223,983 results match your criteria variants

Genetic Variability of the Paired Box Transcription Factor; PAX8 Gene: Guidance Towards Treatment Strategies in a Cohort of Congenital Hypothyroidism.

Horm Metab Res 2021 Apr 16. Epub 2021 Apr 16.

Genetic and Endocrinology Unit, Pediatric Department, Menoufia University, Shebin ElKoum, Menofia, Egypt.

The contribution of PAX8 genetic variants to congenital hypothyroidism (CH) is not well understood. We aimed to study the genetic variability of exons 3 and 5 of PAX8 gene among a cohort of children with congenital hypothyroidism in correspondence to their clinical aspect. Blood samples were collected from 117 children (63 girls and 54 boys) with CH and enrolled as cases (Group I). Read More

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Anti-GM1 IgM antibody positive axonal variant of Guillain-Barre-syndrome in a pediatric patient with dengue fever.

J Neuroimmunol 2021 Apr 13;355:577572. Epub 2021 Apr 13.

Section of Adult Neurology, Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines- Manila, Manila, Philippines.

Introduction: While children of all ages may be affected by Guillain-Barre-Syndrome (GBS), there are no reports of Dengue Fever (DF) as the preceding or concurrent infection in this age group. In addition, the presence of anti-GM1 IgM antibody, commonly seen in Multifocal Motor Neuropathy, is rarely encountered in both axonal and demyelinating variants of GBS. Moreover, only few neuromuscular ultrasound findings of the axonal variant in children were reported in the literature. Read More

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Insight into the drug resistance whole genome of Mycobacterium tuberculosis isolates from Khyber Pakhtunkhwa, Pakistan.

Infect Genet Evol 2021 Apr 13:104861. Epub 2021 Apr 13.

State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, and Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang District, Shanghai 200240, China; Peng Cheng Laboratory, Vanke Cloud City Phase I Building 8, Xili Street, Nanshan District, Shenzhen, Guangdong 518055, China. Electronic address:

Whole genome sequencing (WGS) is one of the most reliable methods for detection of drug resistance, genetic diversity in other virulence factor and also evolutionary dynamics of Mycobacterium tuberculosis complex (MTBC). First-line anti-tuberculosis drugs are the major weapons against Mycobacterium tuberculosis (MTB). However, the emergence of drug resistance remained a major obstacle towards global tuberculosis (TB) control program 2030, especially in high burden countries including Pakistan. Read More

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A multi-phenotype genome-wide association study of clades causing tuberculosis in a Ghanaian- and South African cohort.

Genomics 2021 Apr 13. Epub 2021 Apr 13.

DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Despite decades of research and advancements in diagnostics and treatment, tuberculosis remains a major public health concern. New computational methods are needed to interrogate the intersection of host- and bacterial genomes. Paired host genotype datum and infecting bacterial isolate information were analysed for associations using a multinomial logistic regression framework implemented in SNPTest. Read More

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Loss of coordinated expression between ribosomal and mitochondrial genes revealed by comprehensive characterization of a large family with a rare Mendelian disorder.

Genomics 2021 Apr 13. Epub 2021 Apr 13.

Department of Molecular Biosciences, University of Texas at Austin, Austin, USA. Electronic address:

Non-canonical intronic variants are a poorly characterized yet highly prevalent class of alterations associated with Mendelian disorders. Here, we report the first RNA expression and splicing analysis from a family whose members carry a non-canonical splice variant in an intron of RPL11 (c.396 + 3A > G). Read More

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Structural and functional characterization of NDBP-4 family antimicrobial peptides from the scorpion Mesomexovis variegatus.

Peptides 2021 Apr 13:170553. Epub 2021 Apr 13.

Instituto de Biotecnología, Universidad Nacional Autónoma de México, Avenida Universidad, 2001, Colonia Chamilpa, Cuernavaca, Morelos, 62210, Mexico. Electronic address:

Six peptides, belonging to the NDBP-4 family of scorpion antimicrobial peptides were structurally and functionally characterized. The sequence of the mature peptides VpCT1, VpCT2, VpCT3 and VpCT4 was inferred by transcriptomic analysis of the venom gland of the scorpion Mesomexovis variegatus. Analysis of their amino acid sequences revealed patterns that are also present in previously reported peptides that show differences in their hemolytic and antimicrobial activities in vitro. Read More

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Association of metabolites with obesity based on two gene variants, MC4R and BDNF.

