Powerful Electron-Transfer Screen-Printed Platforms as Biosensing Tools: The Case of Uric Acid Biosensor

The use of carbon nanomaterials (CNMs) in sensors and biosensor realization is one of the hottest topics today in analytical chemistry. In this work, a comparative in-depth study, exploiting different nanomaterial (MWNT-CO2H, -NH2, -OH and GNP) modified screen-printed electrodes (SPEs), is reported. In particular, the sensitivity, the heterogeneous electron transfer constant (k0), and the peak-to-peak separation (ΔE) have been calculated and analyzed. After which, an electrochemical amperometric sensor capable of determining uric acid (UA), based on the nano-modified platforms previously characterized, is presented. The disposable UA biosensor, fabricated modifying working electrode (WE) with Prussian Blue (PB), carbon nanotubes, and uricase enzyme, showed remarkable analytical performances toward UA with high sensitivity (CO2H 418 μA μM−1 cm−2 and bare SPE-based biosensor, 33 μA μM−1 cm−2), low detection limits (CO2H 0.5 nM and bare SPE-based biosensors, 280 nM), and good repeatability (CO2H and bare SPE-based biosensors, 5% and 10%, respectively). Moreover, the reproducibility (RSD%) of these platforms in tests conducted for UA determination in buffer and urine samples results are equal to 6% and 15%, respectively. These results demonstrate that the nanoengineered electrode exhibited good selectivity and sensitivity toward UA even in the presence of interfering species, thus paving the way for its application in other bio-fluids such as simple point-of-care (POC) devices.

Determination of the convective heat transfer constant (c and n) in a solar still

The geometry of a solar still determines the convection constants C and n, which in turn affect the convection heat transfer coefficient’s value and mass. A method for determining the value of convection heat transfer constants C and n has already been developed by the researchers. Therefore, this study aimed to use several methods and theories to find the value of convection heat transfer constants C and n. The results are then compared with the results of the study. The solar still used in this study has one slope. To reduce variables that cannot be controlled, the data collection was conducted indoors using a halogen lamp that can be regulated as a heat source for 24 hours nonstop. The sea surface height in the solar still was maintained at a height of 20 mm, using a height regulator. Temperature was measured using a data logger set to enter data every hour. The desalinised clean water was stored in bottles placed on scales that were recorded every one hour. Room temperature was maintained in the range of 35 to 36 oC. The data in this study were used to calculate the heat transfer constants C and n to obtain the value of the convection heat transfer coefficient and mass calculation. This study compares the calculation models of Tiwari, Dunkle and Power. The following calculation model results: Tiwari model, C = 0.082 and n = 0.612; Dunkle model, C = 0.075 and n = 1/3; Power model, C = 0.815 and n = 0.611. The C and n values obtained with these four approaches reveal that the results from the Power model calculation are the closest to the actual mass, showing a percentage deviation of 1.63%.

DCE-MRI is more sensitive than IVIM-DWI for assessing anti-angiogenic treatment-induced changes in colorectal liver metastases

