Increasing the Clinical Efficacy of NK and Antibody-Mediated Cancer Immunotherapy: Potential Predictors of Successful Clinical Outcome Based on Observations in High-Risk Neuroblastoma

Disease recurrence is frequent in high-risk neuroblastoma (NBL) patients even after multi-modality aggressive treatment [a combination of chemotherapy, surgical resection, local radiation therapy, autologous stem cell transplantation, and cis-retinoic acid (CRA)]. Recent clinical studies have explored the use of monoclonal antibodies (mAbs) that bind to disialoganglioside (GD2), highly expressed in NBL, as a means to enable immune effector cells to destroy NBL cells via antibody-dependent cell-mediated cytotoxicity (ADCC). Preclinical data indicate that ADCC can be more effective when appropriate effector cells are activated by cytokines. Clinical studies have pursued this by administering anti-GD2 mAb in combination with ADCC-enhancing cytokines (IL2 and GM-CSF), a regimen that has demonstrated improved cancer-free survival. More recently, early clinical studies have used a fusion protein that consists of the anti-GD2 mAb directly linked to IL2, and anti-tumor responses were seen in the Phase II setting. Analyses of genes that code for receptors that influence ADCC activity and natural killer (NK) cell function [Fc receptor (FcR), killer immunoglublin-like receptor (KIR), and KIR-ligand (KIR-L)] suggest patients with anti-tumor activity are more likely to have certain genotype profiles. Further analyses will need to be conducted to determine whether these genotypes can be used as predictive markers for favorable therapeutic outcome. In this review, we discuss factors that affect response to mAb-based tumor therapies such as hu14.18-IL2. Many of our observations have been made in the context of NBL; however, we will also include some observations made with mAbs targeting other tumor types that are consistent with results in NBL. Therefore, we hypothesize that the NBL observations discussed here may also be relevant to mAb therapy for other cancers, in which ADCC is known to play a role

Description of Telemark Skiing Technique Using Full Body Inertial Measurement Unit

Researchers involved in skiing investigations postulate Telemark skiing as an alternative technique to Alpine skiing, which may be associated with lower injury risk. A free heel of the boot, and a boot that enables flexion of the toe, are characteristic features. The aim of this research was to compare three types of turns on Telemark skis, through a biomechanical description of each skiing technique. Seven professional skiers were investigated. Two cameras and the MyoMotion Research Pro system were utilized. Eighteen wireless IMU sensors were mounted on each skier’s body. For every skier, five runs were recorded for each of the three turning techniques. Velocity of run, range of movement, angular velocity in joints, time sequences, and order of initialization of movement were obtained. A higher velocity of skiing was obtained during the parallel (14.2 m/s) and rotational turns (14.9 m/s), compared to a low–high turn (8.9 m/s). A comparison of knee angles, revealed similar minimum (18 and 16 degrees) and maximum (143 and 147 degrees) values achieved during the parallel and rotational techniques, which differed considerably from the low–high technique (27 and 121 degrees, respectively). There were no significant differences in trunk rotation angles. A detailed analysis of the Telemark skiing technique revealed novel information on how turns are executed by well-trained skiers and the impact of different approaches

Intra-Articular Injections of Autologous Adipose Tissue or Platelet-Rich Plasma Comparably Improve Clinical and Functional Outcomes in Patients with Knee Osteoarthritis

The use of biologic therapies for the management of knee osteoarthritis (OA) has largely increased in recent years. The purpose of this study was to evaluate the efficiency and the therapeutic potential of platelet-rich plasma (PRP) and autologous adipose tissue (AAT) injections as a treatment for knee OA. Sixty participants were enrolled in the study: 20 healthy ones and 40 with minimal to moderate knee OA (KL I-III). The OA patients were randomly assigned either to the PRP or to the AAT group. The PRP samples showed a low expression level of NF-κB-responsive gene CCL5 and high expression levels of classic inflammatory and TNF-l INF responses. The AAT injection product was prepared using a Lipogems device, and its regenerative potential as well as the ability for expansion of mesenchymal stem cells were tested in the cell culture conditions. The patient assessments were carried out five times. Significant improvement was observed regardless of the treatment method in the VAS, KOOS, WOMAC and IKDC 2000 subjective evaluations as well as in the functional parameters. Intra-articular injections of AAT or PRP improved pain, symptoms, quality of life and functional capacity with a comparable effectiveness in the patients with mild to moderate knee osteoarthritis

Kinetic study of the pyrolysis and gasification of Rosa multiflora and Miscanthus giganteus biomasses via thermogravimetric analysis