Biochim Biophys Acta Mol Basis Dis 2021 Apr 13:166144. Epub 2021 Apr 13.

H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan; Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan. Electronic address:

Previous genome-wide association analyses for obesity related genes demonstrated the association of BDNF variant rs6265 and MC4R gene variant rs17782313 with body mass index (BMI). However, the associated metabolite pathways are still behind the curtain. The aimed of current study is to investigate the associations of metabolic changes in obesity with MC4R gene variant rs17782313 and BDNF variant rs6265. Read More

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The molecular basis of spectral tuning in blue- and red-shifted flavin-binding fluorescent proteins.

J Biol Chem 2021 Apr 13:100662. Epub 2021 Apr 13.

Institut für Molekulare Enzymtechnologie, Heinrich-Heine-Universität Düsseldorf, Forschungszentrum Jülich GmbH, D-52425 Jülich, Germany; IBG-1: Biotechnology: Forschungszentrum Jülich GmbH, D-52425 Jülich, Germany. Electronic address:

Photoactive biological systems modify the optical properties of their chromophores, known as spectral tuning. Determining the molecular origin of spectral tuning is instrumental for understanding function and developing applications of these biomolecules. Spectral tuning in flavin-binding fluorescent proteins (FbFPs), an emerging class of fluorescent reporters, is limited by their dependency on protein-bound flavins, whose structure and hence electronic properties cannot be altered by mutation. Read More

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The position of single-base deletions in the VNTR sequence of the carboxyl ester lipase (CEL) gene determines proteotoxicity.

J Biol Chem 2021 Apr 13:100661. Epub 2021 Apr 13.

The Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway; Center for Diabetes Research, Department of Clinical Science, University of Bergen, Norway; Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.

Variable number of tandem repeat (VNTR) sequences in the genome can have functional consequences that contribute to human disease. This is the case for the CEL gene, which is specifically expressed in pancreatic acinar cells and encodes the digestive enzyme carboxyl ester lipase. Rare single-base deletions (DELs) within the first (DEL1) or fourth (DEL4) VNTR segment of CEL cause MODY8, an inherited disorder characterized by exocrine pancreatic dysfunction and diabetes. Read More

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Notable sequence homology of the ORF10 protein introspects the architecture of SARS-CoV-2.

Int J Biol Macromol 2021 Apr 13. Epub 2021 Apr 13.

University of Pittsburgh School of Medicine, Department of Medicine, Division of Hematology/Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. Electronic address:

The current COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)shows similar pathology to MERS and SARS-CoV, with a current estimated fatality rate of 1.4%. Open reading frame 10 (ORF10) is a unique SARS-CoV-2 accessory protein, which contains eleven cytotoxic T lymphocyte (CTL) epitopes each of nine amino acids in length. Read More

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Toward a fine-scale population health monitoring system.

Cell 2021 Apr;184(8):2068-2083.e11

Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address:

Understanding population health disparities is an essential component of equitable precision health efforts. Epidemiology research often relies on definitions of race and ethnicity, but these population labels may not adequately capture disease burdens and environmental factors impacting specific sub-populations. Here, we propose a framework for repurposing data from electronic health records (EHRs) in concert with genomic data to explore the demographic ties that can impact disease burdens. Read More

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Reply to Lack of evidence for a role of PIWIL1 variants in human male infertility.

Cell 2021 Apr;184(8):1943-1944

State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences-University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai 200438, China. Electronic address:

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Lack of evidence for a role of PIWIL1 variants in human male infertility.

Cell 2021 Apr;184(8):1941-1942

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. Electronic address:

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A form of muscular dystrophy associated with pathogenic variants in JAG2.

Am J Hum Genet 2021 Apr 9. Epub 2021 Apr 9.