Background Diffusion weighted imaging (DWI) with intravoxel incoherent motion (IVIM) modelling can inform on tissue perfusion without exogenous contrast administration. Dynamic-contrast-enhanced (DCE) MRI can also characterise tissue perfusion, but requires a bolus injection of a Gadolinium-based contrast agent. This study compares the use of DCE-MRI and IVIM-DWI methods in assessing response to anti-angiogenic treatment in patients with colorectal liver metastases in a cohort with confirmed treatment response. Methods This prospective imaging study enrolled 25 participants with colorectal liver metastases to receive Regorafenib treatment. A target metastasis > 2 cm in each patient was imaged before and at 15 days after treatment on a 1.5T MR scanner using slice-matched IVIM-DWI and DCE-MRI protocols. MRI data were motion-corrected and tumour volumes of interest drawn on b=900 s/mm2 diffusion-weighted images were transferred to DCE-MRI data for further analysis. The median value of four IVIM-DWI parameters [diffusion coefficient D (10−3 mm2/s), perfusion fraction f (ml/ml), pseudodiffusion coefficient D* (10−3 mm2/s), and their product fD* (mm2/s)] and three DCE-MRI parameters [volume transfer constant Ktrans (min−1), enhancement fraction EF (%), and their product KEF (min−1)] were recorded at each visit, before and after treatment. Changes in pre- and post-treatment measurements of all MR parameters were assessed using Wilcoxon signed-rank tests (P<0.05 was considered significant). DCE-MRI and IVIM-DWI parameter correlations were evaluated with Spearman rank tests. Functional MR parameters were also compared against Response Evaluation Criteria In Solid Tumours v.1.1 (RECIST) evaluations. Results Significant treatment-induced reductions of DCE-MRI parameters across the cohort were observed for EF (91.2 to 50.8%, P<0.001), KEF (0.095 to 0.045 min−1, P<0.001) and Ktrans (0.109 to 0.078 min−1, P=0.002). For IVIM-DWI, only D (a non-perfusion parameter) increased significantly post treatment (0.83 to 0.97 × 10−3 mm2/s, P<0.001), while perfusion-related parameters showed no change. No strong correlations were found between DCE-MRI and IVIM-DWI parameters. A moderate correlation was found, after treatment, between Ktrans and D* (r=0.60; P=0.002) and fD* (r=0.67; P<0.001). When compared to RECIST v.1.1 evaluations, KEF and D correctly identified most clinical responders, whilst non-responders were incorrectly identified. Conclusion IVIM-DWI perfusion-related parameters showed limited sensitivity to the anti-angiogenic effects of Regorafenib treatment in colorectal liver metastases and showed low correlation with DCE-MRI parameters, despite profound and significant post-treatment reductions in DCE-MRI measurements. Trial registration NCT03010722 clinicaltrials.gov; registration date 6th January 2015.

In Vitro Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Amphotericin B against Candida auris

The aims of this study were to characterize the antifungal activity of amphotericin B against Candida auris in a static in vitro system and to evaluate different dosing schedules and MIC scenarios by means of semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) modelling and simulation. A two-compartment model consisting of a drug-susceptible and a drug-resistant subpopulation successfully characterized the time-kill data and a modified Emax sigmoidal model best described the effect of the drug. The model incorporated growth rate constants for both subpopulations, a death rate constant and a transfer constant between both compartments. Additionally, the model included a parameter to account for the delay in growth in the absence or presence of the drug. Amphotericin B displayed a concentration-dependent fungicidal activity. The developed PK/PD model was able to characterize properly the antifungal activity of amphotericin B against C. auris. Finally, simulation analysis revealed that none of the simulated standard dosing scenarios of 0.6, 1 and 1.5 mg/kg/day over a week treatment showed successful activity against C. auris infection. Simulations also pointed out that an MIC of 1 mg/L would be linked to treatment failure for C. auris invasive infections and therefore, the resistance rate to amphotericin B may be higher than previously reported.

Evaluation of Angiogenesis and Pathological Classification of Extrahepatic Cholangiocarcinoma by Dynamic MR Imaging for E-Healthcare

For staging cholangiocarcinoma and determining respectability, MR is an accurate noninvasive method which provides size of tumor and vascular patency information. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive inspection method for evaluating the vascular structure and functional characteristics of tumor tissue. However, some limitations should be noted about the technology. At present, the technology cannot be used alone, which is just an assisted method during the conventional MRI examination. 50 ECC patients, admitted to Indira Gandhi Medical College and Hospital between 2016 and 2019, were selected as research subjects. They were classified pathologically according to the Steiner classification system. After image processing, regions of interest (ROIs) were selected from the image to measure the rate constant (Kep), extravascular space volume fraction (Ve), and tissue volume transfer constant (Ktrans). There were 15 cases with highly differentiated carcinoma, 23 cases with moderately differentiated carcinoma, and 12 cases with lowly differentiated carcinoma. Non-VEGF expression was noted in 21 cases, with low expression noted in 15 cases, moderate expression noted in 14 cases, and no high expression case noted. The relevant parameters in the dynamic MRI image can quantitatively reflect the angiogenesis and pathological classification of ECC, which is suggested in the clinical treatment of ECC. The Ktrans, Kep, and Ve values of the ECC patients were all not associated with the pathological classification, with no significant difference ( P < 0.05 ). Besides, due to the fact that the patient cannot completely hold his breath, the air leak reduces the image quality.

