182 results on '"diagnostic tools"'
Search Results
2. Targeted next-generation sequencing to diagnose disorders of HDL cholesterol
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Singh N. Sadananda, Jia Nee Foo, Meng Tiak Toh, Lubomira Cermakova, Laia Trigueros-Motos, Teddy Chan, Herty Liany, Jennifer A. Collins, Sima Gerami, Roshni R. Singaraja, Michael R. Hayden, Gordon A. Francis, Jiri Frohlich, Chiea Chuen Khor, and Liam R. Brunham
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ATP binding cassette transporter A1 ,diagnostic tools ,genetics ,genomics ,high density lipoprotein ,atherosclerosis ,Biochemistry ,QD415-436 - Abstract
A low level of HDL cholesterol (HDL-C) is a common clinical scenario and an important marker for increased cardiovascular risk. Many patients with very low or very high HDL-C have a rare mutation in one of several genes, but identification of the molecular abnormality in patients with extreme HDL-C is rarely performed in clinical practice. We investigated the accuracy and diagnostic yield of a targeted next-generation sequencing (NGS) assay for extreme levels of HDL-C. We developed a targeted NGS panel to capture the exons, intron/exon boundaries, and untranslated regions of 26 genes with highly penetrant effects on plasma lipid levels. We sequenced 141 patients with extreme HDL-C levels and prioritized variants in accordance with medical genetics guidelines. We identified 35 pathogenic and probably pathogenic variants in HDL genes, including 21 novel variants, and performed functional validation on a subset of these. Overall, a molecular diagnosis was established in 35.9% of patients with low HDL-C and 5.2% with high HDL-C, and all prioritized variants identified by NGS were confirmed by Sanger sequencing. Our results suggest that a molecular diagnosis can be identified in a substantial proportion of patients with low HDL-C using targeted NGS.
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- 2015
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3. Circulating Exosomes of Neuronal Origin as Potential Early Biomarkers for Development of Stroke
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Ghada Yousif, Aijaz Parray, Yousef Haik, Ashfaq Shuaib, Shahnaz Qadri, and Mahmoud Y Haik
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0301 basic medicine ,Pharmacology ,business.industry ,General Medicine ,Disease ,medicine.disease ,Diagnostic tools ,Bioinformatics ,Human genetics ,Microvesicles ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Neuroimaging ,030220 oncology & carcinogenesis ,Potential biomarkers ,Genetics ,medicine ,Molecular Medicine ,Biomarker (medicine) ,business ,Stroke - Abstract
Stroke is one of the major causes of morbidity and mortality globally, with devastating effects. It is diagnosed mainly by clinical assessment and brain imaging; however, it is challenging to discriminate stroke from similar conditions with parallel presentations. While brain imaging provides detection of stroke infarcts, it does not provide useful information on the biology and prognosis of the underlying disease process. The complex pathophysiology of stroke infarcts is a barrier in developing sensitive diagnostic tools, which consequently has a detrimental effect on development of treatment regimens. Early diagnosis of stroke is vital for better management, but currently there is no diagnostic blood-based biomarker. The cargo of exosomes can give an insight into the physiological or pathophysiological status of the cell. Exosomes have gained great interest as a means of intercellular communication and recently have been explored as a potential biomarker tool. Circulating exosomes in the blood result from of a contribution from all tissues. The sub-population of exosomes released from brain cells circulating in body fluids are known as neuronal exosomes. This overview presents the vital diagnostic function that could be performed by circulating exosomes of neuronal origin in identifying the subtype of stroke, its severity, and the recovery stages. A number of potential biomarkers that are obtained from circulating exosomes have showed promising potential to function as stroke biomarkers; however, further work is needed to characterize the neuronal exosomes and its payload and to determine the pathways it uses in the complex pathophysiology of stroke. The identification is a subset of exosomal biomarkers that are specific to stroke will enhance the early detection and prognosis of the disease.
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- 2021
4. Estimation of skin impedance models with experimental data and a proposed model for human skin impedance
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Dhruba Jyoti Bora and Rajdeep Dasgupta
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Skin impedance ,integumentary system ,Computer science ,Experimental data ,Human skin ,Cell Biology ,Biological tissue ,Diagnostic tools ,Models, Biological ,Modeling and Simulation ,Biological property ,Genetic algorithm ,Electric Impedance ,Genetics ,Humans ,Biological system ,Molecular Biology ,Electrical impedance ,Algorithms ,Skin ,Research Article ,Biotechnology - Abstract
The skin is a complex biological tissue whose impedance varies with frequency. The properties and structure of skin changes with the location on the body, age, geographical location and other factors. Considering these factors, skin impedance analysis is a sophisticated data analysis. However, despite all these variations, various researchers have always worked to develop an equivalent electrical model of the skin. The two most important categories of electrical models are RC‐based model and CPE‐based model which focus on the physiological stratification and biological properties of skin, respectively. In this work, experimental skin impedance data is acquired from ten sites on the body to find the fitting model. It is observed that a hybrid of fractional‐order CPE‐based model and higher‐order RC layered‐based model can provide the best fitting electrical model of skin. A new model is developed with this hybrid orders. Genetic algorithm is used for the extraction of parameter components. Least error of fitting has been observed for the proposed model as compared with the other models. This model can be used in correlating many skin problems and in the development of diagnostic tools. It will offer an additional supportive tool in‐vitro to the medical specialist.
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- 2020
5. Latest Developments in Polypoidal Choroidal Vasculopathy: Epidemiology, Etiology, Diagnosis, and Treatment
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Chui Ming Gemmy Cheung, Jay Chhablani, Vishal Govindahar, Timothy Y Y Lai, Voraporn Chaikitmongkol, and Hideki Koizumi
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medicine.medical_specialty ,Treatment response ,genetic structures ,Fundus Oculi ,diagnosis ,Review Article ,Global Health ,Diagnostic tools ,polypoidal choroidal vasculopathy ,complex mixtures ,Pathogenesis ,03 medical and health sciences ,Polyps ,0302 clinical medicine ,Epidemiology ,medicine ,Humans ,genetics ,Disease process ,Fluorescein Angiography ,age-related macular degeneration ,treatment ,Choroid ,business.industry ,Disease Management ,Choroid Diseases ,General Medicine ,Macular degeneration ,Prognosis ,medicine.disease ,Dermatology ,eye diseases ,Natural history ,Ophthalmology ,030221 ophthalmology & optometry ,Etiology ,sense organs ,Morbidity ,business ,Tomography, Optical Coherence ,030217 neurology & neurosurgery - Abstract
Polypoidal choroidal vasculopathy (PCV) is a condition characterized by multiple, recurrent, serosanguineous pigment epithelial detachments, and neurosensory retinal detachments due to abnormal aneurysmal neovascular lesions. It is generally considered as a variant of neovascular age-related macular degeneration, but there are some differences between the clinical presentation, natural history, and treatment response between patients with PCV and typical neovascular age-related macular degeneration patients. Over the past decade, new research and technological advancements have greatly improved our understanding of the PCV disease process and the management of PCV. This review aims to summarize the recent research findings to highlight the epidemiology, pathogenesis, genetics, the application of various diagnostic tools for PCV, and the available treatment options for PCV.
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- 2020
6. An evaluation of liposome-based diagnostics of pulmonary and extrapulmonary tuberculosis
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Prakash S. Bisen, Priya Shrama, Aishwarya Joshi, Ravi Pn Mishra, Rajeev K. Tyagi, Nikunj Tandel, and Anish Z Joseph
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0301 basic medicine ,medicine.medical_specialty ,Tuberculosis ,Disease ,Diagnostic tools ,Sensitivity and Specificity ,Theranostic Nanomedicine ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,Global health ,Humans ,Intensive care medicine ,Tuberculosis, Pulmonary ,Molecular Biology ,Liposome ,business.industry ,Extrapulmonary tuberculosis ,Mycobacterium tuberculosis ,medicine.disease ,Molecular diagnostics ,Active tuberculosis ,030104 developmental biology ,Molecular Diagnostic Techniques ,030220 oncology & carcinogenesis ,Liposomes ,Nanoparticles ,Molecular Medicine ,business - Abstract
Introduction: Tuberculosis (TB) is still one of the major global health threats and delayed diagnosis or misdiagnosis continues to fuel the global epidemic. The conventional diagnostic approaches have shortcomings that might hinder the process of diagnosis of the disease and ultimately affect the prognosis.Area covered: We emphasize on the process of the synthesis of liposomes, its physicochemical properties affecting the formulation and their utilization in the field of molecular diagnostics for TB. The review also sheds a light on other nanoparticle-based molecular diagnostic approaches for TB. Despite the advent of science, we are yet to have a diagnostic tool that is simple, rapid, sensitive, and specific, and most importantly, one that enables us to demarcate patients with active tuberculosis from those with quiescent lesions, prior vaccination, or other diseases.Expert opinion: The utility of liposomes for diagnostic purposes has been attempted so as to overcome the challenges posed by conventional diagnostic tools for TB. Through this review, we present insights into liposome formulation and selection processes, various studies that report the use of liposome-based diagnostic tools for TB, as well as the limitations associated with the same that can be improvised to make the technology more efficient.
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- 2020
7. PGT‐A preimplantation genetic testing for aneuploidies and embryo selection in routine ART cycles: Time to step back?
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Romualdo Sciorio and Maurizio Dattilo
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0301 basic medicine ,animal structures ,Chromosome number ,Pregnancy Rate ,Reproductive Techniques, Assisted ,Embryonic Development ,Fertilization in Vitro ,030105 genetics & heredity ,Bioinformatics ,Diagnostic tools ,03 medical and health sciences ,Pregnancy ,Genetics ,medicine ,Humans ,Genetic Testing ,Preimplantation Diagnosis ,Genetics (clinical) ,Selection (genetic algorithm) ,Genetic testing ,medicine.diagnostic_test ,Mosaicism ,business.industry ,Embryo ,medicine.disease ,Clinical Practice ,Blastocyst ,030104 developmental biology ,embryonic structures ,Chromosome abnormality ,Female ,business ,Trophectoderm biopsy - Abstract
Embryo aneuploidies may be responsible for implantation failures, miscarriages and affects IVF outcomes. A variety of technologies have been implemented to individuate euploid embryos in IVF treatments, which is named preimplantation genetic testing for aneuploidies (PGT-A). According to this strategy, a better embryo selection should increase IVF results. In reality, several issues remain unaddressed including the sampling strategy, involving the test outcomes, and the frequent occurrence of embryo mosaicism, affecting the criteria for selection of supposed viable embryos and possibly posing an ethical dilemma. Safety issues are in place, including perinatal and postnatal consequences of embryo sampling and the epigenetic weaknesses from a prolonged in vitro culture, necessary for trophectoderm biopsy. On the other side, chromosome number mistakes are progressively recognized as physiologic events in the early pre-implantation embryo with many corrective mechanisms in place and their destiny in the post-implantation development is unclear. Accordingly, the increasing precision of the diagnostic tools should be used to investigate the effect of such interventions within rigorous research programs in the sake of improved clinical outcomes. Meantime the diagnosis of embryo aneuploidies in IVF cycles should be considered as a research tool and systematic implementation in clinical practice may appear unjustified.
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- 2020
8. Pyrazinamide resistance of novel mutations inpncAand their dynamic behavior
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Dong-Qing Wei, Muhammad Tahir Khan, Arif Ali, Sathishkumar Chinnasamy, Khalid Akhtar, Athar Shafiq, Abbas Khan, and Sajid Ali
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Genetics ,0303 health sciences ,010304 chemical physics ,General Chemical Engineering ,Mutant ,General Chemistry ,Pyrazinamide ,Biology ,Diagnostic tools ,biology.organism_classification ,01 natural sciences ,Mycobacterium tuberculosis ,03 medical and health sciences ,chemistry.chemical_compound ,Pyrazinoic acid ,chemistry ,0103 physical sciences ,PncA ,medicine ,biology.protein ,Coding region ,Polymerase ,030304 developmental biology ,medicine.drug - Abstract
Pyrazinamide (PZA) is one of the essential anti-mycobacterium drugs, active against non-replicating Mycobacterium tuberculosis (MTB) isolates. PZA is converted into its active state, called pyrazinoic acid (POA), by action of pncA encoding pyrazinamidase (PZase). In the majority of PZA-resistance isolates, pncA harbored mutations in the coding region. In our recent report, we detected a number of novel variants in PZA-resistance (PZAR) MTB isolates, whose resistance mechanisms were yet to be determined. Here we performed several analyses to unveil the PZAR mechanism of R123P, T76P, G150A, and H71R mutants (MTs) through molecular dynamics (MD) simulations. In brief, culture positive MTB isolates were subjected to PZA susceptibility tests using the WHO recommended concentration of PZA (100 μg ml−1). The PZAR samples were screened for mutations in pncA along sensitive isolates through polymerase chain reactions and sequencing. A large number of variants (GeneBank accession no. MH461111), including R123P, T76P, G150A, and H71R, have been spotted in more than 70% of isolates. However, the mechanism of PZAR for mutants (MTs) R123P, T76P, G150A, and H71R was unknown. For the MTs and native PZase structures (WT), thermodynamic properties were compared using molecular dynamics simulations for 100 ns. The MTs structural activity was compared to the WT. Folding effect and pocket volume variations have been detected when comparing between WT and MTs. Geometric matching further confirmed the effect of R123P, T76P, G150A, and H71R mutations on PZase dynamics, making them vulnerable for activating the pro-drug into POA. This study offers a better understanding for management of PZAR TB. The results may be used as alternative diagnostic tools to infer PZA resistance at a structural dynamics level.
