{"paper_id":"b87eed55-5649-4db9-bfc7-d61ae3be1cc5","body_text":"Osteopathy is a complementary medical practice involving manual manipulation to treat the joints and myofascial system function [ 1 - 10 ]. It was first described in the United States in the 19th century and has been developed and is practiced worldwide [ 2 ,  11 ,  12 ]. In France, the Kouchner law of March 2002 created the title \"osteopath\" for these non-healthcare professionals (non-doctors, non-physiotherapists) [ 6 ]. The decree of March 25, 2007, regulated its practice, making it possible to consult these professional therapists for first-line treatment [ 13 ,  14 ]. It is important to note, however, that this specialty includes several backgrounds of non-healthcare professionals as well as healthcare professionals such as doctors and physical therapists. The law states that osteopaths may perform external, non-instrumental manipulations for the prevention and treatment of functional disorders but not for organic diseases requiring medical, surgical, or drug treatments or physical agents [ 13 ,  14 ]. Osteopaths are represented by several societies in France depending on the practitioner's background [ 15 ].\nThe reasons for consulting osteopaths are diverse, but musculoskeletal pain is the main cause, representing 61% of visits. Other reasons include perinatal and pediatric conditions (11.8%), cranial and neurological disorders (9.1%), visceral disorders (5%), and preventive care (0.2%) [ 2 ,  16 ]. Osteopathic consultations for children are often for sleep disorders, unexplained crying, cranial asymmetries, and gastroesophageal reflux [ 2 ,  16 ].\nOsteopathy includes numerous techniques, for example, osteopathic manipulative treatment (OMT), which uses hands-on interventions for diagnosis and treatment, and myofascial release (MFR) for targeting fascial tension [ 4 - 10 ]. Additional methods such as cervical, visceral, and thoracic spine manipulation focus on specific regions and joints [ 5 ,  7 ,  17 - 19 ] in particular, balanced ligamentous tension, diaphragm doming, indirect diaphragm release, high-velocity low amplitude, lymphatic pump, and rib raising techniques [ 2 ]. Pediatric integrative manual therapy (PIMT) has been developed for infants and children [ 20 ].\nDespite the marked increase in the number of scientific articles published in recent decades, osteopathy is still considered to be an \"unconventional healthcare practice\" whose benefits and risks have not been sufficiently defined.\nThe aim of this study was to perform a systematic review (SR) of publications in the literature with a high level of evidence [ 21 ] for the main indications of osteopathy. The secondary aim was to assess French osteopathy society recommendations in relation to the existing literature and guidelines from the French National Health Authority (HAS), which is the highest healthcare regulatory body in France.\n\nMaterial and methods\nThis systematic review was performed according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [ 22 ], with one modification: when level one evidence studies were available, level two to five studies were excluded.\nEligibility Criteria\nInclusion criteria were accessible, level one evidence, French and English language studies that evaluated the indications for osteopathy, such as systematic reviews, meta-analyses, and randomized clinical trials (RCT), and level two to three evidence studies, when no level one studies were available. Any official recommendations available on the sites of French professional healthcare organizations and societies were included.\nThe level of evidence assessment was based on the Oxford Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence classification [ 21 ].\nExclusion criteria were level two to five evidence studies when a level one study was available, unavailable abstracts, non-retrievable manuscripts, manual treatments that were not osteopathic, and articles published before January 2012.\nOutcomes\nThe primary outcome was the level of evidence in the literature supporting osteopathic practices [ 21 ].\nThe secondary outcome was to assess French professional osteopathy recommendations and French HAS guidelines in relation to the scientific literature.\nSearch Strategy\nAn in-depth search of the literature from January 2012 to January 2022 was performed in the PubMed and Cochrane databases. Keywords included \"specific indications\" AND (\"osteopathic manipulative therapy,\" OR \"manual therapy\", OR \"osteopathic manipulative treatment\", OR \"osteopathic manipulative medicine\"). The search also included French HAS (previously called ANAES for Agence nationale d'accréditation et d'évaluation en santé) recommendations using keywords for \"specific indications\" AND (\"ostéopathie\" OR \"thérapie manuelle\" OR \"manipulation\", OR \"recommendation de bonne pratique\"). Indication keywords were based on the indications recommended by French osteopathy organizations, syndicates, and societies.