11,797 results match your criteria Factor IX

Plasma factor IX: The tip of the iceberg?

Haemophilia 2021 May 8. Epub 2021 May 8.

Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta and Department of Pediatrics, Emory University, Atlanta, GA, USA.

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Identification of a modified coagulation factor X with enhanced activation properties as potential hemostatic agent.

Blood Cells Mol Dis 2021 Apr 23;89:102570. Epub 2021 Apr 23.

Research and Development, CSL Behring Innovation GmbH, Marburg, Germany.

Hemophilia A and hemophilia B are X-linked inherited bleeding disorders caused by a deficiency of coagulation factor VIII and IX, respectively. Standard of care is prophylactic factor replacement therapy; however, the development of neutralizing antibodies against these factors represents serious complications underlining the need for alternative treatment approaches. Human coagulation factor X has a central role within the blood coagulation system making it an attractive target for the development of alternative treatment strategies for patients with hemophilia. Read More

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Efficacy and safety of subcutaneous prophylaxis with dalcinonacog alfa in adults with haemophilia B.

Haemophilia 2021 May 6. Epub 2021 May 6.

Catalyst Biosciences, San Francisco, CA, USA.

Aim: Phase 2b study to assess efficacy, safety, thrombogenicity, immunogenicity and tolerability with 28 days of daily dosing of subcutaneous (SQ) dalcinonacog alfa as prophylaxis for haemophilia B (HB).

Methods: Adult males with a confirmed diagnosis of congenital HB (factor IX [FIX] activity <2%) received daily dalcinonacog alfa 100 IU/kg SQ until day 28. The primary efficacy endpoint was the number of participants who achieved a steady-state FIX activity level ≥12%. Read More

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Group B Streptococcus chimeric capsular polysaccharides as novel multivalent vaccine candidates.

Glycoconj J 2021 May 6. Epub 2021 May 6.

GSK, Siena, Italy.

The capsular polysaccharide of the human pathogen Group B Streptococcus is a key virulence factor and vaccine candidate that induces protective antibodies when conjugated to carrier proteins. It consists of long polymeric chains of oligosaccharide repeating units, and each of the ten capsular serotypes described so far presents a unique chemical structure with distinct antigenic properties; therefore, broad protection against this pathogen could be achieved by a combination of ten glycoconjugates. Capsular polysaccharide biosynthesis and assembly follow a polymerase-dependent pathway that is widespread in encapsulated bacteria and is encoded by a polycistronic operon. Read More

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Renal dysfunction and podocyturia in pre-eclampsia may be explained by increased urinary VEGF.

Nephrol Dial Transplant 2021 May 5. Epub 2021 May 5.

Complications of Diabetes Unit, Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Background: Preeclampsia has a major impact on renal function as shown by the development of proteinuria and podocyturia. How the systemic, Fms-like tyrosine kinase-1 (sFlt-1)-driven inhibition of vascular endothelial growth factor (VEGF) activity detected in preeclampsia directly affects renal function remains unknown. Aim of the study was to clarify whether a non-canonical, renal centered escape from VEGF inhibition in case of preeclamptic pregnancy might have a direct impact on the renal function. Read More

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Preclinical Development of Plant-based Oral Immune Modulatory Therapy for Hemophilia B.

Plant Biotechnol J 2021 May 5. Epub 2021 May 5.

Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Anti-drug antibody (ADA) formation is a major complication in treatment of the X-linked bleeding disorder hemophilia B (deficiency in coagulation factor IX, FIX). Current clinical immune tolerance protocols are often not effective due to complications such as anaphylactic reactions against FIX. Plant-based oral tolerance induction may address this problem, as illustrated by the recent first regulatory approval of orally delivered plant cells to treat peanut allergy. Read More

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A Rare Cause of Isolated Prolonged Activated Partial Thromboplastin Time: An Overview of Prekallikrein Deficiency and the Contact System.

J Investig Med High Impact Case Rep 2021 Jan-Dec;9:23247096211012187

MetroWest Medical Center, Framingham, MA, USA.

