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GNEN-1: a spontaneously immortalized cell line from gastric neuroendocrine neoplasia.

Endocr Connect 2021 Aug 1. Epub 2021 Aug 1.

J Arola, Deparement of pathology, University of Helsinki, Helsinki, Finland.

Mixed neuroendocrine-non-neuroendocrine neoplasms (MINEN) are rare tumors that consist of at least 30% of both neuroendocrine and non-neuroendocrine components. The data concerning pathogenesis of MINEN suggest a monoclonal origin. We describe a spontaneously immortalized cell line derived from gastric MINEN called GNEN-1. Read More

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Optimized CRISPR-mediated gene knockin reveals FOXP3-independent maintenance of human Treg identity.

Cell Rep 2021 Aug;36(5):109494

Department of Surgery, University of British Columbia, Vancouver, BC V5Z 1M9, Canada; BC Children's Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada; School of Biomedical Engineering, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address:

Regulatory T cell (Treg) therapy is a promising curative approach for a variety of immune-mediated conditions. CRISPR-based genome editing allows precise insertion of transgenes through homology-directed repair, but its use in human Tregs has been limited. We report an optimized protocol for CRISPR-mediated gene knockin in human Tregs with high-yield expansion. Read More

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A kinesin 1-protrudin complex mediates AMPA receptor synaptic removal during long-term depression.

Cell Rep 2021 Aug;36(5):109499

Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, 28049 Madrid, Spain. Electronic address:

The synaptic removal of AMPA-type glutamate receptors (AMPARs) is a core mechanism for hippocampal long-term depression (LTD). In this study, we address the role of microtubule-dependent transport of AMPARs as a driver for vesicular trafficking and sorting during LTD. Here, we show that the kinesin-1 motor KIF5A/C is strictly required for LTD expression in CA3-to-CA1 hippocampal synapses. Read More

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Tracing colonic embryonic transcriptional profiles and their reactivation upon intestinal damage.

Cell Rep 2021 Aug;36(5):109484

Department of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Electronic address:

We lack a holistic understanding of the genetic programs orchestrating embryonic colon morphogenesis and governing damage response in the adult. A window into these programs is the transcriptomes of the epithelial and mesenchymal cell populations in the colon. Performing unbiased single-cell transcriptomic analyses of the developing mouse colon at different embryonic stages (embryonic day 14. Read More

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A subthreshold synaptic mechanism regulating BDNF expression and resting synaptic strength.

Cell Rep 2021 Aug;36(5):109467

Department of Pharmacology, Vanderbilt University, Nashville, TN 37235, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37235, USA. Electronic address:

Recent studies have demonstrated that protein translation can be regulated by spontaneous excitatory neurotransmission. However, the impact of spontaneous neurotransmitter release on gene transcription remains unclear. Here, we study the effects of the balance between inhibitory and excitatory spontaneous neurotransmission on brain-derived neurotrophic factor (BDNF) regulation and synaptic plasticity. Read More

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Severe deficiency of the voltage-gated sodium channel Na1.2 elevates neuronal excitability in adult mice.

Cell Rep 2021 Aug;36(5):109495

Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN 47907, USA; Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN 47907, USA. Electronic address:

Scn2a encodes the voltage-gated sodium channel Na1.2, a main mediator of neuronal action potential firing. The current paradigm suggests that Na1. Read More

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Activation of a hippocampal CREB-pCREB-miRNA-MEF2 axis modulates individual variation of spatial learning and memory capability.

Cell Rep 2021 Aug;36(5):109477

Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan; Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan. Electronic address:

Phenotypic variation is a fundamental prerequisite for cell and organism evolution by natural selection. Whereas the role of stochastic gene expression in phenotypic diversity of genetically identical cells is well studied, not much is known regarding the relationship between stochastic gene expression and individual behavioral variation in animals. We demonstrate that a specific miRNA (miR-466f-3p) is upregulated in the hippocampus of a portion of individual inbred mice upon a Morris water maze task. Read More

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Ketogenesis impact on liver metabolism revealed by proteomics of lysine β-hydroxybutyrylation.

