229 results match your criteria Hemophilia Overview

Post-authorization pharmacovigilance for hemophilia in Europe and the USA: Independence and transparency are keys.

Blood Rev 2021 Mar 20:100828. Epub 2021 Mar 20.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy.

The regulatory process is currently designed to ensure drug safety during the pre-marketing process. Due to limitations of the pivotal studies owing to their short duration and small number of highly selected cases, some adverse drug reactions (ADRs) are not detected, particularly the rarest and those which appear a long time after exposure. Thus it is essential to foster pharmacovigilance run totally independently from marketing authorization holders in order to attain transparent surveillance. Read More

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Assessing Plasmin Generation in Health and Disease.

Int J Mol Sci 2021 Mar 9;22(5). Epub 2021 Mar 9.

Synapse Research Institute, 6217 KD Maastricht, The Netherlands.

Fibrinolysis is an important process in hemostasis responsible for dissolving the clot during wound healing. Plasmin is a central enzyme in this process via its capacity to cleave fibrin. The kinetics of plasmin generation (PG) and inhibition during fibrinolysis have been poorly understood until the recent development of assays to quantify these metrics. Read More

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Haemophilia, state of the art and new therapeutic opportunities, a regulatory perspective.

Br J Clin Pharmacol 2021 Mar 27. Epub 2021 Mar 27.

National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Rome, Italy.

Haemophilia A and B are rare bleeding disorders. Over the past decades, they have been transformed from debilitating diseases to manageable conditions in the Western world. However, optimizing haemophilia care remains challenging in developing countries. Read More

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Thrombotic thrombocytopenic Purpura: A nurse's perspective on a decade of treatment in Sheffield, United Kingdom.

Transfus Apher Sci 2021 Apr 1;60(2):103090. Epub 2021 Mar 1.

Advanced Nurse Practitioner in Haemophilia & Other Haemostasis Disorders, Sheffield Haemophilia & Thrombosis Centre, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, United Kingdom. Electronic address:

TTP is a rare, life threatening condition, with an annual incidence of 3-11 cases per million people. A deficiency of a vWF multimer cleaving protein, ADAMTS13 is the cause of the condition. Quick & accurate diagnosis is crucial in the safe & effective treatment of individuals presenting with this condition. Read More

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Current Clinical Applications of In Vivo Gene Therapy with AAVs.

Mol Ther 2021 02 10;29(2):464-488. Epub 2020 Dec 10.

Centre de Recherche du CHUQ-Université Laval, Québec, QC, Canada. Electronic address:

Hereditary diseases are caused by mutations in genes, and more than 7,000 rare diseases affect over 30 million Americans. For more than 30 years, hundreds of researchers have maintained that genetic modifications would provide effective treatments for many inherited human diseases, offering durable and possibly curative clinical benefit with a single treatment. This review is limited to gene therapy using adeno-associated virus (AAV) because the gene delivered by this vector does not integrate into the patient genome and has a low immunogenicity. Read More

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February 2021

An overview of patients with haemophilia A in China: Epidemiology, disease severity and treatment strategies.

Haemophilia 2021 Jan 27;27(1):e51-e59. Epub 2020 Nov 27.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Institute of Hematology & Blood Diseases Hospital, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

Introduction: Haemophilia A (HA) is a rare X chromosome-linked bleeding disorder resulting in missing or defective clotting factor VIII (FVIII) and causes large disease burden.

Aim: As a member of World Federation of Hemophilia, China seeks to understand the current epidemiology, disease profile and treatment landscape of patients with HA through the Hemophilia Treatment Center Collaboration Network of China (HTCCNC).

Methods: The HTCCNC enabled data collection on patients with HA from 166 member hospitals (2007-2019) across China. Read More

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January 2021

Bleeding of unknown cause and unclassified bleeding disorders; diagnosis, pathophysiology and management.

Haemophilia 2020 Nov 23;26(6):946-957. Epub 2020 Oct 23.

Haemostasis and Thrombosis Centre, Guy's and St Thomas' Hospital NHS Foundation Trust, London, UK.