Prekallikrein (PK) deficiency, also known as Fletcher factor deficiency, is a very rare disorder inherited as an autosomal recessive trait. It is usually identified incidentally in asymptomatic patients with a prolonged activated partial thromboplastin time (aPTT). In this article, we present the case of a 52-year-old woman, with no prior personal or family history of thrombotic or hemorrhagic disorders, who was noted to have substantial protracted aPTT through the routine coagulation assessment before a kidney biopsy. Read More

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Real-world outcomes with recombinant factor IX Fc fusion protein (rFIXFc) prophylaxis: Longitudinal follow-up in a national adult cohort.

Haemophilia 2021 May 3. Epub 2021 May 3.

St James's Hospital, National Coagulation Centre, Dublin, Ireland.

Introduction: In 2017, all people with severe haemophilia B (PWSHB) in Ireland switched from standard half-life (SHL) recombinant FIX (rFIX) to rFIX Fc fusion protein (rFIXFc) prophylaxis.

Aims: To evaluate prophylaxis regimens, bleeding rates and factor usage for two years of rFIXFc prophylaxis in a real-world setting.

Methods: Data collected retrospectively from electronic diaries and medical records of PWSHB for a two-year period on rFIXFc prophylaxis were compared with paired baseline data on SHL rFIX treatment. Read More

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Radiomics of F Fluorodeoxyglucose PET/CT Images Predicts Severe Immune-related Adverse Events in Patients with NSCLC.

Radiol Artif Intell 2020 Jan 29;2(1):e190063. Epub 2020 Jan 29.

Departments of Cancer Physiology (W.M., I.T., J.Q., R.J.G.) and Cancer Epidemiology (M.B.S.), H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612.

Purpose: To investigate the performance of pretreatment fluorine 18 (F) fluorodeoxyglucose PET/CT radiomics in predicting severe immune-related adverse events (irSAEs) among patients with advanced non-small cell lung cancer (NSCLC) treated with immunotherapy, which is important in optimizing treatment plans and alleviating future complications with early interventions.

Materials And Methods: The retrospective arm of this study included 146 patients with histologically confirmed stage IIIB-IV NSCLC who were treated with immune checkpoint blockade between June 2011 and December 2017 and who were split into training ( = 97) and test ( = 49) cohorts. A prospective validation arm enrolled 48 patients before initiation of immunotherapy between January 2018 and June 2019 as an independent test cohort. Read More

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January 2020

Establishment of Pertussis toxin BRP batch 2 for CHO clustering assay.

Pharmeur Bio Sci Notes 2021 ;2021:69-87

Health Canada, Biologic and Radiopharmaceuticals Drugs Directorate, Centre for Biologics Evaluation, 100 Eglantine Dr. A/L 0602B, Ottawa, Ontario, Canada, K1A 0K9.

A joint World Health Organization (WHO) - European Directorate for the Quality of Medicines & HealthCare (EDQM) study was run to calibrate the WHO 5th International Standard (IS) for Blood Coagulation Factor IX (FIX), Concentrate, and European Pharmacopoeia (Ph. Eur.) Human Coagulation Factor IX concentrate Biological Reference Preparation (BRP) Batch 3. Read More

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January 2021

Genetic profile and immunohistochemical study of clear cell renal carcinoma: Pathological-anatomical correlation and prognosis.

Cancer Treat Res Commun 2021 Apr 18;27:100374. Epub 2021 Apr 18.

Department of Urology. Hospital Clínico Universitario de Valencia, Av. Blasco Ibáñez, 17, 46010. Valencia- España. Electronic address:

Introduction: Renal cell carcinoma (RCC) accounts for 2-3% of all tumors being the most frequent solid lesion in the kidney.

Objective: To determine what genetic alterations and immunohistochemical (IHC) of clear cell renal carcinoma (ccRCC) are associated with prognosis and tumor aggressiveness.

Patients And Methods: Experimental analytical study with 57 patients who underwent radical and partial nephrectomy between 2005 and 2011, all with diagnosis of ccRCC and minimum post-operative follow-up of 36 months. Read More

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Biomarkers in Glycogen Storage Diseases: An Update.

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

Efficiency, Quality, and Costs in Health Services Research Group (EFISALUD), Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, 36213 Vigo, Spain.

Glycogen storage diseases (GSDs) are a group of 19 hereditary diseases caused by a lack of one or more enzymes involved in the synthesis or degradation of glycogen and are characterized by deposits or abnormal types of glycogen in tissues. Their frequency is very low and they are considered rare diseases. Except for X-linked type IX, the different types are inherited in an autosomal recessive pattern. Read More

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How to Manage a Patient with Haemophilia and ACS Requiring PCI: A Battle between Bleeding and Thrombosis.