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- 2020
9. Reliable cell and tissue morphology-based diagnosis of endemic Burkitt lymphoma in resource-constrained settings in Ghana
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Lorna Renner, Lars Hviid, R. K. Gyasi, Mette Ølgod Pedersen, Peter Nørgaard, Michael F. Ofori, Vivian Paintsil, Babatunde Duduyemi, Cecilia Smith-Togobo, and Steffen Grann Jensen
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0301 basic medicine ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Endemic Diseases ,Resource constrained ,Plasmodium falciparum ,Genes, myc ,Diagnostic tools ,Ghana ,Diagnostic accuracy ,lcsh:RC254-282 ,Giemsa stain ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Biopsy ,Genetics ,medicine ,Humans ,Malaria, Falciparum ,Child ,Retrospective Studies ,Gene Rearrangement ,medicine.diagnostic_test ,business.industry ,Infant ,Reproducibility of Results ,Tissue morphology ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Burkitt Lymphoma ,Lymphoma ,Sample quality ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,In situ hybridisation ,Child, Preschool ,Endemic Burkitt lymphoma ,Female ,Radiology ,business ,Research Article ,Morphology, C-MYC immunohistochemistry, c-myc FISH - Abstract
Background Endemic Burkitt lymphoma (eBL) is an aggressive B-cell lymphoma, which is a common childhood cancer in areas with intense transmission of Plasmodium falciparum parasites. Early and accurate diagnosis is a prerequisite for successful therapy, but it optimally involves advanced laboratory investigations. These are technologically demanding, expensive, and often difficult to implement in settings where eBL is prevalent. Diagnosis is thus generally based on clinical assessment and morphological examination of tumour biopsies or fine-needle aspirates (FNAs). Methods The purpose of the present study was to assess the accuracy of eBL diagnosis at two tertiary hospitals in Ghana. To that end, we studied FNAs from 29 eBL patients and 21 non-eBL lymphoma patients originally diagnosed in 2018. In addition, we examined 111 archival formalin-fixed and paraffin-embedded (FFPE) biopsies from Ghanaian patients originally diagnosed as eBL (N = 55) or non-eBL (N = 56) between 2010 and 2017. Availability-based subsets of samples were subjected to haematoxylin-eosin or Giemsa staining, C-MYC immunohistochemistry, and fluorescence in situ hybridisation (FISH) analysis of c-myc rearrangements. Results We found a good correlation between original diagnosis and subsequent retrospective assessment, particularly for FNA samples. However, evidence of intact c-myc genes and normal C-MYC expression in samples from some patients originally diagnosed as eBL indicates that morphological assessment alone can lead to eBL over-diagnosis in our study area. In addition, several FFPE samples could not be assessed retrospectively, due to poor sample quality. Therefore, the simpler FNA method of obtaining tumour material is preferable, particularly when careful processing of biopsy specimens cannot be guaranteed. Conclusion We conclude that the accuracy of eBL diagnostic tools available in Ghana is generally adequate, but could be improved by implementation of additional pathology laboratory investigations. Improved attention to adequate preservation of archival samples is recommended.
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- 2019
10. Partial LPL deletions: rare copy-number variants contributing towards severe hypertriglyceridemia
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P. Barton Duell, Clive R. Pullinger, Robert A. Hegele, Irina Movsesyan, Jian Wang, Mary J. Malloy, John F. Robinson, Jacqueline S. Dron, James Feng, John P. Kane, Adam D. McIntyre, Priya Manjoo, and Henian Cao
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0301 basic medicine ,human genetics ,QD415-436 ,030204 cardiovascular system & hematology ,Biology ,Biochemistry ,DNA sequencing ,diagnostic tools ,genetic testing ,03 medical and health sciences ,symbols.namesake ,Exon ,0302 clinical medicine ,Endocrinology ,Genetic variation ,medicine ,Copy-number variation ,dyslipidemias ,Gene ,Genetic testing ,Genetics ,Sanger sequencing ,medicine.diagnostic_test ,Cell Biology ,Human genetics ,bioinformatic analysis ,3. Good health ,030104 developmental biology ,symbols ,next-generation sequencing - Abstract
Severe hypertriglyceridemia (HTG) is a relatively common form of dyslipidemia with a complex pathophysiology and serious health complications. HTG can develop in the presence of rare genetic factors disrupting genes involved in the triglyceride (TG) metabolic pathway, including large-scale copy-number variants (CNVs). Improvements in next-generation sequencing technologies and bioinformatic analyses have better allowed assessment of CNVs as possible causes of or contributors to severe HTG. We screened targeted sequencing data of 632 patients with severe HTG and identified partial deletions of the LPL gene, encoding the central enzyme involved in the metabolism of TG-rich lipoproteins, in four individuals (0.63%). We confirmed the genomic breakpoints in each patient with Sanger sequencing. Three patients carried an identical heterozygous deletion spanning the 5′ untranslated region (UTR) to LPL exon 2, and one patient carried a heterozygous deletion spanning the 5′UTR to LPL exon 1. All four heterozygous CNV carriers were determined to have multifactorial severe HTG. The predicted null nature of our identified LPL deletions may contribute to relatively higher TG levels and a more severe clinical phenotype than other forms of genetic variation associated with the disease, particularly in the polygenic state. The identification of novel CNVs in patients with severe HTG suggests that methods for CNV detection should be included in the diagnostic workup and molecular genetic evaluation of patients with high TG levels.
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- 2019
11. Liquid biopsy tracking of lung tumor evolutions over time
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Katherine A. Scilla, Diego de Miguel Perez, Vincenzo Adamo, Umberto Malapelle, Alessandro Russo, Christian Rolfo, Ranee Mehra, Muthukumar Gunasekaran, Brandon Cooper, Rena G. Lapidus, Russo, A., De Miguel Perez, D., Gunasekaran, M., Scilla, K., Lapidus, R., Cooper, B., Mehra, R., Adamo, V., Malapelle, U., and Rolfo, C.
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Genotyping Techniques ,EGFR ,NSCLC ,Diagnostic tools ,circulating tumor cell ,Circulating Tumor DNA ,Pathology and Forensic Medicine ,03 medical and health sciences ,ALK, bTMB, cfDNA, circulating tumor cells, EGFR, liquid biopsy, NGS, NSCLC, real-time PCR ,SCLC, Biomarkers, Tumor, Circulating Tumor DNA, Genetic Testing, Genotyping Techniques, Humans, Liquid Biopsy, Lung Neoplasms, Neoplastic Cells, Circulating ,0302 clinical medicine ,Circulating tumor cell ,Biomarkers, Tumor ,Genetics ,medicine ,Humans ,Genetic Testing ,cfDNA ,Liquid biopsy ,Lung cancer ,Molecular Biology ,Genotyping ,liquid biopsy ,business.industry ,SCLC ,Neoplastic Cells, Circulating ,medicine.disease ,bTMB ,030104 developmental biology ,Real-time polymerase chain reaction ,ALK ,NGS ,030220 oncology & carcinogenesis ,Molecular Medicine ,Lung tumor ,real-time PCR ,business - Abstract
Introduction: The rise of the personalized era in lung cancer prompted the evaluation of novel diagnostic tools to overcome some of the limits of traditional tumor genotyping. Liquid biopsy refers to a multitude of minimally invasive techniques that can allow a real-time biomolecular characterization of the tumor through the analysis of human body fluids. Areas covered: Herein we provide a comprehensive overview of the role of liquid biopsy in lung cancer, mainly focusing on the most studied members of the liquid biopsy family, cell-free DNA (cfDNA) and circulating tumor cells (CTCs). Expert opinion: Among the different components of the large liquid biopsy family, cfDNA is the most studied and widely adopted source for tumor genotyping in lung cancer, already entered clinical practice for detection of both sensitizing and resistance EGFR mutations. However, the impressive technological advances made in the last few years are expanding its potential applications, allowing a more comprehensive plasma genotyping through next-generation sequencing and moving from advanced/metastatic disease to novel frontiers, such as early detection and minimal residual disease evaluation.
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- 2019
12. Coronavirus Disease 2019 Diagnostics: Key to Africa's Recovery
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Sara Baptista, Emmanuel Nepolo, Sanushka Naidoo, Blessing Mbabie Oyedemi, Sara Suliman, Jesse Gitaka, Shymaa Enany, and Repositório da Universidade de Lisboa
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Biochemistry & Molecular Biology ,Coronavirus disease 2019 (COVID-19) ,diagnosis ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,RT-PCR ,Disease ,Biology ,medicine.disease_cause ,Diagnostic tools ,Vaccine Related ,Rare Diseases ,COVID-19 Testing ,Biodefense ,Development economics ,Pandemic ,Genetics ,medicine ,Humans ,Molecular Biology ,Lung ,Coronavirus ,screening and diagnosis ,SARS-CoV-2 ,Prevention ,Outbreak ,COVID-19 ,Cell Biology ,General Medicine ,4.1 Discovery and preclinical testing of markers and technologies ,Vaccination ,Detection ,Infectious Diseases ,Emerging Infectious Diseases ,Good Health and Well Being ,Section B: Infectious Diseases: Pathogenesis, Immune Responses, Vaccines, Diagnostics, and the Broad Impact of Them on Society ,Pneumonia & Influenza ,Immunization ,Biochemistry and Cell Biology ,Infection - Abstract
© Copyright 2021, Mary Ann Liebert, Inc., publishers, With the coronavirus disease of 2019 (COVID-19) becoming a full-blown outbreak in Africa, coupled with many other challenges faced on the African continent, it is apparent that Africa continues to need diagnostics to enable case identification and recovery to this and future challenges. With the slow vaccination rates across the continent, reliable diagnostic tests will be in demand, likely for years to come. Thus, access to reliable diagnostic tools to detect the severe acute respiratory syndrome of the coronavirus-2 (SARS-CoV-2), the virus responsible for COVID-19, remain a critical pillar to monitor and contain new waves of COVID-19. Increasing the local capacity to manufacture and roll-out vaccines and decentralized COVID-19 testing are paramount for fighting the pandemic in Africa., SS is supported by an award from the Massachusetts Life Sciences Center Accelerating Coronavirus Testing Solutions (A.C.T.S). JG is funded by the African Academy of Sciences (Grants numbers GCA/MNCH/Round8/207/008 and SARSCov2-4-20-010) and the Royal Society, UK, Grant number FLR\R1\201314.
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- 2021
13. Successful genetic screening and creating awareness of familial hypercholesterolemia and other heritable Dyslipidemias in the Netherlands
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Albert Wiegman, Linda Zuurbier, Joep C. Defesche, Human Genetics, ACS - Atherosclerosis & ischemic syndromes, Paediatric Metabolic Diseases, ACS - Diabetes & metabolism, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and ACS - Heart failure & arrhythmias
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0301 basic medicine ,medicine.medical_specialty ,Personalized treatment ,Familial hypercholesterolemia ,Review ,Disease ,030204 cardiovascular system & hematology ,QH426-470 ,Diagnostic tools ,Hyperlipoproteinemia Type II ,03 medical and health sciences ,0302 clinical medicine ,Genetic screening ,medicine ,Genetics ,Humans ,Genetic Testing ,Genetics (clinical) ,Dyslipidemias ,Netherlands ,business.industry ,PCSK9 ,High-Throughput Nucleotide Sequencing ,Awareness ,medicine.disease ,Lipids ,030104 developmental biology ,Cholesterol ,Dyslipidemia ,Family medicine ,Pharmacogenomics ,Christian ministry ,business - Abstract
The genetic screening program for familial hypercholesterolemia (FH) in the Netherlands, which was embraced by the Dutch Ministry of Health from 1994 to 2014, has led to twenty years of identification of at least 1500 FH cases per year. Although funding by the government was terminated in 2014, the approach had proven its effectiveness and had built the foundation for the development of more sophisticated diagnostic tools, clinical collaborations, and new molecular-based treatments for FH patients. As such, the community was driven to continue the program, insurance companies were convinced to collaborate, and multiple approaches were launched to find new index cases with FH. Additionally, the screening was extended, now also including other heritable dyslipidemias. For this purpose, a diagnostic next-generation sequencing (NGS) panel was developed, which not only comprised the culprit LDLR, APOB, and PCSK9 genes, but also 24 other genes that are causally associated with genetic dyslipidemias. Moreover, the NGS technique enabled further optimization by including pharmacogenomic genes in the panel. Using such a panel, more patients that are prone to cardiovascular diseases are being identified nowadays and receive more personalized treatment. Moreover, the NGS output teaches us more and more about the dyslipidemic landscape that is less straightforward than we originally thought. Still, continuous progress is being made that underlines the strength of genetics in dyslipidemia, such as discovery of alternative genomic pathogenic mechanisms of disease development and polygenic contribution.
