Imperial College London

Professor SirMagdiYacoub

Faculty of MedicineNational Heart & Lung Institute

Emeritus Professor
 
 
 
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Contact

 

+44 (0)1895 828 893m.yacoub

 
 
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Location

 

Heart Science Centre, HarefieldHarefield HospitalHarefield Hospital

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Summary

 

Publications

Publication Type
Year
to

2072 results found

Allouba M, Walsh R, Afify A, Hosny M, Halawa S, Galal A, Fathy M, Theotokis PI, Boraey A, Ellithy A, Buchan R, Govind R, Whiffin N, Anwer S, ElGuindy A, Ware JS, Barton PJR, Yacoub M, Aguib Yet al., 2023, Ethnicity, consanguinity, and genetic architecture of hypertrophic cardiomyopathy, European Heart Journal, Pages: 1-13, ISSN: 0195-668X

AIMS: Hypertrophic cardiomyopathy (HCM) is characterized by phenotypic heterogeneity that is partly explained by the diversity of genetic variants contributing to disease. Accurate interpretation of these variants constitutes a major challenge for diagnosis and implementing precision medicine, especially in understudied populations. The aim is to define the genetic architecture of HCM in North African cohorts with high consanguinity using ancestry-matched cases and controls. METHODS AND RESULTS: Prospective Egyptian patients (n = 514) and controls (n = 400) underwent clinical phenotyping and genetic testing. Rare variants in 13 validated HCM genes were classified according to standard clinical guidelines and compared with a prospective HCM cohort of majority European ancestry (n = 684). A higher prevalence of homozygous variants was observed in Egyptian patients (4.1% vs. 0.1%, P = 2 × 10-7), with variants in the minor HCM genes MYL2, MYL3, and CSRP3 more likely to present in homozygosity than the major genes, suggesting these variants are less penetrant in heterozygosity. Biallelic variants in the recessive HCM gene TRIM63 were detected in 2.1% of patients (five-fold greater than European patients), highlighting the importance of recessive inheritance in consanguineous populations. Finally, rare variants in Egyptian HCM patients were less likely to be classified as (likely) pathogenic compared with Europeans (40.8% vs. 61.6%, P = 1.6 × 10-5) due to the underrepresentation of Middle Eastern populations in current reference resources. This proportion increased to 53.3% after incorporating methods that leverage new ancestry-matched controls presented here. CONCLUSION: Studying consanguineous populations reveals novel insights with relevance to genetic testing and our understanding of the genetic architecture of HCM.

Journal article

Romeih S, Elkafrawy F, Shaaban M, Hassan A, Samuel I, Gergis M, El mozy W, Yacoub Met al., 2023, Validation of cardiac index measured by four-dimensional cardiac magnetic resonance flow against the invasively measured cardiac index in patients with pulmonary hypertension, Pulmonary Circulation, Vol: 13, ISSN: 2045-8932

The purpose of this study was to validate cardiac index (CI) measured noninvasively by four-dimensional (4D) and two-dimensional (2D) cardiovascular magnetic resonance (CMR) flows against the invasively measured CI by right heart catheterization (RHC) in patients with pulmonary hypertension (PH). Thirty patients with PH (mean age: 32 ± 10 years) were included. 4D and 2D flow measured CI within 24 h from RHC measured CI invasively. Qualitative analysis of 4D pulmonary flow (vortex presence and eccentricity of flow) was performed. All patients had helical right-sided flow with vortex formation; the mean vortex diameter was 29 ± 7 mm, occupying 69% of the main pulmonary artery (MPA) lumen. MPA was dilated (42 ± 9 mm). Mean CI measured by 4D flow CMR was closer to mean CI measured invasively (indirect Fick method CI = 2.1 ± 0.8 L/min/m2 vs. PA 4D flow = 2.3 ± 0.7 L/min/m2 “bias 0.22 ± 0.25 L/min, p = 0.001,” and Ao 4D flow = 2.3 ± 0.7 L/min/m2 “bias 0.2 ± 0.28 L/min, p = 0.001”), while 2D flow had a higher mean CI (PA 2D flow = 2.5 ± 0.7 L/min/m2 “bias 0.45 ± 0.7 L/min, p = 0.001” and Ao 2D flow = 2.5 ± 0.8 L/min/m2 “bias 0.45 ± 0.67 L/min, p = 0.001”). The correlation coefficients among the different comparisons of CI showed: a low correlation between the 2D flow-indirect Fick method (Ao r2 = 0.37, PA r2 = 0.32) and a high correlation between the 4D flow-indirect Fick method (Ao r2 = 0.86, PA r2 = 0.89). There is an excellent agreement between CI measured by 4D flow and CI measured invasively. 4D flow, a noninvasive imaging technique, could accurately measure CI better than the conventional 2D flow in patients with PH.