\nStudy Selection\nTwo independent researchers conducted the research and independently assessed the articles for inclusion or exclusion based on predetermined criteria. In cases where there was a discrepancy or uncertainty regarding the inclusion or exclusion of an article, a third researcher was consulted to provide additional input and help reach a consensus decision. Duplicates were removed by an automatic tool using Rayan Software® [ 23 ]. A three-step process was followed for PubMed and Cochrane articles. First, the title was screened for inclusion based on eligibility criteria and to exclude duplicates. Then, the abstract was analyzed to confirm inclusion and to group articles by indication, and categories such as preventive treatment, musculoskeletal complaints, neurosensory complaints, digestive complaints, pulmonary complaints, pediatric issues, and women's health concerns were created. Finally, the full-text manuscript was analyzed for data extraction.\nAll recommendations from French healthcare or regulatory organizations and societies for osteopathic practices corresponding to the specific indication were included.\nData Extraction\nData extraction included the main indication for each disease category, manual techniques used, conclusion, recommendations, and level of evidence.\nData Synthesis\nIn the review, a narrative synthesis was performed to provide a comprehensive summary and interpretation of the findings from included studies. These studies were grouped together into predefined categories, such as preventive treatment, musculoskeletal disorders, neurosensory disorders, digestive disorders, pulmonary disorders, pediatric disorders, and women's health. A meta-analysis or a quantitative summary could not be performed because of the type of analysis.\nResults\nStudy Selection\nA total of 11,295 articles were initially identified through database searches. After removing duplicates (3249), articles before 2012 (3457), and other low-evidence studies such as case reports, editorial comments, letters, and opinions, 3462 articles remained for title and abstract screening. Following the screening process, 694 articles were considered to be potentially eligible for inclusion, and their full-text versions were assessed for eligibility. A total of 51 articles met the inclusion criteria and were included in the SR. Eight HAS guidelines were also included in the analysis (Figure  1 ).\nPRISMA - Preferred Reporting Items for Systematic Reviews and Meta-Analyses, HAS- Haute autorité de santé (French National Authority for Health), SFR- Société Francaise de Rhumatologie (French Society of Rheumatology), SNFGE- Société savante médicale française d’hépato-gastroentérologie et d’oncologie digestive (French National Society of Gastroenterology and Digesstive Oncology)\nIndications for Osteopathy\nBased on the analysis of French osteopathy organization and society guidelines, 41 osteopathic indications were evaluated (Appendix 1, Table  1 ) [ 24 - 29 ].\nGER - gastroesophageal reflux, ADHD - attention deficit hyperactivity disorder\nMusculoskeletal Indications\nLower back pain (LBP): In one randomized controlled study, Nguyen et al. compared two osteopathic techniques for the treatment of LBP, and found that standard OMT was more beneficial for LBP-specific activity limitations than a control sham treatment, while both techniques were beneficial to functional status [ 30 ]. Several systematic reviews showed that OMT reduced LBP and improved function [ 1 ,  10 ,  31 ]. MFR was shown to be the most effective technique for reducing chronic LBP pain [ 31 ].\nNeck pain: A systematic review by Gross et al. showed that the effect of cervical manipulation was similar to that of cervical mobilization for pain, function, and patient satisfaction in adults with neck pain [ 32 ]. Corp et al. performed a systematic review and concluded that osteopathy, as part of manual therapy, can improve neck pain [ 33 ]. A study by Bagagiolo et al. suggested that OMT was effective for musculoskeletal disorders, including neck pain [ 1 ]. Masaracchio et al. performed an SR and a meta-analysis and concluded that thoracic spine manipulation (TSM) provided a short-term benefit for neck pain, but further research was needed to determine its long-term effectiveness [ 18 ]. An SR and meta-analysis by Fredin et al. concluded that a combination of osteopathy and exercise therapy was not more effective in reducing the severity of neck pain, neck disability, or in improving the quality of life than exercise therapy alone [ 4 ].