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Many heart transplant biopsies currently diagnosed as no rejection have mild molecular antibody-mediated rejection-related changes.

J Heart Lung Transplant 2021 Aug 26. Epub 2021 Aug 26.

Medical University of Vienna, Vienna, Austria.

Background: The Molecular Microscope (MMDx) system classifies heart transplant endomyocardial biopsies as No-rejection (NR), Early-injury, T cell-mediated (TCMR), antibody-mediated (ABMR), mixed, and possible rejection (possible TCMR, possible ABMR). Rejection-like gene expression patterns in NR biopsies have not been described. We extended the MMDx methodology, using a larger data set, to define a new "Minor" category characterized by low-level inflammation in non-rejecting biopsies. Read More

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Bone Marrow versus Peripheral Blood Graft for Haploidentical HCT with Post Transplantation Cyclophosphamide.

Transplant Cell Ther 2021 Sep 16. Epub 2021 Sep 16.

Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.

Background: In the COVID-19 pandemic era, the numbers of haploidentical hematopoietic cell transplantation (HCT) with peripheral blood (PB) versus bone marrow (BM) grafts increased significantly, which may be associated with adverse outcomes.

Methods: We compared outcomes of BM vs PB grafts in patients ≥18 years with hematological malignancy who underwent T-cell replete haploidentical HCT and graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide, tacrolimus and mycophenolate mofetil.

Findings: Of 264 patients, 180 (68%) received BM and 84 (32%) received PB graft. Read More

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September 2021

Clonal expansion of CD8+ T cells reflects graft-versus-leukemia activity and precedes durable remission following DLI.

Blood Adv 2021 Sep 17. Epub 2021 Sep 17.

Institute of Immunology, Hannover Mecial School, Germany.

Donor lymphocyte infusion (DLI) is a standard of care for relapse of AML after allogeneic hematopoietic stem cell transplantation (aHSCT). Currently it is poorly understood how and when CD8+ αβ T cells exert graft-versus-leukemia (GvL) activity after DLI. Also, there is no reliable biomarker to monitor GvL activity of the infused CD8+ T cells. Read More

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September 2021

The Risk of Postkidney Transplant Outcomes by Induction Choice Differs by Recipient Age.

Transplant Direct 2021 Jul 18;7(7):e715. Epub 2021 Jun 18.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.

Background: Among adult kidney transplant (KT) recipients, the risk of post-KT adverse outcomes differs by type of induction immunosuppression. Immune response to induction differs as recipients age; yet, choice of induction is barely tailored by age likely due to a lack of evidence of the risks and benefits.

Methods: Using Scientific Registry of Transplant Recipients data, we identified 39336 first-time KT recipients (2010-2016). Read More

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Less invasive multivessel coronary artery bypass grafting: now is the time.

Curr Opin Cardiol 2021 Aug 26. Epub 2021 Aug 26.

Division of Cardiothoracic Surgery, Apollo Hospital, Bannerghatta Road, Bangalore Manipal Hospitals, Sector 6, Dwarka, New Delhi, India Society of Minimally Invasive Cardiovascular and Thoracic Surgeons of India Indian Association of Cardiovascular Thoracic Surgeons of India Association of Thoracic and Cardiovascular Surgeons of Asia Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.

Purpose Of Review: Less invasive multivessel coronary artery bypass grafting techniques have seen a progressive evolution over the last two decades. In their current state, they are easily reproduced and applicable to most patients requiring multivessel revascularization. The purpose of this review is to highlight their importance among a spectrum of evolving therapies and the accruing evidence in their favour. Read More

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Efficacy of platelet-rich fibrin on bone formation, part 2: Guided bone regeneration, sinus elevation and implant therapy.

Int J Oral Implantol (Berl) 2021 08;14(3):285-302

Purpose: To investigate the effect of platelet-rich fibrin on bone formation by investigating its use in guided bone regeneration, sinus elevation and implant therapy.

Materials And Methods: This systematic review and meta-analysis were conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The eligibility criteria comprised human controlled clinical trials comparing the clinical outcomes of platelet-rich fibrin with those of other treatment modalities. Read More

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Prognostic value of myocardial flow reserve obtained by 82-rubidium positron emission tomography in long-term follow-up after heart transplantation.