Journal article

Soppa G, Bilkhu R, Jahangiri M, Yacoub Met al., 2023, Valve Sparing Aortic Root Procedure: Yacoub’s Procedure, Essentials of Operative Cardiac Surgery, Second Edition, Pages: 177-186, ISBN: 9783031145568

Aortic root replacement is performed for pathology of the aortic root, including aneurysm, dissection, connective tissue disease and in some cases, endocarditis of the aortic valve. Valve-sparing aortic root replacement (VSRR) is performed for aortic aneurysm when the aortic valve leaflets are normal and the aortic valve annulus is not dilated. The remodelling technique of aortic root replacement was originally described by Yacoub and colleagues and has the advantage of preserving the physiological properties of the aortic root. In this chapter, we describe our operative technique of VSRR using the remodelling technique.

Book chapter

Pang KT, Ghim M, Sarathchandra P, Warboys CM, Yacoub MH, Chester AH, Weinberg PDet al., 2022, Shear-mediated ALK5 expression regulates endothelial activation, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 642, Pages: 90-96, ISSN: 0006-291X

Journal article

Zabielska-Kaczorowska MA, Wierzbicka B, Kalmes A, Slominska EM, Yacoub MH, Smolenski RTet al., 2022, Beneficial Effects of RNS60 in Cardiac Ischemic Injury, CURRENT ISSUES IN MOLECULAR BIOLOGY, Vol: 44, Pages: 4877-4887, ISSN: 1467-3037

Journal article

Jedrzejewska A, Braczko A, Kawecka A, Hellmann M, Siondalski P, Slominska E, Kutryb-Zajac B, Yacoub MH, Smolenski RTet al., 2022, Novel Targets for a Combination of Mechanical Unloading with Pharmacotherapy in Advanced Heart Failure, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 23

Journal article

Halawa S, Latif N, Tseng Y-T, Ibrahim AM, Chester AH, Moustafa A, Aguib Y, Yacoub MHet al., 2022, Profiling Genome-Wide DNA Methylation Patterns in Human Aortic and Mitral Valves, FRONTIERS IN CARDIOVASCULAR MEDICINE, Vol: 9, ISSN: 2297-055X

Journal article

Vizza CD, Lang IM, Badagliacca R, Benza RL, Rosenkranz S, White RJ, Adir Y, Andreassen AK, Balasubramanian V, Bartolome S, Blanco I, Bourge RC, Carlsen J, Conde Camacho RE, D'Alto M, Farber HW, Frantz RP, Ford HJ, Ghio S, Gomberg-Maitland M, Humbert M, Naeije R, Orfanos SE, Oudiz RJ, Perrone S, Shlobin OA, Simon MA, Sitbon O, Torres F, Vachiery JL, Wang K-Y, Yacoub MH, Liu Y, Golden G, Matsubara Het al., 2022, Aggressive Afterload Lowering to Improve the Right Ventricle A New Target for Medical Therapy in Pulmonary Arterial Hypertension?, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 205, Pages: 751-760, ISSN: 1073-449X

Journal article

Latif N, Sarathchandra P, Mccormack A, Yacoub M, Chester Aet al., 2022, Atypical expression of smooth muscle markers and co-activators and their regulation in rheumatic aortic and calcified bicuspid valves, Frontiers in Cardiovascular Medicine, Vol: 9, Pages: 1-13, ISSN: 2297-055X

