1,180 results match your criteria Annual Review Of Pharmacology And Toxicology[Journal]


Pushing Forward the Future Tense: Perspectives of a Scientist.

Authors:
Lee E Limbird

Annu Rev Pharmacol Toxicol 2021 Aug 2. Epub 2021 Aug 2.

Department of Life and Physical Sciences, Fisk University, Nashville, Tennessee 37208, USA; email:

This review is a somewhat chronological tale of my scientific life, emphasizing the why of the questions we asked in the lab and lessons learned that may be of value to nascent scientists. The reader will come to realize that the flow of my life has been driven by a combined life of the mind and life of the soul, intertwining like the strands of DNA. Expected final online publication date for the , Volume 62 is January 2022. Read More

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Experimental Models of SARS-CoV-2 Infection: Possible Platforms to Study COVID-19 Pathogenesis and Potential Treatments.

Annu Rev Pharmacol Toxicol 2021 Feb 19. Epub 2021 Feb 19.

Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; email:

In December 2019, a novel coronavirus crossed species barriers to infect humans and was effectively transmitted from person to person, leading including vaccines and antiviral drugs that could prevent or limit the burden or transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health priority. It is thus of utmost importance to assess possible therapeutic strategies against SARS-CoV-2 using experimental models that recapitulate aspects of the human disease. Here, we review available models currently being developed and used to study SARS-CoV-2 infection and highlight their application to screen potential therapeutic approaches, including repurposed antiviral drugs and vaccines. Read More

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February 2021

New Drugs, Old Targets: Tweaking the Dopamine System to Treat Psychostimulant Use Disorders.

Annu Rev Pharmacol Toxicol 2021 01;61:609-628

Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA; email:

The abuse of illicit psychostimulants such as cocaine and methamphetamine continues to pose significant health and societal challenges. Despite considerable efforts to develop medications to treat psychostimulant use disorders, none have proven effective, leaving an underserved patient population and unanswered questions about what mechanism(s) of action should be targeted for developing pharmacotherapies. As both cocaine and methamphetamine rapidly increase dopamine (DA) levels in mesolimbic brain regions, leading to euphoria that in some can lead to addiction, targets in which this increased dopaminergic tone may be mitigated have been explored. Read More

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January 2021

Introduction to the Theme "Old and New Toxicology: Interfaces with Pharmacology".

Annu Rev Pharmacol Toxicol 2021 01;61:1-7

Departments of Pharmacology and Medicine, University of California, San Diego, La Jolla, California 92093, USA.

The theme of Volume 61 is "Old and New Toxicology: Interfaces with Pharmacology." Old toxicology is exemplified by the authors of the autobiographical articles: B.M. Read More

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January 2021

A Serendipitous Path to Pharmacology.

Annu Rev Pharmacol Toxicol 2021 01;61:9-23

School of Biological Sciences, University of Utah, Salt Lake City, Utah 84112, USA; email:

My path to research in neuropharmacology has been a coalescing of my training as a molecular biologist and my intense interest in an esoteric group of animals, the fish-hunting cone snails. Attempting to bridge these two disparate worlds has led me to an idiosyncratic career as a pharmacologist. Read More

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January 2021

Arsenic: A Global Environmental Challenge.

Annu Rev Pharmacol Toxicol 2021 01;61:47-63

Department of Environmental Medicine, New York University School of Medicine, New York, New York 10010, USA; email:

Arsenic is a naturally occurring metalloid and one of the few metals that can be metabolized inside the human body. The pervasive presence of arsenic in nature and anthropogenic sources from agricultural and medical use have perpetuated human exposure to this toxic and carcinogenic element. Highly exposed individuals are susceptible to various illnesses, including skin disorders; cognitive impairment; and cancers of the lung, liver, and kidneys. Read More

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January 2021

Signaling Microdomains in the Spotlight: Visualizing Compartmentalized Signaling Using Genetically Encoded Fluorescent Biosensors.

