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Authors = Damir Hudetz ORCID = 0000-0003-0883-2525

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12 pages, 2167 KiB  
Article
Eccentric Exercises on the Board with 17-Degree Decline Are Equally Effective as Eccentric Exercises on the Standard 25-Degree Decline Board in the Treatment of Patellar Tendinopathy
by Vladimir Knež and Damir Hudetz
Medicina 2023, 59(11), 1916; https://doi.org/10.3390/medicina59111916 - 29 Oct 2023
Cited by 2 | Viewed by 4778
Abstract
Background and Objectives: Patellar tendinopathy is one of the most significant problems in jumping and running athletes. Eccentric quadriceps exercise has been introduced into the therapy of patients with patellar tendinopathy in order to avoid weakening the tendon during rehabilitation. The use [...] Read more.
Background and Objectives: Patellar tendinopathy is one of the most significant problems in jumping and running athletes. Eccentric quadriceps exercise has been introduced into the therapy of patients with patellar tendinopathy in order to avoid weakening the tendon during rehabilitation. The use of decline boards with a decline angle of 25° has been the cornerstone of therapy over the last two decades. Biomechanical studies have suggested that an equal or potentially better outcome could be achieved with lower angles of decline (up to 16°). Materials and Methods: In this present research, we compared the effects of two various decline board angles on the clinical outcome of patients treated for patellar tendinopathy by performing eccentric quadriceps exercises. Patients were randomly allocated into two groups: patients practicing on the standard board with a 25° decline, and patients practicing on the 17° decline (n = 35 per group). Results: After 6 weeks of exercise, we found a significant improvement in all the clinical scores (VISA-P score, KOOS score, Lysholm Knee Questionnaire/Tegner Activity Scale, and VAS scale) of treated patients. However, there was no significant difference between the patients who performed eccentric quadriceps exercises on the standard 25° decline board and those exercising on the 17° decline board. A smaller additional degree of improvement was visible at the end of the follow-up period (at 12 weeks), but, again, no statistical difference could be detected between the investigated groups. We conclude that both treatment options provide similar short-term and midterm benefits regarding improvements in pain and clinical scores. The improvement in clinical scores does not depend on age, sex, BMI, or the professional sport of the patient. Conclusions: Our findings encourage changes in the decline angle of the board in the case of a patient’s discomfort in order to achieve better compliance without affecting the recovery. Full article
(This article belongs to the Section Sports Medicine and Sports Traumatology)
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6 pages, 921 KiB  
Communication
Clinical Outcome of Arthroscopic Repair for Isolated Meniscus Tear in Athletes
by Goran Vrgoč, Filip Vuletić, Grgur Matolić, Alan Ivković, Damir Hudetz, Stjepan Bulat, Frane Bukvić and Saša Janković
Int. J. Environ. Res. Public Health 2023, 20(6), 5088; https://doi.org/10.3390/ijerph20065088 - 14 Mar 2023
Cited by 1 | Viewed by 2410
Abstract
Increased knowledge of the long-term destructive consequences of meniscectomy has created a shift towards operative repair of isolated meniscus lesions. However, in the literature the results of isolated meniscal repair in athletes currently remain underreported. Our objective was to investigate the clinical and [...] Read more.
