31,238 results match your criteria error metabolism


Parkinsonism and iron deposition in two adult patients with L-2-hydroxiglutaric aciduria.

Parkinsonism Relat Disord 2021 Apr 1;86:45-47. Epub 2021 Apr 1.

Neurology Department, Centro Hospitalar Universitário do Porto, Porto, Portugal.

L-2-hydroxiglutaric aciduria (L2HGA) is a rare, childhood-onset, organic aciduria, with characteristic clinical (cerebellar ataxia) and neuroimaging (subcortical leukodystrophy) features. Movement disorders in this condition are usually of hyperkinetic type. Herein is reported the case of two adult siblings with recent L2HGA diagnosis, presenting with dopa-responsive parkinsonism and MRI iron deposition. Read More

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[Identification of characteristic methylation sites in gastric cancer using genomics-based machine learning].

Zhonghua Bing Li Xue Za Zhi 2021 Apr;50(4):363-368

Department of Pathology, Fujian Cancer Hospital, Fuzhou 350014, China.

To construct a prediction model of gastric cancer related methylation using machine learning algorithms based on genomic data. The gene mutation data, gene expression data and methylation chip data of gastric cancer were downloaded from The Caner Genome Atlas database, feature selection was conducted, and support vector machine (radial basis function), random forest and error back propagation (BP) neural network models were constructed; the model was verified in the new data set. Among the three machine learning models, BP neural network had the highest test efficiency (F1 score=0. Read More

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Cerebrotendinous xanthomatosis without neurological involvement.

J Intern Med 2021 Apr 8. Epub 2021 Apr 8.

Department of Neurology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.

Background: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessively inherited inborn error of metabolism. Neurological symptoms are considered to be a clinical hallmark of untreated adult patients. We describe a 'milder CTX phenotype', without neurological involvement. Read More

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Watching a double strand break repair polymerase insert a pro-mutagenic oxidized nucleotide.

Nat Commun 2021 04 6;12(1):2059. Epub 2021 Apr 6.

Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, 27709, USA.

Oxidized dGTP (8-oxo-7,8-dihydro-2´-deoxyguanosine triphosphate, 8-oxodGTP) insertion by DNA polymerases strongly promotes cancer and human disease. How DNA polymerases discriminate against oxidized and undamaged nucleotides, especially in error-prone double strand break (DSB) repair, is poorly understood. High-resolution time-lapse X-ray crystallography snapshots of DSB repair polymerase μ undergoing DNA synthesis reveal that a third active site metal promotes insertion of oxidized and undamaged dGTP in the canonical anti-conformation opposite template cytosine. Read More

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The Adult Phenylketonuria (PKU) Gut Microbiome.

Microorganisms 2021 Mar 4;9(3). Epub 2021 Mar 4.

Department of Microbiology, Immunology, and Genetics, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.

Phenylketonuria (PKU) is an inborn error of phenylalanine metabolism primarily treated through a phenylalanine-restrictive diet that is frequently supplemented with an amino acid formula to maintain proper nutrition. Little is known of the effects of these dietary interventions on the gut microbiome of PKU patients, particularly in adults. In this study, we sequenced the V4 region of the 16S rRNA gene from stool samples collected from adults with PKU ( = 11) and non-PKU controls ( = 21). Read More

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Different Curve Shapes of Fasting Glucose and Various Obesity-Related Indices by Diabetes and Sex.

Int J Environ Res Public Health 2021 Mar 17;18(6). Epub 2021 Mar 17.

Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung 812, Taiwan.

Fasting plasma glucose (FPG) and obesity-related indices are prognostic factors for adverse outcomes in both subjects with and without diabetes. A few studies have investigated sex differences in obesity indices related to the risk of diabetes, however no studies have compared the relationship between FPG and obesity-related indices by diabetes and sex. Therefore, in this study, we compared the curve shapes of FPG and various obesity-related indices by diabetes, and further explored sex differences in these associations. Read More

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Colorectal anastomotic leak: transcriptomic profile analysis.

Br J Surg 2021 Jan 30. Epub 2021 Jan 30.

Department of Surgery, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.

