Widom line prediction by the Soave-Redlich-Kwong and Peng-Robinson equations of state

Using cubic equations of state for a single-component fluid, we compute pseudocritical loci where the isobaric heat capacity is a relative maximum at constant pressure, or at constant temperature. These two loci, called the Widom line and the characteristic isobaric inflection curve (CIIC), are quite different from each other, as we show using the van der Waals equation, based on which the two loci admit a closed-form representation in the (P, T) plane. Similarly, the Redlichâ Kwong (RK) equation leads to a closed-form representation for the CIIC in the (T,v) plane. With the Soaveâ Redlichâ Kwong (SRK) and the Pengâ Robinson (PR) equations we find almost coincident predictions for the above-mentioned pseudocritical loci; furthermore, comparing our results with a correlation obtained by regression of experimental data for CO2and water shows that the increased complexity of the SRK and PR equations (as compared to RK) allows improved agreement with the experimental data

CD200 as a Potential New Player in Inflammation during Rotator Cuff Tendon Injury/Repair: An In Vitro Model

Rotator cuff tendon (RCT) disease results from multifactorial mechanisms, in which inflammation plays a key role. Pro-inflammatory cytokines and tendon stem cell/progenitor cells (TSPCs) have been shown to participate in the inflammatory response. However, the underlying molecular mechanism is still not clear. In this study, flow cytometry analyses of different subpopulations of RCT-derived TSPCs demonstrate that after three days of administration, TNFα alone or in combination with IFNγ significantly decreases the percentage of CD146+CD49d+ and CD146+CD49f+ but not CD146+CD109+ TSPCs populations. In parallel, the same pro-inflammatory cytokines upregulate the expression of CD200 in the CD146+ TSPCs population. Additionally, the TNFα/IFNγ combination modulates the protein expression of STAT1, STAT3, and MMP9, but not fibromodulin. At the gene level, IRF1, CAAT (CAAT/EBPbeta), and DOK2 but not NF-κb, TGRF2 (TGFBR2), and RAS-GAP are modulated. In conclusion, although our study has several important limitations, the results highlight a new potential role of CD200 in regulating inflammation during tendon injuries. In addition, the genes analyzed here might be new potential players in the inflammatory response of TSPCs

Extracellular vesicles from rat-bone-marrow mesenchymal stromal/stem cells improve tendon repair in rat Achilles tendon injury model in dose-dependent manner: A pilot study

Mesenchymal stromal/stem cells (MSCs) are increasingly employed for tissue regeneration, largely mediated through paracrine actions. Currently, extracellular vesicles (EVs) released by MSCs are major mediators of these paracrine effects. We evaluated whether rat-bone-marrow-MSC-derived EVs (rBMSCs-EVs) can ameliorate tendon injury in an in vivo rat model. Pro-collagen1A2 and MMP14 protein are expressed in rBMSC-EVs, and are important factors for extracellular-matrix tendon-remodeling. In addition, we found pro-collagen1A2 in rBMSC-EV surface-membranes by dot blot. In vitro on cells isolated from Achilles tendons, utilized as rBMSC -EVs recipient cells, EVs at both low and high doses induce migration of tenocytes; at higher concentration, they induce proliferation and increase expression of Collagen type I in tenocytes. Pretreatment with trypsin abrogate the effect of EVs on cell proliferation and migration, and the expression of collagen I. When either low- or high-dose rBMSCs-EVs were injected into a rat-Achilles tendon injury-model (immediately after damage), at 30 days, rBMSC-EVs were found to have accelerated the remodeling stage of tendon repair in a dose-dependent manner. At histology and histomorphology evaluation, high doses of rBMSCs-EVs produced better restoration of tendon architecture, with optimal tendon-fiber alignment and lower vascularity. Higher EV-concentrations demonstrated greater expression of collagen type I and lower expression of collagen type III. BMSC-EVs hold promise as a novel cell-free modality for the management of tendon injuries

Predictive score using clinical and blood biomarkers in advanced non-small cell lung cancer (aNSCLC) patients treated with immunotherapy

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Peripheral blood biomarkers as prognostic factors for immunotherapy in advanced non-small cell lung cancer (aNSCLC) patients

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Leflunomide treatment for patients hospitalised with COVID-19: DEFEAT-COVID randomised controlled trial