Objective: We have previously reported that human calcified aortic cusps have abundantexpression of smooth muscle (SM) markers and co-activators. We hypothesised that cells inbicuspid aortic valve (BAV) cusps and those affected by rheumatic heart valve (RHV)disease may follow a similar phenotypic transition into smooth muscle cells, a process thatcould be regulated by transforming growth factors (TGFs).Aims: Cusps from 8 patients with BAV and 7 patients with RHV were analysed for ealy andlate SM markers and regulators of SM gene expression by immunocytochemistry andcompared to healthy aortic valves from 12 unused heart valve donors. The ability of TGFs toinduce these markers in valve endothelial cells (VECs) on two substrates was assessed.Results: 7 out of 8 BAVs and all the RHVs showed an increased and atypical expression ofearly and late SM markers α-SMA, calponin, SM22 and SM-myosin. The SM marker coactivators were aberrantly expressed in 6 of the BAV and 6 of the RHV, in a similar regionalpattern to the expression of SM markers. Additionally, regions of VECs, and endothelial cellslining the vessels within the cusps were found to be positive for SM markers and coactivators in 3 BAV and 6 RHV. Both BAVs and RHVs were significantly thickened andHIF1α expression was prominent in 4 BAVs and 1 RHV. The ability of TGFβs to induce theexpression of SM markers and myocardin was greater in VECs cultured on fibronectin thanon gelatin. Fibronectin was shown to be upregulated in BAVs and RHVs, within the cusps aswell as in the basement membrane.Conclusion: BAVs and RHVs expressed increased numbers of SM marker-positive VICsand VECs. Concomittantly, these cells expressed MRTF-A and myocardin, key regulators ofSM gene expression. TGFβ1 was able to preferentially upregulate SM markers andmyocardin in VECs on fibronectin, and fibronectin was found to be upregulated in BAVs andRHVs. These findings suggest a role of VEC as a source of cells that express SM cel

Journal article

Yacoub MH, 2022, The Ross Operation and the Long Windy Road to the Clinic, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 79, Pages: 816-818, ISSN: 0735-1097

Journal article

El-Mehalmey WA, Latif N, Ibrahim AH, Haikal RR, Mierzejewska P, Smolenski RT, Yacoub MH, Alkordi MHet al., 2022, Nine days extended release of adenosine from biocompatible MOFs under biologically relevant conditions, BIOMATERIALS SCIENCE, Vol: 10, Pages: 1342-1351, ISSN: 2047-4830

Journal article

Ali AM, Dena ASA, Yacoub MH, El-Sherbiny IMet al., 2022, Drag-minimizing spore/pollen-mimicking microparticles for enhanced pulmonary drug delivery: CFD and experimental studies, JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, Vol: 67, ISSN: 1773-2247

Journal article

Emmons-Bell S, Johnson C, Boon-Dooley A, Corris PA, Leary PJ, Rich S, Yacoub M, Roth GAet al., 2022, Prevalence, incidence, and survival of pulmonary arterial hypertension: A systematic review for the global burden of disease 2020 study, Pulmonary Circulation, Vol: 12, ISSN: 2045-8932

Pulmonary arterial hypertension (PAH) is characterized by increased resistance in the pulmonary arterioles as a result of remodeled blood vessels. We sought all available epidemiologic data on population-based prevalence, incidence, and 1-year survival of PAH as part of the Global Burden of Disease Study. We performed a systematic review searching Global Index Medicus (GIM) for keywords related to PAH between 1980 and 2021 and identified population-representative sources of prevalence, incidence, and mortality for clinically diagnosed PAH. Of 6772 articles identified we found 65 with population-level data: 17 for prevalence, 17 for incidence, and 58 reporting case fatality. Reported prevalence ranged from 0.37 cases/100,000 persons in a referral center of French children to 15 cases/100,000 persons in an Australian study. Reported incidence ranged from 0.008 cases/100,000 person-years in Finland, to 1.4 cases/100,000 person-years in a retrospective chart review at a clinic in Utah, United States. Reported 1-year survival ranged from 67% to 99%. All studies with sex-specific estimates of prevalence or incidence reported higher levels in females than males. Studies varied in their size, study design, diagnostic criteria, and sampling procedures. Reported PAH prevalence, incidence, and mortality varied by location and study. Prevalence ranged from 0.4 to 1.4 per 100,000 persons. Harmonization of methods for PAH registries would improve efforts at disease surveillance. Results of this search contribute to ongoing efforts to quantify the global burden of PAH.

