Objective
The coronavirus disease 2019 (COVID‐19) has rapidly developed into a pandemic. Increased levels of ferritin due to cytokine storm and secondary hemophagocytic lymphohistiocytosis were found ...in severe COVID‐19 patients. Therefore, the aim of this study was to determine the role of ferritin in COVID‐19.
Methods
Studies investigating ferritin in COVID‐19 were collected from PubMed, EMBASE, CNKI, SinoMed, and WANFANG. A meta‐analysis was performed to compare the ferritin level between different patient groups: non‐survivors versus survivors; more severe versus less severe; with comorbidity versus without comorbidity; ICU versus non‐ICU; with mechanical ventilation versus without mechanical ventilation.
Results
A total of 52 records involving 10 614 COVID‐19‐confirmed patients between December 25, 2019, and June 1, 2020, were included in this meta‐analysis, and 18 studies were included in the qualitative synthesis. The ferritin level was significantly increased in severe patients compared with the level in non‐severe patients WMD 397.77 (95% CI 306.51‐489.02), P < .001. Non‐survivors had a significantly higher ferritin level compared with the one in survivors WMD 677.17 (95% CI 391.01‐963.33), P < .001. Patients with one or more comorbidities including diabetes, thrombotic complication, and cancer had significantly higher levels of ferritin than those without (P < .01). Severe acute liver injury was significantly associated with high levels of ferritin, and its level was associated with intensive supportive care, including ICU transfer and mechanical ventilation.
Conclusions
Ferritin was associated with poor prognosis and could predict the worsening of COVID‐19 patients.
Serum ferritin resulted as a valuable biomarker in COVID‐19. Indeed, this meta‐analysis revealed the association between the serum ferritin level and clinical characteristics of COVID‐19 patients including disease severity, mortality, comorbidities, and certain treatment. Thus, ferritin was associated with poor prognosis and could predict the worsening of COVID‐19 patients.
The prognostic role of hypercoagulability in COVID-19 patients is ambiguous. D-dimer, may be regarded as a global marker of hemostasis activation in COVID-19. Our study was to assess the predictive ...value of D-dimer for the severity, mortality and incidence of venous thromboembolism (VTE) events in COVID-19 patients. PubMed, EMBASE, Cochrane Library and Web of Science databases were searched. The pooled diagnostic value (95% confidence interval CI) of D-dimer was evaluated with a bivariate mixed-effects binary regression modeling framework. Sensitivity analysis and meta regression were used to determine heterogeneity and test robustness. A Spearman rank correlation tested threshold effect caused by different cut offs and units in D-dimer reports. The pooled sensitivity of the prognostic performance of D-dimer for the severity, mortality and VTE in COVID-19 were 77% (95% CI: 73%-80%), 75% (95% CI: 65%-82%) and 90% (95% CI: 90%-90%) respectively, and the specificity were 71% (95% CI: 64%-77%), 83% (95% CI: 77%-87%) and 60% (95% CI: 60%-60%). D-dimer can predict severe and fatal cases of COVID-19 with moderate accuracy. It also shows high sensitivity but relatively low specificity for detecting COVID-19-related VTE events, indicating that it can be used to screen for patients with VTE.
Robotic wire and arc additive manufacturing (WAAM) systems are required to provide predictable and efficient operations to fabricate solid metallic parts with high morphological fidelity and ...geometric accuracy. Since the metallic parts are fabricated based on a layer-by-layer principle, the interactions between the neighboring beads and layers strongly influence the geometric accuracy of the fabricated part. The layers-overlapping process has been studied and a traditional layers-overlapping model (T-LOM) has been published in the literature. This paper proposes a layers-overlapping strategy (LOS), based on which a revised layers-overlapping model (R-LOM) was proposed for the fabrication of multi-layer multi-bead (MLMB) components with homogeneous layers. A mathematical model for layers-overlapping is presented, which considers the material shortage areas at the edges of the layers. This is important since the material shortage areas result in a situation that the component width is smaller than the expected value. In addition, they will be accumulated when multiple layers are overlapped through normal unidirectional parallel (NUP) paths. The proposed LOS addresses two aspects: (i) the deposition amount of the first bead and the last bead in the lap layers should be increased and (ii) the deposition position of the first bead and the last bead in the lap layers should be moved towards the edges with a given offset distance. Validation experiments were designed and conducted to test the proposed concepts and models. The experimental results indicated that (i) the R-LOM enables the MLMB components to achieve the expected width and (ii) for components deposited with NUP paths, the R-LOM eliminates the effect of accumulation of material shortage areas on the first bead and increases the surface flatness.
