ddPCR provides a sensitive test compared with GeneXpert MTB/RIF and mNGS for suspected Mycobacterium tuberculosis infection

IntroductionThe Metagenomics next-generation sequencing (mNGS) and GeneXpert MTB/RIF assay (Xpert) exhibited a sensitivity for tuberculosis (TB) diagnostic performance. Research that directly compared the clinical performance of ddPCR analysis, mNGS, and Xpert in mycobacterium tuberculosis complex (MTB) infection has not been conducted.MethodsThe study aimed to evaluate the diagnostic performance of ddPCR compared to mNGS and Xpert for the detection of MTB in multiple types of clinical samples. The final clinical diagnosis was used as the reference standard.ResultsOut of 236 patients with suspected active TB infection, 217 underwent synchronous testing for tuberculosis using ddPCR, Xpert, and mNGS on direct clinical samples. During follow-up, 100 out of 217 participants were diagnosed with MTB infection. Compared to the clinical final diagnosis, ddPCR produced the highest sensitivity of 99% compared with mNGS (86%) and Xpert (64%) for all active MTB cases. DiscussionTwenty-two Xpert-negative samples were positive in mNGS tests, which confirmed the clinical diagnosis results from ddPCR and clinical manifestation, radiologic findings. Thirteen mNGS-negative samples were positive in ddPCR assays, which confirmed the clinical final diagnosis.ddPCR provides a higher sensitive compared to Xpert and mNGS for MTB diagnosis, as defined by the high concordance between ddPCR assay and clinical final diagnosis

Clinical and epidemiologic characteristics of hospitalized patients with laboratory-confirmed respiratory syncytial virus infection in eastern china between 2009 and 2013: a retrospective study

Respiratory syncytial virus (RSV) is a leading cause of morbidity and mortality worldwide in children aged <5 years and older adults with acute lower respiratory infections (ALRIs). However, few studies regarding the epidemiology of hospitalizations for RSV infection have been performed previously in China. Here, we aimed to describe the clinical and epidemiologic characteristics of hospitalized patients with laboratory-confirmed RSV infection in eastern China. Active surveillance for hospitalized ALRI patients using a broad case definition based on symptoms was performed from 2009-2013 in 12 sentinel hospitals in eastern China. Clinical and epidemiologic data pertaining to hospitalized patients of all ages with laboratory-confirmed RSV infection by PCR assay were collected and analyzed in this study. From 2009 to 2013, 1046 hospitalized patients with laboratory-confirmed RSV infection were enrolled in this study, and 14.7% of patients had subtype A, 24.2% of patients had subtype B, 23.8% of patients with subtype not performed, and 37.3% of patients had RSV coinfections with other viruses. RSV and influenza coinfections (33.3%) were the most common coinfections noted in this study. Moreover, young children aged <5 years (89.1%, 932/1046), particularly young infants aged <1 year (43.3%, 453/1046), represented the highest proportion of patients with RSV infections. In contrast, older adults aged ?60 years (1.1%, 12/1046) represented the lowest proportion of patients with RSV infections among enrolled patients. The peak RSV infection period occurred mainly during autumn and winter, and 57% and 66% of patients exhibited symptoms such as fever (body temperature ?38°C) and cough separately. Additionally, only a small number of patients were treated with broad-spectrum antiviral drugs, and most of patients were treated with antimicrobial drugs that were not appropriate for RSV infection. RSV is a leading viral pathogen and a common cause of viral infection in young children aged <5 years with ALRIs in eastern China. Effective vaccines and antiviral agents targeting RSV are needed to mitigate its large public health impact

Variant Near FGF5 Has Stronger Effects on Blood Pressure in Chinese With a Higher Body Mass Index

The objective of this study was to investigate the genetic association of 4 candidate variants with blood pressure and test the modifying effects of environmental factors including age, sex, and body mass index (BMI)

Functional variants regulating LGALS1 (Galectin 1) expression affect human susceptibility to influenza A(H7N9)

The fatality of avian influenza A(H7N9) infection in humans was over 30%. To identify human genetic susceptibility to A(H7N9) infection, we performed a genome-wide association study (GWAS) involving 102 A(H7N9) patients and 106 heavily-exposed healthy poultry workers, a sample size critically restricted by the small number of human A(H7N9) cases. To tackle the stringent significance cutoff of GWAS, we utilized an artificial imputation program SnipSnip to improve the association signals. In single-SNP analysis, one of the top SNPs was rs13057866 of LGALS1. The artificial imputation (AI) identified three non-genotyped causal variants, which can be represented by three anchor/partner SNP pairs rs13057866/rs9622682 (AI P = 1.81 × 10-7), rs4820294/rs2899292 (2.13 × 10-7) and rs62236673/rs2899292 (4.25 × 10-7) respectively. Haplotype analysis of rs4820294 and rs2899292 could simulate the signal of a causal variant. The rs4820294/rs2899292 haplotype GG, in association with protection from A(H7N9) infection (OR = 0.26, P = 5.92 × 10-7) correlated to significantly higher levels of LGALS1 mRNA (P = 0.050) and protein expression (P = 0.025) in lymphoblast cell lines. Additionally, rs4820294 was mapped as an eQTL in human primary monocytes and lung tissues. In conclusion, functional variants of LGALS1 causing the expression variations are contributable to the differential susceptibility to influenza A(H7N9).link_to_OA_fulltex