Increased knowledge of the long-term destructive consequences of meniscectomy has created a shift towards operative repair of isolated meniscus lesions. However, in the literature the results of isolated meniscal repair in athletes currently remain underreported. Our objective was to investigate the clinical and functional outcomes as well as survival and return to sport in patients who underwent meniscal repair after isolated meniscal tear, with a focus on athletes (both professional and recreational) in the study population. This retrospective study included 52 athletes who underwent knee surgery for isolated meniscal tear between 2014 and 2020. Patients with concomitant ligamentous and/or chondral injury were not included in this study. The mean age of the patients was 25.5 years (ranging from 12 to 57 years). The mean follow-up period of all patients was 33.3 months (ranging 10 to 80 months). The mean purpose of the study was to report the return to sport. The International Knee Documentation Committee rating (IKDC), Lysholm score, the Knee Osteoarthritis Outcome Score (KOOS) and Tegner activity level were determined at the follow-up. Failure was defined as re-operation with meniscectomy or revision meniscal repair. In total, 44 out of 52 patients (85%) returned to their previous sports activities. At follow-up, the mean Lysholm score was 90, representing a good to excellent result. Assessment of KOOS (mean value 88.8) and IKDC (mean value 89) scores also showed good to excellent results. A mean level of Tegner scale was 6.2, indicating a relatively high level of sports participation. Failure was encountered in 8 out of 52 knees (15%). Therefore, isolated meniscal repair resulted in good to excellent knee function and most athletes can return to their previous level of sports participation. Full article
(This article belongs to the Special Issue Sports Medicine and Physical Rehabilitation)
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15 pages, 3617 KiB  
Communication
Results of Treating Mild to Moderate Knee Osteoarthritis with Autologous Conditioned Adipose Tissue and Leukocyte-Poor Platelet-Rich Plasma
by Vilim Molnar, Eduard Pavelić, Željko Jeleč, Petar Brlek, Vid Matišić, Igor Borić, Damir Hudetz, Eduard Rod, Dinko Vidović, Neven Starčević, Martin Čemerin, David C. Karli and Dragan Primorac
J. Pers. Med. 2023, 13(1), 47; https://doi.org/10.3390/jpm13010047 - 26 Dec 2022
Cited by 4 | Viewed by 3679
Abstract
Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Much progress has been made in regenerative medicine for the symptomatic treatment of KOA, including products containing stromal vascular fraction (SVF) and platelet-rich plasma (PRP). The aim of this study was to [...] Read more.
Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Much progress has been made in regenerative medicine for the symptomatic treatment of KOA, including products containing stromal vascular fraction (SVF) and platelet-rich plasma (PRP). The aim of this study was to evaluate clinical and radiological findings after the application of autologous conditioned adipose tissue (ACA) and leukocyte-poor PRP (LP-PRP) in patients with mild to moderate KOA. A total of 16 patients (eight male and eight female) with changes related to KOA on the magnetic resonance imaging (MRI), but without severe osteophytosis, full-thickness cartilage loss, or subchondral bone involvement were included in this study. Patients received an intraarticular, ultrasound-guided injection of ACA and LP-PRP. Clinical scores, including a visual analog scale for pain (VAS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were evaluated at baseline and at the three and six month follow-ups showing a statistically significant improvements at three and six months post-intervention. Furthermore, the delayed gadolinium-enhanced MRI of the cartilage (dGEMRIC) indices were evaluated at baseline and at the three and six month follow-ups showing no significant changes after treatment with ACA and LP-PRP, which were actually equal to the dGEMRIC indices measured in the control group (hyaluronic acid applied in contralateral knees without osteoarthritis). ACA with LP-PRP presents a viable minimally invasive therapeutic option for the clinical improvement of mild to moderate KOA. However, MFAT produced by different systems is likely to differ in cellular content, which can directly affect the paracrine effect (cytokine secretion) of mesenchymal stem cells and consequently the regeneration process. Full article
(This article belongs to the Special Issue Personalized Medicine for Orthopaedic Disorders)
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17 pages, 6028 KiB  
Article
Polychromatic Flow Cytometric Analysis of Stromal Vascular Fraction from Lipoaspirate and Microfragmented Counterparts Reveals Sex-Related Immunophenotype Differences
by Lucija Zenic, Denis Polancec, Damir Hudetz, Zeljko Jelec, Eduard Rod, Dinko Vidovic, Mario Staresinic, Srecko Sabalic, Trpimir Vrdoljak, Tadija Petrovic, Fabijan Cukelj, Vilim Molnar, Martin Cemerin, Vid Matisic, Petar Brlek, Zrinka Djukic Koroljevic, Igor Boric, Gordan Lauc and Dragan Primorac
Genes 2021, 12(12), 1999; https://doi.org/10.3390/genes12121999 - 16 Dec 2021
Cited by 9 | Viewed by 3474
Abstract
Mesenchymal stem/stromal cells or medicinal signaling cells (MSC)-based therapy holds promise as a beneficial strategy for treating knee OA (osteoarthritis), but there is no standardized protocols nor mechanistic understanding. In order to gain a better insight into the human MSC from adipose tissue [...] Read more.