Division of Pediatric Neurology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610, USA; Paul and Sheila Wellstone Muscular Dystrophy Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Department of Neurology, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Institute for Translational Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Electronic address:

JAG2 encodes the Notch ligand Jagged2. The conserved Notch signaling pathway contributes to the development and homeostasis of multiple tissues, including skeletal muscle. We studied an international cohort of 23 individuals with genetically unsolved muscular dystrophy from 13 unrelated families. Read More

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Impact of variant-level batch effects on identification of genetic risk factors in large sequencing studies.

PLoS One 2021 16;16(4):e0249305. Epub 2021 Apr 16.

Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, Florida, United States of America.

Genetic studies have shifted to sequencing-based rare variants discovery after decades of success in identifying common disease variants by Genome-Wide Association Studies using Single Nucleotide Polymorphism chips. Sequencing-based studies require large sample sizes for statistical power and therefore often inadvertently introduce batch effects because samples are typically collected, processed, and sequenced at multiple centers. Conventionally, batch effects are first detected and visualized using Principal Components Analysis and then controlled by including batch covariates in the disease association models. Read More

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No association of genetic variants in TLR4, TNF-α, IL10, IFN-γ, and IL37 in cytomegalovirus-positive renal allograft recipients with active CMV infection-Subanalysis of the prospective randomised VIPP study.

PLoS One 2021 16;16(4):e0246118. Epub 2021 Apr 16.

Department of Nephrology, University Clinic Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.

Background: Cytomegalovirus (CMV) infection is amongst the most important factors complicating solid organ transplantation. In a large prospective randomized clinical trial, valganciclovir prophylaxis reduced the occurrence of CMV infection and disease compared with preemptive therapy in CMV-positive renal allograft recipients (VIPP study; NCT00372229). Here, we present a subanalysis of the VIPP study, investigating single nucleotide polymorphisms (SNPs) in immune-response-related genes and their association with active CMV infection, CMV disease, graft loss or death, rejection, infections, and leukopenia. Read More

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Mutations in chronic myelomonocytic leukemia and their prognostic relevance.

Clin Transl Oncol 2021 Apr 16. Epub 2021 Apr 16.

The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China.

Chronic myelomonocytic leukemia (CMML) is a hematologic malignancy that overlaps with myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) and tends to transform into acute myeloid leukemia (AML). Among cases of CMML, > 90% have gene mutations, primarily involving TET2 (~ 60%), ASXL1 (~ 40%), SRSF2 (~ 50%), and the RAS pathways (~ 30%). These gene mutations are associated with both the clinical phenotypes and the prognosis of CMML, special CMML variants and pre-phases of CMML. Read More

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Coupled-Channel Interpretation of the LHCb Double-J/ψ Spectrum and Hints of a New State Near the J/ψJ/ψ Threshold.

Phys Rev Lett 2021 Apr;126(13):132001

P.N. Lebedev Physical Institute of the Russian Academy of Sciences, 119991, Leninskiy Prospect 53, Moscow, Russia.

Recently, the LHCb Collaboration reported pronounced structures in the invariant mass spectrum of J/ψ pairs produced in proton-proton collisions at the Large Hadron Collider. In this Letter, we argue that the data can be very well described within two variants of a coupled-channel approach employing T matrices consistent with unitarity: (i) with just two channels, J/ψJ/ψ and ψ(2S)J/ψ, as long as energy-dependent interactions in these channels are allowed, or (ii) with three channels J/ψJ/ψ, ψ(2S)J/ψ, and ψ(3770)J/ψ with just constant contact interactions. Both formulations hint at the existence of a near-threshold state in the J/ψJ/ψ system with the quantum numbers J^{PC}=0^{++} or 2^{++}, which we refer to as X(6200). Read More

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Canine parvovirus type 2c in Vietnam continues to produce distinct descendants with new mutations restricted to Vietnamese variants.

Arch Virol 2021 Apr 16. Epub 2021 Apr 16.

