13,683 results match your criteria Genetics of LDL Cholesterol


The small GTPase RAB10 regulates endosomal recycling of the LDL receptor and transferrin receptor in hepatocytes.

J Lipid Res 2022 Jun 23:100248. Epub 2022 Jun 23.

Department of Internal Medicine, University of Michigan, Ann Arbor, MI.

The low-density lipoprotein receptor (LDLR) mediates the hepatic uptake of circulating low-density lipoproteins (LDL), a process that modulates the development of atherosclerotic cardiovascular disease. We recently identified RAB10, encoding a small GTPase, as a positive regulator of LDL uptake in hepatocellular carcinoma cells (HuH7) in a genome-wide CRISPR screen, though the underlying molecular mechanism for this effect was unknown. We now report that RAB10 regulates hepatocyte LDL uptake by promoting the recycling of endocytosed LDLR from RAB11-positive endosomes to the plasma membrane. Read More

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Association of the APOA-5 Genetic Variant rs662799 with Metabolic Changes after an Intervention for 9 Months with a Low-Calorie Diet with a Mediterranean Profile.

Nutrients 2022 Jun 11;14(12). Epub 2022 Jun 11.

Center of Investigation of Endocrinology and Nutrition, Department of Endocrinology and Investigation, Medicine School, Hospital Clinico Universitario, University of Valladolid, 47003 Valladolid, Spain.

In cross-sectional studies, the genetic variant rs662799 of the APOA5 gene is associated with high serum triglyceride concentrations, and in some studies, the effect of short-term dietary interventions has been evaluated. The aim of the present investigation was to evaluate the role of this genetic variant in metabolic changes after the consumption of a low-calorie diet with a Mediterranean pattern for 9 months. A population of 269 Caucasian obese patients was recruited. Read More

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Identification of New Genetic Determinants in Pediatric Patients with Familial Hypercholesterolemia Using a Custom NGS Panel.

Genes (Basel) 2022 Jun 1;13(6). Epub 2022 Jun 1.

Department of Genetics, Polish Mother's Memorial Hospital-Research Institute, 93-338 Lodz, Poland.

The most common form of inherited lipid disorders is familial hypercholesterolemia (FH). It is characterized primarily by high concentrations of the clinical triad of low-density lipoprotein cholesterol, tendon xanthomas and premature CVD. The well-known genetic background are mutations in , and gene. Read More

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Association between SNPs in Leptin Pathway Genes and Anthropometric, Biochemical, and Dietary Markers Related to Obesity.

Genes (Basel) 2022 May 25;13(6). Epub 2022 May 25.

Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Juriquilla, Querétaro 76230, Mexico.

Obesity is one of the main public health problems in Mexico and the world and one from which a large number of pathologies derive. Single nucleotide polymorphisms (SNPs) of various genes have been studied and proven to contribute to the development of multiple diseases. SNPs of the leptin pathway have been associated with the control of hunger and energy expenditure as well as with obesity and type 2 diabetes mellitus. Read More

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The LDL Apolipoprotein B-to-LDL Cholesterol Ratio: Association with Cardiovascular Mortality and a Biomarker of Small, Dense LDLs.

Biomedicines 2022 Jun 2;10(6). Epub 2022 Jun 2.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.

Background And Objective: Small, dense low-density lipoproteins (LDLs) are considered more atherogenic than normal size LDLs. However, the measurement of small, dense LDLs requires sophisticated laboratory methods, such as ultracentrifugation, gradient gel electrophoresis, or nuclear magnetic resonance. We aimed to analyze whether the LDL apolipoprotein B (LDLapoB)-to-LDL cholesterol (LDLC) ratio is associated with cardiovascular mortality and whether this ratio represents a biomarker for small, dense LDLs. Read More

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Anti-obesity Effects of Dark Tea Extracts by Down-regulation of C/EBPα and PPARγ.

In Vivo 2022 Jul-Aug;36(4):1753-1760

College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea;

Background/aim: Dark tea, made by fermentation of tea leaves using microorganisms, is well known for its antiobesity effect; however, studies to identify this effect have not been sufficiently conducted. Herein, the anti-obesity effects of post-fermented dark tea were studied in high-fat diet mouse.

