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Harnessing Photobiomodulation Light for Therapeutic or Prevention of Human Diseases

A special issue of Journal of Clinical Medicine (ISSN 2077-0383).

Deadline for manuscript submissions: closed (28 February 2026) | Viewed by 38881

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Guest Editor
1. Department of Restorative Dental Sciences, UCL-Eastman Dental Institute, Medical Faculty, London WC1E 6DE, UK
2. Department of Surgical Sciences and Integrated Diagnostics, Laser Centre Therapy, University of Genoa, 16132 Genoa, Italy
Interests: laser therapy; photobiomodulation; laser–tissue/matter interaction; oral surgery; oral medicine and pathology; orofacial and neuropathic pain; bone regeneration; suppotive care for cancer; neurorehabilitation
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Special Issue Information

Dear Colleagues,

The human antioxidant system works as a complex unit to regulate reactive oxygen species (ROS). Cellular antioxidant defenses usually maintain ROS/reactive nitrogen species (RNS) at a concentration level that prevents an excess oxidation of cellular molecules. Mitochondrial dysfunction can result in a reduction in thesynthesis of high-energy molecules such as adenosine triphosphate (ATP). Given the fundamental role of the mitochondrial organelle, organs and tissues require effective antioxidant therapy to illuminate the mitochondria, augment ATP production, and regulate ROS and nitric oxide to restore mitochondrial function. This is crucial in the management of several diseases. In this context, photobiomodulation (PBM) therapy has emerged as a non-invasive treatment modality in the management of pain, accelerating tissue repair and regeneration, due to its significant biomodulatory and anti-inflammatory effects. The aim of this Special Issue is to underline the advances of PBM in the management of diseases, as well as the advanced research on regenerative biomaterials and their interactions with the PBM light to optimise clinical performance and ultimately enhance patients’ quality of life. Both original research and review papers are welcomed.

Prof. Dr. Reem Hanna
Guest Editor

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Keywords

  • neurorehabilitation
  • supportive care for cancer
  • reproductive health
  • dental and oral diseases
  • viral and bacterial diseases
  • wound care
  • dermatology
  • sports rehabilitation
  • bone and musculoskeletal diseases
  • PBM mechanism
  • ophthalmology
  • stem cells and regenerative medicine
  • pain and addiction management
  • PBM-tissue interaction

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Published Papers (9 papers)