Mesenchymal stem/stromal cells or medicinal signaling cells (MSC)-based therapy holds promise as a beneficial strategy for treating knee OA (osteoarthritis), but there is no standardized protocols nor mechanistic understanding. In order to gain a better insight into the human MSC from adipose tissue applied for autologous OA treatment, we performed extensive comparative immunophenotyping of the stromal vascular fraction from lipoaspirate or microfragmented lipoaspirates by polychromatic flow cytometry and investigated the cellular components considered responsible for cartilage regeneration. We found an enrichment of the regenerative cellular niche of the clinically applied microfragmented stromal vascular fraction. Sex-related differences were observed in the MSC marker expression and the ratio of the progenitor cells from fresh lipoaspirate, which, in female patients, contained a higher expression of CD90 on the three progenitor cell types including pericytes, a higher expression of CD105 and CD146 on CD31highCD34high endothelial progenitors as well as of CD73 on supra-adventitialadipose stromal cells. Some of these MSC-expression differences were present after microfragmentation and indicated a differential phenotype pattern of the applied MSC mixture in female and male patients. Our results provide a better insight into the heterogeneity of the adipose MSC subpopulations serving as OA therapeutics, with an emphasis on interesting differences between women and men. Full article
(This article belongs to the Special Issue Genetics and Stem Cell Research)
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23 pages, 3005 KiB  
Review
Cytokines and Chemokines Involved in Osteoarthritis Pathogenesis
by Vilim Molnar, Vid Matišić, Ivan Kodvanj, Roko Bjelica, Željko Jeleč, Damir Hudetz, Eduard Rod, Fabijan Čukelj, Trpimir Vrdoljak, Dinko Vidović, Mario Starešinić, Srećko Sabalić, Borut Dobričić, Tadija Petrović, Darko Antičević, Igor Borić, Rok Košir, Uršula Prosenc Zmrzljak and Dragan Primorac
Int. J. Mol. Sci. 2021, 22(17), 9208; https://doi.org/10.3390/ijms22179208 - 26 Aug 2021
Cited by 398 | Viewed by 25898
Abstract
Osteoarthritis is a common cause of disability worldwide. Although commonly referred to as a disease of the joint cartilage, osteoarthritis affects all joint tissues equally. The pathogenesis of this degenerative process is not completely understood; however, a low-grade inflammation leading to an imbalance [...] Read more.
Osteoarthritis is a common cause of disability worldwide. Although commonly referred to as a disease of the joint cartilage, osteoarthritis affects all joint tissues equally. The pathogenesis of this degenerative process is not completely understood; however, a low-grade inflammation leading to an imbalance between anabolic and katabolic processes is a well-established factor. The complex network of cytokines regulating these processes and cell communication has a central role in the development and progression of osteoarthritis. Concentrations of both proinflammatory and anti-inflammatory cytokines were found to be altered depending on the osteoarthritis stage and activity. In this review, we analyzed individual cytokines involved in the immune processes with an emphasis on their function in osteoarthritis. Full article
(This article belongs to the Special Issue Osteoarthritis: From Molecular Pathways to Therapeutic Advances)
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20 pages, 356 KiB  
Review
Comprehensive Review of Knee Osteoarthritis Pharmacological Treatment and the Latest Professional Societies’ Guidelines
by Dragan Primorac, Vilim Molnar, Vid Matišić, Damir Hudetz, Željko Jeleč, Eduard Rod, Fabijan Čukelj, Dinko Vidović, Trpimir Vrdoljak, Borut Dobričić, Darko Antičević, Martina Smolić, Mladen Miškulin, Damir Ćaćić and Igor Borić
Pharmaceuticals 2021, 14(3), 205; https://doi.org/10.3390/ph14030205 - 2 Mar 2021
Cited by 75 | Viewed by 13758
Abstract
Osteoarthritis is the most common musculoskeletal progressive disease, with the knee as the most commonly affected joint in the human body. While several new medications are still under research, many symptomatic therapy options, such as analgesics (opioid and non-opioid), nonsteroid anti-inflammatory drugs, symptomatic [...] Read more.