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- 2021
14. Lipidomic risk score independently and cost-effectively predicts risk of future type 2 diabetes: results from diverse cohorts.
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Mamtani, Manju, Kulkarni, Hemant, Wong, Gerard, Weir, Jacquelyn M., Barlow, Christopher K., Dyer, Thomas D., Almasy, Laura, Mahaney, Michael C., Comuzzie, Anthony G., Glahn, David C., Magliano, Dianna J., Zimmet, Paul, Shaw, Jonathan, Williams-Blangero, Sarah, Duggirala, Ravindranath, Blangero, John, Meikle, Peter J., and Curran, Joanne E.
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BLOOD lipids , *BIOMARKERS , *TYPE 2 diabetes risk factors , *TYPE 2 diabetes diagnosis , *LIQUID chromatography , *ELECTROSPRAY ionization mass spectrometry - Abstract
Background: Detection of type 2 diabetes (T2D) is routinely based on the presence of dysglycemia. Although disturbed lipid metabolism is a hallmark of T2D, the potential of plasma lipidomics as a biomarker of future T2D is unknown. Our objective was to develop and validate a plasma lipidomic risk score (LRS) as a biomarker of future type 2 diabetes and to evaluate its cost-effectiveness for T2D screening. Methods: Plasma LRS, based on significantly associated lipid species from an array of 319 lipid species, was developed in a cohort of initially T2D-free individuals from the San Antonio Family Heart Study (SAFHS). The LRS derived from SAFHS as well as its recalibrated version were validated in an independent cohort from Australia - the AusDiab cohort. The participants were T2D-free at baseline and followed for 9197 person-years in the SAFHS cohort (n = 771) and 5930 person-years in the AusDiab cohort (n = 644). Statistically and clinically improved T2D prediction was evaluated with established statistical parameters in both cohorts. Modeling studies were conducted to determine whether the use of LRS would be cost-effective for T2D screening. The main outcome measures included accuracy and incremental value of the LRS over routinely used clinical predictors of T2D risk; validation of these results in an independent cohort and cost-effectiveness of including LRS in screening/intervention programs for T2D. Results: The LRS was based on plasma concentration of dihydroceramide 18:0, lysoalkylphosphatidylcholine 22:1 and triacyglycerol 16:0/18:0/18:1. The score predicted future T2D independently of prediabetes with an accuracy of 76 %. Even in the subset of initially euglycemic individuals, the LRS improved T2D prediction. In the AusDiab cohort, the LRS continued to predict T2D significantly and independently. When combined with risk-stratification methods currently used in clinical practice, the LRS significantly improved the model fit (p < 0.001), information content (p < 0.001), discrimination (p < 0.001) and reclassification (p < 0.001) in both cohorts. Modeling studies demonstrated that LRS-based risk-stratification combined with metformin supplementation for high-risk individuals was the most cost-effective strategy for T2D prevention. Conclusions: Considering the novelty, incremental value and cost-effectiveness of LRS it should be used for risk-stratification of future T2D. [ABSTRACT FROM AUTHOR]
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- 2016
- Full Text
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15. Identifying ceRNA Networks Associated With the Susceptibility and Persistence of Atrial Fibrillation Through Weighted Gene Co-Expression Network Analysis
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Qiming Liu, Na Liu, Fan Bai, and Yaozhong Liu
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0301 basic medicine ,Computational biology ,QH426-470 ,030204 cardiovascular system & hematology ,Biology ,Diagnostic tools ,susceptibility ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Genetics ,atrial fibrillation ,Epigenetics ,Gene ,Genetics (clinical) ,RWR-M ,Original Research ,Competing endogenous RNA ,WGCNA ,Atrial fibrillation ,persistence ,ceRNA ,medicine.disease ,Phenotype ,Random forest ,030104 developmental biology ,Molecular Medicine ,Gene co-expression network - Abstract
Background: Atrial fibrillation (AF) is the most common arrhythmia. We aimed to construct competing endogenous RNA (ceRNA) networks associated with the susceptibility and persistence of AF by applying the weighted gene co-expression network analysis (WGCNA) and prioritize key genes using the random walk with restart on multiplex networks (RWR-M) algorithm.Methods: RNA sequencing results from 235 left atrial appendage samples were downloaded from the GEO database. The top 5,000 lncRNAs/mRNAs with the highest variance were used to construct a gene co-expression network using the WGCNA method. AF susceptibility- or persistence-associated modules were identified by correlating the module eigengene with the atrial rhythm phenotype. Using a module-specific manner, ceRNA pairs of lncRNA–mRNA were predicted. The RWR-M algorithm was applied to calculate the proximity between lncRNAs and known AF protein-coding genes. Random forest classifiers, based on the expression value of key lncRNA-associated ceRNA pairs, were constructed and validated against an independent data set.Results: From the 21 identified modules, magenta and tan modules were associated with AF susceptibility, whereas turquoise and yellow modules were associated with AF persistence. ceRNA networks in magenta and tan modules were primarily involved in the inflammatory process, whereas ceRNA networks in turquoise and yellow modules were primarily associated with electrical remodeling. A total of 106 previously identified AF-associated protein-coding genes were found in the ceRNA networks, including 16 that were previously implicated in the genome-wide association study. Myocardial infarction–associated transcript (MIAT) and LINC00964 were prioritized as key lncRNAs through RWR-M. The classifiers based on their associated ceRNA pairs were able to distinguish AF from sinus rhythm with respective AUC values of 0.810 and 0.940 in the training set and 0.870 and 0.922 in the independent test set. The AF-related single-nucleotide polymorphism rs35006907 was found in the intronic region of LINC00964 and negatively regulated the LINC00964 expression.Conclusion: Our study constructed AF susceptibility- and persistence-associated ceRNA networks, linked genetics with epigenetics, identified MIAT and LINC00964 as key lncRNAs, and constructed random forest classifiers based on their associated ceRNA pairs. These results will help us to better understand the mechanisms underlying AF from the ceRNA perspective and provide candidate therapeutic and diagnostic tools.
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- 2021
16. Advances in the diagnosis of autoimmune diseases based on citrullinated peptides/proteins
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Elrashdy M. Redwan and Mohammed F. Alghamdi
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0301 basic medicine ,Autoimmunity ,Computational biology ,Autoimmune responses ,Diagnostic tools ,Protein citrullination ,Autoantigens ,Biological fluid ,Pathology and Forensic Medicine ,Autoimmune Diseases ,Sugar test ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,Medicine ,Humans ,Molecular Biology ,Autoimmune disease ,business.industry ,Citrullination ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Molecular Medicine ,business ,Peptides - Abstract
Introduction: Autoimmune diseases are still one of the hard obstacles associated with humanity. There are many exogenous and endogenous etiological factors behind autoimmune diseases, which may be combined or dispersed to stimulate the autoimmune responses. Protein citrullination represents one of these factors. Harnessing specific citrullinated proteins/peptides could early predict and/or diagnose some of the autoimmune diseases. Many generations of diagnostic tools based on citrullinated peptides with comparable specificity/sensitivity are available worldwide.Areas covered: In this review, we discuss the deimination reaction behind the citrullination of most known autoantigens targeted, different generations of diagnostic tools based on citrullinated probes with specificity/sensitivity of each as well as newly developed assays. Furthermore, the most advanced molecular analytical tools to detect the citrullinated residues in the biological fluid and their performance are also evaluated, providing new avenues to early detect autoimmune diseases with high accuracy.Expert opinion: With the current specificity/sensitivity tools available for autoimmune disease detection, emphasis must be placed on developing more advance and effective, early, rapid, and simple diagnostic devices for autoimmune disease monitoring (similar to a portable device for sugar test at home). The molecular analytical devices with dual and/or multiplexe functions should be more simplified and invested in clinical laboratories.
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- 2021
17. The treatment of multiple myeloma in an era of precision medicine
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Nicolas Kint, Michel Delforge, and Sophie Vlayen
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Pharmacology ,medicine.medical_specialty ,Hematology ,business.industry ,Precision medicine ,Diagnostic tools ,medicine.disease ,Characterization methods ,Internal medicine ,Drug Discovery ,Risk stratification ,Genetics ,medicine ,Molecular Medicine ,Medical physics ,business ,Multiple myeloma - Abstract
Introduction: Progress in molecular characterization methods has led to major advances in the field of hematology and oncology, bringing forth new diagnostic tools and therapeutic options. Increase...
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- 2019
18. A new molecular screening tool for the detection of chromosomal abnormalities in donkeys
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Sebastián Demyda-Peyrás, Antonio Molina, Mercedes Valera, Gabriel Anaya‐Calvo, Jesús Dorado, Julia Poyato-Bonilla, and M. Moreno-Millán
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Male ,Infertility ,Biotecnología Agropecuaria ,MICROSATELLITES ,Tecnología GM, clonación de ganado, selección asistida, diagnósticos, tecnología de producción de biomasa, etc ,Breeding ,Biology ,Diagnostic tools ,03 medical and health sciences ,Genes, Y-Linked ,0302 clinical medicine ,Endocrinology ,Genes, X-Linked ,medicine ,Animals ,DIAGNOSTIC TOOL ,MOLECULAR CHARACTERIZATION ,Genetic Testing ,CHROMOSOMAL ABERRATIONS ,Sex Chromosome Aberrations ,Genetics ,030219 obstetrics & reproductive medicine ,EQUUS ASINUS ,Molecular screening ,CHROMOSOMOPATHIES ,0402 animal and dairy science ,Karyotype ,Equidae ,04 agricultural and veterinary sciences ,Gene deletion ,medicine.disease ,040201 dairy & animal science ,Morocco ,Testis determining factor ,CIENCIAS AGRÍCOLAS ,Spain ,Karyotyping ,Microsatellite ,Female ,Animal Science and Zoology ,Microsatellite Repeats ,Biotechnology - Abstract
Chromosomal abnormalities are a major cause of infertility and reproductive problems in equids. Nowadays, their detection is rising due to the use of new diagnostic tools based on molecular markers instead of karyotyping. Reports of this kind of genetic aberrations in domestic donkeys (Equus asinus) are extremely scarce, despite their importance in human activities. In the present study, we analysed the implementation of a short-tandem-repeat (STR)-based molecular method initially developed for horses, as a diagnostic tool to detect chromosomal abnormalities in donkeys. The frequency of five X-linked (LEX003, LEX026, TKY38, TKY270 and UCEDQ502) and one Y-linked (ECAYM2) molecular markers and one Y-linked gene (sex-determining region Y, SRY) was characterized in 121 donkeys from two diverse breeds, the Spanish Andalusian and the African Moroccan breeds. The molecular panel showed 100% sensitivity and 99.67% specificity in detecting 10 different chromosomal abnormalities in the species. In conclusion, this methodology is a valid, rapid and low-cost tool for the detection and characterization of chromosomal abnormalities in domestic donkeys. Fil: Poyato Bonilla, Julia. Universidad de Sevilla; España Fil: Anaya Calvo, Gabriel. Universidad de Córdoba; España Fil: Molina, Antonio. Universidad de Córdoba; España Fil: Valera, Mercedes. Universidad de Sevilla; España Fil: Moreno Millán, Miguel. Universidad de Córdoba; España Fil: Dorado, Jesús. Universidad de Córdoba; España Fil: Demyda Peyrás, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina
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- 2019
19. The accuracy of computer-based diagnostic tools for the identification of concurrent genetic disorders
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Raoul R. Wadhwa, Marvin R. Natowicz, and Deborah Y. Park
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Male ,0301 basic medicine ,Computer science ,Computational biology ,Web Browser ,Diagnostic tools ,Sensitivity and Specificity ,Diagnosis, Differential ,03 medical and health sciences ,Genetics ,Humans ,Diagnosis, Computer-Assisted ,Genetic Testing ,Medical diagnosis ,Genetics (clinical) ,Exome sequencing ,High prevalence ,Genetic Diseases, Inborn ,Computer based ,Computational Biology ,Reproducibility of Results ,Identification (information) ,030104 developmental biology ,Test case ,Child, Preschool ,Differential diagnosis ,Software - Abstract
The increasing use of next-generation sequencing, especially clinical exome sequencing, has revealed that individuals having two coexisting genetic conditions are not uncommon occurrences. This pilot study evaluates the efficacy of two methodologically distinct computational differential diagnosis generating tools-FindZebra and SimulConsult-in identifying multiple genetic conditions in a single patient. Clinical query terms were generated for each of 15 monogenic disorders that were effective in resulting in the top 10 list of differential diagnoses for each of the 15 monogenic conditions when entered into these bioinformatics tools. Then, the terms of over 125 pairings of these conditions were entered using each tool and the resulting list of diagnoses evaluated to determine how often both diagnoses of a pair were represented in that list. Neither tool was successful in identifying both members of a pair of conditions in greater than 40% of test cases. Disorder detection sensitivity was not homogeneous within a tool, with each tool favoring the identification of a subset of genetic conditions. In view of recent exome sequencing data showing an unexpectedly high prevalence of coexistent monogenic conditions, the results from this pilot study highlight a need for the development of computational tools designed to effectively generate differential diagnoses with consideration of the possibility of coexisting conditions.
