المؤلفون: Lara Riem, Olivia DuCharme, Matthew Cousins, Xue Feng, Allison Kenney, Jacob Morris, Stephen J. Tapscott, Rabi Tawil, Jeff Statland, Dennis Shaw, Leo Wang, Michaela Walker, Leann Lewis, Michael A. Jacobs, Doris G. Leung, Seth D. Friedman, Silvia S. Blemker

المصدر: Scientific Reports, Vol 14, Iss 1, Pp 1-15 (2024)

مصطلحات موضوعية: MRI, FSHD, Fat fraction, Muscle volume, Progression, Atrophy, Medicine, Science

الوصف: Abstract Facioscapulohumeral muscular dystrophy (FSHD) affects roughly 1 in 7500 individuals. While at the population level there is a general pattern of affected muscles, there is substantial heterogeneity in muscle expression across- and within-patients. There can also be substantial variation in the pattern of fat and water signal intensity within a single muscle. While quantifying individual muscles across their full length using magnetic resonance imaging (MRI) represents the optimal approach to follow disease progression and evaluate therapeutic response, the ability to automate this process has been limited. The goal of this work was to develop and optimize an artificial intelligence-based image segmentation approach to comprehensively measure muscle volume, fat fraction, fat fraction distribution, and elevated short-tau inversion recovery signal in the musculature of patients with FSHD. Intra-rater, inter-rater, and scan-rescan analyses demonstrated that the developed methods are robust and precise. Representative cases and derived metrics of volume, cross-sectional area, and 3D pixel-maps demonstrate unique intramuscular patterns of disease. Future work focuses on leveraging these AI methods to include upper body output and aggregating individual muscle data across studies to determine best-fit models for characterizing progression and monitoring therapeutic modulation of MRI biomarkers.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/91ec51efc30a43b1bc3b900fc1f1aa19Test

المؤلفون: Campbell, Amy E, Dyle, Michael C, Albanese, Roberto, Matheny, Tyler, Sudheendran, Kavitha, Cortázar, Michael A, Forman, Thomas, Fu, Rui, Gillen, Austin E, Caruthers, Marvin H, Floor, Stephen N, Calviello, Lorenzo, Jagannathan, Sujatha

المصدر: Cell Reports. 42(6)

مصطلحات موضوعية: Biological Sciences, Bioinformatics and Computational Biology, Facioscapulohumeral Muscular Dystrophy, Rare Diseases, Stem Cell Research - Embryonic - Human, Stem Cell Research, Genetics, Brain Disorders, Intellectual and Developmental Disabilities (IDD), Muscular Dystrophy, Aetiology, 2.1 Biological and endogenous factors, Humans, Gene Expression Regulation, Muscular Dystrophy, Facioscapulohumeral, Nonsense Mediated mRNA Decay, RNA, RNA-Binding Proteins, Serine-Arginine Splicing Factors, CP: Molecular biology, DUX4, FSHD, NMD, RNA decay, dystrophy, muscular, quality control, splicing, translation, Biochemistry and Cell Biology, Medical Physiology, Biological sciences

الوصف: Nonsense-mediated RNA decay (NMD) degrades transcripts carrying premature termination codons. NMD is thought to prevent the synthesis of toxic truncated proteins. However, whether loss of NMD results in widespread production of truncated proteins is unclear. A human genetic disease, facioscapulohumeral muscular dystrophy (FSHD), features acute inhibition of NMD upon expression of the disease-causing transcription factor, DUX4. Using a cell-based model of FSHD, we show production of truncated proteins from physiological NMD targets and find that RNA-binding proteins are enriched for aberrant truncations. The NMD isoform of one RNA-binding protein, SRSF3, is translated to produce a stable truncated protein, which is detected in FSHD patient-derived myotubes. Ectopic expression of truncated SRSF3 confers toxicity, and its downregulation is cytoprotective. Our results delineate the genome-scale impact of NMD loss. This widespread production of potentially deleterious truncated proteins has implications for FSHD biology as well as other genetic diseases where NMD is therapeutically modulated.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2qb0b5ndTest