J Nucl Cardiol 2021 Aug 19. Epub 2021 Aug 19.

Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.

Background: Cardiac allograft vasculopathy (CAV) is a leading cause of death following heart transplantation (HTx) and non-invasive prognostic methods in long-term CAV surveillance are needed. We evaluated the prognostic value of myocardial flow reserve (MFR) obtained by 82-rubidium (Rb) positron emission tomography (PET).

Methods: Recipients undergoing dynamic rest-stress Rb PET between April 2013 and June 2017 were retrospectively evaluated in a single-center study. Read More

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Characterization of outcomes and practices utilized in the management of internal carotid artery injury not requiring definitive endovascular management.

Laryngoscope Investig Otolaryngol 2021 Aug 17;6(4):634-640. Epub 2021 Jul 17.

Department of Otolaryngology - Head & Neck Surgery Wexner Medical Center at The Ohio State University Columbus Ohio USA.

Background: After internal carotid artery (ICA) injury during endoscopic skull base surgery, the majority of patients undergo ICA embolization or stenting to treat active extravasation or pseudoaneurysm development. However, management practices when embolization or stenting is not required have not been well described. The objective of this study was to determine how patients with ICA injury but no embolization, stenting, or ligation do long-term and ascertain the reconstruction methods utilized. Read More

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Regulatory T cell activation, proliferation, and reprogramming induced by extracellular vesicles.

J Heart Lung Transplant 2021 Jun 24. Epub 2021 Jun 24.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

Background: Extracellular vesicles (EVs) from heart stromal/progenitor cells modulate innate immunity, with salutary effects in a variety of cardiac disease models. Little is known, however, about the effects of these EVs on adaptive immunity.

Methods: Ex vivo differentiation of naïve CD4 T cells was conducted to assess the effect of EVs on cytokine production and proliferation of Th1, Th2, Th17, and regulatory T (T) cells. Read More

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Highly Sensitized Patients Are Well Served by Receiving a Compatible Organ Offer Based on Acceptable Mismatches.

Front Immunol 2021 25;12:687254. Epub 2021 Jun 25.

Eurotransplant Reference Laboratory, Leiden University Medical Center, Leiden, Netherlands.

Highly sensitized kidney patients accrue on the transplant waiting list due to their broad immunization against non-self Human Leucocyte Antigens (HLA). Although challenging, the best option for highly sensitized patients is transplantation with a crossmatch negative donor without any additional therapeutic intervention. The Eurotransplant Acceptable Mismatch (AM) program was initiated more than 30 years ago with the intention to increase the chance for highly sensitized patients to be transplanted with such a compatible donor. Read More

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Synaptic repair and vision restoration in advanced degenerating eyes by transplantation of retinal progenitor cells.

Stem Cell Reports 2021 Jul 1;16(7):1805-1817. Epub 2021 Jul 1.

Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P.R. China; Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, P.R. China; Department of Ophthalmology, General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China. Electronic address:

Stem cell transplantation shows enormous potential for treatment of incurable retinal degeneration (RD). To determine if and how grafts connect with the neural circuits of the advanced degenerative retina (ADR) and improve vision, we perform calcium imaging of GCaMP5-positive grafts in retinal slices. The organoid-derived C-Kit/SSEA1 (C-Kit) retinal progenitor cells (RPCs) become synaptically organized and build spontaneously active synaptic networks in three major layers of ADR. Read More

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Microbiota long-term dynamics and prediction of acute graft-versus-host disease in pediatric allogeneic stem cell transplantation.

Microbiome 2021 06 28;9(1):148. Epub 2021 Jun 28.

Research Group for Genomic Epidemiology, Technical University of Denmark, Kongens Lyngby, Denmark.

Background: Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) exhibit changes in their gut microbiota and are experiencing a range of complications, including acute graft-versus-host disease (aGvHD). It is unknown if, when, and under which conditions a re-establishment of microbial and immunological homeostasis occurs. It is also unclear whether microbiota long-term dynamics occur at other body sites than the gut such as the mouth or nose. Read More

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Mesenchymal stem cell-based bioengineered constructs enhance vaginal repair in ovariectomized rhesus monkeys.