- Published
- 2018
20. Nanomaterial-based Optical and Electrochemical Biosensors for Amyloid beta and Tau: Potential for early diagnosis of Alzheimer's Disease
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Won Woo Cho, Sungbo Cho, Sang-Myung Lee, Le Minh Tu Phan, Jae Young Kim, Hien Thi Ngoc Le, Somasekhar R. Chinnadayyala, Thi Xoan Hoang, Young Hyo Kim, Thuy Anh Thu Vo, Hoang Lan Pham, and Seong Hye Choi
- Subjects
0301 basic medicine ,Amyloid beta ,Nanotechnology ,tau Proteins ,Disease ,Biosensing Techniques ,Diagnostic tools ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Alzheimer Disease ,Genetics ,medicine ,Dementia ,Electrochemical biosensor ,Humans ,Molecular Biology ,Amyloid beta-Peptides ,biology ,business.industry ,Optical biosensor ,medicine.disease ,Nanostructures ,030104 developmental biology ,Early Diagnosis ,030220 oncology & carcinogenesis ,biology.protein ,Molecular Medicine ,business - Abstract
Alzheimer's disease (AD), a heterogeneous pathological process representing the most common causes of dementia worldwide, has required early and accurate diagnostic tools. Neuropathological hallmarks of AD involve the aberrant accumulation of Amyloid beta (Aβ) into Amyloid plaques and hyperphosphorylated Tau into neurofibrillary tangles, occurring long before the onset of brain dysfunction.The study has identified the potential application of advanced biosensors as standardized clinical diagnostic tools for AD, evolving the way for new and efficient AD control with minimum economic and social burden. After clinical trial, nanobiosensors for measuring Aβ and Tau simultaneously possess innovative diagnosis of AD to provide significant contributions to primary Alzheimer's care intervention.
- Published
- 2021
21. Genome Sequences of Two Marsupial Simplex Viruses, Macropodid Alphaherpesviruses 2 and 4
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Joanne M. Devlin, Julian Motha, Timothy J. Mahony, Paola K. Vaz, and Carol A. Hartley
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Genetics ,biology ,viruses ,Genome Sequences ,Diagnostic tools ,biology.organism_classification ,Genome ,Open reading frame ,Immunology and Microbiology (miscellaneous) ,Human genome ,ORFS ,Molecular Biology ,Marsupial - Abstract
We present the genome sequences of macropodid alphaherpesviruses 2 and 4, two closely related pathogens of macropods. Both encoded 68 nonredundant open reading frames (ORFs) and share 90.6% genome-wide nucleotide identity. These viruses are associated with fatal outbreaks of disease in multiple marsupial species. These sequences will be important for the development of new diagnostic tools.
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- 2021
22. Comparative performance of a new sars-cov-2 rapid detection system
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Gabriele Anichini, Shibily Prathyumnan, Maria Grazia Cusi, Chiara Terrosi, Claudia Gandolfo, Gianni Gori Savellini, and Stefano Marini
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Physiology ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Diagnostic tools ,Real-Time Polymerase Chain Reaction ,Rapid detection ,Microbiology ,Specimen Handling ,Diagnostic platform ,Limit of Detection ,Nasopharynx ,Transport medium ,Genetics ,Medicine ,Humans ,Intensive care medicine ,General Immunology and Microbiology ,Ecology ,business.industry ,SARS-CoV-2 ,COVID-19 ,Cell Biology ,Gold standard (test) ,QR1-502 ,Infectious Diseases ,Molecular Diagnostic Techniques ,COVID-19 Nucleic Acid Testing ,Molecular diagnosis ,business ,Research Article - Abstract
The extraordinary global demand for reagents and diagnostic instruments needed for timely detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has rapidly affected their availability. In order to meet diagnostic needs, it has been necessary to develop new diagnostic procedures. To date, molecular diagnostic tools have represented the gold standard for diagnosis of SARS-CoV-2 infection, and thus an alternative and real-time PCR system was required. To this aim, a molecular rapid test which works with direct real-time RT-PCR may be a relevant aid. In the present work, the accuracy, sensitivity, and specificity of the bKIT Virus Finder COVID-19 rapid molecular test by Hyris Ltd. was evaluated. Moreover, the influence of a different swab storage medium composition was examined relative to that of a routinely used comparator assay. The Hyris Ltd. assay showed an overall agreement of 100% with the comparator based on a panel consisting of 74 retrospective positive nasopharyngeal swabs (NPSs), collected either in universal transport medium (UTM) or using ESwab. No false-positive result was achieved on samples that previously tested negative. Cross-reactivity screening on microorganisms that commonly colonize the human upper respiratory tract was not detected, excluding the risk of false-positive results. Simultaneously, drugs frequently administered to cure respiratory diseases did not interfere with the analytical performance of the assay. Our results showed that the Hyris Ltd. bKIT Virus Finder COVID-19 is a reliable assay for rapid qualitative detection of SARS-CoV-2, providing the advantage of less complex and unambiguous interpretation of results. Indeed, skilled technicians are not required, and thus the Hyris system is suitable as a rapid and easy system for SARS-CoV-2 diagnosis. IMPORTANCE In order to overcome the increased demand for diagnostic tools for the timely detection of SARS-CoV-2 infection, we tested the bKIT Virus Finder COVID-19 molecular rapid test by Hyris Ltd. The new system was confirmed as a reliable assay for rapid SARS-CoV-2 detection, since sensitivity and specificity parameters were fully satisfied. Moreover, the bKIT Virus Finder COVID-19 provides the advantage of easy results interpretation, since skilled technicians are not required, and thus the Hyris system is a valuable SARS-CoV-2 rapid diagnosis system.
- Published
- 2021
23. Next-generation-sequencing-based identification of familial hypercholesterolemia-related mutations in subjects with increased LDL–C levels in a latvian population.
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Radovica-Spalvina, Ilze, Latkovskis, Gustavs, Silamikelis, Ivars, Fridmanis, Davids, Elbere, Ilze, Ventins, Karlis, Ozola, Guna, Erglis, Andrejs, and Klovins, Janis
- Subjects
- *
GENETIC mutation , *HYPERCHOLESTEREMIA , *LOW density lipoproteins , *GENETIC disorders , *CORONARY heart disease risk factors , *GENE amplification , *GENETICS - Abstract
Background: Familial hypercholesterolemia (FH) is one of the commonest monogenic disorders, predominantly inherited as an autosomal dominant trait. When untreated, it results in early coronary heart disease. The vast majority of FH remains undiagnosed in Latvia. The identification and early treatment of affected individuals remain a challenge worldwide. Most cases of FH are caused by mutations in one of four genes, APOB, LDLR, PCSK9, or LDLRAP1. The spectrum of disease-causing variants is very diverse and the variation detection panels usually used in its diagnosis cover only a minority of the disease-causing gene variants. However, DNA-based tests may provide an FH diagnosis for FH patients with no physical symptoms and with no known family history of the disease. Here, we evaluate the use of targeted next-generation sequencing (NGS) to identify cases of FH in a cohort of patients with coronary artery disease (CAD) and individuals with abnormal low-density lipoprotein-cholesterol (LDL–C) levels. Methods: We used targeted amplification of the coding regions of LDLR, APOB, PCSK9, and LDLRAP1, followed by NGS, in 42 CAD patients (LDL–C, 4.1–7.2 mmol/L) and 50 individuals from a population-based cohort (LDL–C, 5.1–9.7 mmol/L). Results: In total, 22 synonymous and 31 nonsynonymous variants, eight variants in close proximity (10 bp) to intron-exon boundaries, and 50 other variants were found. We identified four pathogenic mutations (p.(Arg3527Gln) in APOB, and p.(Gly20Arg), p.(Arg350*), and c.1706–10G > A in LDLR) in seven patients (7.6 %). Three possible pathogenic variants were also found in four patients. Conclusion: NGS-based methods can be used to detect FH in high-risk individuals when they do not meet the defined clinical criteria. [ABSTRACT FROM AUTHOR]
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- 2015
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24. Biomarkers for diagnosis, monitoring of progression, and treatment responses in ankylosing spondylitis and axial spondyloarthritis.
- Author
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Reveille, John
- Subjects
- *
BIOMARKERS , *ANKYLOSING spondylitis , *ANKYLOSING spondylitis treatment , *DISEASE progression , *ERYTHROCYTES , *CONNECTIVE tissues , *CYTOKINES , *DIAGNOSIS - Abstract
With the growing awareness of the impact of chronic back pain and axial spondyloarthritis and recent breakthroughs in genetics and the development of novel treatments which may impact best on early disease, the need for markers that can facilitate early diagnosis and profiling those individuals at the highest risk for a bad outcome has never been greater. The genetic basis of ankylosing spondylitis has been considerably advanced, and HLA-B27 testing has a role in the diagnosis. Knowledge is still incomplete of the rest of the genetic contribution to disease susceptibility, and it is likely premature to use extensive genetic testing (other than HLA-B27) for diagnosis. Serum and plasma biomarkers have been examined extensively in assessing disease activity, treatment response, and as predictors or radiographic severity. For assessing disease activity, other than C-reactive protein and erythrocyte sedimentation rate, the most work has been in examining cytokines (particularly interleukin 17 and 23), matrix metalloproteinase (MMP) markers (particularly MMP3). For assessing those at the highest risk for radiographic progression, biomarkers of bony metabolism, cartilage and connective tissue degradation products, and adipokines have been most extensively assessed. The problem is that no individual biomarkers has been reproducibly shown to assess disease activity or predict outcome, and this area still remains an unmet need, of relevance to industry stakeholders, to regulatory bodies, to the healthcare system, to academic investigators, and finally to patients and providers. [ABSTRACT FROM AUTHOR]
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- 2015
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25. New insights into lung development and diseases: the role of microRNAs1.
- Author
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Johar, Dina, Siragam, Vinayakumar, Mahood, Thomas H., and Keijzer, Richard
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- *
LUNG diseases , *MICRORNA , *APOPTOSIS , *EPIGENETICS , *CELL differentiation , *BRONCHOPULMONARY dysplasia , *GENETICS - Abstract
MicroRNAs (miRNAs) are short endogenous noncoding RNA molecules (∼22 nucleotides) that can regulate gene expression at the post-transcription level. Research interest in the role of miRNAs in lung biology is emerging. MiRNAs have been implicated in a range of processes such as development, homeostasis, and inflammatory diseases in lung tissues and are capable of inducing differentiation, morphogenesis, and apoptosis. In recent years, several studies have reported that miRNAs are differentially regulated in lung development and lung diseases in response to epigenetic changes, providing new insights for their versatile role in various physiological and pathological processes in the lung. In this review, we discuss the contribution of miRNAs to lung development and diseases and possible future implications in the field of lung biology. [ABSTRACT FROM AUTHOR]
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- 2015
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26. New insights into lung development and diseases: the role of microRNAs1.
