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Frontiers in Cellular and Infection... 2022A prosthetic joint infection (PJI) is a devastating complication following total joint arthroplasties with poor prognosis. Identifying an accurate and prompt diagnostic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A prosthetic joint infection (PJI) is a devastating complication following total joint arthroplasties with poor prognosis. Identifying an accurate and prompt diagnostic method is particularly important for PJI. Recently, the diagnostic value of metagenomic next-generation sequencing (mNGS) in detecting PJI has attracted much attention, while the evidence of its accuracy is quite limited. Thus, this study aimed to evaluate the accuracy of mNGS for the diagnosis of PJI.
METHODS
We summarized published studies to identify the potential diagnostic value of mNGS for PJI patients by searching online databases using keywords such as "prosthetic joint infection", "PJI", and "metagenomic sequencing". Ten of 380 studies with 955 patients in total were included. The included studies provided sufficient data for the completion of 2-by-2 tables. We calculated the sensitivity, specificity, and area under the SROC curve (AUC) to evaluate mNGS for PJI diagnosis.
RESULTS
We found that the pooled diagnostic sensitivity and specificity of mNGS for PJI were 0.93 (95% CI, 0.83 to 0.97) and 0.95 (95% CI, 0.92 to 0.97), respectively. Positive and negative likelihood ratios were 18.3 (95% CI, 10.9 to 30.6) and 0.07 (95% CI, 0.03 to 0.18), respectively. The area under the curve was 0.96 (95% CI, 0.93 to 0.97).
CONCLUSION
Metagenomic next-generation sequencing displays high accuracy in the diagnosis of PJI, especially for culture-negative cases.
Topics: Arthritis, Infectious; High-Throughput Nucleotide Sequencing; Humans; Metagenomics; Prosthesis-Related Infections; Sensitivity and Specificity; Synovial Fluid
PubMed: 35755833
DOI: 10.3389/fcimb.2022.875822 -
International Journal of Molecular... Jan 2023Multiple Sclerosis (MS) is, to date, an incurable disease of the nervous system characterized by demyelination. Several genetic mutations are associated with the disease... (Review)
Review
Multiple Sclerosis (MS) is, to date, an incurable disease of the nervous system characterized by demyelination. Several genetic mutations are associated with the disease but they are not able to explain all the diagnosticated cases. Thus, it is suggested that altered gene expression may play a role in human pathologies. In this review, we explored the role of the transcriptomic profile in MS to investigate the main altered biological processes and pathways involved in the disease. Herein, we focused our attention on RNA-seq methods that in recent years are producing a huge amount of data rapidly replacing microarrays, both with bulk and single-cells. The studies evidenced that different MS stages have specific molecular signatures and non-coding RNAs may play a key role in the disease. Sex-dependence was observed before and after treatments used to alleviate symptomatology activating different biological processes in a drug-dependent manner. New pathways, such as neddylation, were found deregulated in MS and inflammation was linked to neuron degeneration areas through spatial transcriptomics. It is evident that the use of RNA-seq in the study of complex pathologies, such as MS, is a valid strategy to shed light on new involved mechanisms.
Topics: Humans; Transcriptome; Multiple Sclerosis; Gene Expression Profiling; RNA-Seq
PubMed: 36674968
DOI: 10.3390/ijms24021448 -
International Journal of Infectious... May 2024Early diagnosis of infectious diseases remains a challenge. This study assessed the diagnostic value of mNGS in infections and explored the effect of various factors on... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Early diagnosis of infectious diseases remains a challenge. This study assessed the diagnostic value of mNGS in infections and explored the effect of various factors on the accuracy of mNGS.
METHODS
An electronic article search of PubMed, Cochrane Library, and Embase was performed. A total of 85 papers were eligible for inclusion and analysis. Stata 12.0 was used for statistical calculation to evaluate the efficacy of mNGS for the diagnosis of infectious diseases.
RESULTS
The AUC of 85 studies was 0.88 (95%CI, 0.85-0.90). The AUC of the clinical comprehensive diagnosis and conventional test groups was 0.92 (95%CI, 0.89-0.94) and 0.82 (95%CI, 0.78-0.85), respectively. The results of subgroup analysis indicated that the PLR and NLR were 12.67 (95%CI, 6.01-26.70) and 0.05 (95%CI, 0.03-0.10), respectively, in arthrosis infections. The PLR was 24.41 (95%CI, 5.70-104.58) in central system infections and the NLR of immunocompromised patients was 0.08 (95%CI, 0.01-0.62).