\nIdiopathic scoliosis (IS): Czaprowski performed an SR to investigate the efficacy of nonspecific manual therapy (NMT), in particular manual therapy, chiropractic, and osteopathy, in the treatment of children and adolescents with IS [ 5 ]. Six studies were included and the results of the small number of studies in the literature were contradictory. These studies had certain methodological biases, such as small patient groups, incomplete descriptions of study groups, lack of follow-up, and an absence of control groups. The author concluded that the efficacy of NMT was limited for this indication [ 5 ].\nSciatica and cruralgia: Lewis et al. performed an SR and meta-analysis (MA) to investigate the clinical effectiveness of different treatment strategies for sciatica [ 34 ]. They identified 122 relevant studies, including 90 RCTs, and grouped interventions into 21 treatment strategies. The study found that there was a statistically significant improvement in overall recovery following disc surgery, epidural injections, non-opioid analgesia, manipulation (spinal OMT), and acupuncture compared to inactive controls or conventional care [ 34 ].\nCervical radiculopathy: Boyles et al. performed an SR of RCTs to investigate the effectiveness of manual therapy in treating cervical radiculopathy [ 19 ]. They identified four studies with a high level of evidence and showed that using manual therapy techniques in association with therapeutic exercise is effective in increasing function and range of motion as well as in decreasing pain and disability [ 19 ].\nAnkle sprain: A RCT by Eisenhart et al. found that patients with acute grade 1-2 ankle sprain who received OMT in the emergency department experienced statistically significant improvement in edema, pain, and range of motion [ 35 ]. An SR by Seah et al. showed that the outcome of functional treatment options, including OMT, were statistically better than immobilization for mild-to-moderate ankle sprains in primary care, while severe sprains required a short period of immobilization [ 36 ].\nLateral epicondylitis: The results in the literature are not conclusive. An SR by Hoogvliet et al. showed that OMT provided a short-term benefit [ 37 ]. Bisset et al. found that local elbow manipulation has an immediate benefit for pain-free grip strength and the pressure pain threshold, but studies were based on a single treatment session and lacked long-term follow-up [ 38 ].\nTemporomandibular joint disorder (TMD): In an RCT by Cuccia et al., patients who received OMT required less pain medication than those who received standard conservative therapy [ 6 ]. This beneficial effect seems to be optimized when combined with orofacial treatment [ 7 ]. An SR by Calixtre et al. provided evidence to support the benefits of OMT depending on the technique. They concluded that osteopathy is beneficial but recommended further studies for stronger clinical proof [ 8 ]. A meta-analysis by Martins et al. reported a significant improvement in active mouth opening and pain, in particular, a short-term benefit [ 9 ].\nArmijo-Olivo et al. performed an SR to evaluate the effectiveness of manual therapy and therapeutic exercise for TMD [ 39 ]. They found low-level evidence with no clear results to show that exercise was more effective than other conservative treatments for TMD. Nevertheless, the effects of manual therapy alone or in combination with exercises were found to be promising [ 39 ].\nNeurosensory and Psychological Indications\nTension headache (TH): Krøll et al. performed an SR and MA to investigate the effects of various treatments, including OMT, on the frequency of TH and quality of life. Results showed that OMT could reduce the frequency of headaches and improve the quality of life during follow-up, although the overall level of evidence was low [ 40 ]. In a related RCT, Espí-López et al. compared the effect of different OMT techniques on the quality of life of patients with tension-type headaches [ 41 ]. They found that all three treatments (suboccipital inhibitory pressure, suboccipital spinal manipulation, and a combination of the two) were effective in improving various dimensions of the patients' quality of life, with the best results with combined treatment. Treatment was found to be effective after as early as four weeks [ 41 ].\nMigraine headache: Rist et al. performed an SR and MA to investigate the impact of spinal manipulation on migraine pain and disability [ 42 ]. An analysis of RCTs with a pooled total of 677 patients showed that spinal manipulation reduced the severity of pain and the duration of migraines. However, these results should be considered preliminary because of the limitations of the included studies [ 42 ].\nVertigo: Tramontano et al. performed an SR to investigate the effects of OMT in the management of patients with vertigo and balance disorders. Their results showed a weak benefit to balance disorders across different outcomes in all of the included studies (unclear) [ 43 ].