Background: Anastomotic leakage in patients undergoing colorectal surgery is associated with morbidity and mortality. Although multiple risk factors have been identified, the underlying mechanisms are mainly unknown. The aim of this study was to perform a transcriptome analysis of genes underlying the development of anastomotic leakage. Read More

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January 2021

Genotypic and phenotypic features in Turkish patients with classic nonketotic hyperglycinemia.

Metab Brain Dis 2021 Apr 1. Epub 2021 Apr 1.

Metabolism Unit, Sami Ulus Children Hospital, Babur cad. No: 44, Altındağ, Ankara, 06080, Turkey.

Nonketotic hyperglycinemia is an autosomal recessive inborn error of glycine metabolism, characterized by deficient activity of the glycine cleavage enzyme system. Classic nonketotic hyperglycinemia is caused by mutations or genomic changes in genes that encode the protein components of the glycine cleavage enzyme system. We aimed to investigate clinical, biochemical, radiological findings and molecular genetic data in ten Turkish patients with classic nonketotic hyperglycinemia. Read More

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CRISPR/Cas9 generated knockout mice lacking phenylalanine hydroxylase protein as a novel preclinical model for human phenylketonuria.

Sci Rep 2021 Mar 31;11(1):7254. Epub 2021 Mar 31.

Genomic Medicine Unit, Sanofi, 49 New York Avenue, Framingham, MA, 01701, USA.

Phenylketonuria (PKU) is an autosomal recessive inborn error of L-phenylalanine (Phe) metabolism. It is caused by a partial or complete deficiency of the enzyme phenylalanine hydroxylase (PAH), which is necessary for conversion of Phe to tyrosine (Tyr). This metabolic error results in buildup of Phe and reduction of Tyr concentration in blood and in the brain, leading to neurological disease and intellectual deficits. Read More

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Prediction and analysis of multiple protein lysine modified sites based on conditional wasserstein generative adversarial networks.

BMC Bioinformatics 2021 Mar 31;22(1):171. Epub 2021 Mar 31.

Department of Information and Computer Science, University of Science and Technology Beijing, Beijing, 100083, China.

Background: Protein post-translational modification (PTM) is a key issue to investigate the mechanism of protein's function. With the rapid development of proteomics technology, a large amount of protein sequence data has been generated, which highlights the importance of the in-depth study and analysis of PTMs in proteins.

Method: We proposed a new multi-classification machine learning pipeline MultiLyGAN to identity seven types of lysine modified sites. Read More

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Hospital load and increased COVID-19 related mortality in Israel.

Nat Commun 2021 03 26;12(1):1904. Epub 2021 Mar 26.

Department of Statistics and Operations Research, Tel Aviv University, Ramat Aviv, Israel.

The spread of Coronavirus disease 19 (COVID-19) has led to many healthcare systems being overwhelmed by the rapid emergence of new cases. Here, we study the ramifications of hospital load due to COVID-19 morbidity on in-hospital mortality of patients with COVID-19 by analyzing records of all 22,636 COVID-19 patients hospitalized in Israel from mid-July 2020 to mid-January 2021. We show that even under moderately heavy patient load (>500 countrywide hospitalized severely-ill patients; the Israeli Ministry of Health defined 800 severely-ill patients as the maximum capacity allowing adequate treatment), in-hospital mortality rate of patients with COVID-19 significantly increased compared to periods of lower patient load (250-500 severely-ill patients): 14-day mortality rates were 22. Read More

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Platelet autophagic machinery involved in thrombosis through a novel linkage of AMPK-MTOR to sphingolipid metabolism.

Autophagy 2021 Apr 5:1-18. Epub 2021 Apr 5.

Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Basal macroautophagy/autophagy has recently been found in anucleate platelets. Platelet autophagy is involved in platelet activation and thrombus formation. However, the mechanism underlying autophagy in anucleate platelets require further clarification. Read More

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Moxibustion for cognitive impairment: a systematic review and meta-analysis of animal studies.

Integr Med Res 2021 Jun 14;10(2):100680. Epub 2020 Oct 14.

Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.

Background: Cognitive impairment is an age-dependent chronic disorder that exponentially worsens with age; however, its treatment is mostly symptomatic. Moxibustion is widely accepted in East Asia as a treatment for cognitive impairment. This systematic review aimed to verify the efficacy and underlying mechanism of moxibustion in treating cognitive impairment. Read More

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Inherited Metabolic Causes of Stroke in Children: Mechanisms, Types, and Management.