Biomaterials 2021 08 10;275:120863. Epub 2021 May 10.

Department of Obstetrics and Gynaecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China. Electronic address:

Transvaginal meshes repair for treating pelvic organ prolapse (POP) was halted by the U. S. Food and Drug Administration (FDA) because they can lead to severe complications. Read More

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Cancer immunotherapy by NC410, a LAIR-2 Fc protein blocking human LAIR-collagen interaction.

Elife 2021 06 14;10. Epub 2021 Jun 14.

Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.

Collagens are a primary component of the extracellular matrix and are functional ligands for the inhibitory immune receptor leukocyte-associated immunoglobulin-like receptor (LAIR)-1. LAIR-2 is a secreted protein that can act as a decoy receptor by binding collagen with higher affinity than LAIR-1. We propose that collagens promote immune evasion by interacting with LAIR-1 expressed on immune cells, and that LAIR-2 releases LAIR-1-mediated immune suppression. Read More

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Post-allogeneic hematopoietic stem cell transplantation viral reactivations and viremias: a focused review on human herpesvirus-6, BK virus and adenovirus.

Ther Adv Infect Dis 2021 Jan-Dec;8:20499361211018027. Epub 2021 May 24.

Division of Hematology and Oncology, Department of Medicine, UMass Memorial Medical Center, 55 Lake Avenue North, Worcester, MA, 01655, USA.

Human cytomegalovirus and Epstein-Barr virus have been recognized as potential drivers of morbidity and mortality of patients undergoing allogeneic stem cell transplantation for years. Specific protocols for monitoring, prophylaxis and pre-emptive therapy are in place in many transplant settings. In this review, we focus on the next three most frequent viruses, human herpesvirus-6, BK virus and adenovirus, causing reactivation and/or viremia after allogeneic transplant, which are increasingly detected in patients in the post-transplant period owing to emerging techniques of molecular biology, recipients' characteristics, treatment modalities used for conditioning and factors related donors or stem cell source. Read More

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Transplantation of reprogrammed peripheral blood cells differentiates into retinal ganglion cells in the mouse eye with NMDA-induced injury.

J Cell Physiol 2021 Jun 8. Epub 2021 Jun 8.

Hunan Key Laboratory of Ophthalmology, Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan, China.

The generation of patient-specific induced pluripotent stem cells (iPSCs) holds significant implications for replacement therapy in treating optic neuropathies such as glaucoma. Stem-cell-based therapy targeted at replacing and replenishing retinal ganglion cells is progressing at a fast pace. However, clinical application necessitates an efficient and robust approach for cell manufacturing. Read More

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Potential of Induced Pluripotent Stem Cells for Use in Gene Therapy: History, Molecular Bases, and Medical Perspectives.

Biomolecules 2021 05 7;11(5). Epub 2021 May 7.

Department of Molecular Biology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Medykow 18 Street, 40-752 Katowice, Poland.

Induced pluripotent stem cells (iPSCs) are defined as reprogrammed somatic cells exhibiting embryonic stem cell characteristics. Since their discovery in 2006, efforts have been made to utilize iPSCs in clinical settings. One of the promising fields of medicine, in which genetically patient-specific stem cells may prove themselves useful, is gene therapy. Read More

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Efficacy of platelet-rich fibrin on bone formation, part 1: Alveolar ridge preservation.

Int J Oral Implantol (Berl) 2021 05;14(2):181-194

Purpose: To investigate the use of platelet-rich fibrin for alveolar ridge preservation compared to natural healing, bone graft material and platelet-rich fibrin in combination with bone graft material.

Materials And Methods: The present systematic review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. The review examined randomised controlled trials comparing the clinical outcomes of platelet-rich fibrin with those of other modalities for alveolar ridge preservation. Read More

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NIR-II-activated biocompatible hollow nanocarbons for cancer photothermal therapy.

