Cross-sectional Ct distributions from qPCR tests can provide an early warning signal for the spread of COVID-19 in communities

BackgroundSARS-CoV-2 PCR testing data has been widely used for COVID-19 surveillance. Existing COVID-19 forecasting models mainly rely on case counts obtained from qPCR results, even though the binary PCR results provide a limited picture of the pandemic trajectory. Most forecasting models have failed to accurately predict the COVID-19 waves before they occur. Recently a model utilizing cross-sectional population cycle threshold (Ct—the number of cycles required for the fluorescent signal to cross the background threshold) values obtained from PCR tests (Ct-based model) was developed to overcome the limitations of using only binary PCR results. In this study, we aimed to improve on COVID-19 forecasting models using features derived from the Ct-based model, to detect epidemic waves earlier than case-based trajectories.MethodsPCR data was collected weekly at Northeastern University (NU) between August 2020 and January 2022. Campus and county epidemic trajectories were generated from case counts. A novel forecasting approach was developed by enhancing a recent deep learning model with Ct-based features and applied in Suffolk County and NU campus. For this, cross-sectional Ct values from PCR data were used to generate Ct-based epidemic trajectories, including effective reproductive rate (Rt) and incidence. The improvement in forecasting performance was compared using absolute errors and residual squared errors with respect to actual observed cases at the 7-day and 14-day forecasting horizons. The model was also tested prospectively over the period January 2022 to April 2022.ResultsRt curves estimated from the Ct-based model indicated epidemic waves 12 to 14 days earlier than Rt curves from NU campus and Suffolk County cases, with a correlation of 0.57. Enhancing the forecasting models with Ct-based information significantly decreased absolute error (decrease of 49.4 and 221.5 for the 7 and 14-day forecasting horizons) and residual squared error (40.6 and 217.1 for the 7 and 14-day forecasting horizons) compared to the original model without Ct features.ConclusionCt-based epidemic trajectories can herald an earlier signal for impending epidemic waves in the community and forecast transmission peaks. Moreover, COVID-19 forecasting models can be enhanced using these Ct features to improve their forecasting accuracy. In this study, we make the case that public health agencies should publish Ct values along with the binary positive/negative PCR results. Early and accurate forecasting of epidemic waves can inform public health policies and countermeasures which can mitigate spread

Sinapic acid prevents hypertension and cardiovascular remodeling in pharmacological model of nitric oxide inhibited rats.

Hypertensive heart disease is a constellation of abnormalities that includes cardiac fibrosis in response to elevated blood pressure, systolic and diastolic dysfunction. The present study was undertaken to examine the effect of sinapic acid on high blood pressure and cardiovascular remodeling.An experimental hypertensive animal model was induced by L-NAME intake on rats. Sinapic acid (SA) was orally administered at a dose of 10, 20 and 40 mg/kg body weight (b.w.). Blood pressure was measured by tail cuff plethysmography system. Cardiac and vascular function was evaluated by Langendorff isolated heart system and organ bath studies, respectively. Fibrotic remodeling of heart and aorta was assessed by histopathologic analyses. Oxidative stress was measured by biochemical assays. mRNA and protein expressions were assessed by RT-qPCR and western blot, respectively. In order to confirm the protective role of SA on endothelial cells through its antioxidant property, we have utilized the in vitro model of H2O2-induced oxidative stress in EA.hy926 endothelial cells.Rats with hypertension showed elevated blood pressure, declined myocardial performance associated with myocardial hypertrophy and fibrosis, diminished vascular response, nitric oxide (NO) metabolites level, elevated markers of oxidative stress (TBARS, LOOH), ACE activity, depleted antioxidant system (SOD, CAT, GPx, reduced GSH), aberrant expression of TGF-β, β-MHC, eNOS mRNAs and eNOS protein. Remarkably, SA attenuated high blood pressure, myocardial, vascular dysfunction, cardiac fibrosis, oxidative stress and ACE activity. Level of NO metabolites, antioxidant system, and altered gene expression were also repaired by SA treatment. Results of in vitro study showed that, SA protects endothelial cells from oxidative stress and enhance the production of NO in a concentration dependent manner.Taken together, these results suggest that SA may have beneficial role in the treatment of hypertensive heart disease by attenuating fibrosis and oxidative stress through its antioxidant potential

Sinapic acid prevents deregulated expression of cardiovascular genes.