We carried out metagenomic shotgun sequencing and a metagenome-wide association study (MGWAS) of fecal, dental and salivary samples from a cohort of individuals with rheumatoid arthritis (RA) and ...healthy controls. Concordance was observed between the gut and oral microbiomes, suggesting overlap in the abundance and function of species at different body sites. Dysbiosis was detected in the gut and oral microbiomes of RA patients, but it was partially resolved after RA treatment. Alterations in the gut, dental or saliva microbiome distinguished individuals with RA from healthy controls, were correlated with clinical measures and could be used to stratify individuals on the basis of their response to therapy. In particular, Haemophilus spp. were depleted in individuals with RA at all three sites and negatively correlated with levels of serum autoantibodies, whereas Lactobacillus salivarius was over-represented in individuals with RA at all three sites and was present in increased amounts in cases of very active RA. Functionally, the redox environment, transport and metabolism of iron, sulfur, zinc and arginine were altered in the microbiota of individuals with RA. Molecular mimicry of human antigens related to RA was also detectable. Our results establish specific alterations in the gut and oral microbiomes in individuals with RA and suggest potential ways of using microbiome composition for prognosis and diagnosis.
In this paper, we derive an ambiguity function (AF) for the transmit beamspace (TB)-based MIMO radar for the case of far-field targets and narrow-band waveforms. The effects of transmit coherent ...processing gain and waveform diversity are incorporated into the AF definition. To cover all the phase information conveyed by different factors, we introduce the equivalent transmit phase centers. The newly defined AF serves as a generalized AF form for which the phased-array (PA) and traditional MIMO radar AFs are important special cases. We establish relationships among the defined TB-based MIMO radar AF and the existing AF results, including the Woodward's AF, the AFs defined for traditional colocated MIMO radar, and also the PA radar AF, respectively. Moreover, we compare the TB-based MIMO radar AF with the square-summation-form AF definition and identify two limiting cases to bound its "clear region" in Doppler-delay domain that is free of sidelobes. Corresponding bounds for these two cases are derived, and it is shown that the bound for the worst case is inversely proportional to the number of transmitted waveforms K, whereas the bound for the best case is independent of K. The actual "clear region" of the TB-based MIMO radar AF depends on the array configuration and is in between of the worst- and best-case bounds. We propose a new TB design strategy to reduce the levels of the AF sidelobes and show in simulations that proper design of the TB matrix leads to reduction of the relative sidelobe levels of the TB-based MIMO radar AF.
Rapid manufacturing technologies have made it possible to reduce material wastes and to remanufacture valuable dies and tools. This paper focuses on reasonable utilization of materials and energies ...in gas metal arc welding (GMAW) for rapid manufacturing. During the weld-based additive manufacturing process, geometries of the deposited weld beads should be monitored and controlled. Using a composite filtering technique, a computer vision-sensing system was designed. Features of the weld bead image were analyzed. A corresponding image processing technology was used to extract parameters of the deposited weld beads. An on-line control of the deposited beads was realized based on a segmented neuron self-learning controller. The results show that the proposed control system is capable of keeping the deposited bead width of a thin-walled part consistent, making an efficient use of materials and energies possible.
► A vision sensing system was designed for bead width detection. ► An improved proportional summational differential controller was developed. ► Keeping bead width consistent was realized based on closed-loop control. ► Material and energy saving were realized in weld-based rapid manufacturing.