\nPediatric Indications\nCranial malformation and plagiocephaly: An RCT by Pastor-Pons et al. showed significantly greater improvement in the average Oblique Diameter (ODDI) for infants in the PIMT group, which decreased from 107.9% to 103.9% than in the control group. Other studies have confirmed these results and suggest that PIMT can improve cranial asymmetries in infants with nonsynostotic occipital plagiocephaly [ 44 ,  45 ].\nTorticollis: Pastor-Pons et al. found PIMT to be effective in the treatment of cervical movement limitations in infants with positional plagiocephaly (PP), in particular with significant improvement in active rotation range of motion and neuromotor development. The results of the SR by Ellwood et al. were similar [ 46 ]. OMT was found to be moderately effective in increasing the range of motion in patients with torticollis.\nPremature births: Lanaro et al. analyzed five RCTs including 1306 infants. They found that osteopathy reduced the length of hospital stay and costs with no reported adverse events [ 47 ].\nOther pediatric indications: There was insufficient evidence to confirm the effectiveness of manipulative therapies for idiopathic scoliosis [ 48 - 50 ] and ADHD [ 51 ]. The results for infant colic were mixed, and methodological limitations made it impossible to draw definite conclusions [ 52 - 54 ]. The study by Jones et al. did not show any significant benefits to OMT for child asthma [ 55 ]. A study by Danielo Jouhier et al. showed that OMT did not improve exclusive breastfeeding at one month [ 56 ].\nGynecological\nFertility: The SR by Ruffini et al. examined the effectiveness of OMT for infertility. The evaluated outcomes were hormone levels, conception, pregnancy rates, and quality of life [ 57 ]. Results suggested that OMT improved conception rates in women with secondary idiopathic infertility. However, the definitions of successful delivery rates and pregnancy complications were inconsistent, and adverse events were not reported [ 57 ].\nEndometriosis: A prospective cohort study by Daraï et al. showed that OMT improved symptoms and quality of life in patients with colorectal endometriosis [ 58 ]. This same group also performed a prospective pilot study evaluating OMT in patients with deep infiltrating endometriosis (DIE) and colorectal involvement that showed significant improvement in quality of life [ 59 ].\nBack and pelvic pain in pregnancy: Franke et al. found in their systematic review that osteopathy benefits pregnant or postpartum women with LBP [ 60 ]. Licciardone et al., in an RCT of 144 pregnant women, determined that osteopathy mitigates back-specific functioning decline in the third trimester [ 61 ]. Hall et al. concluded from their review of 1198 pregnant women that evidence is limited for manual therapies addressing pregnancy-related LBP and pelvic pain [ 62 ].\nDigestive\nGastroesophageal reflux (GERD): Lynen et al. performed an RCT in 70 patients with GERD and found that visceral OMT resulted in a statistically significant improvement in the Quality of Life in Reflux and Dyspepsia questionnaire [ 17 ]. Similar results were reported by Eguaras et al. [ 63 ].\nConstipation: A pilot study by Belvaux et al. in 21 female patients with chronic constipation suggests that visceral OMT could improve functional constipation and defecation disorders [ 64 ].\nIrritable bowel syndrome (IBS): Attali et al. performed an RCT in 31 consecutive refractory IBS patients and found that visceral osteopathy improved short-term and long-term outcomes in patients with IBS [ 65 ].\nPulmonary\nAsthma: An SR of manual therapies for the treatment of patients with bronchial asthma by Hondras et al. concluded that there was insufficient evidence to recommend the use of manual therapy for patients with asthma [ 66 ].\nHAS Recommendation\nThe indications for osteopathy recommended by the HAS [ 67 - 74 ] are summarized in Table  2 .\nHAS- Haute autorité de santé (French National Authority for Health), SFR- Société Francaise de Rhumatologie (French Society of Rheumatology), SNFGE- Société savante médicale française d’hépato-gastroentérologie et d’oncologie digestive (French National Society of Gastroenterology and Digesstive Oncology), IBS - irritable bowel syndrome\nThe summary of the included studies and their findings is presented in Table  3 .