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Neutrophil Extracellular Traps (NETs) and Hypercoagulability in Plasma Cell Dyscrasias-Is This Phenomenon Worthy of Exploration?

J Clin Med 2021 Nov 11;10(22). Epub 2021 Nov 11.

Department of Laboratory Medicine, Medical University of Warsaw, Banacha 1a, 02-091 Warsaw, Poland.

Plasma cell dyscrasias (PCDs) are neoplastic diseases derived from plasma cells. Patients suffering from PCDs are at high risk of hypercoagulability and thrombosis. These conditions are associated with disease-related factors, patient-related factors, or the use of immunomodulatory drugs. Read More

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November 2021

Role of Cell-Free DNA and Deoxyribonucleases in Tumor Progression.

Int J Mol Sci 2021 Nov 12;22(22). Epub 2021 Nov 12.

Institute of Chemical Biology and Fundamental Medicine, SB RAS, Lavrentiev Ave., 8, 630090 Novosibirsk, Russia.

Many studies have reported an increase in the level of circulating cell-free DNA (cfDNA) in the blood of patients with cancer. cfDNA mainly comes from tumor cells and, therefore, carries features of its genomic profile. Moreover, tumor-derived cfDNA can act like oncoviruses, entering the cells of vulnerable organs, transforming them and forming metastatic nodes. Read More

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November 2021

Elevated Myeloperoxidase-DNA Complex Levels in Sera of Patients with IgA Vasculitis.

Pathobiology 2021 Nov 23:1-6. Epub 2021 Nov 23.

Department of Dermatology, St. Marianna University School of Medicine, Kawasaki, Japan.

Introduction: IgA vasculitis is a systemic disease that results from the entrapment of circulating IgA-containing immune complexes in small-vessel walls in the skin, kidneys, and gastrointestinal tract. An excessive formation of neutrophil extracellular traps (NETs) is involved in the pathogenesis of vasculitis, especially in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This study aimed to clarify whether NETs are implicated in IgA vasculitis. Read More

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November 2021

Characterization of Campylobacter jejuni-Neutrophil Interactions.

Curr Protoc 2021 Nov;1(11):e294

Department of Microbiology, University of Tennessee, Knoxville, Tennessee.

Campylobacter jejuni is the leading cause of bacterial-derived gastroenteritis worldwide, infecting 96 million individuals annually. During infection, inflammation and tissue pathology occur in the lower gastrointestinal tract, including the recruitment of leukocytes. Neutrophils are the most abundant leukocyte in humans, and recruitment is associated with bacterial infections and the development of various inflammatory disorders, including inflammatory bowel disease. Read More

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November 2021

Neutrophil extracellular traps modulate inflammatory markers and uptake of oxidized LDL by human and murine macrophages.

PLoS One 2021 19;16(11):e0259894. Epub 2021 Nov 19.

Department of Cardiothoracic Surgery, Heart Center of The University of Cologne, Cologne, Germany.

Neutrophil extracellular traps (NETs) are web-like structures, which are released upon neutrophil activation. It has previously been demonstrated that NETs are present in atherosclerotic lesions of both humans and animal models thus playing a decisive role in atherosclerosis. Besides, macrophages have a crucial role in disease progression, whereby classically activated M1 macrophages sustain inflammation and alternatively activated M2 macrophages display anti-inflammatory effects. Read More

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November 2021

MapCell: Learning a Comparative Cell Type Distance Metric With Siamese Neural Nets With Applications Toward Cell-Type Identification Across Experimental Datasets.

Front Cell Dev Biol 2021 2;9:767897. Epub 2021 Nov 2.

Molecular Engineering Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore.

Large collections of annotated single-cell RNA sequencing (scRNA-seq) experiments are being generated across different organs, conditions and organisms on different platforms. The diversity, volume and complexity of this aggregated data requires new analysis techniques to extract actionable knowledge. Fundamental to most analysis are key abilities such as: identification of similar cells across different experiments and transferring annotations from an annotated dataset to an unannotated one. Read More

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November 2021

Plasma and Wound Fluids from Trauma Patients Suppress Neutrophil Extracellular Respiratory Burst.

J Trauma Acute Care Surg 2021 Nov 15. Epub 2021 Nov 15.

Department of Surgery, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA 02215. Deparment of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea. Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia. Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China. The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA.

Background: Trauma increases susceptibility to secondary bacterial infections. The events suppressing antimicrobial immunity are unclear. Neutrophils (PMN) migrate towards bacteria using chemotaxis (CTX), trap them in extracellular NETs and kill them using respiratory burst (RB). Read More

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November 2021

Primary neuroendocrine tumors of the ovary: Management and outcomes.