Journal article

Vikhorev P, Vikhoreva N, Yeung W, Li A, Sean L, dos Remedios C, Blair C, Maya G, Campbell K, Yacoub M, de Tombe P, Marston Set al., 2022, Titin-truncating mutations associated with dilated cardiomyopathy alter length-dependent activation and its modulation via phosphorylation, Cardiovascular Research, Vol: 118, Pages: 241-253, ISSN: 0008-6363

Aims Dilated cardiomyopathy (DCM) is associated with mutations in many genes encoding sarcomere proteins. Truncating mutations in the titin gene TTN are the most frequent. Proteomic and functional characterizations are required to elucidate the origin of the disease and the pathogenic mechanisms of TTN-truncating variants.Methods and results We isolated myofibrils from DCM hearts carrying truncating TTN mutations and measured the Ca2+ sensitivity of force and its length dependence. Simultaneous measurement of force and adenosine triphosphate (ATP) consumption in skinned cardiomyocytes was also performed. Phosphorylation levels of troponin I (TnI) and myosin binding protein-C (MyBP-C) were manipulated using protein kinase A and λ phosphatase. mRNA sequencing was employed to overview gene expression profiles. We found that Ca2+ sensitivity of myofibrils carrying TTN mutations was significantly higher than in myofibrils from donor hearts. The length dependence of the Ca2+ sensitivity was absent in DCM myofibrils with TTN-truncating variants. No significant difference was found in the expression level of TTN mRNA between the DCM and donor groups. TTN exon usage and splicing were also similar. However, we identified down-regulation of genes encoding Z-disk proteins, while the atrial-specific regulatory myosin light chain gene, MYL7, was up-regulated in DCM patients with TTN-truncating variants.Conclusion Titin-truncating mutations lead to decreased length-dependent activation and increased elasticity of myofibrils. Phosphorylation levels of TnI and MyBP-C seen in the left ventricles are essential for the length-dependent changes in Ca2+ sensitivity in healthy donors, but they are reduced in DCM patients with TTN-truncating variants. A decrease in expression of Z-disk proteins may explain the observed decrease in myofibril passive stiffness and length-dependent activation.

Journal article

Latif N, Tseng Y-T, Yacoub MH, 2021, Starry Night by Van Gogh and morphogenesis of a tissue engineered heart valve., Global Cardiology Science & Practice, Vol: 2021, Pages: 1-2, ISSN: 2305-7823

Journal article

Halawa S, Pullamsetti SS, Bangham CRM, Stenmark KR, Dorfmuller P, Frid MG, Butrous G, Morrell NW, de Jesus Perez VA, Stuart DI, O'Gallagher K, Shah AM, Aguib Y, Yacoub MHet al., 2021, Potential long-term effects of SARS-CoV-2 infection on the pulmonary vasculature: a global perspective, NATURE REVIEWS CARDIOLOGY, Vol: 19, Pages: 314-331, ISSN: 1759-5002

Journal article

Pelliccia F, Seggewiss H, Cecchi F, Calabro P, Limongelli G, Alfieri O, Ferrazzi P, Yacoub MH, Olivotto Iet al., 2021, Septal Ablation Versus Surgical Myomectomy for Hypertrophic Obstructive Cardiomyopathy, CURRENT CARDIOLOGY REPORTS, Vol: 23, ISSN: 1523-3782

Journal article

Chester AH, McCormack A, Miller EJ, Ahmed MN, Yacoub MHet al., 2021, Coronary vasodilation mediated by T cells expressing choline acetyltransferase, AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, Vol: 321, Pages: H933-H939, ISSN: 0363-6135