المؤلفون: Cinzia Bettio, Federico Banchelli, Valentina Salsi, Roberto Vicini, Oscar Crisafulli, Lucia Ruggiero, Giulia Ricci, Elisabetta Bucci, Corrado Angelini, Angela Berardinelli, Silvia Bonanno, Maria Grazia D’Angelo, Antonio Di Muzio, Massimiliano Filosto, Erica Frezza, Lorenzo Maggi, Tiziana Mongini, Elena Pegoraro, Carmelo Rodolico, Marina Scarlato, Gaetano Vattemi, Daniele Velardo, Giuliano Tomelleri, Roberto D’Amico, Giuseppe D’Antona, Rossella Tupler

المصدر: BMC Musculoskeletal Disorders, Vol 25, Iss 1, Pp 1-9 (2024)

مصطلحات موضوعية: FSHD, Neuromuscular diseases, Sport medicine, Physical activity, Rare disease, Health promotion, Diseases of the musculoskeletal system, RC925-935

الوصف: Abstract Background In facioscapulohumeral muscular dystrophy (FSHD), it is not known whether physical activity (PA) practiced at young age is associated with the clinical presentation of disease. To assess this issue, we performed a retrospective cohort study concerning the previous practice of sports and, among them, those with medium-high cardiovascular commitment in clinically categorized carriers of a D4Z4 reduced allele (DRA). Methods People aged between 18 and 60 were recruited as being DRA carriers. Subcategory (classical phenotype, A; incomplete phenotype, B; asymptomatic carriers, C; complex phenotype, D) and FSHD score, which measures muscle functional impairment, were assessed for all participants. Information on PAs was retrieved by using an online survey dealing with the practice of sports at a young age. Results 368 participants were included in the study, average age 36.6 years (SD = 9.4), 47.6% male. The FSHD subcategory A was observed in 157 (42.7%) participants with average (± SD) FSHD score of 5.8 ± 3.0; the incomplete phenotype (category B) in 46 (12.5%) participants (average score 2.2 ± 1.7) and the D phenotype in 61 (16.6%, average score 6.5 ± 3.8). Asymptomatic carriers were 104 (subcategory C, 28.3%, score 0.0 ± 0.2). Time from symptoms onset was higher for patients with A (15.8 ± 11.1 years) and D phenotype (13.3 ± 11.9) than for patients with B phenotype (7.3 ± 9.0). The practice of sports was associated with lower FSHD score (-17%) in participants with A phenotype (MR = 0.83, 95% CI = 0.73–0.95, p = 0.007) and by 33% in participants with D phenotype (MR = 0.67, 95% CI = 0.51–0.89, p = 0.006). Conversely, no improvement was observed in participants with incomplete phenotype with mild severity (B). Conclusions PAs at a young age are associated with a lower clinical score in the adult A and D FSHD subcategories. These results corroborate the need to consider PAs at the young age as a fundamental indicator for the correct clinical stratification of the disease and its possible evolution.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2474Test

الوصول الحر: https://doaj.org/article/61de057bf13d4fb78dcd7f9489634400Test

المؤلفون: Statland, Jeffrey, Campbell, Craig, Desai, Urvi, Karam, Chafic, Díaz-Manera, Jordi, Guptill, Jeffrey, Korngut, Lawrence, Genge, Angela, Tawil, Rabi, Elman, Lauren, Joyce, Nanette, Wagner, Kathryn, Manousakis, Georgios, Amato, Anthony, Butterfield, Russell, Shieh, Perry, Wicklund, Matthew, Gamez, Josep, Bodkin, Cynthia, Pestronk, Alan, Weihl, Conrad, Vilchez-Padilla, Juan, Johnson, Nicholas, Mathews, Katherine, Miller, Barry, Leneus, Ashley, Fowler, Marcie, van de Rijn, Marc, Attie, Kenneth

المصدر: Muscle and Nerve. 66(1)

مصطلحات موضوعية: FSHD, controlled trial, facioscapulohumeral muscular dystrophy, randomized, Adolescent, Adult, Cytomegalovirus Infections, Humans, Magnetic Resonance Imaging, Muscle Contraction, Muscle, Skeletal, Muscular Dystrophy, Facioscapulohumeral