Annu Rev Pharmacol Toxicol 2021 01;61:587-608

Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, USA; email:

How cells muster a network of interlinking signaling pathways to faithfully convert diverse external cues to specific functional outcomes remains a central question in biology. Through their ability to convert dynamic biochemical activities to rapid and precise optical readouts, genetically encoded fluorescent biosensors have become instrumental in unraveling the molecular logic controlling the specificity of intracellular signaling. In this review, we discuss how the use of genetically encoded fluorescent biosensors to visualize dynamic signaling events within their native cellular context is elucidating the different strategies employed by cells to organize signaling activities into discrete compartments, or signaling microdomains, to ensure functional specificity. Read More

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January 2021

Cholinergic Capsules and Academic Admonitions.

Authors:
Palmer Taylor

Annu Rev Pharmacol Toxicol 2021 01;61:25-46

Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, and School of Medicine, University of California, San Diego, La Jolla, California 92093, USA; email:

Herein, I intend to capture highlights shared with my academic and research colleagues over the 60 years I devoted initially to my graduate and postdoctoral training and then to academic endeavors starting as an assistant professor in a new medical school at the University of California, San Diego (UCSD). During this period, the Department of Pharmacology emerged from a division within the Department of Medicine to become the first basic science department, solely within the School of Medicine at UCSD in 1979. As part of the school's plans to reorganize and to retain me at UCSD, I was appointed as founding chair. Read More

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January 2021

Engineering the Microbiome to Prevent Adverse Events: Challenges and Opportunities.

Annu Rev Pharmacol Toxicol 2021 01 13;61:159-179. Epub 2020 Oct 13.

Department of Systems and Computational Biology, Albert Einstein College of Medicine, New York, NY 10461, USA; email:

In the past decade of microbiome research, we have learned about numerous adverse interactions between the microbiome and medical interventions such as drugs, radiation, and surgery. What if we could alter our microbiomes to prevent these events? In this review, we discuss potential routes to mitigate microbiome adverse events, including applications from the emerging field of microbiome engineering. We highlight cases where the microbiome acts directly on a treatment, such as via differential drug metabolism, and cases where a treatment directly harms the microbiome, such as in radiation therapy. Read More

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January 2021

Pharmacology of Chimeric Antigen Receptor-Modified T Cells.

Annu Rev Pharmacol Toxicol 2021 01 9;61:805-829. Epub 2020 Oct 9.

Department of Pathology and Laboratory Medicine and Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email:

Cell-based immunotherapies using T cells that are engineered to express a chimeric antigen receptor (CAR-T cells) are an effective treatment option for several B cell malignancies. Compared with most drugs, CAR-T cell products are highly complex, as each cell product is composed of a heterogeneous mixture of millions of cells. The biodistribution and kinetics of CAR-T cells, following administration, are unique given the ability of T cells to actively migrate as well as replicate within the patient. Read More

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January 2021

Antisense Drugs Make Sense for Neurological Diseases.

Annu Rev Pharmacol Toxicol 2021 01 9;61:831-852. Epub 2020 Oct 9.

Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA.

The genetic basis for most inherited neurodegenerative diseases has been identified, yet there are limited disease-modifying therapies for these patients. A new class of drugs-antisense oligonucleotides (ASOs)-show promise as a therapeutic platform for treating neurological diseases. ASOs are designed to bind to the RNAs either by promoting degradation of the targeted RNA or by elevating expression by RNA splicing. Read More

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January 2021

Model-Informed Precision Dosing: Background, Requirements, Validation, Implementation, and Forward Trajectory of Individualizing Drug Therapy.

Annu Rev Pharmacol Toxicol 2021 01 9;61:225-245. Epub 2020 Oct 9.

Certara, Princeton, New Jersey 08540, USA.

Model-informed precision dosing (MIPD) has become synonymous with modern approaches for individualizing drug therapy, in which the characteristics of each patient are considered as opposed to applying a one-size-fits-all alternative. This review provides a brief account of the current knowledge, practices, and opinions on MIPD while defining an achievable vision for MIPD in clinical care based on available evidence. We begin with a historical perspective on variability in dose requirements and then discuss technical aspects of MIPD, including the need for clinical decision support tools, practical validation, and implementation of MIPD in health care. Read More

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January 2021

Sex Differences in the Inflammatory Response: Pharmacological Opportunities for Therapeutics for Coronary Artery Disease.