Journal article

Nagy M, Hosny H, Sawy AE, Mahgoub A, Yacoub MHet al., 2021, Characterization of morphology and function of the 'neo-atria' after a modified Mustard operation., Glob Cardiol Sci Pract, Vol: 2021, ISSN: 2305-7823

Background: There is a pressing need to improve early and long-term results of the Mustard operation. A modification of the operation was introduced at the Aswan Heart Centre for this purpose which relies on creating new functional atria rather than the two rigid channels in the classical Mustard operation. Objectives: To evaluate the morphology and function of the neo-atria, shortly after modified mustard operation for a 'neglected' patient with TGA, VSD and severe pulmonary hypertension. Methods: A 6-year-old with neglected TGA, VSD and pulmonary hypertension presented with severe cyanosis, clubbing and haemoconcentration (Hb 22 g/dL), underwent the modified Aswan-Mustard operation (MAM) with rapid smooth postoperative recovery. Repeated 2D echograms and multi-slice CT scans, followed by 3D segmentation, were performed after the operation. The size, shape, and morphology of the neo-atria were measured and measurements of the patterns of instantaneous filling and emptying of the right and left ventricles were quantified. Results: The neo-systemic venous atrium consisted of three components with a combined volume of 78 mL/m2, all of which contributed to the reservoir, conduit, and importantly contractile function of the neo-atrium. The pulmonary venous atrium consisted of two components with a combined volume of 66 mL/m2. These measurements were made at atrial end diastole. The volumes of the systemic venous and the pulmonary venous diminished to 51 and 54 mL/m2, respectively, at the end atrial systole - indicating relatively preserved contractile functions. Conclusion: Following the modified Aswan-Mustard operation, neo-atrial function was relatively well preserved compared to the classical operation. The long-term results of these findings and their effects on quality of life need to be studied further.

Journal article

Torii R, Yacoub MH, 2021, CT-based fractional flow reserve: development and expanded application., Glob Cardiol Sci Pract, Vol: 2021, ISSN: 2305-7823

Computations of fractional flow reserve, based on CT coronary angiography and computational fluid dynamics (CT-based FFR) to assess the severity of coronary artery stenosis, was introduced around a decade ago and is now one of the most successful applications of computational fluid dynamic modelling in clinical practice. Although the mathematical modelling framework behind this approach and the clinical operational model vary, its clinical efficacy has been demonstrated well in general. In this review, technical elements behind CT-based FFR computation are summarised with some key assumptions and challenges. Examples of these challenges include the complexity of the model (such as blood viscosity and vessel wall compliance modelling), whose impact has been debated in the research. Efforts made to address the practical challenge of processing time are also reviewed. Then, further application areas-myocardial bridge, renal stenosis and lower limb stenosis-are discussed along with specific challenges expected in these areas.

Journal article

Parra-Izquierdo I, Sanchez-Bayuela T, Lopez J, Gomez C, Perez-Riesgo E, San Roman JA, Sanchez Crespo M, Yacoub M, Chester AH, Garcia-Rodriguez Cet al., 2021, Interferons Are Pro-Inflammatory Cytokines in Sheared-Stressed Human Aortic Valve Endothelial Cells, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 22

Journal article

Gemechu T, Parry EHO, Yacoub MH, Phillips DIW, Kotit Set al., 2021, Community-based prevalence of rheumatic heart disease in rural Ethiopia: Five-year follow-up, PLOS NEGLECTED TROPICAL DISEASES, Vol: 15, ISSN: 1935-2735

Journal article

Yacoub MH, Afifi A, Hosny H, Nagy M, Shehata N, Abou Gamrah M, El Sawy A, Simry W, Mahgoub A, Francis N, El Nashar H, Tseng Y-T, Romeih S, Aguib Het al., 2021, A New Technique for Shaping the Aortic Sinuses and Conserving Dynamism in the Remodeling Operation, ANNALS OF THORACIC SURGERY, Vol: 112, Pages: 1218-1226, ISSN: 0003-4975

