundheitsinformation.de (accessed 21 July 2017).
Lühnen J., Albrecht M., Mühlhauser I., Steckelberg A. Leitlinie evidenzbasierte Gesundheitsinformation [Guideline evidence-based health information]. Hamburg 2017. http://www.leitlinie-gesundheitsinformation.de (accessed 21 July 2017).
Lühnen J., Albrecht M., Mühlhauser I., Steckelberg A. Leitlinie evidenzbasierte Gesundheitsinformation [Guideline evidence-based health information]. Hamburg 2017. http://www.leitlinie-gesundheitsinformation.de (accessed 21 July 2017).
A) Piloting of photos in evidence-based health information - focus group study
Methods
Barmer GEK. Osteoporose verstehen – Knochenbrüchen vorbeugen. Informationen für bessere Entscheidungen [Understand osteoporosis – prevent bone fractures. Information to make better decisions]. 2011. https://www.gesundheit.uni-hamburg.de/pdfs/osteoporose-web-finale-version-200911.pdf (accessed 13 Dec 2017).
Intervention
Recruitment and consent
Data collection
Data analysis
Results
N = 37 | |
---|---|
Women | 26 |
Age, mean (SD) | 50.6 (14.2) |
Missing value | 1 |
Migration background | 12 |
Mother tongue: German | 26 |
Graduation: | |
None | 3 |
Primary school | 1 |
Junior High school | 5 |
High school | 14 |
Qualification for technical college | 1 |
Qualification for university | 12 |
Missing value | 1 |
Generic category | Subcategory | Characteristics | Examples |
---|---|---|---|
Comprehension | Photo supports comprehension | “One sees how the measurement is done.” (P2) | |
Photo raises questions | “Fishing is supposed to prevent osteoporosis? Or should it encourage the back and forth (movement) or fish consumption?” (P34). | ||
Perception of photos | Age | Negative | “Too many elderly people, it affects young people as well”. (P29) |
Social status | Negative | “Not all classes are displayed. Rather the upper class I would say from the pictures, the rich upper class basically.” (Transcript Hannover) | |
Citizenship | Negative | “Only pictures of white Europeans can be seen. None of people with migration background” (P5) | |
General | Positive | “All pictures break up the texts” (P37) | |
Negative | “Everybody looks too happy; it looks like they are promoting a vacation or have just arrived from wonderland.” (P17) | ||
Congruence between photos and content | Congruence between photos and content | Congruence | “… and actually I liked page 20/21 and the rendition the most. How can I prevent. There are associations straight away, at one glance: movement, nutrition and medical consultation, things like that. This was well done” (Transcript Stralsund 1/2) |
No congruence | “But what else was striking, on page 21the pictures and statements do not match. Which woman is smoking there?” (Transcript Stralsund 1/2) | ||
Congruence between photos and narratives | Congruence between number of narratives and photos | “These four pictures and two statements on page 7. They do not match at all. Same on page 33.” (Transcript Stralsund 3) | |
Alternatives | Number of photos | Delete a photo | “On some pages, the number of pictures is unnecessary and doubled.” (P6) |
Add a photo | “Maybe pictures of sports, specifically for prevention of osteoporosis.” (P19) | ||
Size of photos | Reduce the image | “Chapter 2 page 22, pictures of the food shown should be downsized and other food named in the text should be included.” (P29) | |
Replace photos | Table instead of photo | “Page 22 - instead of pictures rather another table with food.” (Transcript Stralsund 1/2) | |
Another category of picture instead of photo | “Page 20 - pictograms instead of pictures.” (P21) | ||
Swap photo | “31, careful, pitfall, I don’t think the picture fits (maybe edge of the carpet)” (P28) | ||
Move photos | “Page 21- the picture with the glass of milk and the bread do not fit in on this page, rather page 22 instead.” (P2) |
Comprehension
“Fishing is supposed to prevent osteoporosis? Or should it encourage the back and forth (movement) or fish consumption?” (P34).