Materials And Methods: Obesity was induced through a high-fat diet in C57BL/6 mice, and then dark tea extract powder (DTP) was orally administered daily for 12 weeks to evaluate the body and organ weights. Read More

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ASSOCIATION BETWEEN APOLIPOPROTEIN E POLYMORPHISMS AND EPILEPSY IN CHILDREN.

Acta Clin Croat 2021 Dec;60(4):595-601

1Department of Pediatrics, University Hospital Center Sestre milosrdnice, Zagreb, Croatia;2Department of Neurology, University Hospital Center Sestre milosrdnice, Zagreb, Croatia.

Apolipoprotein E (APOE) plays an important role in lipid metabolism and is a proven risk factor for development of dementia and other neurodegenerative diseases. The aim of the study was to determine the possible connection between particular APOE alleles, blood lipid profile and different types of epilepsy in children. Alleles of the APOE gene, blood cholesterol (total, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol, and triglyceride levels were analyzed in blood samples of 111 children with epilepsy and 118 age- and sex-matched children without epilepsy. Read More

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December 2021

Macronutrient intake modulates impact of EcoRI polymorphism of ApoB gene on lipid profile and inflammatory markers in patients with type 2 diabetes.

Sci Rep 2022 Jun 22;12(1):10504. Epub 2022 Jun 22.

Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS), Tehran, PO Box: 141556117, Iran.

We sought to examine whether dietary intakes may affect the relationship between ApoB EcoRI and lipid profile, as well as serum inflammatory markers, in patients with type 2 diabetes (T2DM). This current study consisted of 648 diabetic patients. Dietary intake was calculated by a food frequency questionnaire. Read More

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Effects of blood lipids and lipid-modifying drugs on intracranial aneurysms.

Eur J Neurol 2022 Jun 21. Epub 2022 Jun 21.

Beijing Neurosurgical Institute, Capital Medical University, China.

Objectives: We used 2-sample Mendelian randomization (MR) to examine the effects of blood lipids and lipid-modifying drugs on intracranial aneurysm (IA).

Methods: Genetic variants for the effects of high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (apo-A1), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo-B), and triglycerides and targets for lipid-modifying drugs were selected from the genome-wide discovery analyses of the UK Biobank. Summary-level data on IAs were obtained from the International Stroke Genetics Consortium (ISGC). Read More

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Molecular and cellular biology of PCSK9: impact on glucose homeostasis.

J Drug Target 2022 Jun 29:1-13. Epub 2022 Jun 29.

General, Organic and Biomedical Chemistry Unit, Faculty of Medicine and Pharmacy, Research Institute for Health Sciences and Technology, University of Mons - UMONS, Mons, Belgium.

Proprotein convertase substilisin/kexin 9 (PCSK9) inhibitors (PCSK9i) revolutionised the lipid-lowering therapy. However, a risk of type 2 diabetes mellitus (T2DM) is evoked under PCSK9i therapy. In this review, we summarise the current knowledge on the link of PCSK9 with T2DM. Read More

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[Mechanism and material basis of Sparganii Rhizoma and vinegar-processed Sparganii Rhizoma in treatment of hyperlipidemia based on network pharmacology].

Zhongguo Zhong Yao Za Zhi 2022 May;47(10):2767-2777

School of Pharmacy, Nanjing University of Chinese Medicine Nanjing 210046, China.

The present study explored the effective components, functional targets, and mechanism of Sparganii Rhizoma(vinegar-processed Sparganii Rhizoma) in the treatment of hyperlipidemia based on network pharmacology and experimental verification. In the network pharmacology, the screening of active components, target prediction, and pathway enrichment analysis of Sparganii Rhizoma were carried out, followed by the comparison with targets and pathways related to hyperlipidemia. In the experimental verification, the hyperlipidemia model in rats was induced to detect hemorheological parameters and coagulation function. Read More

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[Mechanism of Astragali Radix-Puerariae Lobatae Radix combination in regulating type 2 diabetes mellitus through AMPK signaling pathway: based on network pharmacology and experimental verification].

Zhongguo Zhong Yao Za Zhi 2022 May;47(10):2738-2749

Jiangxi University of Chinese Medicine Nanchang 330004, China.