Journal article

Aguib Y, Allouba M, Walsh R, Ibrahim AM, Halawa S, Afify A, Hosny M, Theotokis PI, Galal A, Elshorbagy S, Roshdy M, Kassem HS, Ellithy A, Buchan R, Whiffin N, Anwer S, Cook S, Moustafa A, ElGuindy A, Ware J, Barton P, Yacoub Met al., 2021, New variant with a previously unrecognized mechanism of pathogenicity in hypertrophic cardiomyopathy, Circulation, Vol: 144, Pages: 754-757, ISSN: 0009-7322

Journal article

Al Kindi HN, Ibrahim AM, Roshdy M, Abdelghany BS, Yehia D, Masoud AN, Simry W, Aguib Y, Yacoub MHet al., 2021, Clinical, cellular, and molecular characterisation of cardiac rhabdomyoma in tuberous sclerosis, CARDIOLOGY IN THE YOUNG, Vol: 31, Pages: 1297-1305, ISSN: 1047-9511

Journal article

Yacoub MH, Hosny H, Afifi A, Nagy M, Mahgoub A, Simry W, AbouZeina MG, Doss R, El Sawy A, Shehata N, Elafifi A, Abdullahh H, Romeih Set al., 2021, Novel concepts and early results of repairing common arterial trunk, EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, Vol: 61, Pages: 562-571, ISSN: 1010-7940

Journal article

Pang KT, Ghim M, Liu C, Tay HM, Fhu CW, Chia RN, Qiu B, Sarathchandra P, Chester AH, Yacoub MH, Wilkinson FL, Weston R, Warboys CM, Hou HW, Weinberg PD, Wang Xet al., 2021, Leucine-Rich alpha-2-Glycoprotein 1 Suppresses Endothelial Cell Activation Through ADAM10-Mediated Shedding of TNF-alpha Receptor, FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, Vol: 9, ISSN: 2296-634X

Journal article

Afifi A, Hosny H, Mahgoub A, Yacoub Met al., 2021, The Ross procedure—the loose jacket technique, Annals of Cardiothoracic Surgery, Vol: 10, Pages: 544-545, ISSN: 2225-319X

Journal article

Latif N, Mahgoub A, Nagy M, Sarathchandra P, Yacoub MHet al., 2021, Severe degeneration of a sub-coronary pulmonary autograft in a young adult, Global Cardiology Science & Practice, Vol: 2021, ISSN: 2305-7823

Background. The pulmonary autograft is currently the best valve substitute in terms of longevity and performance. However, there is no agreement about the optimal method of insertion (sub-coronary position or freestanding root). Objectives. We sought to examine the clinical status, detailed imaging and morphometric changes in an explanted pulmonary autograft 22 years after sub-coronary implantation. Methods. A 30-year-old female underwent pulmonary autograft replacement of a severely stenotic valve at the age of 7 years, after presenting to us with signs of moderate to severe heart failure. She underwent clinical examination, detailed imaging including echocardiographic and CT examination with computerised image analysis. The explanted valve was examined by morphometry. Results. Clinical examination showed signs of heart failure (NYHA III). Trans-thoracic and trans-oesophageal 2D echo showed severe malfunction of both the aortic and pulmonary valves associated with dilatation and hypertrophy of both the right and left ventricles. Surgical correction was performed by replacing both the pulmonary and aortic valves with Medtronic 27mm Freestyle valves. The pulmonary autograft showed degeneration of the trilamellar layering of the leaflets, loss and disorganisation of GAGs, increased collagen with fibrotic overgrowth, and markers of fibrosis, inflammation, and calcification. Post-operative imaging showed good correction of the haemodynamic lesions. Conclusion. The pulmonary autograft implanted into the sub-coronary position presented with adverse remodelling, which was detrimental to the functionality and longevity of the valve. Authorship. NL, AM, MN all contributed equally to this paper.

Journal article

Al-Shafai KN, Al-Hashemi M, Manickam C, Musa R, Selvaraj S, Syed N, Vempalli F, Ali M, Yacoub M, Estivill Xet al., 2021, Genetic evaluation of cardiomyopathies in Qatar identifies enrichment of pathogenic sarcomere gene variants and possible founder disease mutations in the Arabs, MOLECULAR GENETICS & GENOMIC MEDICINE, Vol: 9, ISSN: 2324-9269

Journal article

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