\nLBP - low back pain, OMT - osteopathic manual therapy, RCT - randomized controlled trial, CLBP - chronic low back pain, MFR - myofascial release, SRs/MAs - systematic reviews/meta-analyses, NSLBP - nonspecific low back pain, CNSNP - chronic nonspecific neck pain, CNCP - chronic non-cancer pain, IBS - irritable bowel syndrome, CPGs - clinical practice guidelines, MT - manual therapy, ET - exercise therapy, IS - idiopathic scoliosis, CR - cervical radiculopathy, TMD - temporomandibular joint disorder, TTH - tension-type headache, GERD - gastroesophageal reflux disease, KESS - Knowles-Eccersley-Scott Symptom Questionnaire, VAS - Visual Analog Scale, FEV1 - forced expiratory volume in one second, FVC - forced vital capacity, AROM - active rotation range of motion, PP- positional plagiocephaly, ODDI - Oblique Diameter Difference Index, PIMT- pediatric integrative manual therapy, NSOP - nonsynostotic occipital plagiocephaly, EDI - Ear Deviation Index, CPI - Cranial Proportional Index, CVA - cranial vault asymmetry, SBA - skull base asymmetry, TCVA - total cranial vault asymmetry, AIMS - Alberta Infant Motor Scale, CMT - congenital muscular torticollis, WHOQOL-BREF - World Health Organization Quality of Life-Brief version, ADHD - attention deficit hyperactivity disorder, QOL - quality of life.\nSummary of the recommendations for osteopathy in relation to HAS and the results in the literature (Table  4 )\nHAS- Haute Autorité de Santé (French National Authority for Health), N-O - no opinion, GERD - gastroesophageal reflux disease, TMJ- temporomandibular joint, ADHD - attention deficit hyperactivity disorder\nMost of the 41 indications examined (33/41, 80.49%) are not mentioned in HAS recommendations, while 18 (43.9%) lack high-evidence studies in the overall scientific literature. A total of five indications (12.2%) were recommended by HAS, and nine (21.95%) were supported by high-level evidence in the literature. The results are inconclusive for two indications (4.88%) for HAS and for seven indications (17.07%) in the literature.\nDiscussion\nThe main finding of this review is that only nine of the osteopathy indications proposed by the French osteopathy societies are justified in the literature, while five are supported by French HAS recommendations.\nOur review shows that the main indication for osteopathy is the musculoskeletal system, with the greatest number of RCTs and SRs. This confirms previous reviews on this topic [ 2 ,  16 ]. Although it is sometimes underestimated by orthopedic surgeons, rheumatologists, and general practitioners, osteopathy has been shown to be effective for pain control and the management of certain conditions such as LBP in adults and pregnant women, acute sciatica, mild to moderate ankle sprain, and TMD [ 1 ,  6 - 8 ,  10 ,  19 ,  30 ,  31 ,  34 - 36 ,  39 ]. All included SRs and meta-analyses agree on the beneficial effect of OMT for nonspecific LBP [ 1 ,  10 ,  31 ], in particular, the RCT by Nguyen et al., which reported improved functional scores [ 30 ]. However, the only difference between OMT and sham groups in that study was -3.4 at three months and -4.3 at 12 months on the Quebec Back Pain Disability Index (QBPDI) scores [ 30 ], which raises concerns that results may not reach the minimally clinically important difference (MCID). Osteopathy also seems to be beneficial for acute sciatica and cervical radiculopathy [ 19 ,  34 ]. The benefits of osteopathy for various spinal conditions are highly important to orthopedic surgeons, who could include this technique as an adjunctive strategy for optimal results, to reduce the side effects of medication, and to limit the indication for surgery. The use of osteopathy could be even more critical for LBP and pelvic pain in pregnant women because of the limited options in this population [ 60 ]. However, it must be noted that the level of evidence for these recommendations is low.\nModerate-level evidence was found for osteopathy in the treatment of acute ankle sprains [ 35 ,  36 ]. Most of the articles in the SR by Seah and Mani-Babu used OMT as an adjunctive therapy. However, it is important to note that the exact contribution of osteopathic manipulation to the observed improvements remains unclear because it is often combined with other functional treatments [ 36 ]. Although certain studies have shown that osteopathy helps improve TMD, with better mouth opening and reduced pain [ 6 ,  7 ,  9 ], the quality of evidence varies across studies, and does not clearly show that osteopathy is better than standard treatment options [ 6 - 9 ,  39 ].\nThe results in the literature on osteopathic treatment for neck pain are mixed, with methodological quality and levels of evidence ranging from very low to moderate, making it difficult to determine the role of this technique [ 18 ,  32 ,  33 ]. HAS recommendations are cautious for this indication [ 68 ] and associated with precautions for cervical manipulation [ 75 ]. HAS notes that cervical imaging is not always necessary in the absence of red flags. In cases of non-traumatic neck pain, imaging is immediately indicated when associated with red flags such as neurological signs and symptoms, and should be considered for episodes that last more than 4 to six weeks. Further high-quality research is needed to confirm the efficacy and safety of osteopathic treatment and improve clinical practices for neck pain management [ 75 ]. The indications for lateral and medial epicondylitis are inconclusive and report only short-term benefits, with no long-term studies [ 37 ,  38 ]. Osteopathy has not been shown to be beneficial for idiopathic scoliosis [ 5 ].