Objective To evaluate the clinical efficacy and safety of leflunomide (L) added to the standard-of-care (SOC) treatment in COVID-19 patients hospitalised with moderate/critical clinical symptoms. Design Prospective, open-label, multicentre, stratified, randomised clinical trial. Setting Five hospitals in UK and India, from September 2020 to May 2021. Participants Adults with PCR confirmed COVID-19 infection with moderate/critical symptoms within 15 days of onset. Intervention Leflunomide 100 mg/day (3 days) followed by 10–20 mg/day (7 days) added to standard care. Primary outcomes The time to clinical improvement (TTCI) defined as two-point reduction on a clinical status scale or live discharge prior to 28 days; safety profile measured by the incidence of adverse events (AEs) within 28 days. Results Eligible patients (n=214; age 56.3±14.9 years; 33% female) were randomised to SOC+L (n=104) and SOC group (n=110), stratified according to their clinical risk profile. TTCI was 7 vs 8 days in SOC+L vs SOC group (HR 1.317; 95% CI 0.980 to 1.768; p=0.070). Incidence of serious AEs was similar between the groups and none was attributed to leflunomide. In sensitivity analyses, excluding 10 patients not fulfilling the inclusion criteria and 3 who withdrew consent before leflunomide treatment, TTCI was 7 vs 8 days (HR 1.416, 95% CI 1.041 to 1.935; p=0.028), indicating a trend in favour of the intervention group. All-cause mortality rate was similar between groups, 9/104 vs 10/110. Duration of oxygen dependence was shorter in the SOC+L group being a median 6 days (IQR 4–8) compared with 7 days (IQR 5–10) in SOC group (p=0.047). Conclusion Leflunomide, added to the SOC treatment for COVID-19, was safe and well tolerated but had no major impact on clinical outcomes. It may shorten the time of oxygen dependence by 1 day and thereby improve TTCI/hospital discharge in moderately affected COVID-19 patients

Tamoxifen in treatment of hepatocellular carcinoma: a randomised controlled trial

Background Results from small randomised trials on tamoxifen in the treatment of hepatocellular carcinoma (HCC) are conflicting, We studied whether the addition of tamoxifen to best supportive care prolongs survival of patients with HCC. Methods Patients with any stage of HCC were eligible, irrespective of locoregional treatment. Randomisation was centralised, with a minimisation procedure accounting for centre, evidence of disease, and time from diagnosis. Patients were randomly allocated best supportive care alone or in addition to tamoxifen, Tamoxifen was given orally, 40 mg per day, from randomisation until death. Results 496 patients from 30 institutions were randomly allocated treatment from January, 1995, to January, 1997. Information was available for 477 patients. By Sept 15, 1997, 119 (50%) of 240 and 130 (55%) of 237 patients had died in the control and tamoxifen arms, respectively. Median survival was 16 months and 15 months (p=0.54), respectively, No differences were found within subgroups defined by prognostic variables. Relative hazard of death for patients receiving tamoxifen was 1.07 (95% CI 0.83-1.39). Interpretation Our findings show that tamoxifen is not effective in prolonging survival of patients with HCC

Prospective validation of the CLIP score: a new prognostic system for patient with cirrhosis and hepatocellular carcinoma

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage, As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with RCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection

Buoyancy-driven detachment of a wall-bound pendant drop: Interface shape at pinchoff and nonequilibrium surface tension

We present numerical results from phase-field simulations of the buoyancy-driven detachment of an isolated, wall-bound pendant emulsion droplet acted upon by surface tension and wall-normal buoyancy forces alone. Our theoretical approach follows a diffuse-interface model for partially miscible binary mixtures which has been extended to include the influence of static contact angles other than 90 degree, based on a Hermite interpolation formulation of the Cahn boundary condition as first proposed by Jacqmin [J. Fluid Mech. 402, 57 (2000)]. In a previous work, this model has been successfully employed for simulating triphase contact line problems in stable emulsions with nearly immiscible components, and, in particular, applied to the determination of critical Bond numbers for buoyancy-driven detachment as a function of static contact angle. Herein, the shapes of interfaces at pinchoff are investigated as a function of static contact angle and distance to the critical condition. Furthermore, we show numerical results on the nonequilibrium surface tension that help to explain the discrepancy between our numerically determined static contact angle dependence of the critical Bond number and its sharp-interface counterpart based on a static stability analysis of equilibrium shapes after numerical integration of the Young-Laplace equation. Finally, we show the influence of static contact angle and distance to the critical condition on the temporal evolution of the minimum neck radius in the necking regime of drop detachment