Cell Rep 2021 Aug;36(5):109487

Center for Epigenetics and Metabolism, U1233 INSERM, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.

Ketone bodies are bioactive metabolites that function as energy substrates, signaling molecules, and regulators of histone modifications. β-hydroxybutyrate (β-OHB) is utilized in lysine β-hydroxybutyrylation (Kbhb) of histones, and associates with starvation-responsive genes, effectively coupling ketogenic metabolism with gene expression. The emerging diversity of the lysine acylation landscape prompted us to investigate the full proteomic impact of Kbhb. Read More

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Interleukin enhancer binding factor 2 (IEBF 2) was involved in the regulation of the antibacterial immune reactions in fresh water crayfish, Procambarus clarkii.

Dev Comp Immunol 2021 Aug 1:104226. Epub 2021 Aug 1.

School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia autonomous region, 014010, China. Electronic address:

Although interleukin and interleukin analogues which play important immunomodulatory roles in mammals have not yet been reported in invertebrates, interleukin enhancer binding factor (IEBF) which acts as a transcription factor has been recently studied in several crustaceans and it may be involved in innate immune defence against pathogens. In this study, an IEBF 2 homologue was identified in the fresh water crayfish, Procambarus clarkii. The significantly changed expression levels of Pc-iebf 2 after bacterial challenge revealed the possibility of its participation in defence against bacterial infection. Read More

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Chemogenomics identifies acetyl-coenzyme A synthetase as a target for malaria treatment and prevention.

Cell Chem Biol 2021 Jul 28. Epub 2021 Jul 28.

Wellcome Centre for Anti-Infectives Research, Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, UK.

We identify the Plasmodium falciparum acetyl-coenzyme A synthetase (PfAcAS) as a druggable target, using genetic and chemical validation. In vitro evolution of resistance with two antiplasmodial drug-like compounds (MMV019721 and MMV084978) selects for mutations in PfAcAS. Metabolic profiling of compound-treated parasites reveals changes in acetyl-CoA levels for both compounds. Read More

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Oxygen Enrichment Mitigates High-Altitude Hypoxia-Induced Hippocampal Neurodegeneration and Memory Dysfunction Associated with Attenuated Tau Phosphorylation.

High Alt Med Biol 2021 Aug 4. Epub 2021 Aug 4.

Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, China.

Cai, Jing, Junyong Ruan, Xi Shao, Yuanjun Ding, Kangning Xie, Chi Tang, Zedong Yan, Erping Luo, and Da Jing. Oxygen enrichment mitigates high-altitude hypoxia-induced hippocampal neurodegeneration and memory dysfunction associated with attenuated tau phosphorylation. 00:000-000, 2021. Read More

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Production of Transgenic Handmade Cloned Goat () Embryos by Targeted Integration into Rosa 26 Locus Using Transcription Activator-like Effector Nucleases.

Cell Reprogram 2021 Aug 4. Epub 2021 Aug 4.

Embryo Biotechnology Laboratory, Animal Biotechnology Centre, ICAR-National Dairy Research Institute, Karnal, India.

Transgenic goats are ideal bioreactors for the production of therapeutic proteins in their mammary glands. However, random integration of the transgene within-host genome often culminates in unstable expression and unpredictable phenotypes. Targeting desired genes to a safe locus in the goat genome using advanced targeted genome-editing tools, such as transcription activator-like effector nucleases (TALENs) might assist in overcoming these hurdles. Read More

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An Study of the Effects of Crocin on the Modulation of , , , and Expression in Human Dental Pulp Stem Cells.

Cell Reprogram 2021 Aug 4. Epub 2021 Aug 4.

Department of Immunology, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran.

Dental pulp stem cells (DPSCs) have been recommended as promising candidate for cell-based therapeutic applications due to high potentials in tissue repair/regeneration and modulation of immune responses. The gene expression change strategy by natural plant enhancers is an available opportunity to improve the stemness properties of these cells. The objective of this research was the evaluation of Crocin effects (saffron plant's bioactive compound) on immunoregulation and tissue regeneration-related biomarkers expression in human DPSCs. Read More

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Defective Natural Killer Cells in Melanoma: Role of NKG2D in Pathogenesis and Immunotherapy.