Medicina (Kaunas) 2021 Apr 7;57(4). Epub 2021 Apr 7.

Second Cardiology Department, Hippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece.

We present the case of a 70-year-old man with a history of haemophilia B, who presented to our hospital with a non-ST-elevation myocardial infarction. The patient, following consultation by a haemophilia expert, was revascularized with percutaneous coronary intervention (PCI) under adequate clotting factor administration. Patients with haemophilia and acute coronary syndrome, are susceptible to periprocedural bleeding and thrombotic events during PCI, and therefore a balanced management plan should always be implemented by a multidisciplinary team. Read More

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Differential regulation of the platelet GPIb-IX complex by anti-GPIbβ antibodies.

J Thromb Haemost 2021 Apr 29. Epub 2021 Apr 29.

Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA.

Background: Platelets' initial recognition of endothelial damage proceeds through the interaction between collagen, plasma von Willebrand factor (VWF), and the platelet glycoprotein (GP)Ib-IX complex (CD42). GPIb-IX complex consists of one GPIbα, one GPIX, and two GPIbβ subunits. Once platelets are immobilized to the subendothelial matrix, shear generated by blood flow unfolds a membrane-proximal mechanosensory domain (MSD) in GPIbα, exposing a conserved trigger sequence and activating the receptor. Read More

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The Cost-effectiveness of Gene Therapy for Severe Hemophilia B: Microsimulation Study from the United States Perspective.

Blood 2021 Apr 25. Epub 2021 Apr 25.

St. Jude Children's Research Hospital, Memphis, Tennessee, United States.

Adeno-associated virus (AAV)-mediated gene therapy is a novel treatment promising to reduce morbidity associated with hemophilia. While multiple clinical trials continue to evaluate efficacy and safety, limited cost-effectiveness data have been published. This study compared the potential cost-effectiveness of AAV-mediated factor IX(FIX)-Padua gene therapy for severe hemophilia B patients in the United States (US) to on-demand FIX replacement and primary FIX prophylaxis, using either standard or extended half-life FIX products. Read More

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Rational Clinical Dose Selection of Adeno-Associated Virus-Mediated Gene Therapy Based on Allometric Principles.

Clin Pharmacol Ther 2021 Apr 21. Epub 2021 Apr 21.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA.

One of the challenges in translational medicine is to select first-in-human doses of investigational drugs based on findings in preclinical studies. Despite substantial progress in the optimization of recombinant adeno-associated virus (AAV) vectors of in vivo gene therapy for treating various diseases, there remain significant limitations to the use of preclinical data to guide dose selection in clinical trials. Here we introduce a novel concept of gene efficiency factor (GEF) to describe the efficiency of the gene transfer system and describe and apply the concept of GEF in AAV-mediated in vivo gene transfer systems. Read More

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Activation of von Willebrand factor via mechanical unfolding of its discontinuous autoinhibitory module.

Nat Commun 2021 04 21;12(1):2360. Epub 2021 Apr 21.

Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.

Von Willebrand factor (VWF) activates in response to shear flow to initiate hemostasis, while aberrant activation could lead to thrombosis. Above a critical shear force, the A1 domain of VWF becomes activated and captures platelets via the GPIb-IX complex. Here we show that the shear-responsive element controlling VWF activation resides in the discontinuous autoinhibitory module (AIM) flanking A1. Read More

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Fluorescence artifact correction in the thrombin generation assay: Necessity for correction algorithms in procoagulant samples.

Res Pract Thromb Haemost 2021 Mar 26;5(3):447-455. Epub 2021 Mar 26.

Office of Tissues and Advanced Therapies Center for Biologics Evaluation and Research US Food and Drug Administration Silver Spring MD USA.

Introduction: The thrombin generation (TG) test is a global hemostasis assay sensitive to procoagulant conditions. However, some TG assays may underestimate elevated TG when the thrombin fluorogenic substrate is depleted or fluorescence is attenuated by the inner filter effect (IFE).

Objectives: We sought to elucidate the extent to which procoagulant conditions require correcting for fluorogenic substrate depletion and/or IFE. Read More

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Consensus Recommendations for Intramuscular COVID-19 Vaccination in Patients with Hemophilia.