Immunology Department, Institute of Biotechnology (IBT), Vietnam Academy of Science and Technology (VAST), 18. Hoang Quoc Viet Rd., Cau Giay, Hanoi, Vietnam.

Viral protein 2 (VP2) of canine parvovirus (CPV) exhibits a high degree of genetic and antigenic diversity. We analyzed 88 Vietnamese CPV-VP2 sequences (1755 bp), 34 from this study and 54 from previous studies, and discovered a new sublineage, "new var.", within the lineage CPV-2c-"new", characterized by the mutation 5G/447M, which is restricted to the Vietnamese isolates. Read More

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Study of complex structural variations of X-linked deafness-2 (DFNX2) based on single-molecule sequencing.

Biosci Rep 2021 Apr 16. Epub 2021 Apr 16.

PLA General Hospital, Beijing, China.

X-linked deafness-2 (DFNX2) is cochlear incomplete partition type III (IP-III), one of inner ear malformations characterized by an abnormally wide opening in the bone separating the basal turn of the cochlea from the internal auditory canal, fixation of the stapes and cerebrospinal fluid (CSF) gusher upon stapedectomy or cochleostomy. The causative gene of DFNX2 was POU3F4. To investigate the genetic causes of X-linked deafness-2 (DFNX2) and compare the efficiency of different sequencing methods, twelve unrelated patients were enrolled in this study. Read More

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[Haptoglobin as a biomarker].

Biomed Khim 2021 Mar;67(2):105-118

Petersburg Institute of Nuclear Physics B.P. Konstantinova National Research Center "Kurchatov Institute", Gatchina, Russia.

Haptoglobin (Hp) is a blood plasma glycoprotein that binds free hemoglobin (Hb) and plays a critical role in tissue protection and the prevention of oxidative damage. In addition, it has a number of regulatory functions. Haptoglobin is an acute phase protein, its concentration in plasma changes in pathology, and the test for its concentration is part of normal clinical practice. Read More

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Impact of January 2021 curfew measures on SARS-CoV-2 B.1.1.7 circulation in France.

Euro Surveill 2021 Apr;26(15)

Tokyo Tech World Research Hub Initiative, Institute of Innovative Research, Tokyo Institute of Technology, Tokyo, Japan.

Following the spread of the SARS-CoV-2 B.1.1. Read More

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Polysulfates block SARS-CoV-2 uptake via electrostatic interactions.

Angew Chem Int Ed Engl 2021 Apr 16. Epub 2021 Apr 16.

Freie Universitat Berlin, Dept. of Biology, Chemistry and Pharmacy, Takustr. 3, Institute for Chemistry and Biochemistry, 14195, Berlin, GERMANY.

Here we report that negatively charged polysulfates can bind to the spike protein of SARS-CoV-2 via electrostatic interactions. Using a plaque reduction assay, we compare inhibition of SARS-CoV-2 by heparin, pentosan sulfate, linear polyglycerol sulfate (LPGS) and hyperbranched polyglycerol sulfate (HPGS). Highly sulfated LPGS is the optimal inhibitor, with a half-maximal inhibitory concentration (IC 50 ) of 67 μg/mL (approx. Read More

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Hedgehog signaling pathway gene variant influences bronchopulmonary dysplasia in extremely low birth weight infants.

World J Pediatr 2021 Apr 16. Epub 2021 Apr 16.

Newborn Medicine Division, The Regional Neonatal Intensive Care Unit, Maria Fareri Children's Hospital At Westchester Medical Center, Valhalla, NY, USA.

Background: Genome wide association study identified hedgehog interacting protein gene (HHIP) variants with chronic obstructive pulmonary disease and asthma. Loss of HHIP, a key regulator of the hedgehog signaling pathway, leads to impaired lung morphogenesis and lethality in animal models, through unimpeded sonic hedgehog expression blocking mesenchymal-expressed fibroblast growth factor 10 (FGF10). Since bronchopulmonary dysplasia (BPD) is also associated with altered lung development and worsens with stimuli including mechanical ventilation, reactive oxygen species, and inflammation, HHIP and FGF10 may be candidate genes. Read More

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Targeted sequencing and integrative analysis to prioritize candidate genes in neurodevelopmental disorders.