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Research

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13 pages, 2794 KB  
Article
Assessment of Dose-Dependent Effects of 1064 nm Photobiomodulation Therapy on Tenocyte- and Bursa-Derived Cell Proliferation In Vitro
by Zachary W. Sigman, Stefan Minyayluk, Andrew K. Chow, Sophia Blaine, Mary Beth McCarthy, Mark Cote, Marco T. Di Stefano, Monica Monici, Scott A. Sigman and Augustus D. Mazzocca
J. Clin. Med. 2026, 15(7), 2716; https://doi.org/10.3390/jcm15072716 - 3 Apr 2026
Viewed by 448
Abstract
Background/Objectives: Photobiomodulation Therapy (PBMT) is widely used in musculoskeletal rehabilitation. Although its clinical use continues to expand, the dose-dependent metabolic responses on specific musculoskeletal cell populations remain undefined. This study assessed the effects of 1064 nm PBMT on primary human tenocytes and [...] Read more.
Background/Objectives: Photobiomodulation Therapy (PBMT) is widely used in musculoskeletal rehabilitation. Although its clinical use continues to expand, the dose-dependent metabolic responses on specific musculoskeletal cell populations remain undefined. This study assessed the effects of 1064 nm PBMT on primary human tenocytes and bursa-derived cells across varying fluence and irradiance. Methods: Primary tenocytes and bursa-derived cells were cultured in 24-well plates and exposed to Hiro TT 1064 nm laser at fluences ranging from 1.5 to 6.0 J/cm2 and irradiance levels of 90 or 125 mW/cm2. Treatments were administered once daily for three consecutive days. Cellular activity was assessed using an XTT assay and bright field microscopy was performed to assess cell morphology and confluency. Statistical analysis was compared to evaluate dose-dependent effects. Results: PBMT demonstrated tissue-dependent effects on cellular metabolic activity and proliferation. In tenocytes, moderate fluence (4.5–6.0 J/cm2) significantly increased metabolic activity compared with control. In contrast, bursa-derived cells exhibited smaller magnitude changes, with most treatment groups demonstrating neutral or modest deviations from control. Conclusions: PBMT of 1064 nm wavelenght produced distinct dose-dependent responses in musculoskeletal cell types, with tenocytes demonstrating a threshold-dependent response and bursa-derived cells showing attenuated effects. These findings support the need for tissue-specific parameters when applying PBMT in clinical tendon-related applications. Full article
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13 pages, 673 KB  
Article
Photobiomodulation Therapy (PBMT) with Dual-Wavelength Enhances Reduction of Inflammation After Third Molar Extraction Compared with Red Laser PBMT: A Randomized Clinical Trial
by Davisson Alves Pereira, Mariana Silva Bonatto, Carlos José Soares, Samara de Souza Santos, Roberto Sales e Pessoa, Maurício Andres Tinajero Aroni and Guilherme José Pimentel Lopes de Oliveira
J. Clin. Med. 2026, 15(7), 2467; https://doi.org/10.3390/jcm15072467 - 24 Mar 2026
Viewed by 413
Abstract
Background/Objectives: Photobiomodulation (PBMT) has been shown to improve tissue healing; however, the best protocol for different clinical challenges is not clearly determined. Despite the good previous outcomes of the PBMT in healing of the third molar surgical sites, the ideal protocol of PBMT [...] Read more.
Background/Objectives: Photobiomodulation (PBMT) has been shown to improve tissue healing; however, the best protocol for different clinical challenges is not clearly determined. Despite the good previous outcomes of the PBMT in healing of the third molar surgical sites, the ideal protocol of PBMT was not determined. The objective of this split-mouth double-blinded randomized clinical trial was to compare the effect of photobiomodulation (PBMT) with red and infrared wavelengths combined and PBMT with only red wavelength on the healing of post-extraction alveoli of third molars. Methods: Twenty patients underwent third molar extraction. The alveoli were treated randomly in a split mouth model with: PBMT with red laser (R-PBMT) or PBMT with red and infrared laser combined (IR-R-PBMT). PBMT was applied immediately, and 3 and 7 days after surgery. Patients were clinically evaluated in relation to repair (bleeding, exudate, color, and consistency of the tissues), degree of the edema, and through the application of a VAS scale (pain, edema, bleeding, chewing, and mouth opening) in the baseline period, and 3, 7, 14, 30, and 90 days after the surgical procedure. In addition, bone tissue density and structure were measured by radiographic analysis at 7 and 90 days postoperatively. Results: Clinical analysis showed that IR-R-PBMT induce more reduction in the edema 7 days after surgery compared with the R-PBMT; however, no significant differences were noted between groups in other parameters. Conclusions: IR-R-PBMT reduces the edema after 7 days of third molar extraction compared with the R-PBMT. Registration: This study was registered with the Brazilian Registry of Clinical Trials (REBEC-RBR-103g7j28; date of registration 12 July 2023) under number U1111-1297-6962. Full article