This study aims to explore the mechanism of Astragali Radix-Puerariae Lobatae Radix(AP) combination in the treatment of type 2 diabetes mellitus(T2 DM) based on network pharmacology and experiment. The effective components and targets of the pair were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and targets of T2 DM from each disease database. On this basis, the common targets of the medicinals and the disease were screened out. Read More

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Genetic interactions drive heterogeneity in causal variant effect sizes for gene expression and complex traits.

Am J Hum Genet 2022 Jun 15. Epub 2022 Jun 15.

Genetics, Stanford University School of Medicine, Stanford, CA, USA; Biology, Stanford University, Stanford, CA, USA. Electronic address:

Despite the growing number of genome-wide association studies (GWASs), it remains unclear to what extent gene-by-gene and gene-by-environment interactions influence complex traits in humans. The magnitude of genetic interactions in complex traits has been difficult to quantify because GWASs are generally underpowered to detect individual interactions of small effect. Here, we develop a method to test for genetic interactions that aggregates information across all trait-associated loci. Read More

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Protective roles of apremilast via Sirtuin 1 in atherosclerosis.

Authors:
Dongkui Sui Hua Yu

Bioengineered 2022 05;13(5):13872-13881

Department of Cardiovascular Medicine, Affiliated Hospital of Jiujiang University, Jiujiang, Jiangxi, China.

Atherosclerosis is an inflammatory disease with a high level of cholesterol in the blood. Apremilast is a new anti-inflammatory drug that possesses a potential anti-atherosclerosis effect. RT-qPCR and western blot were undertaken to assay the levels of Sirtuin 1 (SIRT1), oxidized low density lipoprotein receptor 1 (LOX-1), and CD36 molecule (CD36). Read More

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Genetic polymorphisms and plasma concentrations of leptin (rs7799039) and adiponectin (rs17300539) are associated with obesity in children and adolescents.

Rev Paul Pediatr 2022 10;40:e2021030. Epub 2022 Jun 10.

Universidade Federal de Mato Grosso, Cuiabá, MT, Brazil.

Objective: The aim of this study was to compare the anthropometric, biochemical, and hormonal characteristics and the presence of genetic polymorphisms of leptin, adiponectin, and tumor necrosis factor alpha (TNF-α) between eutrophic and obese children and adolescents.

Methods: This is a case-control study involving 104 children and adolescents. All subjects were assessed for anthropometric characteristics and clinical, laboratory, and genetic polymorphism parameters. Read More

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Association of Common and Rare Genetic Variation in the 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Gene and Cataract Risk.

J Am Heart Assoc 2022 Jun 15;11(12):e025361. Epub 2022 Jun 15.

Laboratory for Molecular Cardiology Department of Cardiology Copenhagen University Hospital, Rigshospitalet Copenhagen Denmark.

Background Results from animal models and observational studies have raised concerns regarding the potential cataractogenic effects of statin treatment. We investigated whether common and rare genetic variants in are associated with cataract risk, to gauge the likely long-term effects of statin treatment on lenticular opacities. Methods and Results We used genotyping data and exome sequencing data of unrelated European individuals in the UK Biobank to test the association between genetically proxied inhibition of and cataract risk. Read More

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Low-Density Lipoprotein Cholesterol Attributable Cardiovascular Disease Risk Is Sex Specific.

J Am Heart Assoc 2022 Jun 14;11(12):e024248. Epub 2022 Jun 14.

Department of Vascular Medicine Amsterdam University Medical Centerslocation AMCUniversity of Amsterdam Netherlands.

Background Epidemiological studies show that women are generally at lower risk for cardiovascular disease than men. Here, we investigated the sex-specific differential effect of genetically increased low-density lipoprotein cholesterol (LDL-C) on cardiovascular disease (CVD) and other lipid-associated diseases. Methods and Results This is a 2-sample Mendelian randomization study that uses individual participant data from 425 043 participants from the UK Biobank, including 229 279 female participants. Read More

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Considerations for routinely testing for high Lp(a).

Curr Opin Lipidol 2022 06;33(3):213-218

Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, The Netherlands.

