RESEARCH
Used to measure outcomes in numerous research studies and clinical trials involving >8000 patients for a range of aesthetic treatments and products.
Advancing Knowledge &
Improving Health Outcomes
INDUSTRY
Used as a case study in a FDA publication about the use of PROs in medical device studies. See our LEARN MORE section for examples of Label Claims that include the FACE-Q.
BENCHMARKING
Included in the UK Royal College of Surgeons national cosmetic surgery quality improvement initiative to measure outcomes for blepharoplasty, rhinoplasty, and rhytidectomy.
PATIENT CARE
Increasingly used in clinical practice to measure outcomes from the patient perspective.
Basic Scale Structure
The FACE-Q is designed to provide clinicians and researchers with the ability to customize the questionnaire to suit their needs. The FACE-Q Aesthetics module measures 3 overarching domains: Facial Appearance, Quality of Life and Adverse Effects. Each domain includes multiple independently functioning scales. The conceptual framework shown below was developed from 85 qualitative interviews with facial aesthetic patients, careful examination of the research literature and engagement with 26 healthcare professionals working with facial rejuvenation patients.
FACIAL APPEARANCE
The FACE-Q Aesthetics module contains a comprehensive set of 23 appearance scales. These scales include 16 scales that measure the appearance of the face overall and of specific facial features and areas and 7 scales that measure the appearance of facial lines overall and for specific areas of the face.
ADVERSE EFFECTS
The FACE-Q Aesthetics module includes a set of 6 checklists that can be used to measure adverse effects associated with aesthetic treatments. These checklists cover the cheeks, lower face and neck area, eyes, forehead, eyebrows and scalp area, lips, nose, and skin.
QUALITY OF LIFE
The FACE-Q Aesthetic module includes a set of 10 scales that measure aspects of quality of life. These scales include an aging appraisal scale that measures perception of appearance in the context of facial aging and an age visual analog scale that measures perceived age in comparison to actual age. For screening purposes, this FACE-Q module has a scale that measures expectations on how appearance and quality of life might change after treatment and an appearance-related psychosocial distress scale. There are 2 scales relevant to the early recovery period that measure early symptoms and early life impact of treatment. This domain also includes psychological and social function scales and scales to measure satisfaction with the decision to have treatment and the overall result of treatment.
FACE-Q | AESTHETICS
| APPEARANCE | QUALITY OF LIFE | ADVERSE EFFECTS | |
| Area Under Chin | Cheekbones | Aging Appraisal | Cheeks, Lower Face, & Neck |
| Cheeks | Chin | Age Visual Analogue | Eyes |
| Crows Feet | Eyelashes | Appearance-Related Distress | Forehead, Eyebrows, & Scalp |
| Eyes | Face Overall | Early Life Impact of Treatment | Lips |
| Forehead & Eyebrows | Forehead Lines | Expectations | Nose |
| Lines Between Eyebrows | Lines Overall | Psychological Function | Skin |
| Lip Lines | Lips | Recovery Early Symptoms | |
| Lower Eyelids | Lower Face & Jawline | Decision Satisfaction | |
| Marionette Line | Nasolabial Folds | Outcome Satisfaction | |
| Neck | Nose | Social Function | |
| Nostrils | Skin | ||
| Upper Eyelids | |||
Publications
Select a section to see list of relevant publications
FACE-Q | AESTHETICS DEVELOPMENT AND VALIDATION PUBLICATIONS
- Kaur M, Pusic A, Gibbons C, Klassen AF. Implementing electronic patient-reported outcome measures in outpatient cosmetic surgery clinics: an exploratory qualitative study. Aesthet Surg J. 2018 Oct.
- Klassen AF, Cano SJ, Grotting JC, Baker SB, Carruthers J, Carruthers A, Van Laeken N, Sykes JM, Schwitzer JA, Pusic AL. FACE-Q Eye Module for Measuring Patient-Reported Outcomes Following Cosmetic Eye Treatments. JAMA Facial Plast Surg. 2017 Jan 1;19(1):7-14
- Klassen AF, Cano SJ, Alderman A, East C, Badia L, Baker SB, Robson S, Pusic AL. Self-Report Scales to Measure Expectations and Appearance-Related Psychosocial Distress in Patients Seeking Cosmetic Treatments. Aesthet Surg J. 2016 Oct;36(9):1068-78. Epub 2016 May 24.