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15 pages, 2346 KB  
Article
Neurometabolite Changes After Transcranial Photobiomodulation in Major Depressive Disorder: A Randomized Controlled Trial Investigating Dose-Dependent Effects
by David R. A. Coelho, Ümit Tural, Aura Maria Hurtado Puerto, Katherine Anne Collins, Maia Beth Gersten, Zamfira Parincu, Kari Siu, Dan Vlad Iosifescu, Eva-Maria Ratai, Paolo Cassano and Akila Weerasekera
J. Clin. Med. 2025, 14(10), 3402; https://doi.org/10.3390/jcm14103402 - 13 May 2025
Cited by 2 | Viewed by 2807
Abstract
Background: Transcranial photobiomodulation (t-PBM) is a promising non-invasive therapy for Major Depressive Disorder (MDD). MDD is associated with altered brain metabolism, including changes in N-acetylaspartate (NAA), choline (Cho), and creatine (Cr). This study assessed the effects of varying t-PBM doses on neurometabolite levels [...] Read more.
Background: Transcranial photobiomodulation (t-PBM) is a promising non-invasive therapy for Major Depressive Disorder (MDD). MDD is associated with altered brain metabolism, including changes in N-acetylaspartate (NAA), choline (Cho), and creatine (Cr). This study assessed the effects of varying t-PBM doses on neurometabolite levels in the dorsolateral prefrontal cortex (dlPFC) and their correlations with clinical outcomes. Methods: In this randomized, sham-controlled, cross-over study, 33 adults with MDD received one session of t-PBM at low, medium, and high doses and a sham treatment. Proton magnetic resonance spectroscopy (1H-MRS) measured NAA, Cho, and Cr pre- and post-treatment. Clinical outcomes were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Symptoms of Depression Questionnaire (SDQ). Statistical analyses included paired t-tests or Wilcoxon signed-rank tests for neurometabolite changes, and linear mixed-effects regression models for t-PBM dose, neurometabolites, and time effects. Results: NAA levels increased significantly (7.52 ± 0.777 to 8.12 ± 1.05 mmol/L for one session; 7.36 ± 0.85 to 7.85 ± 0.68 mmol/L across all sessions); however, these changes were not associated with specific t-PBM doses or sham. No significant changes were observed for Cho and Cr levels. Positive correlations were found between Cho levels and MADRS scores (r = 0.59, p = 0.017), and negative correlations between Cr levels and SDQ scores at the medium dose (r = −0.91, p = 0.011). Conclusions: While NAA levels increased, and correlations between neurometabolites and clinical outcomes were observed, these findings do not suggest a specific effect of t-PBM. Larger randomized controlled trials with optimized dosing protocols, extended follow-up, and advanced spectroscopy are needed to clarify the neurometabolic therapeutic potential of t-PBM in MDD. Full article
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15 pages, 3258 KB  
Article
Health-Related Quality of Life with Iatrogenic Inferior Alveolar Nerve Injuries Treated with Photobiomodulation: A Comparative Study
by João Mendes de Abreu, Tiago Nunes, Pedro A. Almiro, José Figueiredo and Ana Corte-Real
J. Clin. Med. 2024, 13(23), 7237; https://doi.org/10.3390/jcm13237237 - 28 Nov 2024
Cited by 4 | Viewed by 4247
Abstract
Background/Objectives: Photobiomodulation therapy (PBM) creates a biostimulatory or modulatory effect, promoting tissue regeneration and improving patients’ health-related quality of life (HRQoL). PBM has shown promise as an effective treatment and management strategy for peripheral nerve injuries, including inferior alveolar nerve (IAN) damage. [...] Read more.