“What kind of vegetable is that?” (P34)
Perception of photos
“For me, there are too many portraits.” (Transcript Stralsund 3)
“Everybody looks too happy; it looks like they are promoting a vacation or have just arrived from wonderland.” (P17)
“What is striking, there are no people with migration background, just white Europeans, no Asians, no Blacks. That's striking.” (Transcript Hannover)
“Only pictures of white Europeans can be seen. None of the people with a migration background.” (P5)
“Not all classes are displayed. Rather the upper class I would say from the pictures, the rich upper class basically.” (Transcript Hannover)
“On Thursday, where I got the brochure, when I saw that: privately insured, typical German.” (Transcript Hannover)
“When it comes to prevention, 54, 67, and 73 are not very suitable I have to say. Prevention should be - well, there should be at least one or two pictures where younger ones are shown. Actually, prevention starts at a younger age.” (Transcript Stralsund 3)
Congruence between photos and content
“It is easier to identify with. Text and picture. You match it with the other one. I cannot tell right now if he actually said that…” (Transcript Stralsund 1/2)
“These four pictures and two statements on page 7. They do not match at all. Same on page 33.” (Transcript Stralsund 3)
“But something else was striking, on page 21 the pictures and statements do not match. Which woman is smoking there?” (Transcript Stralsund 1/2)
“In general I think that the pictures emphasize the written text and it shows what is said in the text…it indicates what is in the text and that is enough.” (Transcript Stralsund 1/2)
“… And actually I liked page 20/12 and the rendition the most. How can I prevent. There are associations straight away, at one glance: movement, nutrition and medical consultation, things like that. This was well done.” (Transcript Stralsund 1/2)
Alternatives
“On some pages, the number of pictures is unnecessary and doubled.” (P6)
“Maybe pictures of sports, specifically those for prevention of osteoporosis.” (P19)
“Chapter 2 page 22, pictures of the food shown should be downsized and other food named in the text should be included.” (P29)
“31, careful, pitfall, I don’t think the picture fits (maybe edge of the carpet)” (P28)
B) A systematic review of pictures provided in health information material within the scope of the guideline development project
- Lühnen J.
- Albrecht M.
- Hanssen K.
- Hildebrandt J.
- Steckelberg A.
Lühnen J., Albrecht M., Mühlhauser I., Steckelberg A. Leitlinie evidenzbasierte Gesundheitsinformation [Guideline evidence-based health information]. Hamburg 2017. http://www.leitlinie-gesundheitsinformation.de (accessed 21 July 2017).
Methods
- Lühnen J.
- Albrecht M.
- Hanssen K.
- Hildebrandt J.
- Steckelberg A.
Lühnen J., Albrecht M., Mühlhauser I., Steckelberg A. Leitlinie evidenzbasierte Gesundheitsinformation [Guideline evidence-based health information]. Hamburg 2017. http://www.leitlinie-gesundheitsinformation.de (accessed 21 July 2017).
The Grading of Recommendations Assessment Development and Evaluation (GRADE) Working Group. GRADE guidelines - best practices using the GRADE framework. 2014. https://gradepro.org/guidelines-development#develop-publics (accessed 21 July 2017).
Lühnen J., Albrecht M., Mühlhauser I., Steckelberg A. Leitlinie evidenzbasierte Gesundheitsinformation [Guideline evidence-based health information]. Hamburg 2017. http://www.leitlinie-gesundheitsinformation.de (accessed 21 July 2017).
Intervention, comparison and study design
Lühnen J., Albrecht M., Mühlhauser I., Steckelberg A. Leitlinie evidenzbasierte Gesundheitsinformation [Guideline evidence-based health information]. Hamburg 2017. http://www.leitlinie-gesundheitsinformation.de (accessed 21 July 2017).
What effects do anatomical pictures used in health information have compared to text only?
What effects do cartoons used in health information have compared to text only?
What effects do photos used in health information have compared to text only?
What effects do pictographs used in health information have compared to text only?
What effects do drawings used in health information have compared to text only?