Bleeding of unknown cause (BUC), also known as unclassified bleeding disorders (UBD), has been defined as a clear bleeding tendency in the presence of normal haemostatic tests. There are challenges in the diagnosis and management of these patients. BUC/UBD encompasses a heterogenous group of disorders which may include undiagnosed rare monogenic diseases, polygenic reasons for bleeding; and patients without a clear bleeding disorder but with a previous bleeding event. Read More

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November 2020

2021 clinical trials update: Innovations in hemophilia therapy.

Am J Hematol 2021 01 2;96(1):128-144. Epub 2020 Nov 2.

Department of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.

Therapies engineered to prolong clotting factor protein circulation time, manipulate the balance of pro-coagulant and anti-coagulant proteins, or introduce new genetic material to enable endogenous factor protein production dominate the clinical trial landscape of hemophilia. The availability of clotting factor concentrates and the establishment of primary prophylaxis have dramatically improved health outcomes for hemophilia patients. But, the burden of hemostatic therapy remains significant, and many barriers to consistent longitudinal use of prophylaxis exist. Read More

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January 2021

COVID-19 in benign hematology: emerging challenges and special considerations for healthcare professionals.

Expert Rev Hematol 2020 10 15;13(10):1081-1092. Epub 2020 Sep 15.

Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut Medical Center , Beirut, Lebanon.

Introduction: Many patients with inherited or acquired benign hematological disorders are at increased risk of developing severe complications from COVID-19. These patients, therefore, require specific advice regarding isolation and changes to their usual treatment schedules. Their disease can also be associated with significant burden, and they necessitate life-long and regular access to therapy, and regular follow-up consultations and hospital visits. Read More

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October 2020

Ready for Repair? Gene Editing Enters the Clinic for the Treatment of Human Disease.

Mol Ther Methods Clin Dev 2020 Sep 3;18:532-557. Epub 2020 Jul 3.

Department of Pediatrics, Erasmus University Medical Center, Rotterdam, the Netherlands.

We present an overview of clinical trials involving gene editing using clustered interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9), transcription activator-like effector nucleases (TALENs), or zinc finger nucleases (ZFNs) and discuss the underlying mechanisms. In cancer immunotherapy, gene editing is applied in T cells, transgenic T cell receptor (tTCR)-T cells, or chimeric antigen receptor (CAR)-T cells to improve adoptive cell therapy for multiple cancer types. This involves knockouts of immune checkpoint regulators such as PD-1, components of the endogenous TCR and histocompatibility leukocyte antigen (HLA) complex to generate universal allogeneic CAR-T cells, and CD7 to prevent self-destruction in adoptive cell therapy. Read More

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September 2020

An overview of vaccine design against different pathogens and cancer.

Expert Rev Vaccines 2020 08 10;19(8):699-726. Epub 2020 Aug 10.

Iranian Comprehensive Hemophilia Care Center , Tehran, Iran.

Introduction: Due to overcome the hardness of the vaccine design, computational vaccinology is emerging widely. Prediction of T cell and B cell epitopes, antigen processing analysis, antigenicity analysis, population coverage, conservancy analysis, allergenicity assessment, toxicity prediction, and protein-peptide docking are important steps in the process of designing and developing potent vaccines against various viruses and cancers. In order to perform all of the analyses, several bioinformatics tools and online web servers have been developed. Read More

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von Willebrand disease: Diagnosis and treatment, treatment of women, and genomic approach to diagnosis.

Haemophilia 2021 Feb 23;27 Suppl 3:66-74. Epub 2020 Jun 23.

Research Institute, Bloodworks Northwest, Seattle, WA, USA.

von Willebrand disease (VWD) is the most common inherited bleeding disorder. VWD is caused by deficiencies in von Willebrand factor (VWF), a critical adhesive haemostatic protein. This review provides an overview of VWD diagnosis and treatment, special considerations in treating women with VWD, and current genomic approaches to VWD. Read More

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February 2021

An overview of the pathfinder clinical trials program: Long-term efficacy and safety of N8-GP in patients with hemophilia A.

J Thromb Haemost 2020 09;18 Suppl 1:26-33

Haemophilia, Haemostasis and Thrombosis Centre, Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK.