CONCLUSION
mNGS demonstrated satisfactory diagnostic performance for infections, especially for bone and joint infections and central system infections. Moreover, mNGS also has a high value in the exclusion of infection in immunocompromised patients.
Topics: Humans; High-Throughput Nucleotide Sequencing; Arthritis, Infectious; Immunocompromised Host; Metagenome; Metagenomics; Sepsis; Communicable Diseases; Sensitivity and Specificity
PubMed: 38458421
DOI: 10.1016/j.ijid.2024.106996 -
International Journal of Molecular... Jan 2023The prediction of chronological age from methylation-based biomarkers represents one of the most promising applications in the field of forensic sciences. Age-prediction... (Review)
Review
The prediction of chronological age from methylation-based biomarkers represents one of the most promising applications in the field of forensic sciences. Age-prediction models developed so far are not easily applicable for forensic caseworkers. Among the several attempts to pursue this objective, the formulation of single-locus models might represent a good strategy. The present work aimed to develop an accurate single-locus model for age prediction exploiting , a gene for which epigenetic alterations are most highly correlated with age. We carried out a systematic review of different published pyrosequencing datasets in which methylation of the promoter was analysed to formulate age prediction models. Nine of these, with available datasets involving 2298 participants, were selected. We found that irrespective of which model was adopted, a very strong relationship between methylation levels and age exists. In particular, the model giving the best age-prediction accuracy was the gradient boosting regressor with a prediction error of about 5.5 years. The findings reported here strongly support the use of for the formulation of a single-locus epigenetic model, but the inclusion of additional, non-redundant markers is a fundamental requirement to apply a molecular model to forensic applications with more robust results.
Topics: Child, Preschool; Humans; Aging; CpG Islands; DNA Methylation; Epigenesis, Genetic; Forensic Genetics
PubMed: 36768576
DOI: 10.3390/ijms24032254 -
Oral Diseases Jul 2021This systematic review was to evaluate the change of oral microbiome based on next-generation sequencing (NGS)-metagenomic analysis following periodontal interventions... (Review)
Review
OBJECTIVES
This systematic review was to evaluate the change of oral microbiome based on next-generation sequencing (NGS)-metagenomic analysis following periodontal interventions among systematically healthy subjects.
MATERIALS AND METHODS
A structured search strategy consisting of "metagenomics" and "oral diseases" was applied to PubMed, EMBASE, and Web of Science to identify effective papers. The included studies were original studies published in English, using metagenomic approach to analyze the effectiveness of periodontal intervention on oral microbiome among systematically healthy human subjects with periodontitis.
RESULTS
A total of 12 papers were included in this review. Due to the heterogeneity of selected study, quantitative analysis was not performed. The findings as to how alpha diversity changed after interventions were not consistent across studies. Six studies illustrated clear separation of microbial composition between dental plaque samples collected before and after intervention using principal coordinates/component analysis. The most commonly detected genera before intervention were Porphyromonas, Treponema, Tannerella, and Prevotella, while Streptococcus and Actinomyces usually increased and became the dominant genera after intervention. Correlation network analysis revealed that after intervention, the topology of network was different compared to the corresponding pre-interventional samples.
CONCLUSION
Existing evidence of metagenomic studies depicts a complex change in oral microbiome after periodontal intervention.
Topics: High-Throughput Nucleotide Sequencing; Humans; Metagenome; Metagenomics; Microbiota; Periodontitis
PubMed: 32390250
DOI: 10.1111/odi.13405 -
European Journal of Medical Research Jul 2023RNA sequencing has emerged as the standard method for transcriptome profiling of several human diseases. We performed a systematic review detailing the state of RNA-seq...
RNA sequencing has emerged as the standard method for transcriptome profiling of several human diseases. We performed a systematic review detailing the state of RNA-seq analyses in Africa from its inception till February 2022. Our goal was to provide an update on the state of RNA-seq analyses in Africa, including research gaps, funding information, participants information, authorship and collaborations. Following the PRISMA guidelines, we performed an exhaustive literature search for RNA-seq studies conducted in Africa, using PubMed, Scopus and Academic Search Complete (EBSCOhost). The output was exported to Endnote X9 for analyses. The initial literature search yielded 10,369 articles spread across PubMed (4916), Scopus (4847) and EBSCOhost (580). By applying our exclusion criteria, 28 full-text articles remained and were thoroughly analyzed. Overall, 17 human diseases were studied, including cancers (10/28), infectious disease (4/28), parasitic disease (4/28), autoimmune disorders (2/28) and neglected tropical diseases (2/28). Majority of the articles were published in PLoS Pathogens, BioMed Central and Nature. The National Institutes of Health (42.4%), the Bill & Melinda Gates Foundation (7.5%) and the Wellcome Trust (7.5%) were the top funders of the research studies. Eleven African countries contributed to the participant group, with 57% located in Eastern Africa, 23.1% from Western and 16.7% from Southern Africa. The extremely low number of RNA-seq research studies in Africa is worrying and calls for an immediate investment in research by the African governments. The funding agencies and institutional review boards should also ensure that African collaborators are treated equitably in the course of the research projects.