Background/Objectives: Photobiomodulation therapy (PBM) creates a biostimulatory or modulatory effect, promoting tissue regeneration and improving patients’ health-related quality of life (HRQoL). PBM has shown promise as an effective treatment and management strategy for peripheral nerve injuries, including inferior alveolar nerve (IAN) damage. This study aims to assess the impact of PBM on HRQoL in patients with iatrogenic IAN injuries. Methods: A prospective study was implemented to investigate the research question. PBM treatments were administered weekly, with patient discharge contingent upon either complete recovery or stabilization of associated signs and symptoms. HRQoL was assessed using the EQ-5D-5L questionnaire at the initial and final appointments. Results: The study included 71 participants, divided into 3 groups based on etiology: inferior third molar surgery, mandibular orthognathic surgery, and dental implant surgery. The results showed a widespread reduction of symptoms along with a statistically significant improvement (p < 0.001) across four of the five dimensions of the EQ-5D-5L questionnaire, as well as in patients’ perceived health levels in both Groups I and II. Group III patients also demonstrated a notable improvement; however, due to the small sample size, statistical analysis was not conducted for this group. Conclusions: PBM demonstrated a comparable ability to enhance HRQoL and alleviate symptoms in patients with IAN injuries within different etiologies. These findings underscore the effectiveness of the protocol used in this study and highlight potential avenues for expanding research in this field. Full article
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25 pages, 2650 KB  
Article
The Efficacy of Multiwavelength Red and Near-Infrared Transdermal Photobiomodulation Light Therapy in Enhancing Female Fertility Outcomes and Improving Reproductive Health: A Prospective Case Series with 9-Month Follow-Up
by Ruth Phypers, Venera Berisha-Muharremi and Reem Hanna
J. Clin. Med. 2024, 13(23), 7101; https://doi.org/10.3390/jcm13237101 - 24 Nov 2024
Cited by 3 | Viewed by 14537
Abstract
Background/Objectives: Female infertility due to unexpected causes exhibits a great challenge for both clinicians and women who are trying to conceive. The present clinical case series study aimed to evaluate the efficacy of multiple wavelengths of red and near-infrared (NIR) laser photobiomodulation [...] Read more.
Background/Objectives: Female infertility due to unexpected causes exhibits a great challenge for both clinicians and women who are trying to conceive. The present clinical case series study aimed to evaluate the efficacy of multiple wavelengths of red and near-infrared (NIR) laser photobiomodulation (PBM) for increasing the potential of fertility in women and improving reproductive health in unexplained infertility issues. The objectives were to assess the following: (1) any adverse effects; (2) the possibility of producing an effective PBM protocol; (3) and healthy live birth. The inclusion criteria were to related to females who failed to conceive naturally beyond two years, multiple miscarriages, molar pregnancy, non-viable embryos from in vitro fertilisation (IVF) cycles, and failure to complete successful implantation of viable pre-implantation genetic tested (PGT-A) embryos. Methods: Case series of three female subjects with unexplained age-related infertility issues, which included a failure to conceive naturally beyond two years, multiple miscarriages, molar pregnancy, non-viable embryos from IVF cycles, and failure to complete successful implantation of viable pre-implantation genetic tested (PGT-A) embryos. In each case, previous conditions were recorded and then compared with outcomes after the patient received a course of PBM treatments. In every case, fertility outcomes improved. Three cases resulted in a full-term pregnancy and the birth of a healthy baby. PBM treatments were given at weekly and/or at two-week intervals using IR and NIR wavelengths between 600 nm and 1000 nm in the lead up to natural conception, IVF oocyte retrieval, blastocyst/embryo implantation, and/or the production of viable embryos. Results: In every case, fertility outcomes improved. Improvements in reproductive health outcomes in each case give reason to suggest that PBM may help to improve unexplained age-related infertility. Conclusions: Our study demonstrated that multiwavelength of red and NIR PBM with either an LED or laser, or a combination, improved female fertility and reproductive health and contributed to healthy live births in females diagnosed with unexplained age-related infertility. Extensive studies with robust data are warranted to validate our PBM dosimetry and treatment protocols. Moreover, understanding the genetic and phenotype biomarkers is important to standardise a range of PBM light dosimetry. Full article
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Review