Crit Rev Immunol 2021 ;41(2):45-76

Department of Microbiology, Immunology, & Molecular Genetics, David Geffen School of Medicine, Johnson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA 90025-1747, USA.

Melanoma is the most aggressive and deadliest form of skin cancer, and its prognosis is very poor. Although the early detection is responsive to many treatments, metastatic melanoma is refractory to most of them. In the United States, skin melanoma is the fifth most common type of cancer in men and the sixth in women. Read More

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January 2021

MiR-18a-5p Promotes Proliferation, Migration, and Invasion of Endometrial Cancer Cells by Targeting THBD.

Crit Rev Eukaryot Gene Expr 2021 ;31(2):63-73

Department of Obstetrics and Gynecology, Dafeng Hospital of Traditional Chinese Medicine, Yancheng, Jiangsu, China.

The purpose of this study was to elucidate the role that the miR-18a-5p/THBD regulatory pathway plays in endometrial cancer (EC), which could provide a theoretical basis for potential therapeutic targets. Differentially expressed genes in EC tissue and normal tissue were determined by bioinformatics analysis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to compare the expression of miR-18a-5p and THBD mRNA in normal human endometrial cells and human EC cells. Read More

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January 2021

Knockdown of miR-543 Inhibits the Proliferation and Migration of Small-Cell Lung Carcinoma Cells and Induces Apoptosis.

Crit Rev Eukaryot Gene Expr 2021 ;31(2):25-33

Department of Respiratory and Critical Care Medicine, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, Guangxi, China.

This article aims to explore the effects and possible mechanism of miR-543 on small-cell lung carcinoma (SCLC) cells. The respective levels of miR-543 in lung carcinoma tissues, para-cancerous tissues, human normal lung cells MRC-9, and SCLC cells were detected by RT-qPCR. The proliferation, apoptosis, and migration of SCLC cells were detected after the miR-543 level in SCLC cells was altered by miRNA mimics and inhibitors. Read More

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January 2021

Differential Expression of miRNA in the Peripheral Blood Mononuclear Cells in Myasthenia Gravis with Muscle-Specific Receptor Tyrosine Kinase Antibodies.

Crit Rev Eukaryot Gene Expr 2021 ;31(2):1-15

Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.

To determine if differential profile of miRNAs in peripheral blood mononuclear cells (PBMCs) could be identified in muscle-specific receptor tyrosine kinase antibody positive myasthenia gravis (MuSK-MG) and linked to disease stage, a case-control method was used to compare the difference in miRNA expression profiles of PBMCs using next generation sequencing (NGS) in MuSK-MG patients and healthy controls (HCs). Six significant miRNAs from the discovery set were then validated using RT-qPCR in 11 MuSK-MG patients and 10 HCs. A unique miRNA prediction algorithm was used to predict the target genes of differentially expressed miRNAs and a network of miRNA gene pathways. Read More

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January 2021

Variant , Defective piRNA Processing, and Azoospermia.

N Engl J Med 2021 Aug 4. Epub 2021 Aug 4.

From the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).

Background: P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are short (21 to 35 nucleotides in length) and noncoding and are found almost exclusively in germ cells, where they regulate aberrant expression of transposable elements and postmeiotic gene expression. Critical to the processing of piRNAs is the protein poly(A)-specific RNase-like domain containing 1 (PNLDC1), which trims their 3' ends and, when disrupted in mice, causes azoospermia and male infertility.

Methods: We performed exome sequencing on DNA samples from 924 men who had received a diagnosis of nonobstructive azoospermia. Read More

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The AMP-Dependent Kinase Pathway is Upregulated in BAP1 Mutant Uveal Melanoma.

Pigment Cell Melanoma Res 2021 Aug 4. Epub 2021 Aug 4.

Department of Cancer Biology, Thomas Jefferson University.

Metastatic uveal melanoma (UM) responds poorly to targeted therapies and immune checkpoint inhibitors. Loss of BRCA1-associated protein 1 (BAP1) via inactivating mutations in the BAP1 gene is associated with UM progression. Thus, molecular alterations caused by BAP1 dysfunction may be novel therapeutic targets for metastatic UM. Read More

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Blocking MCT4 SUMOylation inhibits the growth of breast cancer cells.