Outcome measures
Searching strategy

Quality Assessment and Data Synthesis
Cochrane Effective Practice and Organisation of Care (EPOC) Group. Suggested risk of bias criteria for EPOC reviews. EPOC Resources for review authors. 2015. http://epoc.cochrane.org/epoc-specific-resources-review-authors (accessed 29 Nov 2016).
Results

Study characteristics
Category | Author, Year (Country) | Intervention | Participants | Outcome Measures |
---|---|---|---|---|
ANATOMICAL PICTURES | Hollands, 2013 (UK) | Online information, full-body magnetic resonance imaging (MRI) scan images to visualize cardiovascular risk related to internal or external body fat | Healthy volunteers (n = 901), mean age 27 years | Credibility |
Bol, 2015 (Netherlands) | Online information, anatomical drawings to illustrate surgical procedures | Patients with colorectal cancer (n = 216), mean age 68 years | Knowledge Understanding Attractiveness / Acceptance | |
PHOTOS | Portraits of medical staff and patients in order to evoke emotions | |||
CARTOONS | Delp, 1996 (USA) | Cartoons to illustrate instructions for wound care | Patients of an emergency department with lacerations necessitating wound repair (n = 205), mean age 21 years | Comprehension Readability Attractiveness / Acceptance |
PICTOGRAPHS | King, 2012 (USA) | Medication information leaflet for a fictitious medication, symbols to illustrate medication directives | Low health-literate population (n = 161), mean age 33,8 years | Knowledge |
Mansoor, 2003 (South Africa) | Medicine label and patient information leaflet, pictographs to illustrate medication directives | Persons with low literacy and with English as second language (n = 60), aged between 21-65 years | Comprehension Knowledge Readability Attractiveness / Acceptance | |
Sahm, 2012 (Ireland) | Prescription instructions, graphic aid to visually depict dose and timing of the medication | Patients of an outpatient clinic (n = 94), over 18 years of age | Knowledge | |
Thompsen, 2010 (Kanada & USA) | Pictorial-based information pamphlets about the medication methotrexate | Healthy volunteers (n = 100), aged between 18-65 years | Comprehension Knowledge Readability Attractiveness / Acceptance | |
Yin, 2011 (USA) | Dosing instruction for infant acetaminophen, pictographic diagram of dose | Parents and their children at an urban public hospital pediatric clinic (n = 302), mean age approximately 31 years | Comprehension | |
DRAWINGS | Austin, 1994 (USA) | Drawings to illustrate discharge instructions | Patients with lacerations at a rural trauma center (n = 101), no information on age | Comprehension |
Brotherstone, 2006 (UK) | Visual illustrations to enhance understanding of the preventive aim of flexible sigmoidoscopy screening | Healthy volunteers (n = 65), aged between 60-64 years | Comprehension | |
Henry, 2008 (Canada) | A handout outlining the risks of surgery, illustrations representing complications | Patients undergoing otologic surgery in a tertiary centre (n = 51), mean age 42 years | Knowledge | |
Kools, 2006 (Netherlands) | Instructions for using asthma devices (inhaler chamber and peak flow meter), drawings to visualize the actions | Healthy volunteers (n = 99), aged between 20-60 years | Comprehension Readability | |
Liu, 2009 (USA) | Six short health-related texts, explanatory illustrations | Students (n = 30), mean age 22 years and older adults (n = 26), mean age 72 years | Comprehension Readability |
Risk of bias and quality of evidence

Cochrane Effective Practice and Organisation of Care (EPOC) Group. Suggested risk of bias criteria for EPOC reviews. EPOC Resources for review authors. 2015. http://epoc.cochrane.org/epoc-specific-resources-review-authors (accessed 29 Nov 2016).