Osteoarthritis is the most common musculoskeletal progressive disease, with the knee as the most commonly affected joint in the human body. While several new medications are still under research, many symptomatic therapy options, such as analgesics (opioid and non-opioid), nonsteroid anti-inflammatory drugs, symptomatic slow-acting drugs in osteoarthritis, and preparations for topical administration, are being used, with a diverse clinical response and inconsistent conclusions across various professional societies guidelines. The concept of pharmacogenomic-guided therapy, which lies on principles of the right medication for the right patient in the right dose at the right time, can significantly increase the patient’s response to symptom relief therapy in knee osteoarthritis. Corticosteroid intra-articular injections and hyaluronic acid injections provoke numerous discussions and disagreements among different guidelines, even though they are currently used in daily clinical practice. Biological options, such as platelet-rich plasma and mesenchymal stem cell injections, have shown good results in the treatment of osteoarthritis symptoms, greatly increasing the patient’s quality of life, especially when combined with other therapeutic options. Non-inclusion of the latter therapies in the guidelines, and their inconsistent stance on numerous therapy options, requires larger and well-designed studies to examine the true effects of these therapies and update the existing guidelines. Full article
(This article belongs to the Special Issue Drug and Therapy for Osteoarthritis (OA))
35 pages, 2504 KiB  
Review
Knee Osteoarthritis: A Review of Pathogenesis and State-Of-The-Art Non-Operative Therapeutic Considerations
by Dragan Primorac, Vilim Molnar, Eduard Rod, Željko Jeleč, Fabijan Čukelj, Vid Matišić, Trpimir Vrdoljak, Damir Hudetz, Hana Hajsok and Igor Borić
Genes 2020, 11(8), 854; https://doi.org/10.3390/genes11080854 - 26 Jul 2020
Cited by 311 | Viewed by 34940
Abstract
Being the most common musculoskeletal progressive condition, osteoarthritis is an interesting target for research. It is estimated that the prevalence of knee osteoarthritis (OA) among adults 60 years of age or older is approximately 10% in men and 13% in women, making knee [...] Read more.
Being the most common musculoskeletal progressive condition, osteoarthritis is an interesting target for research. It is estimated that the prevalence of knee osteoarthritis (OA) among adults 60 years of age or older is approximately 10% in men and 13% in women, making knee OA one of the leading causes of disability in elderly population. Today, we know that osteoarthritis is not a disease characterized by loss of cartilage due to mechanical loading only, but a condition that affects all of the tissues in the joint, causing detectable changes in tissue architecture, its metabolism and function. All of these changes are mediated by a complex and not yet fully researched interplay of proinflammatory and anti-inflammatory cytokines, chemokines, growth factors and adipokines, all of which can be measured in the serum, synovium and histological samples, potentially serving as biomarkers of disease stage and progression. Another key aspect of disease progression is the epigenome that regulates all the genetic expression through DNA methylation, histone modifications, and mRNA interference. A lot of work has been put into developing non-surgical treatment options to slow down the natural course of osteoarthritis to postpone, or maybe even replace extensive surgeries such as total knee arthroplasty. At the moment, biological treatments such as platelet-rich plasma, bone marrow mesenchymal stem cells and autologous microfragmented adipose tissue containing stromal vascular fraction are ordinarily used. Furthermore, the latter two mentioned cell-based treatment options seem to be the only methods so far that increase the quality of cartilage in osteoarthritis patients. Yet, in the future, gene therapy could potentially become an option for orthopedic patients. In the following review, we summarized all of the latest and most important research in basic sciences, pathogenesis, and non-operative treatment. Full article
(This article belongs to the Special Issue Genes at Ten)
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9 pages, 214 KiB  
Article
A 24-Month Follow-Up Study of the Effect of Intra-Articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis
by Igor Borić, Damir Hudetz, Eduard Rod, Željko Jeleč, Trpimir Vrdoljak, Andrea Skelin, Ozren Polašek, Mihovil Plečko, Irena Trbojević-Akmačić, Gordan Lauc and Dragan Primorac
Genes 2019, 10(12), 1051; https://doi.org/10.3390/genes10121051 - 17 Dec 2019
Cited by 56 | Viewed by 5655
Abstract
Osteoarthritis (OA) is a widely prevalent disease worldwide, and with an increasingly ageing society, it has become a challenge for the field of regenerative medicine. OA is a disease process involving multiple joint tissues, including those not visible on radiography, and is a [...] Read more.