Hamostaseologie 2021 Apr 15. Epub 2021 Apr 15.

Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.

Background:  Currently available coronavirus disease 2019 (COVID-19) vaccines are approved for intramuscular injection and efficacy may not be ensured when given subcutaneously. For years, subcutaneous vaccination was recommended in patients with hemophilia to avoid intramuscular bleeds. Therefore, recommendations for the application of COVID-19 vaccines are needed. Read More

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Biomarkers of Kidney Tubule Health, CKD Progression, and Acute Kidney Injury in SPRINT (Systolic Blood Pressure Intervention Trial) Participants.

Am J Kidney Dis 2021 Apr 12. Epub 2021 Apr 12.

Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, CA; Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, CA; Division of Preventive Medicine, Department of Family Medicine and Public Health, University of California San Diego, San Diego, CA. Electronic address:

Rationale & Objective: SPRINT compared the effect of intensive versus standard systolic blood pressure targets on cardiovascular morbidity and mortality. In this ancillary study, we evaluated the use of exploratory factor analysis (EFA) to combine biomarkers of kidney tubule health in urine and plasma and then study their role in longitudinal eGFR change and risk of acute kidney injury (AKI).

Study Design: Observational cohort nested in a clinical trial. Read More

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Controversies in optimal anemia management: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference.

Kidney Int 2021 Apr 8. Epub 2021 Apr 8.

Inserm Unit 1018, Team 5, CESP, Hôpital Paul Brousse, Paris-Sud University (UPS), Villejuif, France; Versailles Saint-Quentin-en-Yvelines University (Paris-Ile-de-France-Ouest University, UVSQ), Villejuif, France. Electronic address:

In chronic kidney disease, anemia and disordered iron homeostasis are prevalent and associated with significant adverse consequences. In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) issued an anemia guideline for managing the diagnosis, evaluation, and treatment of anemia in chronic kidney disease. Since then, new data have accrued from basic research, epidemiological studies, and randomized trials that warrant a re-examination of previous recommendations. Read More

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Biosensing human blood clotting factor by dual probes: Evaluation by deep long short-term memory networks in time series forecasting.

Biotechnol Appl Biochem 2021 Apr 9. Epub 2021 Apr 9.

Centre for Artificial Intelligence and Robotics, Universiti Teknologi Malaysia, Jalan Sultan Yahya Petra, Kuala Lumpur, Malaysia.

Artificial intelligence of things (AIoT) has become a potential tool for use in a wide range of fields, and its use is expanding in interdisciplinary sciences. On the other hand, in a clinical scenario, human blood-clotting disease (Royal disease) detection has been considered an urgent issue that has to be solved. This study uses AIoT with deep long short-term memory networks for biosensing application and analyzes the potent clinical target, human blood clotting factor IX, by its aptamer/antibody as the probe on the microscaled fingers and gaps of the interdigitated electrode. Read More

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Asymptomatic Joint Bleeding and Joint Health in Hemophilia: A Review of Variables, Methods, and Biomarkers.

J Blood Med 2021 1;12:209-220. Epub 2021 Apr 1.

Katharine Dormandy Haemophilia Centre, Royal Free Hospital, London, UK.

Joint health is a key contributor to quality of life in patients with hemophilia. However, variables that impact long-term joint outcomes have not been comprehensively defined. A systematic literature search identified publications relating to joint health in patients with hemophilia. Read More

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Discovery of potential pharmacodynamic ingredients of Dang-Gui-Si-Ni decoction based on absorbed ingredients and molecular docking.

J Ethnopharmacol 2021 Apr 5;275:114045. Epub 2021 Apr 5.

National Engineering Laboratory for Quality Control Technology of Chinese Herbal Medicines, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China. Electronic address:

Ethnopharmacological Relevance: The Dang-Gui-Si-Ni (DGSN) decoction as a classic prescription has been widely used for thousands of years in the clinical practice of traditional Chinese medicine (TCM). Especially in recent years, the potential efficacy of TCM for the treatment of Raynaud's syndrome has attracted great attention as there are still no specific remedies for this disease. However, the active constituents and underlying mechanisms responsible for the therapeutic benefits are not well understood, which makes it difficult to ensure quality control or to design research and drug development strategies. Read More

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Health care resource utilization and cost burden of hemophilia B in the United States.