- Klassen AF, Cano SJ, Schwitzer JA, Baker SB, Carruthers A, Carruthers J, Chapas A, Pusic AL. Development and Psychometric Validation of the FACE-Q Skin, Lips, and Facial Rhytids Appearance Scales and Adverse Effects Checklists for Cosmetic Procedures. JAMA Dermatol. 2016 Apr;152(4):443-51.
- Klassen AF, Cano SJ, East CA, Baker SB, Badia L, Schwitzer JA, Pusic AL. Development and Psychometric Evaluation of the FACE-Q Scales for Patients Undergoing Rhinoplasty. JAMA Facial Plast Surg. 2016 Jan-Feb;18(1):27-35.
- Schwitzer JA, Klassen AF, Cano SJ, Baker SB, East C, Pusic AL. Measuring Satisfaction with Appearance: Validation of the FACE-Q Scales for the Nose, Forehead, Cheekbones, and Chin. Plast Reconstr Surg. 2015 Oct;136(4 Suppl):140-1.
- Klassen AF, Cano SJ, Schwitzer JA, Scott AM, Pusic AL. FACE-Q scales for health-related quality of life, early life impact, satisfaction with outcomes, and decision to have treatment: development and validation. Plast Reconstr Surg. 2015 Feb;135(2):375-86.
- Panchapakesan V, Klassen AF, Cano SJ, Scott AM, Pusic AL. Development and psychometric evaluation of the FACE-Q Aging Appraisal Scale and Patient-Perceived Age Visual Analog Scale. Aesthet Surg J. 2013 Nov 1;33(8):1099-109.
- Klassen AF, Cano SJ, Scott AM, Pusic AL. Measuring outcomes that matter to face-lift patients: development and validation of FACE-Q appearance appraisal scales and adverse effects checklist for the lower face and neck. Plast Reconstr Surg. 2014 Jan;133(1):21-30.
- Pusic AL, Klassen AF, Scott AM, Cano SJ. Development and psychometric evaluation of the FACE-Q satisfaction with appearance scale: a new patient-reported outcome instrument for facial aesthetics patients. Clin Plast Surg. 2013 Apr;40(2):249-60.
- Klassen AF, Cano SJ, Scott A, Snell L, Pusic AL. Measuring patient-reported outcomes in facial aesthetic patients: development of the FACE-Q. Facial Plast Surg. 2010 Aug;26(4):303-9.
- Kosowski TR, McCarthy C, Reavey PL, Scott AM, Wilkins EG, Cano SJ, Klassen AF, Carr N, Cordeiro PG, Pusic AL. A systematic review of patient-reported outcome measures after facial cosmetic surgery and/or nonsurgical facial rejuvenation. Plast Reconstr Surg. 2009 Jun;123(6):1819-27.
FACE-Q | AESTHETICS NORMATIVE DATA PUBLICATIONS
- Klassen AF, Cano SJ, Pusic AL. FACE-Q Satisfaction with Appearance Scores from Close to 1000 Facial Aesthetic Patients. Plast Reconstr Surg. 2016 Mar;137(3):651e-652e.
FACE-Q | AESTHETICS OTHER PUBLICATIONS
- Dayan S, Maas CS, Grimes PE, Beer K, Monheit G, Snow S, Murphy DK, Lin V. Safety and Effectiveness of VYC-17.5L for Long-Term Correction of Nasolabial Folds. Aesthet Surg J. 2019 Jul 26. [Epub ahead of print]
- Zhou J, Qi Z, Jin X. Modification of Rhytidectomy: Stepped Lift of the Superficial Musculoaponeurotic System. J Craniofac Surg. 2019 Jul;30(5):1466-1470.
- Denadai R, Chou PY, Su YY, Lo CC, Lin HH, Ho CT, Lo LJ. Facial Appearance and Psychosocial Features in Orthognathic Surgery: A FACE-Q- and 3D Facial Image-Based Comparative Study of Patient-, Clinician-, and Lay-Observer-Reported Outcomes. J Clin Med. 2019 Jun 25;8(6).
- Ozer K, Colak O. Micro-Autologous Fat Transplantation Combined With Platelet-Rich Plasma for Facial Filling and Regeneration: A Clinical Perspective in the Shadow of Evidence-Based Medicine. J Craniofac Surg. 2019 May/Jun;30(3):672-677.