Findings
Outcomes | Results |
---|---|
ANATOMICAL PICTURES | |
Knowledge (1 RCT, n = 143) | No significant effect for anatomical pictures and text compared to text-only [31] :9.61 (5.40) vs. 8.93 (5.50), p ≥ 0.05 Knowledge was assessed by 11 free-recall questions. The score ranges from 0 to 22 with higher scores indicating more information was recalled; mean (standard deviation (SD). |
Understanding (1 RCT, n = 143) | No significant effect for anatomical pictures and text compared to text-only [31] :5.86 (0.98) vs. 5.55 (1.25), p ≥ 0.05 Understanding was rated on a 7-point Likert scale (1 item). The score ranges from 1 to 7 with higher scores indicating more satisfaction with understanding; mean (SD). |
Attractiveness (1 RCT, n = 142) | Effect for anatomical pictures and text compared to text-only [31] :5.00 (1.15) vs. 4.16 (1.44), p < 0.001 Attractiveness was rated on a 7-point Likert scale (1 item). The score ranges from 1 to 7 with higher scores indicating more satisfaction with attractiveness; mean (SD). |
Credibility (1 RCT, n = 901) | Small effect for anatomical pictures and text compared to text-only [33] :4.48 (1.58) vs. 4.25 (1.67), p = 0.033 Credibility was rated on a 7-point Likert scale (1 item). The score ranges from 1 to 7 with higher scores indicating higher credibility; mean (SD). |
PHOTOS | |
Knowledge (1 RCT, n = 143) | No significant effect for photos and text compared to text-only [31] :9.55 (4.66) vs. 8.93 (5.50), p ≥ 0.05 Knowledge was assessed by 11 free-recall questions. The score ranges from 0 to 22 with higher scores indicating more information was recalled; mean (standard deviation (SD). |
Understanding (1 RCT, n = 143) | No significant effect for photos and text compared to text-only [31] :5.66 (1.32) vs. 5.55 (1.25), p ≥ 0.05 Understanding was rated on a 7-point Likert scale (1 item). The score ranges from 1 to 7 with higher scores indicating more satisfaction with comprehensibility; mean (SD). |
Attractiveness / Acceptance (1 RCT, n = 143) | No significant effect for photos and text compared to text-only [31] :4.65 (1.19) vs. 4.16 (1.44), p ≥ 0.05 Attractiveness was rated on a 7-point Likert scale (1 item). The score ranges from 1 to 7 with higher scores indicating more satisfaction with attractiveness; mean (SD). |
CARTOONS | |
Comprehension (1 RCT, n = 205) | Effect for cartoon and text compared to text-only [26] :0-1 questions: 3% vs. 33%, 2-3 questions: 51% vs. 61%, 4 questions: 46% vs. 6%; p < 0.001 Comprehension was assessed by 4 open questions. Answers were rated as correct / incorrect. Given is the percentage of participants with n correctly answered questions. |
Readability (1 RCT, n = 205) | Effect for cartoon and text compared to text-only [26] :Very easy: 98% vs. 64%, somewhat easy: 2% vs. 31%, not easy: 0% vs. 5%; p < 0.001 Readability was rated as very easy, somewhat easy or not easy. Given is the percentage of participants for each rating. |
Attractiveness / Acceptance (1 RCT, n = 205) | Effect for cartoon and text compared to text-only [26] :Very satisfied: 97% vs. 66%, somewhat satisfied: 3% vs. 32%, not satisfied: 0% vs. 2%; p < 0.001 Attractiveness / acceptance were assessed by 1 question. Satisfaction with the instruction was rated as very satisfied, somewhat satisfied or not satisfied. Given is the percentage of participants for each rating. |
PICTOGRAPHS | |
Comprehension (3 RCTs, n = 459) | Effect for pictographs and text compared to text-only 22 , 24 :73% vs. 53%, p = 0.005 [22] Comprehension was assessed by 11 questions, each broken down into 2 parts (1. location information in the leaflet quickly and easily; 2. recall of the information in own words). Given is the percentage of participants with a high level of comprehension (>80% correct answers). 43.9% vs. 59.0%, p = 0.01 [24] Comprehension was assessed by observing the accuracy of medication (doses) taken. Given is the percentage of participants who made a dosing error (>20% deviation of recommended dose). No significant effect for pictographs and text compared to text-only [34] :7.98 (1.21) vs. 7.96 (1.37), p = 0.93 Comprehension was assessed by 10 multiple choice questions. The score ranges from 0 to 10 with higher scores indicating better comprehension; mean (SD). |