J Nanobiotechnology 2021 May 13;19(1):137. Epub 2021 May 13.

Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, 518060, China.

Photothermal therapy has attracted extensive attentions in cancer treatment due to its precise spatial-temporal controllability, minimal invasiveness, and negligible side effects. However, two major deficiencies, unsatisfactory heat conversion efficiency and limited tissue penetration depth, hugely impeded its clinical application. In this work, hollow carbon nanosphere modified with polyethylene glycol-graft-polyethylenimine (HPP) was elaborately synthesized. Read More

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Endonasal CNS Delivery System for Blood-Brain Barrier Impermeant Therapeutic Oligonucleotides Using Heterotopic Mucosal Engrafting.

Front Pharmacol 2021 19;12:660841. Epub 2021 Apr 19.

Department of Otolaryngology, Harvard Medical School, Massachusetts Eye and Ear, Boston, MA, United States.

The most significant obstacle in the treatment of neurological disorders is the blood-brain barrier (BBB), which prevents 98% of all potential neuropharmaceuticals from reaching the central nervous system (CNS). Brain derived neurotrophic factor (BDNF) is one of the most intensely studied targets in Parkinson's disease (PD) as it can reverse disease progression. BDNF AntagoNAT's (ATs) are synthetic oligonucleotide-like compounds capable of upregulating endogenous BDNF expression. Read More

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Lower beta cell yield from donor pancreases after controlled circulatory death prevented by shortening acirculatory warm ischemia time and by using IGL-1 cold preservation solution.

PLoS One 2021 3;16(5):e0251055. Epub 2021 May 3.

Diabetes Research Center, Vrije Universiteit Brussel (VUB), Brussels, Belgium.

Organs from donors after controlled circulatory death (DCD III) exhibit a higher risk for graft dysfunction due to an initial period of warm ischemia. This procurement condition can also affect the yield of beta cells in islet isolates from donor pancreases, and hence their use for transplantation. The present study uses data collected and generated by our Beta Cell Bank to compare the number of beta cells in isolates from DCD III (n = 141) with that from donors after brain death (DBD, n = 609), before and after culture, and examines the influence of donor and procurement variables. Read More

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Cyclodextrin-Based Hybrid Polymeric Complex to Overcome Dual Drug Resistance Mechanisms for Cancer Therapy.

Polymers (Basel) 2021 Apr 13;13(8). Epub 2021 Apr 13.

Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, #08-03 Innovis, Singapore 138634, Singapore.

Drug resistance always reduces the efficacy of chemotherapy, and the classical mechanisms of drug resistance include drug pump efflux and anti-apoptosis mediators-mediated non-pump resistance. In addition, the amphiphilic polymeric micelles with good biocompatibility and high stability have been proven to deliver the drug molecules inside the cavity into the cell membrane regardless of the efflux of the cell membrane pump. We designed a cyclodextrin (CD)-based polymeric complex to deliver chemotherapeutic doxorubicin (DOX) and Nur77ΔDBD gene for combating pumps and non-pump resistance simultaneously. Read More

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Multiply restimulated human thymic regulatory T cells express distinct signature regulatory T-cell transcription factors without evidence of exhaustion.

Cytotherapy 2021 Aug 20;23(8):704-714. Epub 2021 Apr 20.

Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota Cancer Center, Minneapolis, Minnesota, USA. Electronic address:

Background Aims: Adoptive transfer of suppressive CD4+CD25+ thymic regulatory T cells (tTregs) can control auto- and alloimmune responses but typically requires in vitro expansion to reach the target cell number for efficacy. Although the adoptive transfer of expanded tTregs purified from umbilical cord blood ameliorates graft-versus-host disease in patients receiving hematopoietic stem cell transplantation for lymphohematopoietic malignancy, individual Treg products of 100 × 10 cells/kg are manufactured over an extended 19-day time period using a process that yields variable products and is both laborious and costly. These limitations could be overcome with the availability of 'off the shelf' Treg. Read More

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Recombinant apoptosis inhibitor of macrophage protein reduces delayed graft function in a murine model of kidney transplantation.