Annu Rev Pharmacol Toxicol 2021 01 9;61:333-359. Epub 2020 Oct 9.

The William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom; email:

Coordinated molecular responses are key to effective initiation and resolution of both acute and chronic inflammation. Vascular inflammation plays an important role in initiating and perpetuating atherosclerotic disease, specifically at the site of plaque and subsequent fibrous cap rupture. Both men and women succumb to this disease process, and although management strategies have focused on revascularization and pharmacological therapies in the acute situation to reverse vessel closure and prevent thrombogenesis, data now suggest that regulation of host inflammation may improve both morbidity and mortality, thus supporting the notion that prevention is better than cure. Read More

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January 2021

Preventing and Treating Anthracycline Cardiotoxicity: New Insights.

Annu Rev Pharmacol Toxicol 2021 01;61:309-332

Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy; email:

Anthracyclines are the cornerstone of many chemotherapy regimens for a variety of cancers. Unfortunately, their use is limited by a cumulative dose-dependent cardiotoxicity. Despite more than five decades of research, the biological mechanisms underlying anthracycline cardiotoxicity are not completely understood. Read More

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January 2021

Pharmacologic Approach to Sinoatrial Node Dysfunction.

Annu Rev Pharmacol Toxicol 2021 01 5;61:757-778. Epub 2020 Oct 5.

Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, 34096 Montpellier, France; email:

The spontaneous activity of the sinoatrial node initiates the heartbeat. Sino-atrial node dysfunction (SND) and sick sinoatrial (sick sinus) syndrome are caused by the heart's inability to generate a normal sinoatrial node action potential. In clinical practice, SND is generally considered an age-related pathology, secondary to degenerative fibrosis of the heart pacemaker tissue. Read More

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January 2021

Challenges and Opportunities in Implementing Pharmacogenetic Testing in Clinical Settings.

Annu Rev Pharmacol Toxicol 2021 01 2;61:65-84. Epub 2020 Oct 2.

Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia V6H 3V4, Canada; email:

The clinical implementation of pharmacogenetic biomarkers continues to grow as new genetic variants associated with drug outcomes are discovered and validated. The number of drug labels that contain pharmacogenetic information also continues to expand. Published, peer-reviewed clinical practice guidelines have also been developed to support the implementation of pharmacogenetic tests. Read More

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January 2021

Epigenetic Neuropharmacology: Drugs Affecting the Epigenome in the Brain.

Authors:
Miklos Toth

Annu Rev Pharmacol Toxicol 2021 01 30;61:181-201. Epub 2020 Sep 30.

Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA; email:

This review explores how different classes of drugs, including those with therapeutic and abuse potential, alter brain functions and behavior via the epigenome. Epigenetics, in its simplest interpretation, is the study of the regulation of a genes' transcriptional potential. The epigenome is established during development but is malleable throughout life by a wide variety of drugs, with both clinical utility and abuse potential. Read More

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January 2021

PHLPPing the Script: Emerging Roles of PHLPP Phosphatases in Cell Signaling.

Annu Rev Pharmacol Toxicol 2021 01 30;61:723-743. Epub 2020 Sep 30.

Department of Pharmacology, University of California, San Diego, La Jolla, California 92093-0721, USA; email:

Whereas protein kinases have been successfully targeted for a variety of diseases, protein phosphatases remain an underutilized therapeutic target, in part because of incomplete characterization of their effects on signaling networks. The pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) is a relatively new player in the cell signaling field, and new roles in controlling the balance among cell survival, proliferation, and apoptosis are being increasingly identified. Originally characterized for its tumor-suppressive function in deactivating the prosurvival kinase Akt, PHLPP may have an opposing role in promoting survival, as recent evidence suggests. Read More

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January 2021

Novel Therapeutic Approach for Excitatory/Inhibitory Imbalance in Neurodevelopmental and Neurodegenerative Diseases.

Annu Rev Pharmacol Toxicol 2021 01 30;61:701-721. Epub 2020 Sep 30.