Knowledge (4 RCTs, n = 362) | Effect for pictographs and text compared to text-only [22] :Question 2: 93.3% vs. 46.7%, p = 0.000; question 4: 73.3% vs. 3.3%, p = 0.000 Knowledge was assessed by 6 open questions. Answers were rated as correct / incorrect. Given is the percentage of participants with correct answers in question 2 and 4. Questions 1, 3, 5 and 6 were answered correctly by most of the participants in both groups. No significant effect for pictographs and text compared to text-only 23 , 28 , 34 :Free-recall ‘must know’: 3.67 (1.47) vs. 3.81 (1.71), p = 0.66; free-recall ‘must call’: 1.63 (1.46) vs. 1.50 (1.17), p = 0.61; MC ‘must know’: 7.79 (1.88) vs. 8.01 (2.02), p = 0.57; MC ‘must call’: 2.54 (1.21) vs. 2.58 (1.38), p = 0.86 [34] Knowledge was assessed by 25 free-recall questions to facts about medication (16 items ‘must know’) and to reasons for calling the rheumatologist (9 items ’must call’) and by 20 multiple choice (MC) questions (12 items ‘must know’ and 8 items ‘must call’). Scores range from 0 to max. 1 point for each correctly answered question (16, 9, 12 and 8 respectively); mean (SD). >79% in all groups, no statistical test for comparison of interest [23] Knowledge was assessed by 2 open questions. Given is the percentage of participants who correctly answered both questions. 6.65 (1.40) vs. 6.54 (1.40), no statistical test for comparison of interest [28] Knowledge was assessed by 2 open questions. The score ranges from 0 to 8 with higher scores indicating better knowledge; mean (SD). |
Readability (2 RCTs, n = 160) | Effect for pictographs and text compared to text-only [22] :Pictographs and text: 98.3%, text only: 1.7%, no statistical test Participants were shown both leaflets (with and without pictographs) and were asked to rate which version is easier to read. Given is percentage of participants. No significant effect for pictographs and text compared to text-only [34] :4.6 (0.7) vs. 4.7 (0.5), p = 0.52 Readability was rated on a 7-point Likert scale (1 item). The score ranges from 1 to 7 with higher scores indicating better readability; mean (SD). |
Attractiveness / Acceptance (2 RCTs, n = 160) | Effect for pictographs and text compared to text-only 22 , 34 :Pictographs and text: 98.3%, text only: 1.7%, no statistical test [22] Participants were shown both leaflets (with and without pictographs) and were asked to rate which version they prefer. Given is percentage of participants. 4.1 (1.0) vs. 3.5 (1.1), p = 0.004 [34] Attractiveness was rated on a 7-point Likert scale (1 item). The score ranges from 1 to 7 with higher scores indicating higher attractiveness; mean (SD). |
DRAWINGS | |
Comprehension (4 RCTs, n = 321) | Effect for drawings and text compared to text-only 25 , 32 :84% vs. 57%, p = 0.027 [25] Comprehension was assessed by 8 free-recall questions. Answers were coded and rated as showing good or poor understanding. Given is the percentage of participants with good understanding. 65% vs. 43%, p = 0.033 [32] Comprehension was assessed by 5 open questions. The score ranges from 0 to 10 with higher scores indicating more correct answers. Given is the percentage of participants with 5 or more correct answers. No definite effect for drawings and text compared to text-only [29] :Intervention 1 (recall): 6.04 (1.71) vs. 4.81 (2.06), significant difference; intervention 2 (recall): 13.04 (4.59) vs. 12.29 (3.29), no significant difference; Intervention 1 (performance): 7.71 (0.86) vs. 6.31 (0.86), significant difference; intervention 2 (performance): 6.79 (1.64) vs. 6.67 (1.01), no significant difference Comprehension was assessed by recall and performance of two instructions (intervention 1: Inhaler chamber, intervention 2: Peak flow meter). The number of correctly recalled propositions was rated. The score ranges from 0 to 11 (intervention 1) and to 26 (intervention 2) respectively; mean (SD). The number of instructional steps performed correctly right away was counted with 8 steps in both instructions; mean (SD). No significant effect for drawings and text compared to text-only [30] :Younger adults: 14.40 (1.99) vs. 15.07 (1.44), older adults: 15.77 (1.92) vs. 15.77 (1.24); no statistical test for comparison of interest Comprehension was assessed by 36 yes / no questions. The score ranges from 0 to 18 with higher scores indicating better comprehension; mean (SD). |
Knowledge (1 RCTs, n = 51) | No significant effect for drawings and text compared to text-only [27] :45% vs. 42%, p = 0.84 Knowledge was assessed by a free-recall question. Rated was the number of risks the participant could recall. Given is the recall rate in percent. |
Readability (2 RCTs, n = 155) | No significant effect for drawings and text compared to text-only 29 , 30 :Intervention 1: 48.29 (18.95) vs. 59.85 (37.90), intervention 2: 57.92 (20.70) vs. 66.36 (32.85); no significant differences [29] Younger adults: 24.86 (6.34) vs. 24.24 (5.07), older adults: 30.96 (4.05) vs. 27.69 (7.71); no statistical test for comparison of interest [30] Readability was assessed as reading time in seconds; mean (SD). |
Lühnen J., Albrecht M., Mühlhauser I., Steckelberg A. Leitlinie evidenzbasierte Gesundheitsinformation [Guideline evidence-based health information]. Hamburg 2017. http://www.leitlinie-gesundheitsinformation.de (accessed 21 July 2017).
Recommendation | Quality of evidence | |
![]() | “Anatomical pictures may be used in addition to the text.” | moderate quality |
![]() | “Cartoons may be used in addition to the text.” | moderate quality |
No recommendation could be given for the use of photos. | moderate quality | |
![]() | “Pictographs may be used in addition to the text.” | moderate quality |
![]() | “Drawings may be used in addition to the text.” | moderate quality |
Discussion and Conclusion
Discussion
Lühnen J., Albrecht M., Mühlhauser I., Steckelberg A. Leitlinie evidenzbasierte Gesundheitsinformation [Guideline evidence-based health information]. Hamburg 2017. http://www.leitlinie-gesundheitsinformation.de (accessed 21 July 2017).
- Choi J.
- Jacelon C.S.
- Kalmakis K.A.
- Choi J.
- Jacelon C.S.
- Kalmakis K.A.
- Choi J.
- Jacelon C.S.
- Kalmakis K.A.
- Choi J.
- Jacelon C.S.
- Kalmakis K.A.
The Grading of Recommendations Assessment Development and Evaluation (GRADE) Working Group. GRADE guidelines - best practices using the GRADE framework. 2014. https://gradepro.org/guidelines-development#develop-publics (accessed 21 July 2017).
Lühnen J., Albrecht M., Mühlhauser I., Steckelberg A. Leitlinie evidenzbasierte Gesundheitsinformation [Guideline evidence-based health information]. Hamburg 2017. http://www.leitlinie-gesundheitsinformation.de (accessed 21 July 2017).
Conclusion
Lühnen J., Albrecht M., Mühlhauser I., Steckelberg A. Leitlinie evidenzbasierte Gesundheitsinformation [Guideline evidence-based health information]. Hamburg 2017. http://www.leitlinie-gesundheitsinformation.de (accessed 21 July 2017).
Lühnen J., Albrecht M., Mühlhauser I., Steckelberg A. Leitlinie evidenzbasierte Gesundheitsinformation [Guideline evidence-based health information]. Hamburg 2017. http://www.leitlinie-gesundheitsinformation.de (accessed 21 July 2017).
Lühnen J., Albrecht M., Mühlhauser I., Steckelberg A. Leitlinie evidenzbasierte Gesundheitsinformation [Guideline evidence-based health information]. Hamburg 2017. http://www.leitlinie-gesundheitsinformation.de (accessed 21 July 2017).
Declarations
Consent for publication
Availability of data and materials
Conflict of Interest
Funding
Authors’ contributions
Acknowledgements
Appendix A. Supplementary data
References
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