<p>(A) Relative expression fold changes of TGF-β and β-MHC mRNAs in heart. (B) Relative expression negative fold change of eNOS mRNA in aorta. (C) Differential eNOS protein expression in aorta and its normalized value with β-actin. Values are expressed as means ± SD. All experiments were done in triplicates. ^*<i>P</i><0.05 vs control; ^#<i>P</i><0.05 vs L-NAME.</p

acid decreases total ROS and improves NO level in EA.hy926 cells.

<p>10 µM SA was pre-treated for 24 h prior to incubation of cells with 300 µM of H₂O₂ for 4 h. (A) Intracellular total ROS level was measured by the fluorescent probe DCFH-DA and the images were obtained by fluorescence microscopy. (B) NO level was measured by the fluorescent probe DAR-4M AM and the images were obtained by fluorescence microscopy. The representative images from three independent experiments are shown. (C) Total ROS fluorescence intensity value was calculated using Adobe Photoshop version 7.0. (D) Fluorescence intensity measurement against NO was calculated using Adobe Photoshop version 7.0. RFU: Relative Fluorescence Unit. Values are expressed as mean ± SEM. ^*<i>P</i><0.05 vs control; ^#<i>P</i><0.05 vs H₂O₂.</p

Sinapic acid improved cardiovascular function in experimental hypertensive rats.

<p>(A) Evaluation of ventricular function in heart of various experimental groups. (B) Cumulative concentration-response curves of Ach induced relaxation in endothelium-intact aortic rings. (C) Cumulative concentration-response curves of SNP induced relaxation in endothelium-intact aortic rings. Values are expressed as mean ± SD. n = 6 per group. ^*<i>P</i><0.05 vs control; ^#<i>P</i><0.05 vs L-NAME.</p

Sinapic acid restores nitric oxide metabolites level and ACE activity in experimental hypertensive rats.

<p>(A) Estimation of nitric oxide metabolites level in various experimental groups. (B) Assessment of ACE activity in various experimental groups. Values are expressed as mean ± SD. n = 6 per group. ^*<i>P</i><0.05 vs control; ^#<i>P</i><0.05 vs L-NAME.</p

Sinapic acid prevented oxidative stress.

<p>U^*  =  enzyme concentration required to inhibit the chromogen produced by 50% in one minute under standard condition. U^#  =  μM of H₂O₂ consumed/minute. U^$  =  μg of GSH utilized/minute. Values are expressed as mean ± SD.</p><p>^*<i>P</i><0.05 vs control;</p>#<p><i>P</i><0.05 vs L-NAME; n  =  6 per group.</p><p>Sinapic acid prevented oxidative stress.</p

Shape memory effect, temperature distribution and mechanical properties of friction stir welded nitinol

Welding of shape memory alloys without deterioration of shape memory effect could vastly extend their applications. To retain shape memory behavior, a solid-state welding technique called friction stir welding was employed in this study. Austenitic NiTi alloy sheets of thickness 1.2 mm were joined at tool rotational speeds of 800,1000, and 1200 rpm. Due to dynamic recrystallization, the grain refinement has occurred in the weld region. The tensile testing has shown superelastic plateau for the welds at 800 and 1000 rpm. The phase transformation behavior of different weld regions was studied in detail using differential scanning calorimeter. A marginal drift in transformation temperatures was observed in the weld. To understand the drift in phase transformation temperatures, finite element analysis was carried out with focus on temperature distribution during welding. Finally, time-dependent shape recovery of a FSW welded joint was studied and it was found that the original position was completely recovered after 27 s at a temperature of 65 degrees C. (C) 2018 Elsevier B.V. All rights reserved