Front Neurol 2021 4;12:633119. Epub 2021 Mar 4.

Department of Genetics and Precision Medicine (GPM), King Abdullah Specialized Children's Hospital, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.

A stroke should be considered in cases of neurologic decompensation associated with inherited metabolic disorders. A resultant stroke could be a classical ischemic stroke (vascular stroke) or more commonly a "metabolic stroke." A metabolic stroke begins with metabolic dysfunctions, usually caused by a stressor, and leads to the rapid onset of prolonged central neurological deficits in the absence of vessel occlusion or rupture. Read More

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Alkaptonuria in Turkey: Clinical and molecular characteristics of 66 patients.

Eur J Med Genet 2021 Mar 18;64(5):104197. Epub 2021 Mar 18.

Department of Pediatric Metabolism and Nutrition, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey; Izmir Biomedicine and Genome Center, Izmir, Turkey. Electronic address:

Alkaptonuria (AKU) is an inborn error of metabolism caused by the deficiency of homogentisate 1,2-dioxygenase (HGD) as a result of a defect in the HGD gene. HGD enzyme deficiency results in accumulation of homogentisic acid (HGA) in the body, which in turn leads to multisystemic clinical symptoms. The present study aimed to investigate the presenting symptoms, age at diagnosis, and clinical and genetic characteristics of AKU patients followed-up in different centers in Turkey. Read More

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Difficulties in the dietary management of a girl with two diseases requiring a special diet.

J Mother Child 2021 Jan 29;22(3):225-228. Epub 2021 Jan 29.

Department of Inborn Errors of Metabolism and Paediatrics, Institute of Mother and Child, Warsaw, Poland.

3-Methylcrotonylglycinuria (3-MCG) is an autosomal recessive inborn error of leucine metabolism caused by the deficiency of 3-methylocrotonyl-CoA carboxylase (3-MCC deficiency). It is the most commonly detected organic aciduria in newborn screening conducted by tandem mass spectrometry (MS/MS) [1, 2]. The clinical phenotype is heterogeneous, ranging from asymptomatic to acute metabolic decompensations [3, 4]. Read More

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January 2021

Amadori rearrangement products as potential biomarkers for inborn errors of amino-acid metabolism.

Commun Biol 2021 Mar 19;4(1):367. Epub 2021 Mar 19.

Radboud University, Institute for Molecules and Materials, FELIX Laboratory, Toernooiveld 7, Nijmegen, the Netherlands.

The identification of disease biomarkers plays a crucial role in developing diagnostic strategies for inborn errors of metabolism and understanding their pathophysiology. A primary metabolite that accumulates in the inborn error phenylketonuria is phenylalanine, however its levels do not always directly correlate with clinical outcomes. Here we combine infrared ion spectroscopy and NMR spectroscopy to identify the Phe-glucose Amadori rearrangement product as a biomarker for phenylketonuria. Read More

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Relationship between urinary energy and urinary nitrogen or carbon excretion in lactating Jersey cows.

J Dairy Sci 2021 Mar 16. Epub 2021 Mar 16.

Department of Animal Science, University of Nebraska-Lincoln 68583. Electronic address:

Measurement of urinary energy (UE) excretion is essential to determine metabolizable energy (ME) supply. Our objectives were to evaluate the accuracy of using urinary N (UN) or C (UC) to estimate UE and ultimately improve the accuracy of estimating ME. Individual animal data (n = 433) were used from 11 studies with Jersey cows at the University of Nebraska-Lincoln, where samples were analyzed after drying (n = 299) or on an as-is basis (n = 134). Read More

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Gene delivery using AAV8 for disease stabilization in a bimodal gene therapy approach for the treatment of ADA-deficient SCID.

Mol Ther Methods Clin Dev 2021 Mar 15;20:765-778. Epub 2021 Feb 15.

Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Adenosine deaminase (ADA) deficiency is an inborn error of metabolism affecting multiple systems and causing severe combined immunodeficiency. We tested intravenous administration of recombinant adeno-associated virus (AAV) 2/8-ADA vector in ADA-deficient neonate and adult mice or as part of a bimodal approach comprised of rAAV treatment at birth followed by infusion of lentiviral vector (LV)-modified lineage-depleted bone marrow cells at 8 weeks. ADA mice treated with rAAV and enzyme replacement therapy (ERT) for 30 days were rescued from the lethal pulmonary insufficiency, surviving out to 180 days without further treatment. Read More

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Validation of plasma amino acid profile using UHPLC-mass spectrometer (QDa) as a screening method in a metabolic disorders reference centre: Performance and accreditation concerns.

Clin Biochem 2021 Mar 15. Epub 2021 Mar 15.

Laboratoire de Biochimie et Biologie Moléculaire, CHRU de Tours, Tours, France; Unité INSERM U1253, équipe "neurogénomique et physiopathologie neuronale", Université de Tours, Tours, France; Centre de référence des maladies héréditaires de métabolisme - filière G2M, France.

Introduction: Amino acid (AA) analysis in plasma is essential for diagnosis and monitoring of inborn errors of metabolism (IEM). The efficacy of patient management is governed by the rapidity of AA profile availability, along with the robustness of the method. French quality guidelines and progress made in analytical techniques have led biologists to develop AA profile exploration via mass spectrometry (MS). Read More

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Preparation and evaluation of fast-dissolving films of etilefrine hydrochloride for practical buccal dosing.

Pharm Dev Technol 2021 Mar 31:1-7. Epub 2021 Mar 31.

Department of Drug Delivery Research, Hoshi University, Tokyo, Japan.

Etilefrine hydrochloride (ET) is an important drug in the treatment of hypotension, and parenteral injections and oral tablets are the conventional dosage forms. However, parenteral injections may cause abnormally high plasma levels as well as pain and necrosis, and oral tablets undergo first-pass metabolism. Although fast-dissolving buccal tablets were previously reported, the initial absorption rate was a little slow and the plasma levels were varied extensively. Read More

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Arginine to ornithine ratio as a diagnostic marker in patients with positive newborn screening for hyperargininemia.

Mol Genet Metab Rep 2021 Jun 3;27:100735. Epub 2021 Mar 3.

Biochemical Genetics, Advanced Diagnostics-Genetics, Genomics and R&D, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA 92675, United States of America.

Arginase deficiency is a rare inborn error of metabolism that interrupts the final step of the urea cycle. Untreated individuals often present with episodic hyperammonemia, developmental delay, cognitive impairment, and spasticity in early childhood. The newborn screening (NBS) algorithms for arginase deficiency vary between individual states in the US but often include hyperargininemia and elevated arginine to ornithine (Arg/Orn) ratio. Read More

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Hand fine motor control in classic galactosemia.

J Inherit Metab Dis 2021 Mar 15. Epub 2021 Mar 15.

Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.

Classic galactosemia (CG) is a rare inborn error of metabolism that results from profound deficiency of galactose-1-P uridylyltransferase (GALT). Despite early detection and rapid and lifelong dietary restriction of galactose, which is the current standard of care, most patients grow to experience a broad range of complications that can include motor difficulties. The goal of this study was to characterize hand fine motor control deficit among children and adults with classic galactosemia (CG). Read More

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Incorporation of anatomical MRI knowledge for enhanced mapping of brain metabolism using functional PET.

Neuroimage 2021 Mar 11;233:117928. Epub 2021 Mar 11.

Monash Biomedical Imaging, Monash University, Melbourne, Victoria, Australia. Electronic address:

Functional positron emission tomography (fPET) imaging using continuous infusion of [18F]-fluorodeoxyglucose (FDG) is a novel neuroimaging technique to track dynamic glucose utilization in the brain. In comparison to conventional static or dynamic bolus PET, fPET maintains a sustained supply of glucose in the blood plasma which improves sensitivity to measure dynamic glucose changes in the brain, and enables mapping of dynamic brain activity in task-based and resting-state fPET studies. However, there is a trade-off between temporal resolution and spatial noise due to the low concentration of FDG and the limited sensitivity of multi-ring PET scanners. Read More

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Polymerase-guided base editing enables in vivo mutagenesis and rapid protein engineering.

Nat Commun 2021 03 11;12(1):1579. Epub 2021 Mar 11.

Department of Bioengineering, 443 Via Ortega, MC 4245, Stanford University, Stanford, CA, USA.