Descriptive analysis of MRI functional changes occurring during reduced dose radiotherapy for myxoid liposarcomas

Objectives: Myxoid liposarcomas (MLS) show enhanced response to radiotherapy due to their distinctive vascular pattern and therefore could be effectively treated with lower radiation doses. This is a descriptive study to explore the use of functional MRI to identify response in a uniform cohort of MLS patients treated with reduced dose radiotherapy Methods: 10 patients with MLS were imaged pre-, during, and post-radiotherapy receiving reduced dose radiotherapy and the response to treatment was histopathologically assessed post-radiotherapy. Apparent diffusion coefficient (ADC), T2* relaxation time, volume transfer constant (Ktrans), initial area under the gadolinium curve over 60 s (IAUGC60) and (Gd) were estimated for a central tumour volume. Results: All parameters showed large inter- and intrasubject variabilities. Pre-treatment (Gd), IAUGC60 and Ktrans were significantly different between responders and non-responders. Post-radiotherapy reductions from baseline were demonstrated for T2*, (Gd), IAUGC60 and Ktrans for responders. No statistically significant ADC differences were demonstrated between the two response groups. Significantly greater early tumour volume reductions were observed for responders. Conclusions: MLS are heterogenous lesions, characterised by a slow gradual contrast-agent uptake. Pre-treatment vascular parameters, early changes to tumour volume, vascular parameters and T2* have potential in identifying response to treatment. The delayed (Gd) is a suitable descriptive parameter, relying simply on T1 measurements. Volume changes precede changes in MLS functionality and could be used to identify early response. Advances in knowledge: MLS are are characterised by slow gradual contrast-agent uptake. Measurement of the delayed contrast-agent uptake (Gd) is simple to implement and able to discriminate response.

Radiology- and gene-based risk stratification in small renal cell carcinoma: A preliminary study

Purpose Most small renal cell carcinomas (small RCCs) will remain indolent after detection, but some stage I RCCs still metastasize. There are no risk-stratification imaging factors that could be used to identify poor-prognosis patients based on genomic profiling. Here, we evaluated the relationships between imaging parameters and RNA expressions in small RCC and attempted to identify imaging factors that could be used as effective biomarkers. Methods We acquired biopsy specimens of 18 clear cell carcinomas that had undergone perfusion CT (pCT) and MRI between April 2018 and March 2019. We performed RNA sequencing, assessed RNA expressions, and calculated each tumor’s cell-cycle progression (CCP) score, which has prognostic value in predicting metastatic progression. We classified the tumors into two groups: clear cell type A (ccA) and type B (ccB). CcA has better survival compared to ccB. We evaluated the following characteristics of each tumor: tumor size, presence of pseudocapsule, and fat. We used the pCT and MRI to measure each tumor’s volume transfer constant (Ktrans), rate constant (Kep), extracellular extravascular volume fraction (VE), fractional plasma volume (VP), and apparent diffusion coefficient (ADC). The correlations between these small RCC imaging parameters and the tumor size and RNA expressions were determined. Results The tumor size was significantly correlated with Kep and inversely correlated with VE, VP, ADC, and hallmark angiogenesis. The CCP score was significantly inversely correlated with Ktrans and Kep. The ccA tumors tended to show a pseudocapsule on MRI. Conclusion Tumor size was correlated with low perfusion, but not with prognostic factors based on genomic profiling. Imaging parameters (e.g., Ktrans and Kep) and tumor characteristics (e.g., pseudocapsule) may enable gene-based risk stratification in small RCC.