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17 pages, 295 KB  
Review
Exploring Photobiomodulation as a Potential Novel Intervention for Developmental Stuttering: A Review and Hypothesis
by Borja Ignacio Ferreras, Manuela Goyeneche, Paolo Cassano, Frank H. Guenther and Victoria Tumanova
J. Clin. Med. 2026, 15(5), 2041; https://doi.org/10.3390/jcm15052041 - 7 Mar 2026
Viewed by 706
Abstract
Developmental stuttering (DS) is a complex neurodevelopmental disorder affecting approximately 5% of children, characterized by involuntary disruptions in speech fluency. Despite its prevalence, the precise pathophysiology remains elusive, and current behavioral and pharmacological interventions often yield variable long-term efficacy. This scoping review evaluates [...] Read more.
Developmental stuttering (DS) is a complex neurodevelopmental disorder affecting approximately 5% of children, characterized by involuntary disruptions in speech fluency. Despite its prevalence, the precise pathophysiology remains elusive, and current behavioral and pharmacological interventions often yield variable long-term efficacy. This scoping review evaluates the therapeutic potential of transcranial photobiomodulation (t-PBM), a non-invasive neuromodulation technique, by summarizing its mechanisms of action with the known neurophysiological deficits of DS. Evidence indicates that DS is associated with reduced regional cerebral blood flow (rCBF) in Broca’s area, mitochondrial dysfunction, and impaired neural connectivity. t-PBM may address these deficits by stimulating cytochrome c oxidase, thereby increasing ATP production and triggering nitric oxide-mediated vasodilation to enhance rCBF. Furthermore, t-PBM promotes neuroplasticity, modulates astrocyte function—potentially counteracting GNPTAB-related deficits—and exhibits anxiolytic effects that may alleviate the secondary psychological burden of DS. By targeting these multifactorial underpinnings, t-PBM may represent a promising, low-risk adjunct or primary intervention for DS, though this remains to be tested empirically. While the theoretical framework is robust, clinical trials are needed to determine whether t-PBM has therapeutic utility, to optimize treatment parameters, establish longitudinal efficacy, and explore synergistic effects with established speech-language therapies. Full article