- Jain M, Savage NE, Spiteri K, Snell BJ. A 3-Dimensional Quantitative Analysis of Volume Loss Following Submental Cryolipolysis. Aesthet Surg J. 2019 May 16. [Epub ahead of print]
- Hassan Y, Leveille CF, Gallo L, Santos J, Thoma A, McRae MH, McRae MC. Reporting Outcomes and Outcome Measures in Open Rhinoplasty: A Systematic Review. Aesthet Surg J. 2019 May 3. [Epub ahead of print]
- Huang A, Austin E, Jagdeo J. Patient-reported outcomes in lasers and light therapy. G Ital Dermatol Venereol. 2019 Apr;154(2):120-126.
- Fuller JC, Levesque PA, Lindsay RW. Analysis of Patient-Perceived Nasal Appearance Evaluations Following Functional Septorhinoplasty With Spreader Graft Placement. JAMA Facial Plast Surg. 2019 Mar 21.
- Xiao H, Zhao Y, Liu L, Xiao M, Qiu W, Functional/Aesthetic Measures of Patient Satisfaction After Rhinoplasty: A Review. Aesthet Surg J. 2019 Feb 5.
- Elegbede A, Mermulla S, Diaconu SC, McNichols C, Liang Y, Liang F, Rasko YM, Grant MP, Nam AJ. Patient-reported Outcomes in Facial Reconstruction: Assessment of FACE-Q Scales and Predictors of Satisfaction. Plast Reconstr Surg Glob Open. 2018 Dec 5;6(12):e2004. eCollection 2018 Dec.
- Wang R, Yang J, Guo K, Zhong A, Tong J, Xiong L, Sun J.Periauricular Purse-String Reinforced with SMAS plication and Malaria Fat Pad Elevation for Mid-and Lower Facial Rejuvenation: FACE-Q Report. Ann Plast Surg. 2018 Dec;81(6S Suppl 1):S59-S65
- Berger M, Weigert R, Pascal E, Hufschmidt K, Casoli V. Assessing Improvement of Patient Satisfaction Following Facelift Surgery Using the FACE-Q Scales: A Prospective and Multicenter Study. Aesthetic Plast Surg. 2018 Nov 28.
- Grow JN, Holding J, Korentager R. Assessing the Efficacy of Deoxycholic Acid for the Treatment of Submental Fat: A Three-Dimensional Study. Aesthet Surg J. 2018 Sep 29. [Epub ahead of print]
- Alouf E, Murphy T, Alouf G. Botulinum Toxin Type A: Evaluation of Onset and Satisfaction. Plast Surg Nurs. 2018 Jul/Sep;38(3):105-113
- Kant SB, Colla C, Van den Kerckhove E, Van der Hulst RRWJ, Piatkowski de Grzymala A. Satisfaction with Facial Appearance and Quality of Life after Treatment of Face Scars with a Transparent Facial Pressure Mask. Facial Plast Surg. 2018 Jun 1.
- Lee ZH, Sinno S, Poudrier G, Motosko CC, Chiodo M, Saia W, Gothard D, Thomson JE, Hazen A. Platelet rich plasma for photodamaged skin: A pilot study. J Cosmet Dermatol. 2018 May 31. [Epub ahead of print]
- Wang R, Yang J, Guo K, Zhong A, Tong J, Xiong L, Sun J. Asian Facelift Technique Refinement With High Patient Satisfaction: FACE-Q Report. Ann Plast Surg. 2018 May 24. [Epub ahead of print]
- Nacopoulos C, Gkouskou K, Karypidis D, Vlastos I, Vesala AM, Choukroun J, Miron RJ, Prokopakis E. Telomere length and genetic variations affecting telomere length as biomarkers for facial regeneration with platelet-rich fibrin based on the low-speed centrifugation concept. J Cosmet Dermatol. 2018 May 15.
- Kappos EA, Temp M, Dirk S, Haug M, Kalbermatten D, Bryant T. Validating Facial Aesthetic Surgery Results with the FACE-Q. Plast Reconstr Surg. 2017 Apr;139(4):839-45.
- Damitz LA. The Utility of Superficial Musculoaponeurotic System Flaps in Facelift Procedures. Ann Plast Surg. 2018 Apr 17.