الوصف: INTRODUCTION/AIMS: Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy without approved therapies. In this study we evaluated whether locally acting ACE-083 could safely increase muscle volume and improve functional outcomes in adults with FSHD. METHODS: Participants were at least 18 years old and had FSHD1/FSHD2. Part 1 was open label, ascending dose, assessing safety and tolerability (primary objective). Part 2 was randomized, double-blind for 6 months, evaluating ACE-083240 mg/muscle vs placebo injected bilaterally every 3 weeks in the biceps brachii (BB) or tibialis anterior (TA) muscles, followed by 6 months of open label. Magnetic resonance imaging measures included total muscle volume (TMV; primary objective), fat fraction (FF), and contractile muscle volume (CMV). Functional measures included 6-minute walk test, 10-meter walk/run, and 4-stair climb (TA group), and performance of upper limb midlevel/elbow score (BB group). Strength, patient-reported outcomes (PROs), and safety were also evaluated. RESULTS: Parts 1 and 2 enrolled 37 and 58 participants, respectively. Among 55 participants evaluable in Part 2, the least-squares mean (90% confidence interval, analysis of covariance) treatment difference for TMV was 16.4% (9.8%-23.0%) in the BB group (P

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4rb044kbTest

المؤلفون: Sanne C.C. Vincenten, Karlien Mul, Daniël vanAs, Julia J. Jansen, Linda Heskamp, Arend Heerschap, Baziel G.M. vanEngelen, Nicol C. Voermans

المصدر: Journal of Cachexia, Sarcopenia and Muscle, Vol 14, Iss 4, Pp 1695-1706 (2023)

مصطلحات موضوعية: FSHD, Muscle imaging, MRI, Biomarker, Clinical outcome, Diseases of the musculoskeletal system, RC925-935, Human anatomy, QM1-695

الوصف: Abstract Background It is unclear how changes in quantitative muscle magnetic resonance imaging (MRI) relate to changes in clinical outcome in facioscapulohumeral muscular dystrophy (FSHD), although this information is crucial for optimal use of MRI as imaging biomarker in trials. We therefore assessed muscle MRI and clinical outcome measures in a large longitudinal prospective cohort study. Methods All patients were assessed by MRI at baseline and at 5‐year follow‐up, employing 2pt‐Dixon and turbo inversion recovery magnitude (TIRM) sequences, after which fat fraction and TIRM positivity of 19 leg muscles were determined bilaterally. The MRI compound score (CoS) was defined as the mean fat fraction of all muscles weighted for cross‐sectional area. Clinical outcome measures included the Ricci‐score, FSHD clinical score (FSHD‐CS), MRC sumscore (MRC‐SS), and motor‐function‐measure (MFM). Results We included 105 FSHD patients [mean age 54 ± 14 years, median Ricci‐score 7 (range 0–10)]. The median change over 5 years' time in the MRI‐CoS was 2.0% (range −4.6 to +12.1; P

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2190-5991Test; https://doaj.org/toc/2190-6009Test

الوصول الحر: https://doaj.org/article/9f75fa9bef2e4cbab604efb78a1219d3Test

المؤلفون: Murray, Roisin

المساهمون: Graham, Christopher, Farrell, Lynn, Lyttle, Nigel, Alty, Jane, Curran, David, Williams, Stefan

مصطلحات موضوعية: FND, Functional Neurological Disorder, Neurological Conditions, FSHD, facioscapulohumeral muscular dystrophy, clinical psychology, healthcare practitioner attitudes, implicit attitudes, qualitative synthesis