Mol Carcinog 2021 Aug 4. Epub 2021 Aug 4.

Department of Immunology, School of Medicine, Nankai University, Tianjin, China.

Monocarboxylate transporter 4 (MCT4) is highly expressed in various types of solid neoplasms including breast cancer (BC); however, the pro-tumor functions underlying its increased expression have not been explained. Here, we examined the roles of posttranslational modifications to MCT4 in BC, particularly SUMOylation. Our findings revealed that SUMOylation of MCT4 inhibited its degradation and stabilized MCT4 protein levels, while ubiquitination facilitated MCT4 degradation. Read More

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A potential signaling axis between RON kinase receptor and hypoxia-inducible factor-1 alpha in pancreatic cancer.

Mol Carcinog 2021 Aug 4. Epub 2021 Aug 4.

Department of Internal Medicine, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona, USA.

The Cancer Genome Atlas (TCGA) of a pancreatic cancer cohort identified high MST1R (RON tyrosine kinase receptor) expression correlated with poor prognosis in human pancreatic cancer. RON expression is null/minimal in normal pancreas but elevates from pan-in lesions through invasive carcinomas. We report using multiple approaches RON directly regulates HIF-1α, a critical driver of genes involved in cancer cell invasion and metastasis. Read More

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ORY-1001, a KDM1A inhibitor, inhibits proliferation, and promotes apoptosis of triple negative breast cancer cells by inactivating androgen receptor.

Drug Dev Res 2021 Aug 4. Epub 2021 Aug 4.

Department of Thyroid and Breast Surgery, The Second People's Hospital of Nantong, Nantong City, Jiangsu Province, China.

Breast cancer (BC), which is widely considered as the most common cancer in women around the world, evokes ~1.7 million new BC cases and 522,000 BC-related deaths each year. Triple negative breast cancer (TNBC) is clinically confirmed as one of the most aggressive subtypes of BC. Read More

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Molecular and functional insights into glutathione S-transferase genes associated with salt stress in Halothece sp. PCC7418.

Plant Cell Environ 2021 Aug 4. Epub 2021 Aug 4.

Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.

Evolution and function of glutathione S-transferase (GST) in primordial oxygenic phototrophs such as cyanobacteria are poorly understood. In this study, we identified and functionally characterized the GST gene family in the halotolerant cyanobacterium Halothece sp. PCC7418. Read More

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A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells.

PLoS One 2021 4;16(8):e0254991. Epub 2021 Aug 4.

School of Mathematics, Statistics and Physics, Newcastle University, Newcastle upon Tyne, United Kingdom.

Human pluripotent stem cells (hPSCs) have the potential to differentiate into all cell types, a property known as pluripotency. A deeper understanding of how pluripotency is regulated is required to assist in controlling pluripotency and differentiation trajectories experimentally. Mathematical modelling provides a non-invasive tool through which to explore, characterise and replicate the regulation of pluripotency and the consequences on cell fate. Read More

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Concatemeric Broccoli reduces mRNA stability and induces aggregates.

PLoS One 2021 4;16(8):e0244166. Epub 2021 Aug 4.

Centre for Structural Systems Biology, Hamburg, Germany.

Fluorogenic aptamers are an alternative to established methodology for real-time imaging of RNA transport and dynamics. We developed Broccoli-aptamer concatemers ranging from 4 to 128 substrate-binding site repeats and characterized their behavior fused to an mCherry-coding mRNA in transient transfection, stable expression, and in recombinant cytomegalovirus infection. Concatemerization of substrate-binding sites increased Broccoli fluorescence up to a concatemer length of 16 copies, upon which fluorescence did not increase and mCherry signals declined. Read More

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Lapatinib and poziotinib overcome ABCB1-mediated paclitaxel resistance in ovarian cancer.

PLoS One 2021 4;16(8):e0254205. Epub 2021 Aug 4.