Cancer Med 2021 Nov 12. Epub 2021 Nov 12.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

Background: There is currently no recognized first-line treatment strategy for ovarian neuroendocrine tumors (NETs). Furthermore, because of the low incidence of ovarian NETs, no studies have reported prognostic statistics derived from large samples. This retrospective study aimed to investigate the clinical behavior of ovarian NETs. Read More

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November 2021

Time to give up traditional methods for the management of gastrointestinal neuroendocrine tumours.

World J Clin Cases 2021 Oct;9(29):8627-8646

Department of Endocrinology and Metabolism, University of Health Sciences Turkey, Keçiören Health Administration and Research Center, Ankara 06190, Turkey.

Neuroendocrine tumors (NETs) are a rare and heterogeneous disease group and constitute 0.5% of all malignancies. The annual incidence of NETs is increasing worldwide. Read More

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October 2021

Uremic serum damages endothelium by provoking excessive neutrophil extracellular trap formation.

Sci Rep 2021 Nov 2;11(1):21439. Epub 2021 Nov 2.

Department of Clinical Immunology, Hallym University Sacred Heart Hospital, Anyang, South Korea.

Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Endothelial cell (EC) dysfunction is a key CKD-specific risk factor; however, the mechanisms by which uremia harms the endothelium are still unclear. We report a role for excessive neutrophil extracellular trap (NET) formation induced by uremic serum on EC injury. Read More

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November 2021

Characterizing the spatial signal of environmental DNA in river systems using a community ecology approach.

Mol Ecol Resour 2021 Nov 1. Epub 2021 Nov 1.

Laboratoire Evolution et Diversité Biologique, Université Toulouse III Paul Sabatier, Toulouse, France.

Environmental DNA (eDNA) is gaining a growing popularity among scientists but its applicability to biodiversity research and management remains limited in river systems by the lack of knowledge about the spatial extent of the downstream transport of eDNA. Here, we assessed the ability of eDNA inventories to retrieve spatial patterns of fish assemblages along two large and species-rich Neotropical rivers. We first examined overall community variation with distance through the distance decay of similarity and compared this pattern to capture-based samples. Read More

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November 2021

Aged neutrophils form mitochondria-dependent vital NETs to promote breast cancer lung metastasis.

J Immunother Cancer 2021 10;9(10)

Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China

Background: Neutrophils-linked premetastatic niche plays a key role in tumor metastasis, but not much is known about the heterogeneity and diverse role of neutrophils in niche formation. Our study focuses on the existence and biological function of a rarely delved subset of neutrophils, named as tumor-associated aged neutrophils (Naged, CXCR4CD62L), involved in premetastatic niche formation during breast cancer metastasis.

Methods: We explored the distributions of Naged in 206 patients and mice models (4T1 and MMTV-PyMT) by flow cytometry. Read More

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October 2021

Predicting Common Audiological Functional Parameters (CAFPAs) as Interpretable Intermediate Representation in a Clinical Decision-Support System for Audiology.

Front Digit Health 2020 15;2:596433. Epub 2020 Dec 15.

Cluster of Excellence Hearing4all, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany.

The application of machine learning for the development of clinical decision-support systems in audiology provides the potential to improve the objectivity and precision of clinical experts' diagnostic decisions. However, for successful clinical application, such a tool needs to be accurate, as well as accepted and trusted by physicians. In the field of audiology, large amounts of patients' data are being measured, but these are distributed over local clinical databases and are heterogeneous with respect to the applied assessment tools. Read More

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December 2020

Effects of Neutrophil Extracellular Traps in Patients With Septic Coagulopathy and Their Interaction With Autophagy.

Front Immunol 2021 11;12:757041. Epub 2021 Oct 11.

Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Introduction: Neutrophil extracellular traps (NETs) act as a critical trigger of inflammation and coagulation. We hypothesized that NETs are associated with septic hypercoagulability.

Materials And Methods: In total, 82 patients admitted with sepsis in the Department of Critical Care Medicine of Peking Union Medical College Hospital were enrolled between February 2017 and April 2018. Read More

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October 2021

Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms.

Cell Res 2021 Oct 26. Epub 2021 Oct 26.

You'an Hospital, Capital Medical University, Beijing, China.

The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0. Read More

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October 2021

Proteinous Components of Neutrophil Extracellular Traps Are Arrested by the Cell Wall Proteins of during Fungal Infection, and Can Be Used in the Host Invasion.

Cells 2021 10 13;10(10). Epub 2021 Oct 13.

Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland.