- Hall MB, Roy S, Buckingham ED. Novel Use of a Volumizing Hyaluronic Acid Filler for Treatment of Infraorbital Hollows. JAMA Facial Plast Surg. 2018 Apr 5.
- Rivkin A, Weinkle SH, Hardas B, Weiss RA, Glaser DA, Biesman BS, Schumacher A, Murphy DK. Safety and Effectiveness of Repeat Treatment With VYC-15L for Lip and Perioral Enhancement: Results From a Prospective Multicenter Study. Aesthet Surg J. 2018 Jan 30. [Epub ahead of print]
- Doyle J, Yang Y, Norris JH, Aslam SA. A quality of life survey in patients with long-term silicone oil or phthisis bulbi. Graefes Arch Clin Exp Ophthalmol. 2018 May;256(5):879-884.
- Chang CS, Chang BL, Lanni M, Wilson AJ, Beer J, Percec I. Perioral Rejuvenation: A Prospective, Quantitative Dynamic Three-Dimensional Analysis of a Dual Modality Treatment. Aesthet Surg J. 2018 Mar 1.
- Radulesco T, Mancini J, Penicaud M, Dessi P, Michel J. Assessing normal values for the FACE-Q rhinoplasty module: An observational study. Clin Otolaryngol. 2018 Feb 16. [Epub ahead of print]
- Fleury CM, Schwitzer JA, Hung RW, Baker SB Adverse Event Incidences following Facial Plastic Surgery Procedures: Incorporating FACE-Q Data to Improve Patient Preparation. Plast Reconstr Surg. 2018 Jan;141(1):28e-33e
- van der Lei B, Bouman T. Validating Facial Aesthetic Surgery Results with the FACE-Q. Plast Reconstr Surg. 2018 Jan;141(1):184e-185e.
- Hindin DI, Muetterties CE, Lee JC, Kumar A, Kawamoto HK, Bradley JP. Internal Distraction Resulted in Improved Patient-Reported Outcomes for Midface Hypoplasia. J Craniofac Surg. 2018 Jan;29(1):139-143.
- Mess SA. Lower Face Rejuvenation with Injections: Botox, Juvederm, and Kybella for Marionette Lines and Jowls. Plast Reconstr Surg Glob Open. 2017 Nov 9;5(11):e1551.
- Weinkle SH, Werschler WP, Teller CF, Sykes JM, Shamban A, Rivkin A, Narurkar VA, Kaminer MS, Dayan S, Cohen JL, Gallagher CJ. Impact of Comprehensive, Minimally Invasive, Multimodal Aesthetic Treatment on Satisfaction With Facial Appearance: The HARMONY Study. Aesthet Surg J. 2017 Dec 13.
- Kaye KO, Kästner S, Paprottka FJ, Gonser P. The liquid facelift: First hands-on experience with facial water jet-assisted liposuction as an additive technique for rhytidectomy – a case series of 25 patients. J Plast Reconstr Aesthet Surg. 2018 Feb;71(2):171-177. Epub 2017 Nov 2.
- East C, Badia L, Marsh D, Pusic A, Klassen AF. Measuring Patient-Reported Outcomes in Rhinoplasty Using the FACE-Q: A Single Site Study. Facial Plast Surg. 2017 Oct;33(5):461-469.
- van der Lei B, Bouman T. Validating Facial Aesthetic Surgery Results with the FACE-Q. Plast Reconstr Surg. 2018 Jan;141(1):184e-185e.
- Tan SK, Leung WK, Tang ATH, Tse ECM, Zwahlen RA. Orthognathic Relevant Scales of FACE-Q: Translation and Validation for Hong Kong Chinese Patients. Plast Reconstr Surg Glob Open. 2017 Dec 28;5(12):e1608.
- Chen B, Song H, Gao Q, Xu M, Wang J, Wang F, Chen S, Wu J, Li H. Measuring satisfaction with appearance: Validation of the FACE-Q scales for double-eyelid blepharoplasty with minor incision in young Asians- retrospective study of 200 cases. J Plast Reconstr Aesthet Surg. 2017 Aug;70(8):1129-1135.
- Qureshi AA, Parikh RP, Sharma K, Myckatyn TM, Tenenbaum MM. Nonsurgical Facial Rejuvenation: Outcomes and Safety of Neuromodulator and Soft-Tissue Filler Procedures Performed in a Resident Cosmetic Clinic. Aesthetic Plast Surg. 2017 Oct;41(5):1177-1183.