Computational Investigation of the Combined Impact of Nonlinear Radiation and Magnetic Field on Three-Dimensional Rotational Nanofluid Flow across a Stretchy Surface

This comparative study inspects the MHD three-dimensional revolving flow and temperature transmission of a radiative stretching surface. The flow of nanofluid is modeled using the Tiwari and Das model. Water is the base fluid, and the nanoparticles are composed of two different types of nanoparticle, i.e., gold and silver (Au and Ag). The non-radiative heat flow notion is examined in a temperature field that results in a nonlinear energy equation. Conformist transformations are used to generate a self-similar arrangement of the leading differential system. The resulting system has an intriguing temperature ratio constraint, which shows whether the flow has a little or significant temperature differential. By using a powerful mathematical technique, numerical results are obtained. The solutions are influenced by both stretching and rotation. The difference in velocity constituents with the elements’ volume fraction is non-monotonic. Results for the rotating nanofluid flow and heat transfer properties for both types of nanoparticles are highlighted with graphs. The impact of physical concentrations, such as heat flux rates and skin friction constants, are examined at the linear extending surface and clarified graphically. Ag-water nanofluid has a high-temperature transfer constant compared to Au-water nanofluid. The velocity profile was also discovered to have a parabolic distribution shape.

Consistency of Pituitary Adenoma: Prediction by Pharmacokinetic Dynamic Contrast-Enhanced MRI and Comparison with Histologic Collagen Content

Prediction of tumor consistency is valuable for planning transsphenoidal surgery for pituitary adenoma. A prospective study was conducted involving 49 participants with pituitary adenoma to determine whether quantitative pharmacokinetic analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is useful for predicting consistency of adenomas. Pharmacokinetic parameters in the adenomas including volume of extravascular extracellular space (EES) per unit volume of tissue (ve), blood plasma volume per unit volume of tissue (vp), volume transfer constant between blood plasma and EES (Ktrans), and rate constant between EES and blood plasma (kep) were obtained. The pharmacokinetic parameters and the histologic percentage of collagen content (PCC) were compared between soft and hard adenomas using Mann–Whitney U test. Pearson’s correlation coefficient was used to correlate pharmacokinetic parameters with PCC. Hard adenomas showed significantly higher PCC (44.08 ± 15.14% vs. 6.62 ± 3.47%, p < 0.01), ve (0.332 ± 0.124% vs. 0.221 ± 0.104%, p < 0.01), and Ktrans (0.775 ± 0.401/min vs. 0.601 ± 0.612/min, p = 0.02) than soft adenomas. Moreover, a significant positive correlation was found between ve and PCC (r = 0.601, p < 0.01). The ve derived using DCE-MRI may have predictive value for consistency of pituitary adenoma.

Consistency of Pituitary Adenoma: Prediction by Pharmacokinetic Dynamic Contrast-enhanced MRI and Comparison with Histologic Collagen Content

Prediction of tumor consistency is valuable for planning transsphenoidal surgery for pituitary adenoma. A prospective study was conducted involving 49 participants with pituitary adenoma to determine whether quantitative pharmacokinetic analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is useful for predicting consistency of adenoma. Pharmacokinetic parameters in the adenomas including volume of extravascular extracellular space (EES) per unit volume of tissue (ve), blood plasma volume per unit volume of tissue (vp), volume transfer constant between blood plasma and EES (Ktrans), and rate constant between EES and blood plasma (kep) were obtained. The pharmacokinetic parameters and the histologic percentage of collagen content (PCC) were compared between soft and hard adenomas using Mann&ndash;Whitney U test. Pearson&rsquo;s correla-tion coefficient was used to correlate pharmacokinetic parameters with PCC. Hard adenomas showed significantly higher PCC (44.08 &plusmn; 15.14% vs. 6.62 &plusmn; 3.47%, p &lt; 0.01), ve (0.332 &plusmn; 0.124% vs. 0.221 &plusmn; 0.104%, p = 0.02), and Ktrans (0.775 &plusmn; 0.401/min vs. 0.601 &plusmn; 0.612/min, p = 0.02) than soft adenomas. Moreover, a significant positive correlation was found between ve and PCC (r = 0.601, p &lt; 0.01). The ve derived using DCE-MRI may have predictive value for consistency of pituitary adenoma.