N8-GP (turoctocog alfa pegol, Esperoct ; Novo Nordisk A/S, Bagsvaerd, Denmark) is a state-of-the-art, extended half-life factor VIII (FVIII) molecule used for prophylactic and on-demand treatment of patients with hemophilia A. The pathfinder clinical trial program, which began with the pathfinder1 trial in 2010, was developed to assess the long-term efficacy and safety of N8-GP in children, adolescents, and adults. The pivotal pathfinder2 (adolescents and adults) and pathfinder5 (children) trials were completed in late 2018, and comprehensive analyses of the end-of-trial results are published together with this article as part of an N8-GP Supplement. Read More

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September 2020

An overview of development in gene therapeutics in China.

Gene Ther 2020 08 11;27(7-8):338-348. Epub 2020 Jun 11.

Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China.

After setbacks related to serious adverse events 20 years ago, gene therapy is now coming back to the central stage worldwide. In the past few years, gene therapy has shown astonishing efficacy against genetic diseases and cancers. In history, China carried out the world's second gene therapy clinical trial in 1991 for hemophilia B and approved the world's first gene therapy product-Gendicine-in 2003. Read More

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Hereditary angioedema in children and adolescents - A consensus update on therapeutic strategies for German-speaking countries.

Pediatr Allergy Immunol 2020 11 16;31(8):974-989. Epub 2020 Jul 16.

Allergology Unit, Department of Dermatology, University Hospital, Zürich, Switzerland.

Background/methods: At a consensus meeting in August 2018, pediatricians and dermatologists from German-speaking countries discussed the therapeutic strategy for the treatment of pediatric patients with type I and II hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) for Germany, Austria, and Switzerland, taking into account the current marketing approval status. HAE-C1-INH is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible and an optimal management of the disease are important to avoid ineffective therapies and to properly treat swelling attacks. Read More

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November 2020

Perioperative management for patients with von Willebrand disease: Defining the optimal approach.

Eur J Haematol 2020 Oct 3;105(4):365-377. Epub 2020 Jul 3.

Haemophilia Centre, Medical Clinic II, Institute of Transfusion Medicine, Goethe University Hospital, Frankfurt am Main, Germany.

von Willebrand disease (VWD) is the most common inherited bleeding disorder characterised by a quantitative or qualitative deficiency in von Willebrand factor (VWF). During invasive surgical procedures, patients with VWD require additional treatment to maintain haemostasis; however, due to the complexity of VWD, there is a lack of consensus on the optimal management. In the perioperative period, patients are usually treated with VWF and factor FVIII (FVIII)-containing concentrates to provide an immediate haemostatic response to prevent excessive bleeding during both elective and emergency surgery. Read More

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October 2020

Acquired bleeding disorders.

Haemophilia 2021 Feb 1;27 Suppl 3:5-13. Epub 2020 Jun 1.

Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Acquired bleeding disorders can accompany hematological, neoplastic, autoimmune, cardiovascular or liver diseases, but can sometimes also arise spontaneously. They can manifest as single factor deficiencies or as complex hemostatic abnormalities. This review addresses (a) acquired hemophilia A, an autoimmune disorder characterized by inhibitory autoantibodies against coagulation factor VIII; (b) acquired von Willebrand syndrome in patients with cardiovascular disorders, where shear stress abnormalities result in destruction of von Willebrand factor; and (c) liver function disorders that comprise complex changes in pro- and anti-hemostatic factors, whose clinical implications are often difficult to predict. Read More

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February 2021

Setting the scene: Historical overview of challenges and what led to advances in comprehensive care in developed countries, the Canadian experience.

David Page

Haemophilia 2020 Apr;26 Suppl 3:4-5

Health Policy, Canadian Hemophilia Society, Montreal, QC, Canada.

The history of the development of comprehensive care for hemophilia and other inherited bleeding disorders in Canada has been long and full of challenges. From limited in-patient treatment with plasma and cryoprecipitate in a few major centres in the 1950s and 1960s, a network of Hemophilia Treatment Centres (HTCs) offering multi-disciplinary comprehensive care, home infusion and prophylaxis was established across the country by the late 1970s and early 1980s, only to be shaken by the widespread contamination of factor concentrates with HIV and HCV in the 1970s and 1980s. In recent years the mission of HTCs has expanded to better serve people with von Willebrand disease, rare factor deficiencies and other rare bleeding disorders, and more fully recognize the needs of women with bleeding disorders. Read More

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octanate: over 20 years of clinical experience in overcoming challenges in haemophilia A treatment.