- East C, Badia L, Marsh D, Pusic A, Klassen AF. Measuring Patient-Reported Outcomes in Rhinoplasty Using the FACE-Q: A Single Site Study. Facial Plast Surg. 2017 Oct;33(5):461-469.
- Cogliandro A, Barone M, Persichetti P. Italian Linguistic Validation of the FACE-Q Instrument. JAMA Facial Plast Surg. 2017 Jul 1;19(4):336-337.
- Geronemus RG, Bank DE, Hardas B, Shamban A, Weichman BM, Murphy DK. Safety and Effectiveness of VYC-15L, a Hyaluronic Acid Filler for Lip and Perioral Enhancement: One-Year Results From a Randomized, Controlled Study. Dermatol Surg. 2017 Mar;43(3):396-404.
- Tenna S, Cogliandro A, Barone M, Panasiti V, Tirindelli M, Nobile C, Persichetti P. Comparative Study Using Autologous Fat Grafts Plus Platelet-Rich Plasma With or Without Fractional CO2 Laser Resurfacing in Treatment of Acne Scars: Analysis of Outcomes and Satisfaction With FACE-Q. Aesthetic Plast Surg. 2017 Jun;41(3):661-666.
- Gualdi A, Cambiaso-Daniel J, Gatti J, Bertossi D, Pietramaggiori G, Scherer SS, Wurzer P, Lumenta DB. Minimal Undermining Suspension Technique (MUST): Combined Eyebrow and Mid-face Lift via Temporal Access. Aesthetic Plast Surg. 2017 Feb;41(1):40-46.
- Derby BM, Codner MA. Evidence-Based Medicine: Face Lift. Plast Reconstr Surg. 2017 Jan;139(1):151e-167e.
- Dobbs T, Hutchings HA, Whitaker IS. UK-based prospective cohort study to anglicise and validate the FACE-Q Skin Cancer Module in patients with facial skin cancer undergoing surgical reconstruction: the PROMISCR (Patient-Reported Outcome Measure in Skin Cancer Reconstruction) study. BMJ Open. 2017 Sep 24;7(9):e016182.
- Barone M, Cogliandro A, Di Stefano N, Aronica R, Tambone V, Persichetti P. Linguistic validation of the “FACE-Q Rhinoplasty Module” in Italian. Eur Arch Otorhinolaryngol. 2017 Mar;274(3):1771-1772.
- Geronemus RG, Bank DE, Hardas B, Shamban A, Weichman BM, Murphy DK. Safety and Effectiveness of VYC-15L, a Hyaluronic Acid Filler for Lip and Perioral Enhancement: One-Year Results From a Randomized, Controlled Study. Dermatol Surg. 2017 Mar;43(3):396-404.
- Tenna S, Cogliandro A, Barone M, Panasiti V, Tirindelli M, Nobile C, Persichetti P. Comparative Study Using Autologous Fat Grafts Plus Platelet-Rich Plasma With or Without Fractional CO2 Laser Resurfacing in Treatment of Acne Scars: Analysis of Outcomes and Satisfaction With FACE-Q. Aesthetic Plast Surg. 2017 Jan 26.
- Hersant B, SidAhmed-Mezi M, Chossat A, Meningaud JP. Multifractional microablative laser combined with spacially modulated ablative (SMA) technology for facial skin rejuvenation. Lasers Surg Med. 2017 Jan;49(1):78-83.
- Ishii LE. Using Patient-Reported Outcome Measures to Optimize Results-From Good to Great. JAMA Facial Plast Surg. 2017 Jan 1;19(1):14-15.
- Adams WP Jr, Toriumi DM, Van Natta BW. Clinical Use of GalaFLEX in Facial and Breast Cosmetic Plastic Surgery. Aesthet Surg J. 2016 Nov; 36(suppl_2): S23-S32.
- Ho D, Jagdeo J. Patient Reported Outcomes from HIV Facial Lipoatrophy Treatment With a Volumizing Hyaluronic Acid Filler: A Prospective, Open-Label, Phase I and II Study. J Drugs Dermatol. 2016 Sep 1;15(9):1064-9.