الوصف: This thesis contains two chapters, including a systematic review chapter and an empirical chapter, followed by a brief reflective appendix. A range of research methodologies were employed to investigate both patient and healthcare practitioners' experiences and attitudes toward neurological presentations. The systematic review is a qualitative synthesis of the literature exploring the lived experience of people with Facioscapulohumeral Muscular Dystrophy (FSHD). The systematic review methodology is outlined in detail. Five descriptive themes and two analytical themes which arose from qualitative synthesis are presented and discussed in the context of models which may be applied to understanding the lived experience of this population and the clinical implications of the review findings. The second chapter is an empirical study of the attitudes of healthcare practitioners toward Functional Neurological Disorder (FND) and associated clinical decision-making. Experimental methods were used to collect quantitative data on the implicit and explicit attitudes of healthcare practitioners regarding the legitimacy of FND, as well as treatment optimism and clinician confidence in working with people with FND. Participants also made treatment recommendations for neurological case vignettes, including FND and non-FND presentations. Statistical analysis revealed uncertainty among clinicians about the legitimacy of FND at implicit and explicit levels. Attitudes about FND-illegitimacy were associated with lower likelihood of referral to physical interventions such as physiotherapy, recommended in best practice guidelines for FND. These findings are discussed in terms of the strengths and limitations of the study and the implications for clinical practice.

الوصول الحر: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.865070Test

المؤلفون: Bettio, Cinzia, Banchelli, Federico, Salsi, Valentina, Vicini, Roberto, Crisafulli, Oscar, Ruggiero, Lucia, Ricci, Giulia, Bucci, Elisabetta, Angelini, Corrado, Berardinelli, Angela, Bonanno, Silvia, D'Angelo, Maria Grazia, Di Muzio, Antonio, Filosto, Massimiliano, Frezza, Erica, Maggi, Lorenzo, Mongini, Tiziana, Pegoraro, Elena, Rodolico, Carmelo, Scarlato, Marina, Vattemi, Gaetano, Velardo, Daniele, Tomelleri, Giuliano, D'Amico, Roberto, D'Antona, Giuseppe, Tupler, Rossella

المساهمون: Bettio, Cinzia, Banchelli, Federico, Salsi, Valentina, Vicini, Roberto, Crisafulli, Oscar, Ruggiero, Lucia, Ricci, Giulia, Bucci, Elisabetta, Angelini, Corrado, Berardinelli, Angela, Bonanno, Silvia, D'Angelo, Maria Grazia, Di Muzio, Antonio, Filosto, Massimiliano, Frezza, Erica, Maggi, Lorenzo, Mongini, Tiziana, Pegoraro, Elena, Rodolico, Carmelo, Scarlato, Marina, Vattemi, Gaetano, Velardo, Daniele, Tomelleri, Giuliano, D'Amico, Roberto, D'Antona, Giuseppe, Tupler, Rossella

مصطلحات موضوعية: FSHD, Health promotion, Neuromuscular diseases, Physical activity, Rare disease, Sport medicine

الوصف: Background: In facioscapulohumeral muscular dystrophy (FSHD), it is not known whether physical activity (PA) practiced at young age is associated with the clinical presentation of disease. To assess this issue, we performed a retrospective cohort study concerning the previous practice of sports and, among them, those with medium-high cardiovascular commitment in clinically categorized carriers of a D4Z4 reduced allele (DRA). Methods: People aged between 18 and 60 were recruited as being DRA carriers. Subcategory (classical phenotype, A; incomplete phenotype, B; asymptomatic carriers, C; complex phenotype, D) and FSHD score, which measures muscle functional impairment, were assessed for all participants. Information on PAs was retrieved by using an online survey dealing with the practice of sports at a young age. Results: 368 participants were included in the study, average age 36.6 years (SD = 9.4), 47.6% male. The FSHD subcategory A was observed in 157 (42.7%) participants with average (± SD) FSHD score of 5.8 ± 3.0; the incomplete phenotype (category B) in 46 (12.5%) participants (average score 2.2 ± 1.7) and the D phenotype in 61 (16.6%, average score 6.5 ± 3.8). Asymptomatic carriers were 104 (subcategory C, 28.3%, score 0.0 ± 0.2). Time from symptoms onset was higher for patients with A (15.8 ± 11.1 years) and D phenotype (13.3 ± 11.9) than for patients with B phenotype (7.3 ± 9.0). The practice of sports was associated with lower FSHD score (-17%) in participants with A phenotype (MR = 0.83, 95% CI = 0.73-0.95, p = 0.007) and by 33% in participants with D phenotype (MR = 0.67, 95% CI = 0.51-0.89, p = 0.006). Conversely, no improvement was observed in participants with incomplete phenotype with mild severity (B). Conclusions: PAs at a young age are associated with a lower clinical score in the adult A and D FSHD subcategories. These results corroborate the need to consider PAs at the young age as a fundamental indicator for the correct clinical stratification of the disease and its possible evolution.