- Author
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Johar, Dina, Siragam, Vinayakumar, Mahood, Thomas H., and Keijzer, Richard
- Subjects
LUNG diseases ,MICRORNA ,APOPTOSIS ,EPIGENETICS ,CELL differentiation ,BRONCHOPULMONARY dysplasia ,GENETICS - Abstract
Copyright of Biochemistry & Cell Biology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2015
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27. Milestones in Personalized Medicine: From the Ancient Time to Nowadays—the Provocation of COVID-19
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Sophie Visvikis-Siest, Danai Theodoridou, Maria-Spyridoula Kontoe, Satish Kumar, Michael Marschler, SIEST, Sofia, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)
- Subjects
0301 basic medicine ,Idiosyncrasy ,Coronavirus disease 2019 (COVID-19) ,lcsh:QH426-470 ,[SDV]Life Sciences [q-bio] ,Review ,Diagnostic tools ,COVID−19 ,03 medical and health sciences ,Therapeutic approach ,0302 clinical medicine ,Global awareness ,Health care ,Genetics ,Genetics (clinical) ,ComputingMilieux_MISCELLANEOUS ,pharmacogenomics ,business.industry ,Ancient time ,public health ,personalized medicine ,3. Good health ,[SDV] Life Sciences [q-bio] ,lcsh:Genetics ,030104 developmental biology ,inflammation ,030220 oncology & carcinogenesis ,Molecular Medicine ,Engineering ethics ,Personalized medicine ,business ,Psychology - Abstract
The first evidence of individual targeting medicine appeared in ancient times thousands of years ago. Various therapeutic approaches have been established since then. However, even nowadays, conventional therapies do not take into consideration individuals' idiosyncrasy and genetic make-up, failing thus to be effective in some cases. Over time, the necessity of a more precise and effective treatment resulted in the development of a scientific field currently known as “personalized medicine.” The numerous technological breakthroughs in this field have acknowledged personalized medicine as the next generation of diagnosis and treatment. Although personalized medicine has attracted a lot of attention the last years, there are still several obstacles hindering its application in clinical practice. These limitations have come to light recently, due to the COVID-19 pandemic. This review describes the “journey” of personalized medicine over time, emphasizing on important milestones achieved through time. Starting from the treatment of malaria, as a first more personalized therapeutic approach, it highlights the need of new diagnostic tools and therapeutic regimens based on individuals' genetic background. Furthermore, it aims at raising global awareness regarding the current limitations and the necessity of a personalized strategy to overpass healthcare problems and hence, the current crisis.
- Published
- 2020
28. Comparative assessment of multiple COVID-19 serological technologies supports continued evaluation of point-of-care lateral flow assays in hospital and community healthcare settings
- Author
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Marit J. van Gils, Eithne MacMahon, Gilberto Betancor, Neophytos Kouphou, Sam Douthwaite, Mark Tan Kia Ik, Jonathan D. Edgeworth, Amita Patel, Suzanne Pickering, Harry Wilson, Gaia Nebbia, Rui Pedro Galão, Carl Graham, Rogier W. Sanders, Jakub Luptak, Kathryn J. A. Steel, Karen Bisnauthsing, Adrian W. Signell, Sam Acors, Blair Merrick, Michael H. Malim, Katie J. Doores, Oliver Hemmings, Rahul Batra, Philip J. M. Brouwer, Rocio Martinez Nunez, Stuart J. D. Neil, Geraldine O'Hara, Laura E. McCoy, Jeffrey Seow, Lorcan O’Connell, Graduate School, AII - Infectious diseases, AII - Inflammatory diseases, and Medical Microbiology and Infection Prevention
- Subjects
Male ,RNA viruses ,Viral Diseases ,Coronaviruses ,Physiology ,Antibodies, Viral ,Diagnostic tools ,Biochemistry ,Serology ,COVID-19 Testing ,Medical Conditions ,Immune Physiology ,Medicine and Health Sciences ,Sampling (medicine) ,Community Health Services ,Biology (General) ,Enzyme-Linked Immunoassays ,Pathology and laboratory medicine ,Virus Testing ,Immunoassay ,0303 health sciences ,Immune System Proteins ,medicine.diagnostic_test ,030302 biochemistry & molecular biology ,Middle Aged ,Nucleocapsid Proteins ,Medical microbiology ,Hospitals ,Infectious Diseases ,Spike Glycoprotein, Coronavirus ,Viruses ,Female ,SARS CoV 2 ,Pathogens ,Coronavirus Infections ,Research Article ,Adult ,medicine.medical_specialty ,SARS coronavirus ,Coronavirus disease 2019 (COVID-19) ,QH301-705.5 ,Head to head ,Point-of-Care Systems ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pneumonia, Viral ,Immunology ,Enzyme-Linked Immunosorbent Assay ,Research and Analysis Methods ,Sensitivity and Specificity ,Microbiology ,Antibodies ,Betacoronavirus ,03 medical and health sciences ,Diagnostic Medicine ,Virology ,Internal medicine ,Genetics ,medicine ,Coronavirus Nucleocapsid Proteins ,Humans ,Seroprevalence ,Serologic Tests ,Immunoassays ,Pandemics ,Molecular Biology ,Aged ,030304 developmental biology ,Point of care ,Biology and life sciences ,Clinical Laboratory Techniques ,SARS-CoV-2 ,business.industry ,Organisms ,Viral pathogens ,COVID-19 ,Proteins ,Covid 19 ,RC581-607 ,Phosphoproteins ,Microbial pathogens ,Luminescent Measurements ,Healthcare settings ,Immunologic Techniques ,Parasitology ,Immunologic diseases. Allergy ,business - Abstract
There is a clear requirement for an accurate SARS-CoV-2 antibody test, both as a complement to existing diagnostic capabilities and for determining community seroprevalence. We therefore evaluated the performance of a variety of antibody testing technologies and their potential use as diagnostic tools. Highly specific in-house ELISAs were developed for the detection of anti-spike (S), -receptor binding domain (RBD) and -nucleocapsid (N) antibodies and used for the cross-comparison of ten commercial serological assays—a chemiluminescence-based platform, two ELISAs and seven colloidal gold lateral flow immunoassays (LFIAs)—on an identical panel of 110 SARS-CoV-2-positive samples and 50 pre-pandemic negatives. There was a wide variation in the performance of the different platforms, with specificity ranging from 82% to 100%, and overall sensitivity from 60.9% to 87.3%. However, the head-to-head comparison of multiple sero-diagnostic assays on identical sample sets revealed that performance is highly dependent on the time of sampling, with sensitivities of over 95% seen in several tests when assessing samples from more than 20 days post onset of symptoms. Furthermore, these analyses identified clear outlying samples that were negative in all tests, but were later shown to be from individuals with mildest disease presentation. Rigorous comparison of antibody testing platforms will inform the deployment of point-of-care technologies in healthcare settings and their use in the monitoring of SARS-CoV-2 infections., Author summary PCR-based throat and nose swab tests for novel coronavirus (SARS-CoV-2) establish if someone is infected with the virus, while antibody tests can determine whether someone has had it in the past. However, for diagnosis later in disease, or in delayed-onset syndromes such as paediatric inflammatory multisystem syndrome (PIMS), antibody tests could form an important part of hospital diagnostic capabilities. They will also be essential for patient management strategies and community seroprevalence studies. We have conducted unbiased, head-to-head comparisons of ten commercial antibody test kits, using blood from patients admitted to hospital with COVID-19 throughout the peak of the epidemic in London, UK. As there was no existing approved diagnostic antibody test, we developed our own sensitive assay and used this to cross-compare the commercial tests. There was a broad range of performance among the tests, but all gave the best results when used 20 days or more after the start of symptoms. Furthermore, antibody levels were higher in individuals with severe illness compared to those with asymptomatic or mild disease. Some of the best-performing tests were rapid lateral flow immunoassays, which are affordable, quick and easy to use, and if they are deployed appropriately could have considerable utility in healthcare settings.
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- 2020
29. Ophthalmic genetics in South America
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Federico M Fernández, Carlos E. Prada, Harry Pachajoa, Robert B. Hufnagel, Juliana Lores, Rene Moya, M Eugenia Inga, Malena Daich Varela, Patricio G Schlottmann, Juliana Maria Ferraz Sallum, and Claudia Arberas
- Subjects
Genetics ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,media_common.quotation_subject ,Public health ,Eye Diseases, Hereditary ,South America ,Diagnostic tools ,Public healthcare ,Patient care ,Article ,Scarcity ,Ophthalmology ,Geography ,Health care ,medicine ,Humans ,Precision Medicine ,business ,Genetics (clinical) ,Strengths and weaknesses ,media_common ,Genetic testing - Abstract
South America comprises of heterogeneous topographies, populations, and health care systems. Therefore, it is not surprising to see differences among the countries regarding expertise, education, and practices of ophthalmic genetics for patients with rare eye diseases. Nevertheless, common challenges such as limited genetics training in medical schools and among ophthalmologists, scarcity of diagnostic tools for phenotyping, and expensive genetic testing not covered by the public healthcare systems, are seen in all of them. Here, we provide a detailed report of the current status of ophthalmic genetics, described by the personal views of local ophthalmologists from Brazil, Colombia, Argentina, and Chile. By reporting our strengths and weaknesses as a region, we intend to highlight the need for guidelines on how to manage these patients aligned with public health policies. Our region contributes to research worldwide, with thousands of well diagnosed patients from a number of unique and genetically diverse populations. The constant expansion of ophthalmic genetics and molecular diagnostics requires us to join forces to collaborate across South America and with other countries to improve access to next-generation diagnostics and ultimately improve patient care.
- Published
- 2020
30. Candidate stress biomarkers for queen failure diagnostics
- Author
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Jeffrey S. Pettis, Abigail Chapman, Leonard J. Foster, Alison McAfee, Joseph P. Milone, and David R. Tarpy
- Subjects
Proteomics ,0106 biological sciences ,Queens ,lcsh:QH426-470 ,lcsh:Biotechnology ,education ,Biology ,Bioinformatics ,Spermatheca ,Diagnostic tools ,01 natural sciences ,Honey bees ,03 medical and health sciences ,Honey Bees ,lcsh:TP248.13-248.65 ,Genetics ,Pesticides ,reproductive and urinary physiology ,Sperm viability ,030304 developmental biology ,0303 health sciences ,Stressors ,Bees ,Protein markers ,lcsh:Genetics ,010602 entomology ,Stress biomarkers ,Biomarkers ,Research Article ,010606 plant biology & botany ,Biotechnology - Abstract
Background Queen failure is a persistent problem in beekeeping operations, but in the absence of overt symptoms it is often difficult, if not impossible, to ascertain the root cause. Stressors like heat-shock, cold-shock, and sublethal pesticide exposure can reduce stored sperm viability and lead to cryptic queen failure. Previously, we suggested candidate protein markers indicating heat-shock in queens. Here, we further investigate these heat-shock markers and test new stressors to identify additional candidate protein markers. Results We found that heat-shocking queens for upwards of 1 h at 40 °C was necessary to induce significant changes in the two strongest candidate heat-shock markers, and that relative humidity significantly influenced the degree of activation. In blind heat-shock experiments, we tested the efficiency of these markers at assigning queens to their respective treatment groups and found that one marker was sufficient to correctly assign queens 75% of the time. Finally, we compared cold-shocked queens at 4 °C and pesticide-exposed queens to controls to identify candidate markers for these additional stressors, and compared relative abundances of all markers to queens designated as ‘healthy’ and ‘failing’ by beekeepers. Queens that failed in the field had higher expression of both heat-shock and pesticide protein markers, but not cold-shock markers. Conclusions This work offers some of the first steps towards developing molecular diagnostic tools to aid in determining cryptic causes of queen failure. Further work will be necessary to determine how long after the stress event a marker’s expression remains elevated, and how accurate these markers will be for field diagnoses.
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- 2020
31. Convergence of prognostic gene signatures suggests underlying mechanisms of human prostate cancer progression
- Author
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Shea P. Connell, Colin Cooper, Bogdan-Alexandru Luca, Vincent Moulton, Daniel Brewer, Christopher Ellis, Ellis, Christopher [0000-0002-1856-7254], Brewer, Daniel S [0000-0003-4753-9794], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Male ,lcsh:QH426-470 ,Datasets as Topic ,Computational biology ,Biology ,Diagnostic tools ,Human prostate ,Article ,Cohort Studies ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Genetics ,medicine ,diagnostic signature ,Biomarkers, Tumor ,Humans ,Neoplasm Invasiveness ,prognostic signature ,Biomarker discovery ,Gene ,Genetics (clinical) ,Gene Expression Profiling ,Cancer ,Aggressive cancer ,biomarkers ,Prostatic Neoplasms ,medicine.disease ,prostate cancer ,Microarray Analysis ,Prognosis ,cancer progression ,Gene Expression Regulation, Neoplastic ,lcsh:Genetics ,030104 developmental biology ,030220 oncology & carcinogenesis ,aggressive cancer ,Disease Progression ,Biomarker (medicine) ,Transcriptome - Abstract
The highly heterogeneous clinical course of human prostate cancer has prompted the development of multiple RNA biomarkers and diagnostic tools to predict outcome for individual patients. Biomarker discovery is often unstable with, for example, small changes in discovery dataset configuration resulting in large alterations in biomarker composition. Our hypothesis, which forms the basis of this current study, is that highly significant overlaps occurring between gene signatures obtained using entirely different approaches indicate genes fundamental for controlling cancer progression. For prostate cancer, we found two sets of signatures that had significant overlaps suggesting important genes (p <, 10&minus, 34 for paired overlaps, hypergeometrical test). These overlapping signatures defined a core set of genes linking hormone signalling (HES6-AR), cell cycle progression (Prolaris) and a molecular subgroup of patients (PCS1) derived by Non Negative Matrix Factorization (NNMF) of control pathways, together designated as SIG-HES6. The second set (designated SIG-DESNT) consisted of the DESNT diagnostic signature and a second NNMF signature PCS3. Stratifications using SIG-HES6 (HES6, PCS1, Prolaris) and SIG-DESNT (DESNT) classifiers frequently detected the same individual high-risk cancers, indicating that the underlying mechanisms associated with SIG-HES6 and SIG-DESNT may act together to promote aggressive cancer development. We show that the use of combinations of a SIG-HES6 signature together with DESNT substantially increases the ability to predict poor outcome, and we propose a model for prostate cancer development involving co-operation between the SIG-HES6 and SIG-DESNT pathways that has implication for therapeutic design.