Blood Adv 2021 Apr;5(7):1954-1962

uniQure, Inc., Lexington, MA.

Hemophilia B is a rare congenital blood disorder characterized by factor IX deficiency. Clinical profiles of hemophilia B range from mild to severe forms of the disease. The objective of this study was to characterize the economic burden associated with differing clinical profiles of hemophilia B from a US health system perspective. Read More

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Thrombin generation potential in the presence of concizumab and rFVIIa, APCC, rFVIII, or rFIX: In vitro and ex vivo analyses.

J Thromb Haemost 2021 Apr 5. Epub 2021 Apr 5.

Global Drug Discovery, Novo Nordisk A/S, Måløv, Denmark.

Background: The anti-tissue factor plasma inhibitor monoclonal antibody concizumab is under clinical investigation for subcutaneous prophylaxis of hemophilia A/B (HA/HB) with or without inhibitors. Breakthrough bleeds while on concizumab prophylaxis may be treated with bypassing agents (recombinant activated factor VIIa [rFVIIa] and activated prothrombin complex concentrate [APCC]), or with factor VIII (FVIII) or factor IX (FIX).

Objectives: To evaluate the effect of combining concizumab with rFVIIa, APCC, rFVIII, and rFIX on thrombin generation (TG) potential. Read More

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Consensus on hemophilia in Mexico.

Gac Med Mex 2021 ;157(Suppl 1):S1-S35

Hematology department, Centro Médico Nacional 20 de Noviembre, ISSSTE, Mexico City. Mexico.

Hemophilia is a hemorrhagic disorder with a sex-linked inherited pattern, characterized by an inability to amplify coagulation due to a deficiency in coagulation factor VIII (hemophilia A or classic) or factor IX (hemophilia B). Sequencing of the genes involved in hemophilia has provided a description and record of the main mutations, as well as a correlation with the various degrees of severity. Hemorrhagic manifestations are related to levels of circulating factor, mainly affecting the musculoskeletal system and specifically the large joints (knees, ankles, and elbows). Read More

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January 2021

Granulocyte Colony Stimulating Factor Expression in Breast Cancer and Its Association with Carbonic Anhydrase IX and Immune Checkpoints.

Cancers (Basel) 2021 Mar 1;13(5). Epub 2021 Mar 1.

Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.

Purpose: Granulocyte colony-stimulating factor (G-CSF) and hypoxia modulate the tumour immune microenvironment. In model systems, hypoxia-induced carbonic anhydrase IX (CAIX) has been associated with G-CSF and immune responses, including M2 polarization of macrophages. We investigated whether these associations exist in human breast cancer specimens, their relation to breast cancer subtypes, and clinical outcome. Read More

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Loneliness and Its Associated Factors Nine Months after the COVID-19 Outbreak: A Cross-National Study.

Int J Environ Res Public Health 2021 03 11;18(6). Epub 2021 Mar 11.

Department of Social Work, Faculty of Social Sciences, Oslo Metropolitan University, 0130 Oslo, Norway.

COVID-19 has been a global healthcare concern impacting multiple aspects of individual and community wellness. As one moves forward with different methods to reduce the infection and mortality rates, it is critical to continue to study the impact that national and local "social distancing" policies have on the daily lives of individuals. The aim of this study was to examine loneliness in relation to risk assessment, measures taken against risks, concerns, and social media use, while adjusting for sociodemographic variables. Read More

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LSD1-BDNF activity in lateral hypothalamus-medial forebrain bundle area is essential for reward seeking behavior.

Prog Neurobiol 2021 Mar 30:102048. Epub 2021 Mar 30.

Department of Biotechnology, Savitribai Phule Pune University, Pune 411 007, India. Electronic address:

Reward induces activity-dependant gene expression and synaptic plasticity-related changes. Lysine-specific histone demethylase 1 (LSD1), a key enzyme driving histone modifications, regulates transcription in neural circuits of memory and emotional behavior. Herein, we focus on the role of LSD1 in modulating the expression of brain derived neurotrophic factor (BDNF), the master regulator of synaptic plasticity, in the lateral hypothalamus-medial forebrain bundle (LH-MFB) circuit during positive reinforcement. Read More

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