Topics: United States; Humans; RNA-Seq; Africa; Gene Expression Profiling; Autoimmune Diseases; Evidence Gaps
PubMed: 37480073
DOI: 10.1186/s40001-023-01206-3 -
Journal of Gastrointestinal and Liver... Jun 2020The coexistence of RAS and BRAF mutations is extremely rare, occurring in approximately 0.05% of patients with metastatic colorectal cancer (mCRC). Starting from a case...
BACKGROUND AND AIMS
The coexistence of RAS and BRAF mutations is extremely rare, occurring in approximately 0.05% of patients with metastatic colorectal cancer (mCRC). Starting from a case presentation, this review aims to examine the prevalence, clinical, histopathological and molecular features of tumors with concomitant mutations.
METHODS
Case report and systematic review. We performed a systematic literature search in PubMed and EMBASE using the following MeSH terms: "coexistence" OR "concomitant" AND "RAS" AND "BRAF" AND "colorectal cancer" from the inception of the databases onwards.
RESULTS
We present the case of a 53-year-old man diagnosed with metastatic rectal adenocarcinoma with both a KRAS and a BRAF mutation. The review included eleven papers reporting on a total of 30 mCRC cases with concomitant RAS and BRAF mutations. The male/female ratio was 11/5. The average age was 58.5 years. The tumor was located in nine cases on the right colon and in two cases in the left colon. 43.3% of subjects had liver metastases, and 6.6% had lung metastases. Next-generation sequencing (NGS) was used in 36.6% of cases and polymerase chain reaction (PCR) in 16.6% of cases. KRAS mutations were present in 83.3% of patients and NRAS mutations in 16.6% of patients. Survival could be assessed in 10 patients and the median was 21.1 months (about 30% lower than the survival in the general mCRC population).
CONCLUSION
The results of this systematic review suggest the need to design a cohort study (either prospective or retrospective) to better characterize the patients with concomitant RAS and BRAF mutations and to establish the optimal treatment for this rare situation.
Topics: Adenocarcinoma; Antineoplastic Protocols; Colorectal Neoplasms; Female; GTP Phosphohydrolases; High-Throughput Nucleotide Sequencing; Humans; Liver Neoplasms; Lung Neoplasms; Male; Membrane Proteins; Middle Aged; Mutation; Neoplasm Metastasis; Neoplasm Staging; Pharmacogenomic Testing; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Rectal Neoplasms; Rectum; Response Evaluation Criteria in Solid Tumors; Survival Analysis
PubMed: 32530992
DOI: 10.15403/jgld-1003 -
NPJ Biofilms and Microbiomes May 2024Childhood stunting is associated with impaired cognitive development and increased risk of infections, morbidity, and mortality. The composition of the enteric... (Review)
Review
Childhood stunting is associated with impaired cognitive development and increased risk of infections, morbidity, and mortality. The composition of the enteric microbiota may contribute to the pathogenesis of stunting. We systematically reviewed and synthesized data from studies using high-throughput genomic sequencing methods to characterize the gut microbiome in stunted versus non-stunted children under 5 years in LMICs. We included 14 studies from Asia, Africa, and South America. Most studies did not report any significant differences in the alpha diversity, while a significantly higher beta diversity was observed in stunted children in four out of seven studies that reported beta diversity. At the phylum level, inconsistent associations with stunting were observed for Bacillota, Pseudomonadota, and Bacteroidota phyla. No single genus was associated with stunted children across all 14 studies, and some associations were incongruent by specific genera. Nonetheless, stunting was associated with an abundance of pathobionts that could drive inflammation, such as Escherichia/Shigella and Campylobacter, and a reduction of butyrate producers, including Faecalibacterium, Megasphera, Blautia, and increased Ruminoccoccus. An abundance of taxa thought to originate in the oropharynx was also reported in duodenal and fecal samples of stunted children, while metabolic pathways, including purine and pyrimidine biosynthesis, vitamin B biosynthesis, and carbohydrate and amino acid degradation pathways, predicted linear growth. Current studies show that stunted children can have distinct microbial patterns compared to non-stunted children, which could contribute to the pathogenesis of stunting.