- Published
- 2020
32. Complement in sepsis-when science meets clinics
- Author
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Markus Huber-Lang and Tom Eirik Mollnes
- Subjects
Multiple Organ Failure ,Biophysics ,Complement C5a ,Diagnostic tools ,Biochemistry ,Sepsis ,03 medical and health sciences ,Immune system ,Structural Biology ,Genetics ,Medicine ,Animals ,Humans ,Receptor ,Molecular Biology ,Complement Activation ,030304 developmental biology ,0303 health sciences ,Innate immune system ,business.industry ,030302 biochemistry & molecular biology ,Organ dysfunction ,VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710 ,Cell Biology ,medicine.disease ,VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710 ,Complement system ,Complement (complexity) ,Immunology ,Complement C3a ,medicine.symptom ,business - Abstract
Sepsis as life‐threatening organ dysfunction caused by microorganisms represents a dreadful challenge for the immune system. The role of the complement system as major column of innate immunity has been extensively studied in various sepsis models, but its translational value remains in the dark. Complement activation products, such as C3a and C5a, and their corresponding receptors provide useful diagnostic tools and promising targets to improve organ function and outcome. However, a monotherapeutic complement intervention irrespective of the current immune function seems insufficient to reverse the complex sepsis mechanisms. Indeed, sepsis‐induced disturbances of cross talking complement, coagulation, and fibrinolytic cascades lead to systemic ‘thromboinflammation’, ultimately followed by multiple‐organ failure. We propose to reliably monitor the complement function in the patient and to re‐establish the immune balance by patient‐tailored combined therapies, such as complement and Toll‐like receptor inhibition. Our working hypothesis aims at blocking the ‘explosive’ innate immune recognition systems early on before downstream mediators are released and the inflammatory response becomes irreversible, a strategy that we name ‘upstream approach’. © 2020 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
- Published
- 2020
33. A Front Line on Klebsiella pneumoniae Capsular Polysaccharide Knowledge: Fourier Transform Infrared Spectroscopy as an Accurate and Fast Typing Tool
- Author
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Luísa Peixe, Clara Sousa, Ângela Novais, João A. Lopes, and Carla Rodrigues
- Subjects
0301 basic medicine ,Physiology ,Computer science ,Klebsiella pneumoniae ,030106 microbiology ,Population ,lcsh:QR1-502 ,Genomics ,Locus (genetics) ,Computational biology ,Diagnostic tools ,Biochemistry ,Microbiology ,lcsh:Microbiology ,Clinical Science and Epidemiology ,03 medical and health sciences ,Genetics ,Typing ,nosocomial outbreaks ,education ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Comparative genomics ,cps locus ,education.field_of_study ,biology ,capsular typing ,Strain typing ,biology.organism_classification ,QR1-502 ,3. Good health ,Computer Science Applications ,030104 developmental biology ,Modeling and Simulation ,biochemical data ,strain typing ,Research Article - Abstract
Klebsiella pneumoniae is nowadays recognized as one of the most defiant human pathogens, whose infections are increasingly more challenging to treat and control. Whole-genome sequencing (WGS) has been key for clarifying the population structure of K. pneumoniae, and it is still instrumental to provide insights into potential pathogenicity and evolutionary markers, such as the capsular locus. However, this information and WGS are still far from being accessible and translated into routine clinical microbiology laboratories as quick and cost-efficient strain diagnostic tools. Here, we propose a biochemical fingerprinting approach based on Fourier transform infrared spectroscopy (FT-IR) and multivariate data analysis tools for K. pneumoniae capsular typing that, because of its high resolution, speed, and low cost, can be an asset to provide enough information to support real-time epidemiology and infection control decisions. Besides, it provides a simple framework for phenotypic/biochemical validation of K. pneumoniae capsular diversity., Genomics-based population analysis of multidrug-resistant (MDR) Klebsiella pneumoniae motivated a renewed interest on the capsule as an evolutionary and virulence marker of clinically relevant strains. Whole-genome sequencing (WGS)-based approaches have provided great insights into the genetic variability of the capsular locus, but genotypic-biochemical capsular (K)-type correlations are lacking, hindering the establishment of a reliable framework for K-type characterization and typing. To fill this gap, we combined molecular, comparative genomics, and multivariate data analysis tools with biochemical data on the capsular locus to support the usefulness of Fourier transform infrared (FT-IR) spectroscopy as a reliable K typing tool. To validate our approach, we used a representative collection of well-defined MDR K. pneumoniae lineages involved in local or nationwide epidemics in multiple countries. With this, we demonstrate a high accuracy and resolution of our FT-IR-based spectroscopy approach for K-type discrimination that is even higher than that provided by WGS. Moreover, the specific associations established between certain K types and specific K. pneumoniae lineages with high clinical relevance, together with the accuracy, simplicity, short time to result, and inexpensive features of the method, support the value of the developed FT-IR-based approach for an easy, fast, and cost-effective strain typing. This fulfills a still unmet need for tools to support real-time monitoring and control of K. pneumoniae infections. In addition, the genotypic-biochemical correlations established provide insights on sugar composition/structure of newly defined K. pneumoniae capsular types. IMPORTANCE Klebsiella pneumoniae is nowadays recognized as one of the most defiant human pathogens, whose infections are increasingly more challenging to treat and control. Whole-genome sequencing (WGS) has been key for clarifying the population structure of K. pneumoniae, and it is still instrumental to provide insights into potential pathogenicity and evolutionary markers, such as the capsular locus. However, this information and WGS are still far from being accessible and translated into routine clinical microbiology laboratories as quick and cost-efficient strain diagnostic tools. Here, we propose a biochemical fingerprinting approach based on Fourier transform infrared spectroscopy (FT-IR) and multivariate data analysis tools for K. pneumoniae capsular typing that, because of its high resolution, speed, and low cost, can be an asset to provide enough information to support real-time epidemiology and infection control decisions. Besides, it provides a simple framework for phenotypic/biochemical validation of K. pneumoniae capsular diversity.
- Published
- 2020
34. Overview of current microRNA biomarker signatures as potential diagnostic tools for leukaemic conditions
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Duncan Ayers, Joseph Borg, and Alfred Buhagiar
- Subjects
0301 basic medicine ,lcsh:QH426-470 ,Biopsy ,Gene regulatory network ,Computational biology ,Diagnostic tools ,Biochemistry ,Article ,03 medical and health sciences ,0302 clinical medicine ,AML ,hemic and lymphatic diseases ,microRNA ,Genetics ,medicine ,Leukaemia ,Liquid biopsy ,CML ,Molecular Biology ,miRNA ,Cell specific ,Leukemia ,business.industry ,Chronic lymphocytic leukemia -- Case studies ,Biochemistry (medical) ,Acute myeloid leukemia -- Diagnosis ,MicroRNA ,Review article ,Biomarker (cell) ,lcsh:Genetics ,Chronic myeloid leukemia -- Molecular aspects ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Bone marrow ,ALL ,business ,CLL - Abstract
Haematological malignancies encompass all variations of leukaemia at both the chronic and acute level, together with the specific cell type induced into tumourigenesis. Current diagnostic protocols for leukaemic conditions rely heavily on cytomorphology and other histological examinations from bone marrow aspirates, with the latter being a highly invasive surgical procedure for the patient. The discovery of microRNAs as one of the key gene regulatory networks in the past two decades has enabled researchers to investigate the possibility of exploiting the identification of dysregulated expression profiles for specific microRNAs present in the leukaemic patient's bloodstream as novel liquid biopsy diagnostic tools. This review article serves to consolidate recent global research efforts aiming to achieve such scopes., peer-reviewed
- Published
- 2020
35. The Undiagnosed Diseases Network International: Five Years and More!
- Author
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Béla Melegh, Marco Salvatore, Helene Cederroth, W.A. Gahl, Olaf Riess, Gareth Baynam, Paul Lasko, Kenjiro Kosaki, Domenica Taruscio, Eric W. Klee, and Stephen C. Groft
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Biomedical Research ,Time Factors ,International Cooperation ,Endocrinology, Diabetes and Metabolism ,International scale ,Disease ,030105 genetics & heredity ,Global Health ,Diagnostic tools ,Undiagnosed Diseases ,Biochemistry ,03 medical and health sciences ,Rare Diseases ,0302 clinical medicine ,Endocrinology ,Genetics ,medicine ,Global health ,Humans ,Medical diagnosis ,Intensive care medicine ,Molecular Biology ,Information Services ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,business.industry ,Medical practice ,Cohort ,business ,030217 neurology & neurosurgery ,Rare disease - Abstract
Undiagnosed rare diseases (URDs) account for a significant portion of the overall rare disease burden, depending upon the country. Hence, URDs represent an unmet medical need. A specific challenge posed by the ensemble of the URD patient cohort is the heterogeneity of its composition; the group, indeed, includes very rare, still unidentified conditions as well as clinical variants of recognized rare diseases. Exact disease recognition requires new approaches that cut across national and institutional boundaries, may need the implementation of methods new to diagnostics, and embrace clinical care and research. To address these issues, the Undiagnosed Diseases Network International (UDNI) was established in 2014, with the major aims of providing diagnoses to patients, implementing additional diagnostic tools, and fostering research on novel diseases, their mechanisms, and their pathways. The UDNI involves centres with internationally recognized expertise, and its scientific resources and know-how aim to fill the knowledge gaps that impede diagnosis, in particularly for ultra-rare diseases. Consequently, the UDNI fosters the translation of research into medical practice, aided by active patient involvement. The goals of the UDNI are to work collaboratively and at an international scale to: 1) provide diagnoses for individuals who have conditions that have eluded diagnosis by clinical experts; 2) gain insights into the etiology and pathogenesis of novel diseases; 3) contribute to standards of diagnosing unsolved patients; and 4) share the results of UDNI research in a timely manner and as broadly as possible.
- Published
- 2020
36. Insect Vectors of Phytoplasma Diseases in the Tropics: Molecular Biology and Sustainable Management
- Author
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Thimmanna, V. V. Kavyashri, S. Onkara Naik, N. Nagaraju, and A. K. Chakravarthy
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Genetics ,biology ,Disease management (agriculture) ,Phytoplasma ,Sustainable management ,Vector (epidemiology) ,fungi ,Plant species ,Biological dispersal ,Tropics ,biology.organism_classification ,Diagnostic tools - Abstract
Phytoplasmas are pleomorphic, non-culturable, wall-less prokaryotes that colonize phloem tissues of several plant species inflicting yellows-type diseases. They are transmitted between plants by vegetative propagation, and insect vectors are the chief means of dissemination of phytoplasmas. This chapter summarizes recent progress in phytoplasma research, focusing on molecular division, phytoplasma–insect vector interactions, molecular mechanisms of insect transmissibility, vector dispersal, serological and molecular diagnostic tools for detection and characterization of phytoplasma, practices for sustainable disease management, and important phytoplasma diseases in India.
- Published
- 2020
37. Determining minimum numbers of di-allelic diagnostic markers required to identify introgressions in diploid cross-species hybrid individuals from different types of inter- and backcross populations
- Author
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Joseane Padilha da Silva and Alexandre Rodrigues Caetano
- Subjects
hybrid identification ,0106 biological sciences ,0301 basic medicine ,Diagnostic marker ,QH426-470 ,Power test ,Biology ,Diagnostic tools ,01 natural sciences ,broodstock management ,03 medical and health sciences ,030104 developmental biology ,cross-species hybridization ,Evolutionary biology ,Backcrossing ,Genetics ,Identification (biology) ,Ploidy ,Allele ,Animal Genetics ,Molecular Biology ,Genotyping ,010606 plant biology & botany - Abstract
Cross-species hybridizations have been extensively used to generate animals and plants better suited for draft and food and fiber production since Roman times, and are still important in current agricultural practices with growing uses especially in aquaculture. Diagnostic tools based on marker panels with sufficient numbers of markers for accurate identification of cross-species hybrid individuals from intercrossed and backcrossed populations are increasingly necessary for practical, accurate species-purity certification and management of commercial broodstocks. Minimal numbers of di-allelic markers with species-specific alleles required to accurately identify hybrid individuals in intercrossed and advanced backcrossed populations were estimated using power analysis, and ranged from 5 to 191 (α = .05), and from 7 to 293 (α = .01), considering backcross 1 (BC1) to BC6 populations, respectively. Numbers of markers required for accurate hybrid identification observed in simulated BC1 to BC6 populations ranged from 5 to 1,131 and 7 to 8,065, considering error rates ≤ 5% and ≤ 1%, respectively. Estimated and observed numbers of diagnostic markers required for accurate hybrid identification up to four generations of backcrossing fall within practical operational limits of most commercial platforms currently available for genotyping low-density SNP marker panels. Therefore, cost-effective assay panels could be developed to provide practical tools for accurate species-purity certification.