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/38183077; info:eu-repo/semantics/altIdentifier/wos/WOS:001137106900004; volume:25; issue:35; firstpage:1; lastpage:9; numberofpages:9; journal:BMC MUSCULOSKELETAL DISORDERS; https://hdl.handle.net/11562/1116767Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85181508675; https://doi.org/10.1186/s12891-023-07150-xTest

الإتاحة: https://doi.org/10.1186/s12891-023-07150-xTest
https://hdl.handle.net/11562/1116767Test

المؤلفون: Allen, Jodi, Stone-Ghariani, Aoife, Quezada, Gabriella, Banks, Donna, Rose, Frank, Knight, William, Newman, Jill, Newman, William, Anderson, Philip, Smith, Christina

مصطلحات موضوعية: Swallowing, Myotonic Dystrophy Type 1 (DM1), Facioscapulohumeral Muscular Dystrophy (FSHD), Spinal Muscular Atrophy (SMA), Advisory Group

الوصف: Background: Dysphagia is common in adults living with neuromuscular disease (NMD). Increased life expectancy, secondary to improvements in standards of care, requires the recognition and treatment of dysphagia with an increased priority. Evidence to support the establishment of healthcare pathways is, however, lacking. The experiences of people living with NMD (pplwNMD) and their caregivers are valuable to guide targeted, value-based healthcare. Objective: To generate preliminary considerations for neuromuscular dysphagia care and future research in the United Kingdom, based on the experiences of those living with, or caring for, people with NMD. Methods: Two surveys (one for adults living with NMD and dysphagia, and a second for caregivers) were co-designed with an advisory group of people living with NMD. Surveys were electronically distributed to adults living with NMD and their caregivers between 18th May and 26th July 2020. Distribution was through UK disease registries, charity websites, newsletters, and social media. Results: Adults living with NMD receive little information or education that they are likely to develop swallowing difficulties. Most respondents report wanting this information prior to developing these difficulties. Difficulties with swallowing food and medication are common in this group, and instrumental assessment is considered a helpful assessment tool. Both adults living with NMD and caregivers want earlier access to neuromuscular swallowing specialists and training in how best to manage their difficulties. Conclusions: Improvement is needed in the dysphagia healthcare pathway for adults living with NMD to help mitigate any profound physical and psychological consequences that may be caused by dysphagia. Education about swallowing difficulties and early referral to a neuromuscular swallowing specialist are important to pplwNMD and their caregivers. Further research is required to better understand the experiences of pplwNMD and their caregivers to inform the development of dysphagia ...

وصف الملف: 389-410; application/pdf

العلاقة: Journal of Neuromuscular Diseases; https://eresearch.qmu.ac.uk/handle/20.500.12289/13722/13722.pdfTest; Allen, J., Stone-Ghariani, A., Quezada, G., Banks, D., Rose, F., Knight, W., Newman, J., Newman, W., Anderson, P. and Smith, C. (2024) ‘Living with dysphagia: a survey exploring the experiences of adults living with neuromuscular disease and their caregivers in the united kingdom’, Journal of Neuromuscular Diseases, 11(2), pp. 389–410. Available at: https://doi.org/10.3233/JND-230002Test.; https://eresearch.qmu.ac.uk/handle/20.500.12289/13722Test; https://doi.org/10.3233/JND-230002Test

الإتاحة: https://doi.org/20.500.12289/13722/13722.pdfTest
https://doi.org/20.500.12289/13722Test
https://doi.org/10.3233/JND-230002Test
https://eresearch.qmu.ac.uk/handle/20.500.12289/13722/13722.pdfTest
https://hdl.handle.net/20.500.12289/13722/13722.pdfTest
https://eresearch.qmu.ac.uk/handle/20.500.12289/13722Test
https://hdl.handle.net/20.500.12289/13722Test