One of defense mechanisms of the human immune system to counteract infection by the opportunistic fungal pathogen is the recruitment of neutrophils to the site of invasion, and the subsequent production of neutrophil extracellular traps (NETs) that efficiently capture and kill the invader cells. In the current study, we demonstrate that within these structures composed of chromatin and proteins, the latter play a pivotal role in the entrapment of the fungal pathogen. The proteinous components of NETs, such as the granular enzymes elastase, myeloperoxidase and lactotransferrin, as well as histones and cathelicidin-derived peptide LL-37, are involved in contact with the surface of cells. Read More

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October 2021

Cathepsin C inhibition as a potential treatment strategy in cancer.

Biochem Pharmacol 2021 Dec 20;194:114803. Epub 2021 Oct 20.

Experimental and Clinical Research Center, Charité und Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft (MDC), Berlin, Germany; Nephrology and Intensive Care Medicine, Charité-Universitätsmedizin, Berlin, Germany.

Epidemiological studies established an association between chronic inflammation and higher risk of cancer. Inhibition of proteolytic enzymes represents a potential treatment strategy for cancer and prevention of cancer metastasis. Cathepsin C (CatC) is a highly conserved lysosomal cysteine dipeptidyl aminopeptidase required for the activation of pro-inflammatory neutrophil serine proteases (NSPs, elastase, proteinase 3, cathepsin G and NSP-4). Read More

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December 2021

Comorbidity-associated glutamine deficiency is a predisposition to severe COVID-19.

Cell Death Differ 2021 Oct 18. Epub 2021 Oct 18.

Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, ON, M5G 2M9, Canada.

SARS-CoV-2 vaccinations have greatly reduced COVID-19 cases, but we must continue to develop our understanding of the nature of the disease and its effects on human immunity. Previously, we suggested that a dysregulated STAT3 pathway following SARS-Co-2 infection ultimately leads to PAI-1 activation and cascades of pathologies. The major COVID-19-associated metabolic risks (old age, hypertension, cardiovascular diseases, diabetes, and obesity) share high PAI-1 levels and could predispose certain groups to severe COVID-19 complications. Read More

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October 2021

Neutrophil Activation: Influence of Antimony Tolerant and Susceptible Clinical Strains of and Meglumine Antimoniate.

Front Cell Infect Microbiol 2021 22;11:710006. Epub 2021 Sep 22.

Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Cali, Colombia.

Emerging evidence indicates that innate host response contributes to the therapeutic effect of antimicrobial medications. Recent studies have shown that parasites derived by selection for resistance to pentavalent antimony (SbV) as meglumine antimoniate (MA) modulate the activation of neutrophils. However, whether modulation of neutrophil activation extends to natural resistance to this antileishmanial drug has not been established. Read More

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October 2021

Neuroendocrine Tumors of the Gastrointestinal Tract: A Focused Review and Practical Approach for Gastroenterologists.

GE Port J Gastroenterol 2021 Sep 20;28(5):336-348. Epub 2021 Jan 20.

Gastroenterology Department, Instituto Português de Oncologia do Porto, Porto, Portugal.

Neuroendocrine tumors (NETs) are rare tumors derived from the neuroendocrine cell system, and more commonly found in the gastrointestinal (GI) tract. Over the last decades, the incidence of GI-NETs has been steadily increasing, partly due to the expanding indications for endoscopy. Most patients with NETs are asymptomatic, and their NETs are noticed during screening examinations; thus, endoscopists are on the frontline of the diagnosis of GI-NETs. Read More

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September 2021

Editorial: Pharmacological Approaches Targeting Neutrophilic Inflammation.

Front Pharmacol 2021 13;12:763140. Epub 2021 Sep 13.

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.

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September 2021

Insights in ChAdOx1 nCov-19 Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT).

Blood 2021 Sep 29. Epub 2021 Sep 29.

McMaster University, Hamilton, Ontario, Canada.

SARS-CoV-2 vaccine ChAdOx1 nCov-19 (AstraZeneca) causes a thromboembolic complication termed vaccine-induced immune thrombotic thrombocytopenia (VITT). Using biophysical techniques, mouse models and analysis of VITT patient samples we identified determinants of this vaccine-induced adverse reaction. Super-resolution microscopy visualized vaccine components forming antigenic complexes with platelet factor 4 (PF4) on platelet surfaces to which anti-PF4 antibodies obtained from VITT patients bound. Read More

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September 2021

Neutrophils as Regulators and Biomarkers of Cardiovascular Inflammation in the Context of Abdominal Aortic Aneurysms.

Biomedicines 2021 Sep 16;9(9). Epub 2021 Sep 16.

Department of General Surgery, Division of Vascular Surgery, Medical University of Vienna, University Hospital Vienna, 1090 Vienna, Austria.