- Chang BL, Wilson AJ, Taglienti AJ, Chang CS, Folsom N, Percec I. Patient Perceived Benefit in Facial Aesthetic Procedures: FACE-Q as a Tool to Study Botulinum Toxin Injection Outcomes. Aesthet Surg J. 2016 Jul;36(7):810-20.
- Tepavcevic B, Radak D, Jovanovic M, Radak S, Tepavcevic DK. The Impact of Facial Lipofilling on Patient-Perceived Improvement in Facial Appearance and Quality of Life. Facial Plast Surg. 2016 Jun;32(3):296-303.
- Klassen AF, Cano SJ, Pusic AL. Use of FACE-Q to Measure Quality of Life Following Aesthetic Facial Treatments. JAMA Facial Plast Surg. 2016 Mar-Apr;18(2):148-9.
- Hibler BP, Schwitzer J, Rossi AM. Assessing Improvement of Facial Appearance and Quality of Life after Minimally-Invasive Cosmetic Dermatology Procedures Using the FACE-Q Scales. J Drugs Dermatol. 2016 Jan;15(1):62-7.
- Ishii LE. Including the Patient Voice in Aesthetic Rhinoplasty Outcomes: A New Patient-Reported Outcome Tool for Rhinoplasty. JAMA Facial Plast Surg. 2016 Jan-Feb;18(1):35-6.
- Schwitzer JA, Albino FP, Mathis RK, Scott AM, Gamble L, Baker SB. Assessing Patient-Reported Outcomes Following Orthognathic Surgery and Osseous Genioplasty. J Craniofac Surg. 2015 Nov;26(8):2293-8.
- Sinno S, Schwitzer JA, Anzai L, Thorne C. Facelift Satisfaction Using the FACE-Q. Plast Reconstr Surg. 2015 Oct;136(4 Suppl):144.
- Raspaldo H, Chantrey J, Belhaouari L, Saleh R, Murphy DK. Juvéderm volbella with lidocaine for lip and perioral enhancement: a prospective, randomized, controlled trial. Plast Reconstr Surg Glob Open. 2015 Apr 7;3(3):e321.
- Pusic A, Klassen A, Panchapakesan V, Cano S. Response to “The FACE-Q: the importance of full disclosure and sound methodology in outcomes studies”. Aesthet Surg J. 2014 May 1;34(4):628-31.
- Iorio ML, Stolle E, Brown BJ, Christian CB, Baker SB. Plastic surgery training: evaluating patient satisfaction with facial fillers in a resident clinic. Aesthetic Plast Surg. 2012 Dec;36(6):1361-6.
Our Team
Dr Anne Klassen
McMaster University, Canada
Q-Portfolio
Dr Andrea Pusic
Brigham and Women’s Hospital, USA
Q-Portfolio
Dr Stefan Cano
Modus Outcomes, UK
Q-Portfolio
Setting the Bar in
Patient Reported
Outcome Measurement
Funding Provided By:
BREAST-Q Recon MIDs —> Giving Meaning to Differences in BREAST-Q Scores: Minimal Important Difference for Breast Reconstruction Patients. - PubMed - NCBI @DrStefanCano @andrea_pusic @ThisIsManraj @elena_tsangaris https://t.co/UIDAlao0Cl
Exciting to see the uptake of FACE-Q | Aesthetics! Here's an example:
Significantly Increased Patient Satisfaction Following Liquid Formulation AbobotulinumtoxinA Treatment in Glabellar Lines: FACE-Q Outcomes From a P... - PubMed - NCBI https://t.co/qM8NGZ63kQ
Long-term Patient-reported Outcomes Following Postmastectomy Breast Reconstruction: An 8-year Examination of 3268 Patients. - PubMed - NCBI https://t.co/Gu8iLfwK9T
Comparing Nipple-sparing Mastectomy to Secondary Nipple Reconstruction: A Multi-institutional Study. - PubMed - NCBI https://t.co/ZpV7alzjJd
New CLEFT-Q publication: Further construct validation of the CLEFT-Q: Ability to detect differences in outcome for four cleft-specific surgeries
https://t.co/5srM5Ximje
Great to see FACE-Q Aesthetics used in clinical trials - Safety and Effectiveness of VYC-17.5L for Long-Term Correction of Nasolabial Folds. - PubMed - NCBI https://t.co/wrl2UdvGv8