Purpose Of Review: Lipoprotein(a) (Lp[a]) is a likely causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve disease, confirmed by Mendelian randomization. With reliable assays, it has been established that Lp(a) is linearly associated with ASCVD. Current low-density lipoprotein cholesterol (LDL-C) lowering therapies do not or minimally lower Lp(a). Read More

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Sphingosine-1-phosphate: metabolism, transport, atheroprotection and effect of statin treatment.

Curr Opin Lipidol 2022 06 9;33(3):199-207. Epub 2022 Mar 9.

Faculty of Medicine, Sorbonne University.

Purpose Of Review: To better define the metabolism of sphingosine-1-phosphate (S1P), its transport in plasma and its interactions with S1P receptors on vascular cells, and to evaluate the effect of statin treatment on the subnormal plasma levels of high-density lipoprotein (HDL)-bound S1P characteristic of the atherogenic dyslipidemia of metabolic syndrome (MetS).

Recent Findings: Neither clinical intervention trials targeted to raising high-density lipoprotein-cholesterol (HDL-C) levels nor human genome-wide association studies (GWAS) studies have provided evidence to support an atheroprotective role of HDL. Recently however a large monogenic univariable Mendelian randomization on the N396S mutation in the gene encoding endothelial lipase revealed a causal protective effect of elevated HDL-C on coronary artery disease conferred by reduced enzyme activity. Read More

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Proprotein convertase subtilisin/kexin type 9 inhibition after acute coronary syndrome or prior myocardial infarction.

Curr Opin Lipidol 2022 06;33(3):147-159

Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Purpose Of Review: Lowering low-density lipoprotein cholesterol (LDL-C) with statins or ezetimibe reduces major adverse cardiovascular events (MACE) in patients with coronary heart disease. Additional treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may lower LDL-C to levels not achievable with conventional lipid-lowering agents. This review summarizes findings from two large, placebo-controlled trials that evaluated the cardiovascular efficacy of monoclonal antibodies directed against PCSK9, added to background statin therapy, in patients with established atherosclerotic cardiovascular disease (ASCVD) or recent acute coronary syndrome (ACS) and persistent elevation of atherogenic lipoproteins despite statin treatment. Read More

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Role of circulating polyunsaturated fatty acids on cardiovascular diseases risk: analysis using Mendelian randomization and fatty acid genetic association data from over 114,000 UK Biobank participants.

BMC Med 2022 06 13;20(1):210. Epub 2022 Jun 13.

MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.

Background: Despite early interest in the health effects of polyunsaturated fatty acids (PUFA), there is still substantial controversy and uncertainty on the evidence linking PUFA to cardiovascular diseases (CVDs). We investigated the effect of plasma concentration of omega-3 PUFA (i.e. Read More

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Association of Serum 25(OH)D with Metabolic Syndrome in Chinese Women of Childbearing Age.

Nutrients 2022 May 30;14(11). Epub 2022 May 30.

Key Laboratory of Trace Element Nutrition of National Health Committee, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.

Objective: To analyze the associations between serum 25(OH)D levels and the risk of metabolic syndrome (MetS) and its components, and the related genetic and non-genetic factors in non-diabetic women of childbearing age in China.

Methods: Subjects were randomly selected from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. The data of sociodemographic characteristics and lifestyle factors were obtained through questionnaire survey. Read More

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Observational and Genetic Associations of Modifiable Risk Factors with Aortic Valve Stenosis: A Prospective Cohort Study of 0.5 Million Participants.

Nutrients 2022 May 28;14(11). Epub 2022 May 28.

Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing 100191, China.

Background: Observational studies have shown that modifiable risk factors are associated with aortic valve stenosis (AVS). However, the causality behind these associations remains largely unknown.

Objectives: To explore the associations of modifiable risk factors, including metabolic factors, biochemical measures, education, and lifestyles with AVS and their potential causal associations. Read More

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Dyslipidemia in Children Treated with a BRAF Inhibitor for Low-Grade Gliomas: A New Side Effect?

Cancers (Basel) 2022 May 29;14(11). Epub 2022 May 29.

Neuroncology Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy.