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

Metodologia ekstrakcji wskaźnika stanu technicznego do modelowania i prognozowania degradacji przekładni mechanicznych

Condition monitoring and prognosis is a key issue in ensuring stable and reliable operation of mechanical transmissions. Wear in a mechanical transmission, which leads to the production of wear particles followed by severe wear, is a slow degradation process that can be monitored by spectral analysis of oil, but the actual degree of degradation is often difficult to evaluate in practical applications due to the complexity of multiple oil spectra. To solve this problem, a health index extraction methodology is proposed to better characterize the degree of degradation compared to relying solely on spectral oil data, which leads to an accurate estimation of the failure time when the transmission no longer fulfils its function. The health index is extracted using a weighted average method with selection of degradation data with allocation steps for weight coefficients that lead to a reasonable mechanical transmission degradation model. First, the degradation data used as input are selected based on source entropy which can describe the information volume contained in each set of spectral oil data. Then, the weight coefficient of each set of degradation data is modelled by measuring the relative scale of the permutation entropy from the selected degradation data. Finally, the selected degradation data are fused, and the health index is extracted. The proposed methodology was verified using a case study involving a degradation dataset of multispectral oil data sampled from several power-shift steering transmissions.Monitorowanie i prognozowanie stanu to kluczowa kwestia dla zapewnienia stabilnej i niezawodnej pracy przekładni mechanicznych. Zużycie w przekładni mechanicznej, które prowadzi do wytwarzania cząsteczek zużycia a następnie ciężkiego zużycia, to proces powolnej degradacji, który może być monitorowany poprzez analizę widmową oleju, ale rzeczywisty stopień degradacji często trudno jest ocenić podczas praktycznego użytkowania z uwagi na złożoność wielu widm oleju. W celu rozwiązania powyższego problemu, zaproponowano metodologię ekstrakcji wskaźnika stanu technicznego, aby lepiej scharakteryzować stopień degradacji niż polegając wyłącznie na danych widmowych oleju; pozwala to na dokładne prognozowanie czasu uszkodzenia, gdy przekładnia przestanie spełniać swoją funkcję. Wskaźnik stanu technicznego ekstrahowany jest za pomocą metody średniej ważonej z wyborem danych o degradacji i etapami alokacji dla współczynników wagowych, dając w efekcie odpowiedni model degradacji przekładni mechanicznej. W pierwszym etapie, dane degradacji stosowane jako dane wejściowe wybierane są na podstawie entropii źródłowej, która może opisywać zakres informacji zawarty w każdym zbiorze danych widmowych oleju. Następnie współczynnik wagowy każdego zestawu danych nt. degradacji modelowany jest przez pomiar względnej skali entropii permutacji z wybranych danych degradacji. Na koniec, wybrane dane degradacji są integrowane i ekstrahowany jest wskaźnik stanu technicznego. Zaproponowana metodologia została zweryfikowana przy użyciu studium przypadku obejmującego zbiór wielowidmowych danych dotyczących degradacji oleju pobranego z kilku przekładni kierowniczych wspomaganych

Określanie progu awarii na podstawie podobieństwa jako metoda pozwalająca na przewidywanie trwałości resztkowej systemu

An accurate determination of the system failure threshold is an essential requirement in achieving an appropriate system residual life prediction and a reasonable planned maintenance strategy optimization afterward for degradation systems. This paper proposes a failure threshold determination method based on quantitative measurement of the similarity between the operating system and the historical systems. The similarity is formulated by a weighted average function and then calculated by a convex quadratic formulation to minimizing the variance between the operating system and the historical systems. With an accurate determination of the system failure threshold in real-time, a better prediction of the residual life for the operating system is achieved. Finally, a real case study for several power-shift steering transmission systems monitored using oil spectral analysis is adopted to illustrate and numerically compare the improved performance of the proposed method.W przypadku systemów podlegających degradacji, dokładne określenie progu awarii systemu stanowi niezbędny warunek dokonania trafnej prognozy jego trwałości resztkowej oraz późniejszej optymalizacji strategii konserwacji rutynowych. W artykule zaproponowano metodę wyznaczania progu awarii opartą na ilościowym pomiarze podobieństwa między systemem użytkowanym obecnie a systemami użytkowanymi uprzednio. Podobieństwo formułuje się na podstawie funkcji średniej ważonej, a następnie oblicza na podstawie wypukłej formy kwadratowej w celu zminimalizowania wariancji między obecnie użytkowanym systemem a uprzednimi systemami. Dzięki dokładnemu określeniu progu awarii systemu w czasie rzeczywistym uzyskuje się lepszą prognostykę trwałości resztkowej obecnie użytkowanego systemu. W końcowej części pracy, w celu zilustrowania i numerycznego porównania ulepszonej wydajności proponowanej metody, zaprezentowano studium przypadku obejmujące kilka układów przeniesienia napędu monitorowanych przy użyciu analizy spektralnej oleju