Ther Adv Hematol 2020 19;11:2040620720914692. Epub 2020 Apr 19.

Haemophilia Centre Rhine Main GmbH, Hessenring 13a, Geb. G, Mörfelden-Walldorf, 64546, Germany.

Treatment of haemophilia A with FVIII replacement has evolved over the past decades to adapt to the needs of patients. octanate®, a plasma-derived, double virus-inactivated, von Willebrand factor (VWF)-containing FVIII concentrate, has been used in clinics worldwide for over 20 years. First licensed in 1998 in Germany, octanate® is approved in over 80 countries for the prevention and treatment of bleeding and for surgical prophylaxis in patients with haemophilia A, and in over 40 countries for immune tolerance induction (ITI). Read More

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The experiences and attitudes of hemophilia carriers around pregnancy: A qualitative systematic review.

J Thromb Haemost 2020 07 12;18(7):1626-1636. Epub 2020 May 12.

Van Creveldkliniek, University Medical Center Utrecht, University Utrecht, Utrecht, The Netherlands.

Background: Hemophilia carriers (HCs) face specific psychosocial challenges related to pregnancy, caused by their inherited bleeding disorder. Optimal support from healthcare providers can only be realized by exploring medical and psychological healthcare requirements.

Objective: To review all published evidence on the experiences and attitudes of HCs regarding reproductive decision-making, prenatal diagnosis, pregnancy, childbirth, and puerperium to provide an accessible overview of this information for health care providers. Read More

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Hemophilia management: Huge impact of a tiny difference.

Res Pract Thromb Haemost 2020 Mar 28;4(3):377-385. Epub 2020 Feb 28.

Pediatric Hematology Amsterdam UMC Emma Children's Hospital University of Amsterdam Amsterdam The Netherlands.

Hemophilia A and B are inherited X-linked disorders of hemostasis, associated with an increased bleeding tendency. Patients with severe hemophilia have undetectable clotting factor levels and experience spontaneous bleeds. In patients with nonsevere hemophilia, the clotting factor levels are 2% to 40% of normal and bleeds predominantly occur after provocative events such as trauma and surgery. Read More

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Physiological Roles of the von Willebrand Factor-Factor VIII Interaction.

Subcell Biochem 2020 ;94:437-464

Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Langenbeckstrasse 1, Building 708, 55131, Mainz, Germany.

Von Willebrand factor (VWF) and coagulation factor VIII (FVIII) circulate as a complex in plasma and have a major role in the hemostatic system. VWF has a dual role in hemostasis. It promotes platelet adhesion by anchoring the platelets to the subendothelial matrix of damaged vessels and it protects FVIII from proteolytic degradation. Read More

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Menstrual and obstetrical bleeding in women with inherited platelet receptor defects-A systematic review.

Haemophilia 2020 Mar 31;26(2):216-227. Epub 2020 Jan 31.

Van Creveldkliniek, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.

Introduction: Women with inherited platelet receptor defects (IPRD) may have an increased risk of heavy menstrual bleeding (HMB) and postpartum haemorrhage (PPH).

Aim: To present a systematic overview of the literature on the prevalence and management of menstrual and obstetrical bleeding in women with IPRD.

Methods: Electronic databases were searched for original patient data on the prevalence and management of HMB and PPH in women with known IPRD or who were being investigated for IPRD. Read More

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Fundamentals for a Systematic Approach to Mild and Moderate Inherited Bleeding Disorders: An EHA Consensus Report.

Hemasphere 2019 10 17;3(4):e286. Epub 2019 Sep 17.

Department of Medicine, Division of Heamtology-Oncology, University of North Carolina at Chapel Hill, NC, USA.

Healthy subjects frequently report minor bleedings that are frequently 'background noise' of normality rather than a true disorder. Nevertheless, unexpected or unusual bleeding may be alarming. Thus, the distinction between normal and pathologic bleeding is critical. Read More

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October 2019

Managing Preoperative Hemostasis in Patients with Inherited and Acquired Bleeding Disorders.