PLoS One 2021 23;16(4):e0249838. Epub 2021 Apr 23.

Department of Microbiology and Immunology, Western University, London, Ontario, Canada.

Reperfusion injury following cold and warm ischemia (IRI) is unavoidable during kidney transplantation and contributes to delayed graft function (DGF) and premature graft loss. Death of tubular epithelial cells (TECs) by necrosis during IRI releases pro-inflammatory mediators (e.g. Read More

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September 2021

Strategies for Dodging the Obstacles in CAR T Cell Therapy.

Front Oncol 2021 1;11:627549. Epub 2021 Apr 1.

Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ, United States.

Chimeric antigen receptor (CAR) T cell therapy has offered cancer patients a new alternative therapeutic choice in recent years. This novel type of therapy holds tremendous promise for the treatment of various hematologic malignancies including B-cell acute lymphoblastic leukemia (B-ALL) and lymphoma. However, CAR T cell therapy has experienced its ups and downs in terms of toxicities and efficacy shortcomings. Read More

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Transcanal Endoscopic Retrograde Mastoidectomy for Cholesteatoma: A Prospective Study.

Ear Nose Throat J 2021 Apr 13:1455613211009439. Epub 2021 Apr 13.

Department of Otorhinolaryngology, 475268Patan Academy of Health Sciences, School of Medicine, Lagankhel, Lalitpur, Nepal.

Objectives: To evaluate the feasibility, morphological, and functional outcomes of endoscopic retrograde transcanal mastoidectomy.

Study Design: Prospective study.

Settings: Tertiary Referral Hospital. Read More

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The Unique Impact of COVID-19 on Human Gut Microbiome Research.

Front Med (Lausanne) 2021 16;8:652464. Epub 2021 Mar 16.

Department of Clinical and Movement Neurosciences, Institute of Neurology, University College London, London, United Kingdom.

The coronavirus (COVID-19) pandemic has disrupted clinical trials globally, with unique implications for research into the human gut microbiome. In this mini-review, we explore the direct and indirect influences of the pandemic on the gut microbiome and how these can affect research and clinical trials. We explore the direct bidirectional relationships between the COVID-19 virus and the gut and lung microbiomes. Read More

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Development of Aptamer-Based Molecular Tools for Rapid Intraoperative Diagnosis and Imaging of Serous Ovarian Cancer.

ACS Appl Mater Interfaces 2021 Apr 31;13(14):16118-16126. Epub 2021 Mar 31.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300350, P. R. China.

Diagnosis and treatment of ovarian cancer are based on intraoperative pathology and debulking surgery. The development of a novel molecular tool is significant for rapid intraoperative pathologic diagnosis, which instructs the decision-making on excision surgery and effective chemotherapy. In this work, we represent a DNA aptamer named mApoc46, which is generated from cell-SELEX by targeting patient-derived primary serous ovarian cancer (pSOC) cells. Read More

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Applications of genetic-epigenetic tissue mapping for plasma DNA in prenatal testing, transplantation and oncology.

Elife 2021 03 23;10. Epub 2021 Mar 23.

Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.

We developed genetic-epigenetic tissue mapping (GETMap) to determine the tissue composition of plasma DNA carrying genetic variants not present in the constitutional genome through comparing their methylation profiles with relevant tissues. We validated this approach by showing that, in pregnant women, circulating DNA carrying fetal-specific alleles was entirely placenta-derived. In lung transplant recipients, we showed that, at 72 hr after transplantation, the lung contributed only a median of 17% to the plasma DNA carrying donor-specific alleles, and hematopoietic cells contributed a median of 78%. Read More

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A New Guide for the Arthroscopically Assisted Latarjet Procedure.

Shinji Imai

JB JS Open Access 2021 Jan-Mar;6(1). Epub 2021 Feb 12.

Department of Orthopaedic Surgery, Shiga University of Medical Science, Otsu, Japan.

The Latarjet procedure is a commonly used treatment for recurrent shoulder instability. However, its neurological complication rate has been reported to be as high as 10%. During the Latarjet procedure, the neurovascular structures are relocated inferiorly and medially. Read More

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February 2021