Mol Neurobiol 2021 Apr 15. Epub 2021 Apr 15.

Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, China.

Neurodevelopmental disorders (NDDs) are a group of diseases characterized by high heterogeneity and frequently co-occurring symptoms. The mutational spectrum in patients with NDDs is largely incomplete. Here, we sequenced 547 genes from 1102 patients with NDDs and validated 1271 potential functional variants, including 108 de novo variants (DNVs) in 78 autosomal genes and seven inherited hemizygous variants in six X chromosomal genes. Read More

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Detection of mink astrovirus in Poland and further phylogenetic comparison with other European and Canadian astroviruses.

Virus Genes 2021 Apr 15. Epub 2021 Apr 15.

Institute of Biological Basis of Animal Production, Faculty of Animal Sciences and Bioeconomy, University of Life Sciences in Lublin, Lublin, Poland.

Mink astrovirus infection remains a poorly understood disease entity, and the aetiological agent itself causes disease with a heterogeneous course, including gastrointestinal and neurological symptoms. This paper presents cases of astrovirus infection in mink from continental Europe. RNA was isolated from the brains and intestines of animals showing symptoms typical of shaking mink syndrome (n = 6). Read More

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Alteration of cofactor specificity of the acrylyl-CoA reductase from Escherichia coli.

Biotechnol Lett 2021 Apr 16. Epub 2021 Apr 16.

Laboratory of Methylotrophy, Federal Research Center, "Pushchino Scientific Center for Biological Research, Russian Academy of Sciences" IBPM RAS, Pushchino, Moscow Region, Russia, 142290.

Objectives: Alteration of the cofactor specificity of acrylyl-CoA reductase (AcuI) catalyzing the NAD(P)H-dependent reduction of acrylyl-CoA to propionyl-CoA is often desirable for designing of artificial metabolic pathways of various appointments.

Results: Several variants of AcuIs from Escherichia coli K-12 with multiple amino acid substitutions to alter the cofactor preference were obtained by site directed mutagenesis and the modified enzymes as His-tagged proteins were characterized. The simultaneous substitutions of arginine-180, arginine-198 and serine-178 residues by alanine in the enzyme pocket sequence as well as other amino acid changes decreased both NADPH- and NADH-dependent activities in comparison to the wild-type enzyme. Read More

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A neurogenetic analysis of female autism.

Brain 2021 Apr 16. Epub 2021 Apr 16.

Department of Pediatrics, Yale School of Medicine, New Haven, CT 06510, USA.

Females versus males are less frequently diagnosed with autism spectrum disorder (ASD), and while understanding sex differences is critical to delineating the systems biology of the condition, female ASD is understudied. We integrated functional MRI and genetic data in a sex-balanced sample of ASD and typically developing youth (8-17 years old) to characterize female-specific pathways of ASD risk. Our primary objectives were to: (i) characterize female ASD (n = 45) brain response to human motion, relative to matched typically developing female youth (n = 45); and (ii) evaluate whether genetic data could provide further insight into the potential relevance of these brain functional differences. Read More

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Toward the Next-Generation COVID-19 Vaccines That Circumvent Antigenic Drift while Defusing Viral Infection.

Ariel Fernández

ACS Pharmacol Transl Sci 2021 Apr 1;4(2):1018-1020. Epub 2021 Mar 1.

Daruma Institute for AI in Pharmaceutical Research, AF Innovation Pharma Consultancy, 4000 Pemberton Court, Winston-Salem, North Carolina 27106, United States.

The emergence of vaccine-resistant variants suggests a complicated endemic scenario in the vaccination aftermath for COVID-19. The situation prompts us to enquire whether the antigen adopted by extant vaccines, the trimeric spike (S) protein, is the optimal in the sense of inducing an immunity that leaves the virus with no evolutionary route of evasion. The patterns of glycosylation camouflage suggest that the answer is negative while also suggesting an alternative antigen that appears to be better optimized, eliciting an additional immune attack as the virus gets primed for cell penetration. Read More

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