Department of Molecular Medicine and Neuroscience Translational Center, The Scripps Research Institute, La Jolla, California 92037, USA; email:

Excitatory/inhibitory (E/I) balance, defined as the balance between excitation and inhibition of synaptic activity in a neuronal network, accounts in part for the normal functioning of the brain, controlling, for example, normal spike rate. In many pathological conditions, this fine balance is perturbed, leading to excessive or diminished excitation relative to inhibition, termed E/I imbalance, reflected in network dysfunction. E/I imbalance has emerged as a contributor to neurological disorders that occur particularly at the extremes of life, including autism spectrum disorder and Alzheimer's disease, pointing to the vulnerability of neuronal networks at these critical life stages. Read More

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January 2021

Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span.

Annu Rev Pharmacol Toxicol 2021 01 30;61:779-803. Epub 2020 Sep 30.

Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA; email:

Senescence is the consequence of a signaling mechanism activated in stressed cells to prevent proliferation of cells with damage. Senescent cells (Sncs) often develop a senescence-associated secretory phenotype to prompt immune clearance, which drives chronic sterile inflammation and plays a causal role in aging and age-related diseases. Sncs accumulate with age and at anatomical sites of disease. Read More

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January 2021

Use of Model-Informed Drug Development to Streamline Development of Long-Acting Products: Can These Successes Be Translated to Long-Acting Hormonal Contraceptives?

Annu Rev Pharmacol Toxicol 2021 01 30;61:745-756. Epub 2020 Sep 30.

Office of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland 20993, USA; email:

Long-acting contraceptives are the most effective reversible contraceptive methods. Increasing patients' access to these contraceptives may translate into fewer unintended pregnancies and lead to substantial individual and public health benefits. However, development of long-acting products can be complex and challenging. Read More

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January 2021

Scavenging Reactive Lipids to Prevent Oxidative Injury.

Annu Rev Pharmacol Toxicol 2021 01 30;61:291-308. Epub 2020 Sep 30.

Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6602, USA; email:

Oxidative injury due to elevated levels of reactive oxygen species is implicated in cardiovascular diseases, Alzheimer's disease, lung and liver diseases, and many cancers. Antioxidant therapies have generally been ineffective at treating these diseases, potentially due to ineffective doses but also due to interference with critical host defense and signaling processes. Therefore, alternative strategies to prevent oxidative injury are needed. Read More

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January 2021

Models of Idiosyncratic Drug-Induced Liver Injury.

Annu Rev Pharmacol Toxicol 2021 01 25;61:247-268. Epub 2020 Sep 25.

Department of Drug Safety Sciences, Division of Clinical Pharmacology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; email:

Drug-induced liver injury (DILI) is a leading cause of attrition during the early and late stages of drug development and after a drug is marketed. DILI is generally classified as either intrinsic or idiosyncratic. Intrinsic DILI is dose dependent and predictable (e. Read More

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January 2021

Pharmacogenomics in Pediatric Oncology: Mitigating Adverse Drug Reactions While Preserving Efficacy.

Annu Rev Pharmacol Toxicol 2021 01 25;61:679-699. Epub 2020 Sep 25.

Department of Pediatrics, Schulich School of Medicine and Dentistry, Western University, London, Ontario N6A 3M7, Canada; email:

Cancer is the leading cause of death in American children older than 1 year of age. Major developments in drugs such as thiopurines and optimization in clinical trial protocols for treating cancer in children have led to a remarkable improvement in survival, from approximately 30% in the 1960s to more than 80% today. Short-term and long-term adverse effects of chemotherapy still affect most survivors of childhood cancer. Read More

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January 2021

TRP Channel Cooperation for Nociception: Therapeutic Opportunities.

Annu Rev Pharmacol Toxicol 2021 01 25;61:655-677. Epub 2020 Sep 25.