Osteoarthritis (OA) is a widely prevalent disease worldwide, and with an increasingly ageing society, it has become a challenge for the field of regenerative medicine. OA is a disease process involving multiple joint tissues, including those not visible on radiography, and is a complex disease process with multiple phenotypes that require evaluation by a multimodality imaging assessment. The purpose of this study was to evaluate the effect of micro-fragmented fat tissue intra-articular injection 24 months after application in two ways: Indirectly using functional magnetic resonance imaging (MRI) assessment analyzing the glycosaminoglycans (GAG) content in cartilage by means of delayed gadolinium (Gd)-enhanced magnetic resonance imaging of cartilage (dGEMRIC), as well as clinical outcome on observed level of GAG using standard orthopedic physical examination including VAS assessment. In our previous study assessing comprehensive results after 12 months, the dGEMRIC results have drawn attention. The present study explores the long-term effect of intra-articular injection of autologous microfragmented adipose tissue to host chondrocytes and cartilage proteoglycans in patients with knee OA. A prospective, non-randomized, interventional, single-center, open-label clinical trial was conducted from January 2016 to April 2018. A total of 17 patients were enrolled in the study, and 32 knees were assessed in a 12-month follow-up, but only 10 patients of them with 18 knees are included in a 24-month follow-up. The rest of the seven patients dropped out of the study 12 months after follow-up: three patients underwent knee arthroplasty, and the remaining four did not fulfil the basic criteria of 24 months involvement in the study. Surgical intervention (lipoaspiration), followed by tissue processing and intra-articular injection of the final microfragmented adipose tissue product into the affected knee(s), was performed in all patients. Patients were assessed for a visual analog scale (VAS), dGEMRIC at the baseline, three, six, 12 and 24 months after the treatment. A magnetic resonance sequence in dGEMRIC due to infiltration of the anionic, negatively-charged contrast gadopentetate dimeglumine (Gd-DTPA2) into the cartilage indicated that the contents of cartilage glycosaminoglycans significantly increased in specific areas of the treated knee joint. Our results suggest that this method of single intra-articular injection of autologous microfragmented adipose tissue improves GAG content on a significant scale, with over half of the measurements suggesting relevant improvement 24 months after intra-articular injection opposed to the expected GAG decrease over the natural course of the disease. Full article
(This article belongs to the Special Issue Stem Cells Application in Clinical Practice: Advances and Challenges)
11 pages, 4024 KiB  
Communication
Immunophenotyping of a Stromal Vascular Fraction from Microfragmented Lipoaspirate Used in Osteoarthritis Cartilage Treatment and Its Lipoaspirate Counterpart
by Denis Polancec, Lucija Zenic, Damir Hudetz, Igor Boric, Zeljko Jelec, Eduard Rod, Trpimir Vrdoljak, Andrea Skelin, Mihovil Plecko, Mirjana Turkalj, Boro Nogalo and Dragan Primorac
Genes 2019, 10(6), 474; https://doi.org/10.3390/genes10060474 - 21 Jun 2019
Cited by 31 | Viewed by 5327
Abstract
Osteoarthritis (OA) is a degenerative joint disease accompanied by pain and loss of function. Adipose tissue harbors mesenchymal stem/stromal cells (MSC), or medicinal signaling cells as suggested by Caplan (Caplan, 2017), used in autologous transplantation in many clinical settings. The aim of the [...] Read more.