Neutrophils represent up to 70% of circulating leukocytes in healthy humans and combat infection mostly by phagocytosis, degranulation and NETosis. It has been reported that neutrophils are centrally involved in abdominal aortic aneurysm (AAA) pathogenesis. The natural course of AAA is growth and rupture, if left undiagnosed or untreated. Read More

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September 2021

Explaining Causal Influence of External Factors on Incidence Rate of Covid-19.

SN Comput Sci 2021 18;2(6):465. Epub 2021 Sep 18.

Information Technology Department, Jadavpur University, Saltlake, kolkata, India.

Classical susceptible-infected-removed model with constant transmission rate and removal rate may not capture real world dynamics of epidemic due to complex influence of multiple external factors on the spread and spatio-temporal variation of transmission rate. Also, explainability of a model is of prime necessity to understand the influence of multiple factors on transmission rate. Thus, we modified discrete global susceptible-infected-removed model with time-varying transmission rate, recovery rate and multiple spatially local models. Read More

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September 2021

Type-4 Phosphodiesterase (PDE4) Blockade Reduces NETosis in Cystic Fibrosis.

Front Pharmacol 2021 8;12:702677. Epub 2021 Sep 8.

Laboratory of Vascular Biology and Pharmacology, Fondazione Mario Negri Sud, Santa Maria Imbaro (CH), Mozzagrogna, Italy.

Neutrophilic inflammation is a key determinant of cystic fibrosis (CF) lung disease. Neutrophil-derived free DNA, released in the form of extracellular traps (NETs), significantly correlates with impaired lung function in patients with CF, underlying their pathogenetic role in CF lung disease. Thus, specific approaches to control NETosis of neutrophils migrated into the lungs may be clinically relevant in CF. Read More

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September 2021

Nets of biotin-derived gold nanoparticles as a label for the C-reactive protein immunoassay.

Anal Bioanal Chem 2021 Nov 24;413(27):6867-6875. Epub 2021 Sep 24.

Saratov State University, 83 Astrakhanskaya Street, Saratov, 410012, Russia.

This study presents a promising approach for the one-pot generation of the biotin-derived gold nanoparticles ([email protected]). We report a direct method for the reduction of tetrachloroauric acid with biotin and generation of the labels due to nets formed via biotin-streptavidin interactions. The synthesized [email protected] have a characteristic plasmon maximum, excellent colloidal stability, and streptavidin coupling efficiency. Read More

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November 2021

NETs decorated with bioactive IL-33 infiltrate inflamed tissues and induce IFN-α production in patients with SLE.

JCI Insight 2021 Nov 8;6(21). Epub 2021 Nov 8.

Laboratory of Rheumatology, Autoimmunity and Inflammation, University of Crete, Medical School, Iraklio, Greece.

IL-33, a nuclear alarmin released during cell death, exerts context-specific effects on adaptive and innate immune cells, eliciting potent inflammatory responses. We screened blood, skin, and kidney tissues from patients with systemic lupus erythematosus (SLE), a systemic autoimmune disease driven by unabated type I IFN production, and found increased amounts of extracellular IL-33 complexed with neutrophil extracellular traps (NETs), correlating with severe, active disease. Using a combination of molecular, imaging, and proteomic approaches, we show that SLE neutrophils, activated by disease immunocomplexes, release IL-33-decorated NETs that stimulate robust IFN-α synthesis by plasmacytoid DCs in a manner dependent on the IL-33 receptor ST2L. Read More

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November 2021

A CNN-based method to reconstruct 3-D spine surfaces from US images in vivo.

Med Image Anal 2021 Dec 1;74:102221. Epub 2021 Sep 1.

Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843, USA. Electronic address:

Three-dimensional (3-D) reconstruction of the spine surface is of strong clinical relevance for the diagnosis and prognosis of spine disorders and intra-operative image guidance. In this paper, we report a new technique to reconstruct lumbar spine surfaces in 3-D from non-invasive ultrasound (US) images acquired in free-hand mode. US images randomly sampled from in vivo scans of 9 rabbits were used to train a U-net convolutional neural network (CNN). Read More

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December 2021

A novel liquid biopsy (NETest) identifies paragangliomas and pheochromocytomas with high accuracy.

Endocr Relat Cancer 2021 Oct 13;28(11):731-744. Epub 2021 Oct 13.

Gastroenterological and Endoscopic Surgery, Yale University School of Medicine, New Haven, Connecticut, USA.

Pheochromocytomas and paragangliomas (PHEOs/PGLs) represent diagnostically challenging and complex neuroendocrine tumors (NETs). Current biomarker tests for PHEOs/PGLs are technically complex or limited. We assessed the diagnostic utility of a NET-specific 51-marker gene blood assay (NETest) in patients with PHEOs/PGLs (n = 81), including ten pediatric patients, and age-/gender-matched controls (n = 142) using a prospective case:control (1:2) analysis. Read More

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October 2021