المؤلفون: Thuy-Hang Nguyen, Maelle Limpens, Sihame Bouhmidi, Lise Paprzycki, Alexandre Legrand, Anne-Emilie Declèves, Philipp Heher, Alexandra Belayew, Christopher R. S. Banerji, Peter S. Zammit, Alexandra Tassin

المصدر: International Journal of Molecular Sciences, Vol 25, Iss 6, p 3327 (2024)

مصطلحات موضوعية: FSHD, DUX4, HIF1α, myogenesis, skeletal muscle, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: FacioScapuloHumeral muscular Dystrophy (FSHD) is one of the most prevalent inherited muscle disorders and is linked to the inappropriate expression of the DUX4 transcription factor in skeletal muscles. The deregulated molecular network causing FSHD muscle dysfunction and pathology is not well understood. It has been shown that the hypoxia response factor HIF1α is critically disturbed in FSHD and has a major role in DUX4-induced cell death. In this study, we further explored the relationship between DUX4 and HIF1α. We found that the DUX4 and HIF1α link differed according to the stage of myogenic differentiation and was conserved between human and mouse muscle. Furthermore, we found that HIF1α knockdown in a mouse model of DUX4 local expression exacerbated DUX4-mediated muscle fibrosis. Our data indicate that the suggested role of HIF1α in DUX4 toxicity is complex and that targeting HIF1α might be challenging in the context of FSHD therapeutic approaches.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/25/6/3327Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/f38a0076c826444eb8ce8da70e5120a5Test

المؤلفون: Claudia Strafella, Valerio Caputo, Sara Bortolani, Eleonora Torchia, Domenica Megalizzi, Giulia Trastulli, Mauro Monforte, Luca Colantoni, Carlo Caltagirone, Enzo Ricci, Giorgio Tasca, Raffaella Cascella, Emiliano Giardina

المصدر: Frontiers in Genetics, Vol 14 (2023)

مصطلحات موضوعية: FSHD, exome, D4Z4, genetics, muscular dystrophy, Genetics, QH426-470

الوصف: Introduction: Despite the progress made in the study of Facioscapulohumeral Dystrophy (FSHD), the wide heterogeneity of disease complicates its diagnosis and the genotype-phenotype correlation among patients and within families. In this context, the present work employed Whole Exome Sequencing (WES) to investigate known and unknown genetic contributors that may be involved in FSHD and may represent potential disease modifiers, even in presence of a D4Z4 Reduced Allele (DRA).Methods: A cohort of 126 patients with clinical signs of FSHD were included in the study, which were characterized by D4Z4 sizing, methylation analysis and WES. Specific protocols were employed for D4Z4 sizing and methylation analysis, whereas the Illumina® Next-Seq 550 system was utilized for WES. The study included both patients with a DRA compatible with FSHD diagnosis and patients with longer D4Z4 alleles. In case of patients harboring relevant variants from WES, the molecular analysis was extended to the family members.Results: The WES data analysis highlighted 20 relevant variants, among which 14 were located in known genetic modifiers (SMCHD1, DNMT3B and LRIF1) and 6 in candidate genes (CTCF, DNMT1, DNMT3A, EZH2 and SUV39H1). Most of them were found together with a permissive short (4–7 RU) or borderline/long DRA (8–20 RU), supporting the possibility that different genes can contribute to disease heterogeneity in presence of a FSHD permissive background. The segregation and methylation analysis among family members, together with clinical findings, provided a more comprehensive picture of patients.Discussion: Our results support FSHD pathomechanism being complex with a multigenic contribution by several known (SMCHD1, DNMT3B, LRIF1) and possibly other candidate genes (CTCF, DNMT1, DNMT3A, EZH2, SUV39H1) to disease penetrance and expressivity. Our results further emphasize the importance of extending the analysis of molecular findings within the proband’s family, with the purpose of providing a broader framework for understanding single cases and allowing finer genotype-phenotype correlations in FSHD-affected families.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fgene.2023.1235589/fullTest; https://doaj.org/toc/1664-8021Test

الوصول الحر: https://doaj.org/article/cc4047e5faa546578eb91081027d9b46Test