Other

Jump to: Research, Review

21 pages, 1704 KB  
Systematic Review
Photobiomodulation Therapy in Hypertension Management—Evidence from a Systematic Review and Meta-Analysis
by Lara Maria Bataglia Espósito, Francisco Costa da Rocha, Praveen R. Arany and Cleber Ferraresi
J. Clin. Med. 2025, 14(19), 6716; https://doi.org/10.3390/jcm14196716 - 23 Sep 2025
Cited by 1 | Viewed by 3385
Abstract
Background: Hypertensive patients have difficulties in controlling blood pressure (BP), resulting in high mortality rates. There is a growing number of lab and human studies investigating the effects of photobiomodulation (PBM) therapy on hypertension. This motivated the current work to systematically assess existing [...] Read more.
Background: Hypertensive patients have difficulties in controlling blood pressure (BP), resulting in high mortality rates. There is a growing number of lab and human studies investigating the effects of photobiomodulation (PBM) therapy on hypertension. This motivated the current work to systematically assess existing literature and group evidence on the utility of PBM in BP management. Methods: A systematic review with meta-analysis was performed on randomized clinical trials (RCTs) and experimental animal studies assessing PBM treatments in hypertensive patients/animals. Five primary databases were assessed by two reviewers. Descriptive and quantitative analyses were performed separately for clinical and experimental studies. Results: A total of 197 articles were screened that identified four RCTs and five experimental studies for final inclusion. The clinical trials noted that PBM treatments reduced systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR), but with very low certainty. Experimental lab studies corroborated that PBM treatments reduced SBP, DBP, and mean arterial pressure (MAP) while increasing nitric oxide levels, again with very low certainty. Overall, RCTs had a high risk of bias, and experimental studies had an unclear risk of bias. Conclusions: PBM treatments have the potential to be an adjunct therapy for the treatment of hypertension, with studies showing a possible reduction in SBP, DBP, MAP, and HR, but the evidence is of very low certainty, coming from RCTs with a high risk of bias and experimental studies with an unclear risk of bias. The current evidence needs to be significantly improved with rigorous, well-designed experimental and clinical studies. Full article
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12 pages, 547 KB  
Study Protocol
A Pilot Study Comparing Intraoral and Transcutaneous Photobiomodulation for Oral Mucositis in Head and Neck Cancer Patients Undergoing Radiotherapy or Chemoradiotherapy
by Jordan Eber, Anna Schohn, Hélène Carinato, Youssef Brahimi, Martin Schmitt and Georges Noël
J. Clin. Med. 2025, 14(7), 2430; https://doi.org/10.3390/jcm14072430 - 2 Apr 2025
Cited by 2 | Viewed by 4964
Abstract
Background: Photobiomodulation (PBM) therapy has shown potential in managing oral mucositis (OM), a frequent and painful side effect of radiotherapy or chemoradiotherapy in head and neck cancer patients. Although PBM is increasingly used in clinical settings, the optimal delivery method—transcutaneous or intraoral—remains [...] Read more.
Background: Photobiomodulation (PBM) therapy has shown potential in managing oral mucositis (OM), a frequent and painful side effect of radiotherapy or chemoradiotherapy in head and neck cancer patients. Although PBM is increasingly used in clinical settings, the optimal delivery method—transcutaneous or intraoral—remains undetermined. Methods: This prospective, single-center, randomized pilot study (clinicaltrials.gov NCT06458517) aims to compare the efficacy of transcutaneous versus intraoral PBM in preventing and managing OM in patients undergoing radiotherapy or chemoradiotherapy for cancers of the oral cavity or oropharynx. Participants will be randomized into two groups: one receiving intraoral PBM with the CareMin650™ device, and the other receiving transcutaneous PBM with the ATP38® device. Results: Primary and secondary outcomes will include the incidence and severity of OM, treatment interruptions, patient-reported pain levels, and quality of life, assessed using validated tools. Conclusions: This study will provide comparative data on two PBM modalities, contributing to the development of standardized PBM protocols in supportive oncology care and informing future multicenter trials aimed at improving patient outcomes during radiotherapy for head and neck cancer. Full article
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14 pages, 495 KB  
Protocol
Efficacy and Safety of Photobiomodulation in MELAS: Protocol for a Series of N-of-1 Trials
by E-Liisa Laakso, Tatjana Ewais, Katie McMahon, Josephine Forbes and Liza Phillips
J. Clin. Med. 2025, 14(6), 2047; https://doi.org/10.3390/jcm14062047 - 17 Mar 2025
Cited by 2 | Viewed by 5312
Abstract
Background: There is no cure for mitochondrial diseases which manifest in numerous ways including fatigue, muscle weakness, and exercise intolerance. Medical treatment varies and focuses on managing symptoms. Photobiomodulation (PBM) can decrease mitochondrial damage thereby increasing energy production and decreasing cell death. [...] Read more.
Background: There is no cure for mitochondrial diseases which manifest in numerous ways including fatigue, muscle weakness, and exercise intolerance. Medical treatment varies and focuses on managing symptoms. Photobiomodulation (PBM) can decrease mitochondrial damage thereby increasing energy production and decreasing cell death. This pilot study will apply PBM to people with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) to examine the safety of application, and if changes occur in symptoms and signs after cross-over application/withdrawal of a sham or active PBM treatment including a two-week period of washout. Methods: This study is an exploratory, prospective series N-of-1 (single patient) studies. The protocol is guided by the CONSORT extension for reporting N-of-1 trials (CENT 2015), chosen due to the rarity of mitochondrial diseases, the fluctuating symptomology, and heterogeneity of the clinical presentation. The primary outcome is patient-reported fatigue assessed using the Checklist of Individual Strength and with concomitant evaluation of safety. Secondary measures are of depression, anxiety and stress, sleepiness, physical activity, blood lactate and creatine kinase, physical measures of sit-to-stand, and heel raise capability. Mitochondrial function will be evaluated using hydrogen magnetic resonance spectroscopy for lactate. PBM will be a participant-administered, home-based therapy using a multiple diode flexible array (BeniLight iLED-Pro Multi-Wave Multi-Pulse belt; 465 nm, 660 nm, 850 nm; average irradiance 5.23 mW/cm2; total joules: 770.1 J/treatment, all sites; 5 KHz; 20% duty ratio) over the anterior thigh muscles, posterior calf muscles and abdomen for 10 min to each site, three times/week. The safety of the intervention will be assessed. Descriptive statistics, causal analyses of time series data and dynamic modelling will be applied as relevant to the variables collected. Hydrogen magnetic resonance spectra will be acquired and averaged to obtain the content of the targeted hydrogen levels. Discussion: The study will provide guidance on whether and how to progress to a larger, randomised cohort study with sham control. Full article
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