Topics: Child, Preschool; Humans; Infant; Infant, Newborn; Bacteria; Feces; Gastrointestinal Microbiome; Growth Disorders; High-Throughput Nucleotide Sequencing
PubMed: 38782939
DOI: 10.1038/s41522-024-00517-5 -
The Science of the Total Environment Mar 2024Livestock facilities are widely regarded as reservoirs of infectious disease, owing to their abundance in particulate matter (PM) and microbial bioaerosols. Over the... (Review)
Review
Livestock facilities are widely regarded as reservoirs of infectious disease, owing to their abundance in particulate matter (PM) and microbial bioaerosols. Over the past decade, bioaerosol studies have increasingly utilised high throughput sequencing (HTS) to achieve superior throughput, taxonomic resolution, and the detection of unculturable organisms. However, the prevailing focus on amplicon sequencing has limited the identification of viruses and microbial taxa at the species-level. Herein, a literature search was conducted to identify methods capable of overcoming the aforementioned limitations. Screening 1531 international publications resulted in 29 eligible for review. Metagenomics capable of providing rich insights were identified in only three instances. Notably, long-read sequencing was not utilised for metagenomics. This review also identified that sample collection methods lack a uniform approach, highlighted by the differences in sampling equipment, flow rates and durations. Further heterogeneity was introduced by the unique sampling conditions, which makes it challenging to ground new findings within the established literature. For instance, winter was associated with increased microbial abundance and antimicrobial resistance, yet less alpha diversity. Researchers implementing metagenomics into the livestock environment should consider season, the microclimate, and livestock growth stage as influential upon their findings. Considering the increasing accessibility of long-read sequencing, future research should explore its viability within a novel uniform testing protocol for bioaerosol emissions.
Topics: Animals; Livestock; Metagenomics; Particulate Matter; High-Throughput Nucleotide Sequencing; Aerosols
PubMed: 38331298
DOI: 10.1016/j.scitotenv.2024.170722 -
Cancer Treatment Reviews Feb 2020Molecular profiling of tumor derived cell free DNA (cfDNA) is gaining ground as a prognostic and predictive biomarker. However to what extent cfDNA reflects the full... (Meta-Analysis)
Meta-Analysis
Molecular profiling of tumor derived cell free DNA (cfDNA) is gaining ground as a prognostic and predictive biomarker. However to what extent cfDNA reflects the full metastatic landscape as currently determined by tumor tissue analysis remains controversial. Though technically challenging, whole exome sequencing (WES) of cfDNA enables thorough evaluation of somatic alterations. Here, we review the feasibility of WES of cfDNA and determine the sensitivity of WES-detected single nucleotide variants (SNVs) in cfDNA on individual patient data level using paired tumor tissue as reference (sharedSNVsAlltissueSNVs×100%). The pooled sensitivity was 50% (95% credible interval (CI): 29-72%). The tissue mutant allele frequency (MAF) of variants exclusively identified in tissue was significantly lower (12.5%, range: 0.5-18%) than the tissue MAF of variants identified in both tissue and cfDNA (23.9%, range: 17-38%), p = 0.004. The overall agreement (sharedSNVsAllSNVs×100%)between SNVs in cfDNA and tumor tissue was 31% (95% CI: 15-49%). The number of detected SNVs was positively correlated with circulating tumor DNA (ctDNA) fraction (p = 0.016). A sub analysis of samples with ctDNA fractions ≥ 25% improved the sensitivity to 69% (95% CI: 46-89%) and agreement to 46% (95% CI: 36-59%), suggesting that WES is mainly feasible for patients with high ctDNA fractions. Pre- and post-analytical procedures were highly variable between studies rendering comparisons problematic. In conclusion, various aspects of WES of cfDNA are largely in its investigative phase, standardization of methodologies is highly needed to bring this promising technique to its clinical potential.
Topics: Bayes Theorem; Biomarkers, Tumor; Cell-Free Nucleic Acids; Circulating Tumor DNA; DNA, Neoplasm; High-Throughput Nucleotide Sequencing; Humans; Mutation; Neoplasms; Polymorphism, Single Nucleotide; Exome Sequencing
PubMed: 31874446
DOI: 10.1016/j.ctrv.2019.101951