- Published
- 2020
38. Large-scale deletions of the ABCA1 gene in patients with hypoalphalipoproteinemia
- Author
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Michael A. Iacocca, Joan H.M. Knoll, Christian Netzer, Henian Cao, Amanda J. Berberich, Jacqueline S. Dron, Ping Yang, Robert A. Hegele, Karine Tremblay, Diane Brisson, Jian Wang, Daniel Gaudet, and Ioanna Gouni-Berthold
- Subjects
0301 basic medicine ,Context (language use) ,Familial hypercholesterolemia ,QD415-436 ,030204 cardiovascular system & hematology ,Biology ,Biochemistry ,DNA sequencing ,diagnostic tools ,03 medical and health sciences ,symbols.namesake ,Exon ,0302 clinical medicine ,Endocrinology ,high density lipoprotein cholesterol ,ATP-binding cassette subfamily A member 1 ,medicine ,Copy-number variation ,Hypoalphalipoproteinemia ,Exome sequencing ,Sanger sequencing ,Genetics ,nutritional and metabolic diseases ,Cell Biology ,medicine.disease ,bioinformatic analysis ,030104 developmental biology ,copy-number variation ,symbols ,lipids (amino acids, peptides, and proteins) ,next-generation sequencing - Abstract
Copy-number variations (CNVs) have been studied in the context of familial hypercholesterolemia but have not yet been evaluated in patients with extreme levels of HDL cholesterol. We evaluated targeted, next-generation sequencing data from patients with very low levels of HDL cholesterol (i.e., hypoalphalipoproteinemia) with the VarSeq-CNV® caller algorithm to screen for CNVs that disrupted the ABCA1, LCAT, or APOA1 genes. In four individuals, we found three unique deletions in ABCA1: a heterozygous deletion of exon 4, a heterozygous deletion that spanned exons 8 to 31, and a heterozygous deletion of the entire ABCA1 gene. Breakpoints were identified with Sanger sequencing, and the full-gene deletion was confirmed by using exome sequencing and the Affymetrix CytoScan HD array. Previously, large-scale deletions in candidate HDL genes had not been associated with hypoalphalipoproteinemia; our findings indicate that CNVs in ABCA1 may be a previously unappreciated genetic determinant of low levels of HDL cholesterol. By coupling bioinformatic analyses with next-generation sequencing data, we can successfully assess the spectrum of genetic determinants of many dyslipidemias, including hypoalphalipoproteinemia.
- Published
- 2018
39. RT-PCR tests for sensitive detection of the major Ranunculus -infecting viruses: field and in vitro applications
- Author
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Sacco E., Borghi, Rabaglio M., Lenzi R., Ciuffo M., Ruffoni B., and Vaira A. M.
- Subjects
Ranunculus ,0106 biological sciences ,0301 basic medicine ,biology ,plant viruses ,Plant Science ,Horticulture ,Diagnostic tools ,biology.organism_classification ,01 natural sciences ,Virology ,diagnostic tools ,In vitro ,03 medical and health sciences ,030104 developmental biology ,Real-time polymerase chain reaction ,Italy ,Plant virus ,Genetics ,in vitro virus eradication ,shoot apical meristem culture ,Agronomy and Crop Science ,010606 plant biology & botany - Abstract
Buttercup (Ranunculus asiaticus, family Ranunculaceae) hybrids are considered a popular and valuable ornamental crop in Europe and are cultivated both for cut flowers and for pot or border plants. In the Liguria region of northern Italy, Ranunculus hybrid cultivation has dramatically increased over recent years and the related sanitary issues regarding virus infection need to be carefully monitored in order to maintain commercial competitiveness. Presently, ELISA is the most used diagnostic tool for virus diagnosis, but if 'mother plants' with high economic value are to be tested, more sensitive molecular diagnostic tools are needed, together with efficient protocols for in vitro culture to eradicate viruses. In this study, new RT-PCR protocols were tested on virus-infected Ranunculus hybrid plants, indexed for the 13 most important Ranunculus-infecting viruses. Rapid, uniform and effective procedures for molecular diagnosis were devised in order to promote an easy technology transfer from scientific institutions to laboratories of small and medium private enterprises. Moreover, an in vitro culture procedure was established for this species, which proved to be extremely effective in virus eradication. Advanced technology and sustainable quality production of high economic value plants are keys for future competitiveness in floriculture.
- Published
- 2018
40. Tailored approaches to rare sarcomas: current challenges and future prospects
- Author
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Mehdi Brahmi, Philippe A. Cassier, Justine Gantzer, and Lauriane Eberst
- Subjects
Pharmacology ,medicine.medical_specialty ,business.industry ,medicine.disease ,Diagnostic tools ,Variety (cybernetics) ,Drug Discovery ,Genetics ,medicine ,Molecular Medicine ,Medical physics ,Sarcoma ,business ,Rare disease - Abstract
Introduction: Based on the emergence of new molecular diagnostic tools over the past decade, sarcomas now gather a variety of rare histological and molecular subtypes. Here, the authors sum...
- Published
- 2018
41. Tissue and plasma proteomics for early stage cancer detection
- Author
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Canhua Huang, Liyuan Peng, Edouard C. Nice, Kui Wang, Mark S. Baker, and David I. Cantor
- Subjects
Proteomics ,0301 basic medicine ,Proteome ,Diagnostic tools ,Bioinformatics ,medicine.disease_cause ,Biochemistry ,03 medical and health sciences ,Early-stage cancer ,0302 clinical medicine ,Neoplasms ,Biomarkers, Tumor ,Genetics ,medicine ,Animals ,Humans ,Biomarker discovery ,Molecular Biology ,Neoplasm Staging ,Disease surveillance ,business.industry ,Computational Biology ,Cancer ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Plasma proteomics ,business ,Carcinogenesis ,Biotechnology - Abstract
The pursuit of novel and effective biomarkers is essential in the struggle against cancer, which is a leading cause of mortality worldwide. Biomarkers can be used as specific diagnostic tools, prognostic predictors, markers of the development of therapeutic resistance or even as therapeutic targets themselves. Through the application of sensitive and specific proteomic techniques, oncoproteomics investigates the proteins associated with cancer processes, to better understand their biological function/s and their associated pathways during tumorigenesis. Such studies seek to identify both potential biomarkers and drug targets in order to improve patient survival and quality of life whilst reducing the global health budget. Tissue and plasma are the most commonly utilised biological samples for such studies as they are readily available, non-invasive and generally acceptable. Here, we outline the relative advantages and disadvantages of the most frequently used techniques for cancer diagnosis, prognosis, treatment and surveillance, concentrating on the latest advances and application of tissue and plasma proteomics for novel cancer biomarker discovery and disease surveillance.
- Published
- 2018
42. Use of next-generation sequencing to detect LDLR gene copy number variation in familial hypercholesterolemia
- Author
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Henian Cao, Robert A. Hegele, Michael A. Iacocca, Jacqueline S. Dron, Adam D. McIntyre, Jian Wang, and John F. Robinson
- Subjects
0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,lipid and lipoprotein metabolism ,Concordance ,Familial hypercholesterolemia ,QD415-436 ,030204 cardiovascular system & hematology ,Biology ,Biochemistry ,DNA sequencing ,diagnostic tools ,LDL ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,medicine ,Multiplex ,Multiplex ligation-dependent probe amplification ,Copy-number variation ,molecular biology/genetics ,coronary heart disease ,Genetic testing ,Genetics ,lipoprotein receptors ,medicine.diagnostic_test ,Cell Biology ,medicine.disease ,3. Good health ,030104 developmental biology ,LDL receptor - Abstract
Familial hypercholesterolemia (FH) is a heritable condition of severely elevated LDL cholesterol, caused predominantly by autosomal codominant mutations in the LDL receptor gene (LDLR). In providing a molecular diagnosis for FH, the current procedure often includes targeted next-generation sequencing (NGS) panels for the detection of small-scale DNA variants, followed by multiplex ligation-dependent probe amplification (MLPA) in LDLR for the detection of whole-exon copy number variants (CNVs). The latter is essential because ∼10% of FH cases are attributed to CNVs in LDLR; accounting for them decreases false negative findings. Here, we determined the potential of replacing MLPA with bioinformatic analysis applied to NGS data, which uses depth-of-coverage analysis as its principal method to identify whole-exon CNV events. In analysis of 388 FH patient samples, there was 100% concordance in LDLR CNV detection between these two methods: 38 reported CNVs identified by MLPA were also successfully detected by our NGS method, while 350 samples negative for CNVs by MLPA were also negative by NGS. This result suggests that MLPA can be removed from the routine diagnostic screening for FH, significantly reducing associated costs, resources, and analysis time, while promoting more widespread assessment of this important class of mutations across diagnostic laboratories.
- Published
- 2017
43. The Revolution Continues: Newly Discovered Systems Expand the CRISPR-Cas Toolkit
- Author
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Ramya Sundaresan, Dipali G. Sashital, Rakhi Rajan, Karthik Murugan, and Kesavan Babu
- Subjects
Models, Molecular ,0301 basic medicine ,Transcription, Genetic ,Protein Conformation ,Computational biology ,Biology ,Diagnostic tools ,Article ,03 medical and health sciences ,Endonuclease ,Bacterial Proteins ,Protein Domains ,Genome editing ,Humans ,CRISPR ,Bacteriophages ,Clustered Regularly Interspaced Short Palindromic Repeats ,Guide RNA ,Molecular Biology ,Gene Editing ,Genetics ,Genome ,Bacteria ,Cas9 ,Cell Biology ,Endonucleases ,eye diseases ,humanities ,030104 developmental biology ,embryonic structures ,biology.protein ,CRISPR-Cas Systems ,Mobile genetic elements ,Genetic Engineering ,human activities ,RNA, Guide, Kinetoplastida - Abstract
CRISPR–Cas systems defend prokaryotes against bacteriophages and mobile genetic elements and serve as the basis for revolutionary tools for genetic engineering. Class 2 CRISPR–Cas systems use single Cas endonucleases paired with guide RNAs to cleave complementary nucleic acid targets, enabling programmable sequence-specific targeting with minimal machinery. Recent discoveries of previously unidentified CRISPR–Cas systems have uncovered a deep reservoir of potential biotechnological tools beyond the well-characterized Type II Cas9 systems. Here we review the current mechanistic understanding of newly discovered single-protein Cas endonucleases. Comparison of these Cas effectors reveals substantial mechanistic diversity, underscoring the phylogenetic divergence of related CRISPR–Cas systems. This diversity has enabled further expansion of CRISPR–Cas biotechnological toolkits, with wide-ranging applications from genome editing to diagnostic tools based on various Cas endonuclease activities. These advances highlight the exciting prospects for future tools based on the continually expanding set of CRISPR–Cas systems.