BRAF inhibitors, in recent years, have played a central role in the disease control of unresectable BRAF-mutated pediatric low-grade gliomas (LGGs). The aim of the study was to investigate the acute and long-term effects of vemurafenib on the lipid metabolism in children treated for an LGG. In our cohort, children treated with vemurafenib ( = 6) exhibited alterations in lipid metabolism a few weeks after starting, as was demonstrated after 1 month ( = 4) by the high plasma levels of the total cholesterol (TC = 221. Read More

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A statistical perspective on baseline adjustment in pharmacogenomic genome-wide association studies of quantitative change.

NPJ Genom Med 2022 Jun 9;7(1):33. Epub 2022 Jun 9.

Biostatistics and Research Decision Sciences, Merck & Co., Inc., Rahway, NJ, 07065, USA.

In pharmacogenetic (PGx) studies, drug response phenotypes are often measured in the form of change in a quantitative trait before and after treatment. There is some debate in recent literature regarding baseline adjustment, or inclusion of pre-treatment or baseline value as a covariate, in PGx genome-wide association studies (GWAS) analysis. Here, we provide a clear statistical perspective on this baseline adjustment issue by running extensive simulations based on nine statistical models to evaluate the influence of baseline adjustment on type I error and power. Read More

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Familial hypercholesterolemia in an Iranian family due to a mutation in the APOE gene (first case report).

J Diabetes Metab Disord 2022 Jun 10;21(1):1201-1205. Epub 2022 Mar 10.

Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.

Familial Hypercholesterolemia is an autosomal, dominant genetic disorder associated with premature cardiovascular disease (CVD). Mutations in the LDLR, APOB, and PCSK9 genes cause the FH phenotype, but in 20% of FH patients, mutations in other genes cause FH. In this regard, we investigated the genetic basis of an Autosomal Dominant Hypercholesterolemia (ADH) phenotype in an Iranian family via next-generation exome sequencing with a panel of hyperlipidemia. Read More

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Attainment of Lipid Targets Following Coronary Artery Bypass Graft Surgery: Can We Do Better?

J Lipid Atheroscler 2022 May 8;11(2):187-196. Epub 2022 Apr 8.

Internal Medicine, Medical School, The University of Western Australia, Perth, WA, Australia.

Objective: Patients undergoing coronary artery bypass graft (CABG) surgery remain at high cardiovascular risk; however, few studies have evaluated lipid management and attainment of lipid targets in these patients. We investigated the proportion of CABG surgery patients who attained low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (HDL-C) targets.

Methods: Data were retrospectively obtained from patients undergoing CABG surgery at an Australian tertiary hospital between February 2015 and August 2020. Read More

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Transferability of genetic risk scores in African populations.

Nat Med 2022 Jun 2;28(6):1163-1166. Epub 2022 Jun 2.

The African Computational Genomics (TACG) Research Group, MRC/UVRI and LSHTM, Entebbe, Uganda.

The poor transferability of genetic risk scores (GRSs) derived from European ancestry data in diverse populations is a cause of concern. We set out to evaluate whether GRSs derived from data of African American individuals and multiancestry data perform better in sub-Saharan Africa (SSA) compared to European ancestry-derived scores. Using summary statistics from the Million Veteran Program (MVP), we showed that GRSs derived from data of African American individuals enhance polygenic prediction of lipid traits in SSA compared to European and multiancestry scores. Read More

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Copy Number Analyses Identified a Novel Gene: Related to Lipid Metabolism in the Pathogenesis of Preeclampsia.

Front Cardiovasc Med 2022 16;9:841249. Epub 2022 May 16.

Department of Biostatistics, Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Preeclampsia is a heterogeneous and complex disease with its pathogenesis mechanism not fully elucidated. A certain subset of patients with preeclampsia exhibit disturbances in lipid metabolism before clinical symptoms. Moreover, there is a tendency for preeclampsia to run in families. Read More

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A method for lipoprotein (a) Isolation from a small volume of plasma with applications for clinical research.

Sci Rep 2022 Jun 1;12(1):9138. Epub 2022 Jun 1.

Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health & Science University, 3161 SW Pavilion Loop, Mail Code UHN62, Portland, OR, 97239, USA.

High levels of circulating Lipoprotein (a) [Lp(a)] are an independent risk factor for CVD. One of the major limitations to investigating Lp(a) biology is the need for large volumes of plasma (4-10 mL) for its isolation. We developed an isolation technique requiring only 0. Read More

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