Markey Cancer Center, College of Medicine, University of Kentucky, Lexington, KY, United States of America.

Conventional frontline treatment for ovarian cancer consists of successive chemotherapy cycles of paclitaxel and platinum. Despite the initial favorable responses for most patients, chemotherapy resistance frequently leads to recurrent or refractory disease. New treatment strategies that circumvent or prevent mechanisms of resistance are needed to improve ovarian cancer therapy. Read More

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Differences in Placental Histology Between Zika Virus-infected Teenagers and Older Women.

Int J Gynecol Pathol 2021 Aug 4. Epub 2021 Aug 4.

Departments of Morphology and Basic Pathology (G.R.S., C.A.L.P., R.C.S.P.) Pathology and Cytology Laboratory, Jundiaí Medical School (JMS) (G.R.S., C.A.L.P.); Pediatrics (Z.C., S.D.P.) Laboratory of Pediatrics Infectology, Jundiai Medical School (FMJ) (Z.C., S.D.P.) Department of Pediatrics, University Hospital of Jundiai Medical School (HU-FMJ) (Z.C., S.D.P.) Jundiai Department of Pathology, AC Camargo Cancer Center (C.A.L.P.) Center of Research about Human Genome and Stem Cells, Bioscience Institute of University of Sao Paulo (CEGH-CEL/IB-USP) (M.Z.) Department of Legal Medicine, University of São Paulo (USP) (E.M.) Foundation for Research Support of the State of Sao Paulo (FAPESP) (E.M.) Sao Paulo School of Advanced Applied Mathematics of Getulio Vargas Foundation (EMAp-FGV), Rio de Janeiro (E.M.) National Council for Scientific and Technological Development (CNPq), Brasilia (E.M.) Brazil Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, New York (S.S.W.) Department of Infectious Maladies and Pediatric Immunodeficiencies, VallD´Hebron Hospital, Barcelona, Spain (A.S.A.) Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine (LSHTM) (L.C.R., E.M.) Royal Society of Medicine, London, UK (E.M.).

In pregnant women, Zika virus (ZIKV) is associated with a congenital syndrome, most frequently involving damage to embryo brain formation and the development of microcephaly. The mechanism(s) by which ZIKV enters the maternal-fetal interface and is transmitted to the fetus remains incompletely determined. We sought to evaluate histologic changes in the placenta of ZIKV-infected pregnant women and to determine if this varied by maternal age. Read More

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Acute Visceral Pain in Rats: Vagal Nerve Block Compared to Bupivacaine Administered Intramuscularly.

Anesth Analg 2021 Aug 4. Epub 2021 Aug 4.

From the Laboratoire d'Anesthésie, Paris-Saclay University and INSERM U1195 Faculté de Médecine de Bicêtre, Le Kremlin-Bicêtre, France; Department of Anesthesiology and Intensive Care Medicine.

Background: Visceral and parietal peritoneum layers have different sensory innervations. Most visceral peritoneum sensory information is conveyed via the vagus nerve to the nucleus of the solitary tract (NTS). We already showed in animal models that intramuscular (i. Read More

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Reliability and Role of Mutation-specific H3F3A (Histone 3-3) G34W Immunohistochemistry to Differentiate Giant Cell Tumor of Bone From its Clinicoradiologic and Histologic Mimics: An Institutional Study.

Appl Immunohistochem Mol Morphol 2021 Aug 4. Epub 2021 Aug 4.

Departments of Pathology Orthopaedic Oncology Radiodiagnosis, Rajiv Gandhi Cancer Institute & Research Centre Department of Musculoskeletal Oncology, Max Institute of Cancer Care, Max Superspeciality Hospital, New Delhi, Delhi Department of Medical Oncology, Homi Bhabha Cancer Hospital and Research Centre, Visakhapatnam, Andhra Pradesh, India.

Giant cell tumor of bone (GCTB) is a benign neoplasm, which can sometimes be a diagnostic challenge, especially in small biopsies, due to its histologic benign and malignant mimics. We evaluated the role of H3.3 G34W immunohistochemistry (IHC) antibody in diagnosing GCTB and its role in differentiating it from its close histologic mimics. Read More

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