Osteoarthritis (OA) is a degenerative joint disease accompanied by pain and loss of function. Adipose tissue harbors mesenchymal stem/stromal cells (MSC), or medicinal signaling cells as suggested by Caplan (Caplan, 2017), used in autologous transplantation in many clinical settings. The aim of the study was to characterize a stromal vascular fraction from microfragmented lipoaspirate (SVF-MLA) applied for cartilage treatment in OA and compare it to that of autologous lipoaspirate (SVF-LA). Samples were first stained using a DuraClone SC prototype tube for the surface detection of CD31, CD34, CD45, CD73, CD90, CD105, CD146 and LIVE/DEAD Yellow Fixable Stain for dead cell detection, followed by DRAQ7 cell nuclear dye staining, and analyzed by flow cytometry. In SVF-LA and SVF-MLA samples, the following population phenotypes were identified within the CD45 fraction: CD31+CD34+CD73±CD90±CD105±CD146± endothelial progenitors (EP), CD31+CD34CD73±CD90±CD105CD146± mature endothelial cells, CD31CD34CD73±CD90+CD105CD146+ pericytes, CD31CD34+CD73±CD90+CD105CD146+ transitional pericytes, and CD31CD34+CD73highCD90+CD105CD146 supra-adventitial-adipose stromal cells (SA-ASC). The immunophenotyping profile of SVF-MLA was dominated by a reduction of leukocytes and SA-ASC, and an increase in EP, evidencing a marked enrichment of this cell population in the course of adipose tissue microfragmentation. The role of EP in pericyte-primed MSC-mediated tissue healing, as well as the observed hormonal implication, is yet to be investigated. Full article
(This article belongs to the Special Issue Stem Cells Application in Clinical Practice: Advances and Challenges)
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17 pages, 5400 KiB  
Article
The Effect of Intra-articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis
by Damir Hudetz, Igor Borić, Eduard Rod, Željko Jeleč, Andrej Radić, Trpimir Vrdoljak, Andrea Skelin, Gordan Lauc, Irena Trbojević-Akmačić, Mihovil Plečko, Ozren Polašek and Dragan Primorac
Genes 2017, 8(10), 270; https://doi.org/10.3390/genes8100270 - 13 Oct 2017
Cited by 91 | Viewed by 9128
Abstract
Osteoarthritis (OA) is one of the leading musculoskeletal disorders in the adult population. It is associated with cartilage damage triggered by the deterioration of the extracellular matrix tissue. The present study explores the effect of intra-articular injection of autologous microfragmented adipose tissue to [...] Read more.
Osteoarthritis (OA) is one of the leading musculoskeletal disorders in the adult population. It is associated with cartilage damage triggered by the deterioration of the extracellular matrix tissue. The present study explores the effect of intra-articular injection of autologous microfragmented adipose tissue to host chondrocytes and cartilage proteoglycans in patients with knee OA. A prospective, non-randomized, interventional, single-center, open-label clinical trial was conducted from January 2016 to April 2017. A total of 17 patients were enrolled in the study, and 32 knees with osteoarthritis were assessed. Surgical intervention (lipoaspiration) followed by tissue processing and intra-articular injection of the final microfragmented adipose tissue product into the affected knee(s) was performed in all patients. Patients were assessed for visual analogue scale (VAS), delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and immunoglobulin G (IgG) glycans at the baseline, three, six and 12 months after the treatment. Magnetic resonance sequence in dGEMRIC due to infiltration of the anionic, negatively charged contrast gadopentetate dimeglumine (Gd-DTPA2−) into the cartilage indicated that the contents of cartilage glycosaminoglycans significantly increased in specific areas of the treated knee joint. In addition, dGEMRIC consequently reflected subsequent changes in the mechanical axis of the lower extremities. The results of our study indicate that the use of autologous and microfragmented adipose tissue in patients with knee OA (measured by dGEMRIC MRI) increased glycosaminoglycan (GAG) content in hyaline cartilage, which is in line with observed VAS and clinical results. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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