Random mutagenesis is a technique used to generate diversity and engineer biological systems. In vivo random mutagenesis generates diversity directly in a host organism, enabling applications such as lineage tracing, continuous evolution, and protein engineering. Here we describe TRIDENT (TaRgeted In vivo Diversification ENabled by T7 RNAP), a platform for targeted, continual, and inducible diversification at genes of interest at mutation rates one-million fold higher than natural genomic error rates. Read More

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Assessment of the effects of repeated freeze thawing and extended bench top processing of plasma samples using untargeted metabolomics.

Metabolomics 2021 03 11;17(3):31. Epub 2021 Mar 11.

Metabolon, 617 Davis Drive, Suite 100, Morrisville, NC, 27560, USA.

Introduction: Clinical metabolomics has utility as a screen for inborn errors of metabolism (IEM) and variant classification in patients with rare disease. It is important to understand and characterize preanalytical factors that influence assay performance during patient sample testing.

Objectives: To evaluate the impact of extended thawing of human EDTA plasma samples on ice prior to extraction as well as repeated freeze-thaw cycling of samples to identify compounds that are unstable prior to metabolomic analysis. Read More

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Value of amniotic fluid homocysteine assay in prenatal diagnosis of combined methylmalonic acidemia and homocystinuria, cobalamin C type.

Orphanet J Rare Dis 2021 Mar 10;16(1):125. Epub 2021 Mar 10.

Department of Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, 200092, China.

Background: Combined methylmalonic acidemia and homocystinuria, cobalamin C type (cblC defect) is the most common inborn error of cobalamin metabolism, and different approaches have been applied to its prenatal diagnosis. To evaluate the reliability of biochemical method for the prenatal diagnosis of cblC defect, we conducted a retrospective study of our 10-year experience at a single center.

Methods: 248 pregnancies whose probands were diagnosed as cblC defect were referred to our center for prenatal diagnosis from January 2010 to December 2019. Read More

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Management of COVID-19 infection in organic acidemias.

Am J Med Genet A 2021 Mar 8. Epub 2021 Mar 8.

Division of Genetic, Genomic, and Metabolic Disorders, Children's Hospital of Michigan, Detroit, Michigan, USA.

The COVID-19 pandemic has affected the health and healthcare of individuals of all ages worldwide. There have been multiple reports and reviews documenting a milder effect and decreased morbidity and mortality in the pediatric population, but there have only been a small number of reports discussing the SARS-CoV-2 infection in the setting of an inborn error of metabolism (IEM). Here, we report two patients with underlying metabolic disorders, propionic acidemia and glutaric aciduria type 1, and discuss their clinical presentation, as well as their infectious and metabolic management. Read More

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Long-term outcome of a patient with Transcobalamin deficiency caused by the homozygous c.1115_1116delCA mutation in TCN2 gene: a case report.

Ital J Pediatr 2021 Mar 8;47(1):54. Epub 2021 Mar 8.

Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.

Background: Transcobalamin deficiency is a rare autosomal recessive inborn error of cobalamin transport (prevalence: < 1/1000000) which clinically manifests in early infancy.

Case Presentation: We describe the case of a 31 years old woman who at the age of 30 days presented with the classical clinical and laboratory signs of an inborn error of vitamin B metabolism. Family history revealed a sister who died at the age of 3 months with a similar clinical syndrome and with pancytopenia. Read More

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Nutrition in Chronic Liver Disease: Consensus Statement of the Indian National Association for Study of the Liver.

J Clin Exp Hepatol 2021 Jan-Feb;11(1):97-143. Epub 2020 Oct 1.

Institute of Liver & Digestive Diseases, BL Kapur Memorial Hospital, New Delhi, 110005, India.

Malnutrition and sarcopenia are common in patients with chronic liver disease and are associated with increased risk of decompensation, infections, wait-list mortality and poorer outcomes after liver transplantation. Assessment of nutritional status and management of malnutrition are therefore essential to improve outcomes in patients with chronic liver disease. This consensus statement of the Indian National Association for Study of the Liver provides a comprehensive review of nutrition in chronic liver disease and gives recommendations for nutritional screening and treatment in specific clinical scenarios of malnutrition in cirrhosis in adults as well as children with chronic liver disease and metabolic disorders. Read More

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October 2020