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Zinc plays a central role in many metabolic processes in the organism and is therefore one of the most important trace elements in horse nutrition. Therefore, the adequate supply and supplementation of zinc is essential for maintaining the health and performance of horses. In this study, the trace element concentration of zinc in different blood sample media will be compared and analyzed with those in faecal samples. Furthermore, reference values for the zinc concentration in fecal samples are to be established in order to present a valid, minimally invasive, diagnostic alternative to the evaluation of blood serum. It should also be critically examined whether the coprological examination is preferable to the serological examination. The evaluation of the trace element concentration of zinc was carried out using a standardized, analytical procedure. Blood (serum, plasma and EDTA blood) and faecal samples were taken from 10 test subjects from 13 federal states, analyzed and compared. The test subjects were horses of all breeds, aged between 3 and 35 years, which were classified as clinically healthy.[1] Furthermore, the horses were used both recreationally and for sport. The horses came from different farms and were kept in conventional stables, open stables and year-round grazing. There was no uniform feeding of concentrates and supplementary feed. The feeding of copper-containing mineral feed was detected in some horses, but was not considered separately in this study. The zinc concentration was analyzed using ICP)OES (optical emission spectrometry with inductively coupled plasma). The faecal samples were prepared and dried beforehand. There was no biologically relevant correlation between the zinc concentration in fecal and serum samples. In the blood samples, however, a strong correlation could be demonstrated between serum and plasma samples, but not between serum and EDTA blood samples. The reference values determined for the zinc concentration in fecal samples are between 29 and 413mg/kg. Reference values for the zinc concentration in fecal samples were determined. Staufenbiel et al. already postulated the first methodological framework for this. Among other things, the coprological examination is the less invasive diagnostic tool. Furthermore, unlike the serological examination, the fecal sample examination provides information about the nutritive supply basis of zinc, which means that a more precise statement can be made about the zinc concentration in the mechanism. Due to its practicability, fecal sample analysis is preferable to serological evaluation. [ABSTRACT FROM AUTHOR]

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This article discusses the results of a study on the use of the immune checkpoint inhibitor durvalumab in patients with triple-negative breast cancer (TNBC). The study found that higher levels of CD4+ T cells before treatment and an expansion of γδ T cells during treatment were associated with a better response to durvalumab. The study also examined changes in immune cell composition during treatment and found that a decrease in certain immune cell populations and an increase in γδ T cells correlated with a higher rate of pathological complete response (pCR) to durvalumab. The authors suggest that these findings could potentially be used as biomarkers to predict patient response to durvalumab, but further research is needed to validate these results. [Extracted from the article]

About 25% of melanoma harbor activating NRAS mutations, which are associated with aggressive disease therefore requiring a rapid antitumor intervention. However, no efficient targeted therapy options are currently available for patients with NRAS‐mutant melanoma. MEK inhibitors (MEKi) appear to display a moderate antitumor activity and also immunological effects in NRAS‐mutant melanoma, providing an ideal backbone for combination treatments. In our study, the MEKi binimetinib, cobimetinib and trametinib combined with the BRAF inhibitors (BRAFi) encorafenib, vemurafenib and dabrafenib were investigated for their ability to inhibit proliferation, induce apoptosis and alter the expression of immune modulatory molecules in sensitive NRAS‐mutant melanoma cells using two‐ and three‐dimensional cell culture models as well as RNA sequencing analyses. Furthermore, NRAS‐mutant melanoma cells resistant to the three BRAFi/MEKi combinations were established to characterize the mechanisms contributing to their resistance. All BRAFi induced a stress response in the sensitive NRAS‐mutant melanoma cells thereby significantly enhancing the antiproliferative and proapoptotic activity of the MEKi analyzed. Furthermore, BRAFi/MEKi combinations upregulated immune relevant molecules, such as ICOS‐L, components of antigen‐presenting machinery and the "don't eat me signal" molecule CD47 in the melanoma cells. The BRAFi/MEKi‐resistant, NRAS‐mutant melanoma cells counteracted the molecular and immunological effects of BRAFi/MEKi by upregulating downstream mitogen‐activated protein kinase pathway molecules, inhibiting apoptosis and promoting immune escape mechanisms. Together, our study reveals potent molecular and immunological effects of BRAFi/MEKi in sensitive NRAS‐mutant melanoma cells that may be exploited in new combinational treatment strategies for patients with NRAS‐mutant melanoma. [ABSTRACT FROM AUTHOR]

Process Analytical Technologies (PATs) are taking a key role in the run for automatization in the biopharmaceutical industry. Spectroscopic methods such as Raman spectroscopy or mid‐infrared (MIR) spectroscopy are getting more recognition in the recent years for inline monitoring of bioprocesses due to their ability to measure various molecules simultaneously. However, their dependency on laborious model calibration making them a challenge to implement. In this study, a novel one‐point calibration that requires a single reference point prior to the inline monitoring of glucose and lactate in bioprocesses with MIR spectroscopy is assessed with 22 mammalian cell perfusion (PER) processes in two different scales and four different products. Concentrations are predicted over all PERs runs with a root mean square error (RMSE) of 0.29 g/L for glucose and 0.24 g/L for lactate, respectively. For comparison conventional partial least square regression (PLSR) models were used and trained with spectroscopic data from six bioreactor runs in two different scales and three products. The general accuracy of those models (RMSE of 0.41 g/L for glucose and 0.16 g/L for lactate) are in the range of the accuracy of the one‐point calibration. This shows the potential of the one‐point calibration as an approach making spectroscopy more accessible for bioprocess development. [ABSTRACT FROM AUTHOR]

(1) Background: In children, SARS-CoV-2 infection is mostly accompanied by mild COVID-19 symptoms. However, multisystem inflammatory syndrome (MIS-C) and long-term sequelae are often severe complications. Therefore, the protection of the pediatric population against SARS-CoV-2 with effective vaccines is particularly important. Here, we compare the humoral and cellular immune responses elicited in children (n = 15, aged 5–11 years) vaccinated with the RBD-based vaccines SOBERANA® 02 and SOBERANA® Plus combined in a heterologous scheme with those from children (n = 10, aged 4–11 years) who recovered from mild symptomatic COVID-19. (2) Methods: Blood samples were taken 14 days after the last dose for vaccinated children and 45–60 days after the infection diagnosis for COVID-19 recovered children. Anti-RBD IgG and ACE2-RBD inhibition were assessed by ELISA; IgA, cytokines, and cytotoxic-related proteins were determined by multiplex assays. Total B and T cell subpopulations and IFN-γ release were measured by multiparametric flow cytometry using a large panel of antibodies after in vitro stimulation with S1 peptides. (3) Results: Significant higher levels of specific anti-RBD IgG and IgA and ACE2-RBD inhibition capacity were found in vaccinated children in comparison to COVID-19 recovered children. Th1-like and Th2-like CD4+ T cells were also significantly higher in vaccinated subjects. IFN-γ secretion was higher in central memory CD4+ T cells of COVID-19 recovered children, but no differences between both groups were found in the CD4+ and CD8+ T cell effector, terminal effector, and naïve T cell subpopulations. In contrast to low levels of IL-4, high levels of IL-2, IL-6, IFN-γ, and IL-10 suggest a predominant Th1 cell polarization. Cytotoxic-related proteins granzyme A and B, perforin, and granulin were also found in the supernatant after S1 stimulation in both vaccinated and recovered children. (4) Conclusions: Vaccination with the heterologous scheme of SOBERANA® 02/SOBERANA® Plus induces a stronger antibody and cellular immune response compared to natural infections in young children. [ABSTRACT FROM AUTHOR]