\nHeadaches, in particular tension-type headaches, are a common public health problem that can significantly influence a person's quality of life [ 40 ,  41 ]. Our review shows that osteopathic treatment can effectively reduce the frequency and severity of headaches while improving quality of life [ 40 ,  41 ]. The mechanism of action of these benefits may be the reduction of pro-inflammatory substances, increase in parasympathetic tone, and the management of underlying factors that contribute to the development of headaches, such as muscle tension, joint dysfunction, and postural imbalances [ 40 ,  41 ,  76 ].\nStudies show that osteopathy may reduce the number of migraines but not improve their severity [ 42 ]. However, the evidence remains inconclusive due to methodological issues and biases. The evidence for vertigo and balance disorders is also insufficient to draw clear conclusions on the effectiveness of osteopathy [ 43 ].\nOur review shows that osteopathy helps reduce the length of hospital stay and the cost of treatment in premature infants [ 47 ]. The mechanisms of action include reducing pro-inflammatory substances and enhancing the lymphatic and immune systems [ 61 ,  77 - 79 ]. Other indications such as cranial malformation and plagiocephaly, torticollis, idiopathic scoliosis, infantile colic, attention-deficit/hyperactivity disorder, and asthma have mixed results and lack consistent evidence for the effectiveness of OMT [ 20 ,  44 - 46 ,  49 - 53 ,  55 ]. While some studies show positive outcomes for these conditions, others have methodological limitations or do not support the use of OMT.\nOur review suggests that the results of osteopathy are promising in women with endometriosis [ 58 ,  59 ]; however, the evidence supporting this assertion is limited. The HAS recommendation also supports this potential benefit, but more robust and well-designed studies are needed [ 71 ].\nThe results of the included studies showed a potential benefit for the symptoms of GERD and IBS; however, the overall quality of the evidence was not strong enough to make a clear recommendation [ 17 ,  63 ,  65 ].\nAlthough OMT is generally well tolerated [ 80 ], only a few studies included in our review clearly defined adverse effects [ 1 ,  10 ,  31 ,  60 ]. Among the nine indications supported by the literature, no severe adverse effects have been reported when adverse events were documented [ 1 ,  10 ,  31 ,  60 ,  80 ]. However, this cannot be confirmed for all indications. Authors must report in detail the approach used to measure adverse events, which need to be specifically defined and categorized.\nLimitations\nThis study has certain limitations. Although some of the conclusions are based on high-level evidence, the results should be interpreted with caution due to the methodological quality of the reviews and trials, which were sometimes low. Blinding was an issue in most of the RCTs due to the difficulty of blinding patients to the osteopath and the absence of sham therapy in the control group. There may also be a performance bias because patients in an RCT receive special care from the osteopath, which could affect the outcomes. The difference in the quality of the included studies is also a limitation. The methodology of the systematic review involved the exclusion of lower-level evidence studies when higher-level evidence was available; this approach may have resulted in the exclusion of relevant studies that could have contributed to a comprehensive analysis. Thus, the results should be extrapolated with caution. The types and duration of the osteopathic treatment also varied, and most studies focused on the short-term outcomes of therapy.\nDespite these limitations, these results have important implications for both clinical practice and future research. Physicians should consider incorporating osteopathic therapy into their treatment plans.\n\nIn conclusion, this systematic review shows that osteopathy has evidence-based benefits for numerous conditions, in particular for musculoskeletal and neurosensory indications. However, more high-quality studies are needed to evaluate and validate the effectiveness of this technique for other indications. Recommendations from the French HAS and in the literature provide a valuable basis for clinicians and patients to understand the potential applications of osteopathy in healthcare. HAS does not recommend systematic radiography of the cervical spine before manipulation.","source_license":"CC-BY-4.0","license_restricted":false}