The outbreak of novel coronavirus disease 2019 (COVID-19) has now become a global pandemic. Coagulopathy has been reported widely in critically ill COVID-19 patients and was related to high ...mortality. However, the comprehensive coagulation profiles have not been examined and the underlying mechanism of the coagulopathy in COVID-19 patients is unclear. To study the coagulation profiles of routine hemostasis tests, natural anticoagulants, coagulant factors and antiphospholipid antibodies in critically ill COVID-19 patients. This single-center and cross-section study included 19 patients with COVID-19, who were admitted to intensive care unit (ICU) at Tongji hospital in Wuhan, China, from Feb 23 to Mar 3, 2020. Demographic data, laboratory parameters, treatments and clinical outcomes of the patients were collected and analyzed. The final date of follow-up was Mar 31, 2020. In this study, 12 thrombotic events occurred in 9 patients, including 4 cerebral infarctions, 7 acro-ischemia and 1 internal jugular vein thrombosis. The common abnormalities of routine coagulation tests included evelated D-Dimer level (100%), prolonged prothrombin time (73.7%) and hyperfibrinogenemia (73.7%). The median activities of natural anticoagulants including protein C, protein S and antithrombin were all below the normal range. Factor VIII activities were significantly above normal range (median value 307%, IQR 198–441) in all patients. Factor V and factor VII activities were significantly lower in near-terminal stage patients. Anti-phospholipid antibodies were present in 10 patients. Strikingly, 4 cerebral infarction events were in patients had anti-phospholipid antibodies of multiple isotypes. Sustained hypercoagulable status and thrombotic events were common in critically ill patients with COVID-19. The low activities of natural anticoagulants, elevated factor VIII level and the presence of antiphospholipid antibodies, together, may contribute to the etiopathology of coagulopathy in COVID-19 patients.
Accumulating evidence has highlighted the roles of long noncoding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) of microRNAs (miRNAs) through their binding sites in the progression of glioma. ...Hereby, we aim to explore the role of LINC00883 as a regulator of miR-136 and its target, NIMA-related kinase 1 (NEK1), thus, its involvement in the drug resistance of glioma cells.
Mechanistic investigations by dual-luciferase reporter, RNA pull-down, and RNA-binding protein immunoprecipitation (RIP) assays indicated that LINC00883 bound to miR-136, thereby blocking miR-136-induced downregulation of NEK1. Through gain-of-function experiments in U251 cells that presented a high drug resistance, we found that ectopic expression of LINC00883 resulted in increased MRP (encoding multidrug resistance-associated protein), limited cell apoptosis, and increased proliferation. Expectedly, depleting LINC00883 yielded tumor-suppressive and anti-chemoresistance effects on U251 cells by increasing miR-136 and inhibiting NEK1. Next, drug-resistant glioma cell line SOWZ1, drug-sensitive glioma cell line SOWZ2, and drug-resistant glioma cell line SOWZ2-BCNU (SOWZ2 cultured in BCNU) were applied to validate the roles of LINC00883 in the regulation of multidrug resistance. LINC00883 knockdown suppressed the viability of SWOZ1, SWOZ2, and SWOZ2-BCNU cells.
In conclusion, LINC00883 knockdown reduces drug resistance in glioma. Hence, our study provides a future strategy to prevent drug resistance-induced therapeutic failure in glioma.
Observational studies have identified associations between smoking, alcohol use, body mass index (BMI), and the levels of vitamin D with primary biliary cholangitis (PBC). However, there was a lack ...of randomization control studies to estimate the causal relationship. This study was to investigate the causal estimates for the effects of those risk factors on PBC.
The genetic instrument variants were extracted from genome-wide association studies in European ancestry. Two-sample mendelian randomization (MR) and multivariable mendelian randomization were used to determine genetically causal estimates. Primary analyses consisted of random-effects and fix-mode inverse-variance-weighted methods, followed by secondary sensitivity analyses to verify the results.
Our study showed that BMI was a causal factor for PBC (OR 1.35; 95% CI=1.03-1.77;
=0.029). In addition, we found that serum vitamin D levels had a protective effect on PBC after adjusting for BMI (OR 0.51; 95% CI=0.32-0.84;
=0.007). However, we failed to identify evidence supporting that genetic causal effect of smoking and alcohol intake were associated with PBC in European countries.
Our results enriched findings from previous epidemiology studies and provided evidence from MR that serum vitamin D concentrations and BMI were independent causal factors for PBC, suggesting that ensuing vitamin D sufficiency and healthy lifestyles might be a cost-effective measure for early intervention for PBC.
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