Semin Thromb Hemost 2020 Feb 30;46(1):17-25. Epub 2019 Dec 30.

Department of Haematology, Oxford University Hospitals NHS FT, Oxford, United Kingdom.

Inherited and acquired bleeding disorders pose significant hemostatic challenges for surgery. Patients at particular risk of bleeding include those with inherited bleeding disorders such as hemophilia, von Willebrand disease, and platelet function defects; those on antiplatelet agents or anticoagulants; and those with acquired conditions such as immune thrombocytopenic purpura, liver disease, or renal impairment. Each has its own specific challenges and close collaboration between the anesthetic, surgical, and hematology teams is crucial. Read More

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February 2020

The Horizon of Gene Therapy in Modern Medicine: Advances and Challenges.

Adv Exp Med Biol 2020 ;1247:33-64

Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Gene therapy as a novel study in molecular medicine will have a significant impact on human health in the near future. In recent years, the scope of gene therapy has been developed and is now beginning to revolutionize therapeutic approaches. Accordingly, many types of diseases are now being studied and treated in clinical trials through various gene delivery vectors. Read More

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A Molecular Revolution in the Treatment of Hemophilia.

Mol Ther 2020 04 13;28(4):997-1015. Epub 2019 Nov 13.

Department of Pediatrics, Indiana University School of Medicine, IUPUI-Wells Center for Pediatric Research, Indianapolis, IN, USA; Laboratory of Glycobiology, Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland. Electronic address:

For decades, the monogenetic bleeding disorders hemophilia A and B (coagulation factor VIII and IX deficiency) have been treated with systemic protein replacement therapy. Now, diverse molecular medicines, ranging from antibody to gene to RNA therapy, are transforming treatment. Traditional replacement therapy requires twice to thrice weekly intravenous infusions of factor. Read More

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An overview of turoctocog alfa pegol (N8-GP; ESPEROCT ) assay performance: Implications for postadministration monitoring.

Haemophilia 2020 Jan 6;26(1):156-163. Epub 2019 Dec 6.

Novo Nordisk A/S, Måløv, Denmark.

Factor replacement therapy with factor VIII (FVIII) concentrates is the current standard of care for patients with haemophilia A. Postadministration monitoring of FVIII activity during on-demand or prophylactic treatment is important, for example to guide a suitable dosing regimen. While the use of two-stage chromogenic substrate (CS) assays is increasing, activated partial thromboplastin time (APTT)-based one-stage clotting (OSC) assays are most commonly used to measure FVIII activity in clinical laboratories. Read More

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January 2020

The many roles of tranexamic acid: An overview of the clinical indications for TXA in medical and surgical patients.

Eur J Haematol 2020 Feb 16;104(2):79-87. Epub 2019 Dec 16.

Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon.

Clinically significant bleeding can occur as a consequence of surgery, trauma, obstetric complications, anticoagulation, and a wide variety of disorders of hemostasis. As the causes of bleeding are diverse and not always immediately apparent, the availability of a safe, effective, and non-specific hemostatic agent is vital in a wide range of clinical settings, with antifibrinolytic agents often utilized for this purpose. Tranexamic acid (TXA) is one of the most commonly used and widely researched antifibrinolytic agents; its role in postpartum hemorrhage, menorrhagia, trauma-associated hemorrhage, and surgical bleeding has been well defined. Read More

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February 2020

Engineering IgG-Like Bispecific Antibodies-An Overview.

Antibodies (Basel) 2018 Aug 1;7(3). Epub 2018 Aug 1.

Protein Engineering and Antibody Technologies, Merck KGaA, Frankfurter Strasse 250, D-64293 Darmstadt, Germany.

Monoclonal antibody therapeutics have proven to be successful treatment options for patients in various indications. Particularly in oncology, therapeutic concepts involving antibodies often rely on the so-called effector functions, such as antibody dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC), which are programed in the antibody Fc region. However, Fc-mediated effector mechanisms often seem to be insufficient in properly activating the immune system to act against tumor cells. Read More

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