- Published
- 2017
44. Puumala hantavirus genetic variability in an endemic region (Northern Sweden)
- Author
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Johansson, Patrik, Olsson, Gert E., Low, Hwee-Teng, Bucht, Göran, Ahlm, Clas, Juto, Per, and Elgh, Fredrik
- Subjects
- *
CLETHRIONOMYS , *HANTAVIRUSES , *VIRUSES , *GENETICS , *PHYLOGENY - Abstract
Abstract: Puumala hantavirus (PUUV), naturally harboured and shed by bank voles (Myodes [Clethrionomys] glareolus), is the etiological agent to nephropathia epidemica (NE), a mild haemorrhagic fever with renal syndrome. Both host and virus are found throughout much of the European continent and in northern Sweden NE is the second most prevalent serious febrile viral infection after influenza. The reliability of diagnostics by PCR depends on genetic variability for the detection of viral nucleic acids in unknown samples. In the present study we evaluated the genetic variability of PUUV isolated from bank voles in an area of northern Sweden highly endemic for NE. Genetic variability among bank voles was also investigated to evaluate co-evolutionary patterns. We found that the viral sequence appeared stable across the 80km study region, with the exception of the southernmost sampling site, which differed from its nearest neighbour by 7%, despite a geographical separation of only 10km. The southernmost sampling site demonstrated a higher degree of genetic similarity to PUUV previously isolated 100km south thereof; two locations appear to constitute a separate PUUV phylogenetic branch. In contrast to the viral genome, no phylogenetic variance was observed in the bank vole mtDNA in this study. Previous studies have shown that as a result of terrestrial mammals’ postglacial re-colonization routes, bank voles and associated PUUV of a southern and a northern lineage established a dichotomous contact zone across the Scandinavian peninsula approximately 100–150km south of the present study sites. Our observations reveal evolutionary divergence of PUUV that has led to dissimilarities within the restricted geographical scale of the northern host re-colonization route as well. These results suggest either a static situation in which PUUV strains are regionally well adapted, or an ongoing process in which strains of PUUV circulate on a geographical scale not yet reliably described. [Copyright &y& Elsevier]
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- 2008
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45. Evaluating the use of PCR for diagnosing invasive aspergillosis
- Author
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Birgit Spiess, Mark Reinwald, Tobias Boch, Dieter Buchheidt, and Wolf-Karsten Hofmann
- Subjects
0301 basic medicine ,medicine.medical_specialty ,030106 microbiology ,Biology ,Diagnostic tools ,Aspergillosis ,Polymerase Chain Reaction ,Sensitivity and Specificity ,Pathology and Forensic Medicine ,law.invention ,Aspergillus fumigatus ,03 medical and health sciences ,law ,Internal medicine ,Genetics ,medicine ,Humans ,DNA, Fungal ,Intensive care medicine ,Molecular Biology ,Polymerase chain reaction ,Invasive Pulmonary Aspergillosis ,Aspergillus species ,High risk patients ,Hematology ,Sequence Analysis, DNA ,medicine.disease ,biology.organism_classification ,Molecular Diagnostic Techniques ,Immunology ,Molecular Medicine ,Early phase - Abstract
Aspergillus species, primarily Aspergillus fumigatus, are still the most emerging fungal pathogens. Within recent years, novel molecular methods have been developed to improve the diagnosis of life-threatening invasive aspergillosis in high risk patients. Especially patients with malignant hematological diseases undergoing intensive chemotherapy are at risk and mortality rates are exceptionally high, in part due to difficulties and delays in establishing a microbiologic diagnosis. Early diagnosis and treatment are crucial for an adequate therapeutical management, but, however, are hardly achieved in the clinical setting because most of the current conventional diagnostic tools either lack specificity or acceptable sensitivity at the critical early phase of the infection. Areas covered: To review the clinical value, advantages and problems as well as drawbacks of molecular approaches, especially polymerase chain reaction (PCR)-based assays to detect genomic DNA of Aspergillus species in clinical samples of immunocompromised, especially hematological patients at high risk for IA, a comprehensive review of the literature was performed and expert opinion was expressed. Expert commentary: The results of numerous attempts to diagnose invasive aspergillosis by PCR-based detection of fungal genome in clinical samples highlight the potential of the PCR technique to improve early diagnosis of invasive aspergillosis in patients with hematological malignancies during intensive antineoplastic treatment, combined with imaging surveillance and serologic diagnostic tools. Further comparative validation of reliable assays in prospective multicenter studies is mandatory and urgently needed in order to establish a harmonization and standardization, so that 'gold standard assays' may be incorporated into diagnostic and therapeutic algorithms that improve the prognosis of patients with life-threatening infections caused by Aspergillus species.
- Published
- 2017
46. Epigenetics studies of fetal alcohol spectrum disorder: where are we now?
- Author
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Alexandre A. Lussier, Joanne Weinberg, and Michael S. Kobor
- Subjects
0301 basic medicine ,clinical cohorts ,Cancer Research ,Embryonic Development ,Biology ,Diagnostic tools ,Health outcomes ,Epigenesis, Genetic ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,Animals ,Humans ,Epigenetics ,Fetal programming ,development ,prenatal alcohol exposure ,epigenetics ,FASD ,DNA Methylation ,Chromatin Assembly and Disassembly ,animal models ,3. Good health ,fetal programming ,030104 developmental biology ,Fetal Alcohol Spectrum Disorders ,Fetal Alcohol Spectrum Disorder ,Prenatal alcohol exposure ,Perspective ,Reprogramming ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Adverse in utero events can alter the development and function of numerous physiological systems, giving rise to lasting neurodevelopmental deficits. In particular, data have shown that prenatal alcohol exposure can reprogram neurobiological systems, altering developmental trajectories and resulting in increased vulnerability to adverse neurobiological, behavioral and health outcomes. Increasing evidence suggests that epigenetic mechanisms are potential mediators for the reprogramming of neurobiological systems, as they may provide a link between the genome, environmental conditions and neurodevelopmental outcomes. This review outlines the current state of epigenetic research in fetal alcohol spectrum disorder, highlighting the role of epigenetic mechanisms in the reprogramming of neurobiological systems by alcohol and as potential diagnostic tools for fetal alcohol spectrum disorder. We also present an assessment of the current limitations in studies of prenatal alcohol exposure, and highlight the future steps needed in the field.
- Published
- 2017
47. Repertoire sequencing and the statistical ensemble approach to adaptive immunity
- Author
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Thierry Mora, Curtis G. Callan, and Aleksandra M. Walczak
- Subjects
0301 basic medicine ,Statistical ensemble ,Genetics ,Applied Mathematics ,Repertoire ,Computational biology ,Biology ,Acquired immune system ,Diagnostic tools ,General Biochemistry, Genetics and Molecular Biology ,DNA sequencing ,Computer Science Applications ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Modeling and Simulation ,Drug Discovery ,Degeneracy (biology) ,030215 immunology ,Sequence (medicine) - Abstract
The recent advent of high-throughput sequencing of immune receptors allows for the study of immune repertoires in unprecedented depth. This should eventually lead to a better understanding of basic immune function and the development of valuable new diagnostic tools. However, the interpretation of these new sequence data can be difficult because the relationship between receptor sequence and immune specificity is generally unknown. In particular, phenotypically similar repertoires will in general be completely different at the sequence level because of cross-reactivity. Here we argue that sequence repertoires need to be considered statistically to overcome this functional degeneracy. New tools are needed to extract the functionally relevant statistical features from sequence data, separating them from individual-specific, stochastic, and other non-reproducible effects.
- Published
- 2017
48. Novel Capsular Polysaccharide Loci and New Diagnostic Tools for High-Throughput Capsular Gene Typing in Streptococcus suis
- Author
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Xiaotong Qiu, Xuemei Bai, Ruiting Lan, Jianguo Xu, and Han Zheng
- Subjects
0301 basic medicine ,Serotype ,Streptococcus suis ,Swine ,030106 microbiology ,Prevalence ,Diagnostic tools ,Applied Microbiology and Biotechnology ,03 medical and health sciences ,Bacterial Proteins ,Streptococcal Infections ,Animals ,Typing ,Gene ,Pathogen ,Bacterial Capsules ,Swine Diseases ,Genetics ,Autoagglutination ,Ecology ,biology ,Public and Environmental Health Microbiology ,biology.organism_classification ,Bacterial Typing Techniques ,High-Throughput Screening Assays ,Food Science ,Biotechnology - Abstract
Streptococcus suis is an important pathogen of pigs and may cause serious disease in humans. Serotyping is an important tool for detection and epidemiological studies of S. suis . Thirty-three reference serotypes and nine novel cps loci (NCLs) are recognized in S. suis . To gain a better understanding of the prevalence and genetic characteristics of NCLs, we investigated the serotype identity of 486 isolates isolated between 2013 and 2015 in China by capsular gene typing methods. Two hundred seventy-six isolates carried NCLs belonging to 16 groups, 8 of which appear to have not been reported previously. These isolates showed autoagglutination, polyagglutination, or nonagglutination with reference antisera and thus were nonserotypeable. Almost all isolates carrying the unknown NCLs were encapsulated, with various capsular thicknesses, indicating that they are most likely novel serotypes. To simultaneously identify the currently recognized 17 NCLs, an 18-plex detection system using the Luminex xTAG universal array technology was developed. Our data also provide valuable genetic information for monitoring the variations within NCLs by investigating the genetic characteristics of different subtypes within NCLs. IMPORTANCE Nonserotypeable Streptococcus suis isolates have been reported in many studies, and 9 novel cps loci (NCLs) have already been identified in nonserotypeable isolates. Moreover, novel cps loci are continually being found. The main purpose of this study was to investigate the prevalence and characteristics of NCLs in S. suis isolates recovered between 2013 and 2015 in China. This study provides valuable genetic information for monitoring the variations within NCLs. Meanwhile, a fast and cost-effective 18-plex detection system that can simultaneously identify the currently recognized 17 NCLs was developed in this study. This system will serve as a valuable tool for detecting known and identifying additional novel cps loci among nonserotypeable S. suis isolates.
- Published
- 2016
49. A novel assessing system for predicting the prognosis of gastric cancer
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Min Shi, Yulin Liao, Shaowei Zhu, Jiani Wu, Rui Zhou, Jianhua Wu, Jingwen Zhang, Wangjun Liao, Dongqiang Zeng, Huiying Sun, Jianping Bin, and Siheng Lin
- Subjects
Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Stromal cell ,RNA, Untranslated ,medicine.medical_treatment ,Biology ,Diagnostic tools ,Young Adult ,Immune system ,Stomach Neoplasms ,Internal medicine ,Genetics ,medicine ,Biomarkers, Tumor ,Tumor Microenvironment ,Humans ,Gene Regulatory Networks ,RNA, Messenger ,Gene ,Survival analysis ,Aged ,Retrospective Studies ,Aged, 80 and over ,Tumor microenvironment ,Immunotherapy ,Middle Aged ,Non-coding RNA ,Prognosis ,Gene Expression Regulation, Neoplastic ,Survival Rate ,MicroRNAs ,Female ,Follow-Up Studies - Abstract
Aim: To develop novel diagnostic tools that can predict the prognosis of gastric cancer. Material & methods: Using RNA expression data from The Cancer Genome Atlas and Gene Expression Omnibus, we established protein-coding RNAs-noncoding RNAs-tumor microenvironment type (PNM) scores, which contain signatures of tumor protein coding genes (P), tumor noncoding genes (N) and immune/stroma cells in tumor microenvironment (M) to predict the prognosis of gastric cancer. Results & conclusion: Based on PNM scores, gastric cancer patients were divided into three subgroups and Kaplan–Meier survival curves revealed significant differences among the subgroups (p
- Published
- 2019
50. Essential genetic findings in neurodevelopmental disorders
- Author
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Ana Rita Cardoso, Maria João Prata, António Amorim, Mónica Lopes-Marques, Catarina Serrano, Luísa Azevedo, Raquel M. Silva, Instituto de Investigação e Inovação em Saúde, and Veritati - Repositório Institucional da Universidade Católica Portuguesa
- Subjects
Mutation / genetics ,lcsh:QH426-470 ,DNA Copy Number Variations ,Genotype ,Population ,lcsh:Medicine ,Neurodevelopmental Disorders / genetics ,de novo mutations ,Gene interaction ,Computational biology ,Review ,Deleterious mutations ,Biology ,Diagnostic tools ,03 medical and health sciences ,0302 clinical medicine ,Genotype-phenotype distinction ,DNA Copy Number Variations / genetics ,Drug Discovery ,Genetics ,Humans ,Genetic Predisposition to Disease ,Copy-number variation ,Indel ,education ,Brain-related genes ,Molecular Biology ,De novo mutations ,Genetic Association Studies ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,Risk alleles ,lcsh:R ,Neurodevelopmental disorders ,Human genetics ,3. Good health ,lcsh:Genetics ,Mutation ,Molecular Medicine ,Gene-Environment Interaction ,Neurodevelopmental Disorders / pathology ,Polymorphisms ,030217 neurology & neurosurgery - Abstract
Neurodevelopmental disorders (NDDs) represent a growing medical challenge in modern societies. Ever-increasing sophisticated diagnostic tools have been continuously revealing a remarkably complex architecture that embraces genetic mutations of distinct types (chromosomal rearrangements, copy number variants, small indels, and nucleotide substitutions) with distinct frequencies in the population (common, rare, de novo). Such a network of interacting players creates difficulties in establishing rigorous genotype-phenotype correlations. Furthermore, individual lifestyles may also contribute to the severity of the symptoms fueling a large spectrum of gene-environment interactions that have a key role on the relationships between genotypes and phenotypes.Herein, a review of the genetic discoveries related to NDDs is presented with the aim to provide useful general information for the medical community. This work was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia, in the framework of the project POCI-01-0145-FEDER-007274 to i3S and UID/ BIM/04501/2013 and UID/BIM/04501/2019 to iBiMED, as well as by national funds (OE), through FCT, in the scope of the framework contract foreseen in the numbers 4, 5, and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19 to RMS, and by FCT research project POCI-01-0145-FEDER-29723. ARC and CS hold FCT PhD fellowships (SFRH/BD/141702/2018-ARC and SFRH/BD/137925/2018-CS). Funders had no role in the design, collection, analysis, interpretation of the data, and writing of the manuscript.
- Published
- 2019
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