Laboratory of Ion Channel Research, VIB-KU Leuven Center for Brain and Disease Research, 3000 Leuven, Belgium; email:

Chronic pain treatment remains a sore challenge, and in our aging society, the number of patients reporting inadequate pain relief continues to grow. Current treatment options all have their drawbacks, including limited efficacy and the propensity of abuse and addiction; the latter is exemplified by the ongoing opioid crisis. Extensive research in the last few decades has focused on mechanisms underlying chronic pain states, thereby producing attractive opportunities for novel, effective and safe pharmaceutical interventions. Read More

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January 2021

Store-Operated Ca Channels: Mechanism, Function, Pharmacology, and Therapeutic Targets.

Annu Rev Pharmacol Toxicol 2021 01 23;61:629-654. Epub 2020 Sep 23.

Department of Physiology, Anatomy and Genetics, Oxford University, Oxford OX1 3PT, United Kingdom; email:

Calcium (Ca) release-activated Ca (CRAC) channels are a major route for Ca entry in eukaryotic cells. These channels are store operated, opening when the endoplasmic reticulum (ER) is depleted of Ca, and are composed of the ER Ca sensor protein STIM and the pore-forming plasma membrane subunit Orai. Recent years have heralded major strides in our understanding of the structure, gating, and function of the channels. Read More

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January 2021

Pharmacogenomics of Antiretroviral Drug Metabolism and Transport.

Annu Rev Pharmacol Toxicol 2021 01 22;61:565-585. Epub 2020 Sep 22.

Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; email:

Antiretroviral therapy has markedly reduced morbidity and mortality for persons living with human immunodeficiency virus (HIV). Individual tailoring of antiretroviral regimens has the potential to further improve the long-term management of HIV through the mitigation of treatment failure and drug-induced toxicities. While the mechanisms underlying anti-HIV drug adverse outcomes are multifactorial, the application of drug-specific pharmacogenomic knowledge is required in order to move toward the personalization of HIV therapy. Read More

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January 2021

The CXCL12/CXCR4/ACKR3 Axis in the Tumor Microenvironment: Signaling, Crosstalk, and Therapeutic Targeting.

Annu Rev Pharmacol Toxicol 2021 01 21;61:541-563. Epub 2020 Sep 21.

Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (CSIC/UAM), 28049 Madrid, Spain.

Elevated expression of the chemokine receptors CXCR4 and ACKR3 and of their cognate ligand CXCL12 is detected in a wide range of tumors and the tumor microenvironment (TME). Yet, the molecular mechanisms by which the CXCL12/CXCR4/ACKR3 axis contributes to the pathogenesis are complex and not fully understood. To dissect the role of this axis in cancer, we discuss its ability to impinge on canonical and less conventional signaling networks in different cancer cell types; its bidirectional crosstalk, notably with receptor tyrosine kinase (RTK) and other factors present in the TME; and the infiltration of immune cells that supporttumor progression. Read More

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January 2021

Clinical Pharmacology and Interplay of Immune Checkpoint Agents: A Yin-Yang Balance.

Annu Rev Pharmacol Toxicol 2021 01 1;61:85-112. Epub 2020 Sep 1.

Sorbonne Université, INSERM, CIC-1901 Paris-Est, CLIP² Galilée, UNICO-GRECO Cardio-oncology Program, and Department of Pharmacology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, F-75013 Paris, France; email:

T cells have a central role in immune system balance. When activated, they may lead to autoimmune diseases. When too anergic, they contribute to infection spread and cancer proliferation. Read More

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January 2021

Targeting Endocannabinoid Signaling: FAAH and MAG Lipase Inhibitors.

Annu Rev Pharmacol Toxicol 2021 01 31;61:441-463. Epub 2020 Aug 31.

Department of Molecular Physiology, Leiden University, 2333 CC Leiden, The Netherlands; email:

Inspired by the medicinal properties of the plant and its principal component (-)--Δ-tetrahydrocannabinol (THC), researchers have developed a variety of compounds to modulate the endocannabinoid system in the human brain. Inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), which are the enzymes responsible for the inactivation of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol, respectively, may exert therapeutic effects without inducing the adverse side effects associated with direct cannabinoid CB receptor stimulation by THC. Here we review the FAAH and MAGL inhibitors that have reached clinical trials, discuss potential caveats, and provide an outlook on where the field is headed. Read More

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January 2021