The thermal behaviour of the Rosa multiflora (3 groups: control, irradiated 3 × 3 seconds, and 3 × 9 seconds by low power laser of wavelength 672 nm) and Miscanthus giganteus (3 groups: R, V, and Z) biomass by thermogravimetric analysis (TGA) was studied at heating rate 3 K per minute from ambient temperature to 950°C. The TGA tests were performed in high purity CO2 (99.998%) with a flow rate 200 mL per minute and 100 mg of sample, milled and sieved to a particle size below 250 μm. In contrast to the majority of the conducted examinations, which are carried out with the use of chars, the measurements were conducted for raw biomass. The kinetics parameters of the biomass conversion process were determined from the experimental data by integral methods (Murray and White; Senum and Yang). The methods used have allowed distinguishing and analysing the different stages of the process, i. e. the primary and secondary pyrolysis as well as gasification. Both methods gave comparable results. The activation energy determined using more accurate Senum and Yang method ranged from 85-88 kJ/mol (primary pyrolysis), from 29-32 kJ/mol (secondary pyrolysis), and from 173-190 kJ/mol (gasification) for Rosa multiflora biomass and from 86-111 kJ/mol (primary pyrolysis), from 22-25 kJ/mol (secondary pyrolysis), and from 181-217 kJ/mol (gasification) for Miscanthus giganteus. The pre-exponential factor was in the range of 5.95 ⋅ 106 to 13.05 ⋅ 106 min–1 (primary pyrolysis), 2.25-4.22 min–1 (secondary pyrolysis), and 13.96 ⋅ 106 to 1.18 ⋅ 108 min–1 (gasification) for Rosa multiflora biomass and 6.94 ⋅ 106 to 1.79 ⋅ 109 min–1 (primary pyrolysis), 0.88-1.62 min–1 (secondary pyrolysis), and 131.54 ⋅ 106 to 1.92 ⋅ 109 min-1 (gasification) for Miscanthus giganteus biomass

Coordinated acquisition of inhibitory and activating receptors and functional properties by developing human natural killer cells

The stages of human natural killer (NK) cell differentiation are not well established. Culturing CD34(+) progenitors with interleukin 7 (IL-7), IL-15, stem cell factor (SCF), FLT-3L, and murine fetal liver cell line (EL08.1D2), we identified 2 nonoverlapping subsets of differentiating CD56(+) cells based on CD117 and CD94 (CD117(high)CD94(–) and CD117(low/–)CD94(+) cells). Both populations expressed CD161 and NKp44, but differed with respect to NKp30, NKp46, NKG2A, NKG2C, NKG2D, CD8, CD16, and KIR. Only the CD117(low/–) CD94(+) population displayed cytotoxicity and interferon-γ production. Both populations arose from a single CD34(+)CD38(–) Lin(–) cell and their percentages changed over time in a reciprocal fashion, with CD117(high)CD94(–) cells predominating early and decreasing due to an increase of the CD117(low/–)CD94(+) population. These 2 subsets represent distinct stages of NKcell differentiation, since purified CD117(high) CD94(–) cells give rise to CD117(low/–)CD94(+) cells. The stromal cell line (EL08.1D2) facilitated the transition from CD117(high)CD94(–) to CD117(low/–)CD94(+) via an intermediate phenotype (CD117(low)CD94(low/–)). EL08.1D2 also maintained the mature phenotype, preventing the reversion of CD117(low/–)CD94(+) cells to the intermediate (CD117(low)CD94(low/–)) phenotype. An analogous population of CD56(+)CD117(high)CD94(–) cells was found in cord blood. The identified stages of NK-cell differentiation provide evidence for coordinated acquisition of HLA-specific inhibitory receptors (ie, CD94/NKG2A) and function in developing human NK cells

Investigating the Effects of the Physicochemical Properties of Cellulose-Derived Biocarbon on Direct Carbon Solid Oxide Fuel Cell Performance

This paper presents a study of the characteristic effects of the physicochemical properties of microcrystalline cellulose and a series of biocarbon samples produced from this raw material through thermal conversion at temperatures ranging from 200 °C to 850 °C. Structural studies revealed that the biocarbon samples produced from cellulose had a relatively low degree of graphitization of the carbon and an isometric shape of the carbon particles. Based on thermal investigations using the differential thermal analysis/differential scanning calorimeter method, obtaining fully formed biocarbon samples from cellulose feedstock was possible at about 400 °C. The highest direct carbon solid oxide fuel cell (DC-SOFC) performance was found for biochar samples obtained via thermal treatment at 400–600 °C. The pyrolytic gases from cellulose decomposition had a considerable impact on the achieved current density and power density of the DC-SOFCs supplied by pure cellulose samples or biochars derived from cellulose feedstock at a lower temperature range of 200–400 °C. For the DC-SOFCs supplied by biochars synthesised at higher temperatures of 600–850 °C, the “shuttle delivery mechanism” had a substantial effect. The impact of the carbon oxide concentration in the anode or carbon bed was important for the performance of the DC-SOFCs. Carbon oxide oxidised at the anode to form carbon dioxide, which interacted with the carbon bed to form more carbon oxide. The application of biochar obtained from cellulose alone without an additional catalyst led to moderate electrochemical power output from the DC-SOFCs. The results show that catalysts for the reverse Boudouard reactions occurring in a biocarbon bed are critical to ensuring high performance and stable operation under electrical load, which is crucial for DC-SOFC development

The Utilisation of Solid Fuels Derived from Waste Pistachio Shells in Direct Carbon Solid Oxide Fuel Cells

The comprehensive results regarding the physicochemical properties of carbonaceous materials that are obtained from pistachio shells support their usage as solid fuels to supply direct carbon solid oxide fuel cells (DC-SOFCs). The influence of preparation conditions on variations in the chemical composition, morphology of the biochar powders, and degree of graphitization of carbonaceous materials were investigated. Based on structural investigations (X-ray diffraction analysis and Raman spectroscopy), it was observed that disordered carbon particles developed during the application of thermal treatments. The use of X-ray fluorescence enabled a comparative analysis of the chemical composition of the inorganic matter in biocarbon-based samples. Additionally, the gasification of carbonaceous-based samples vs. time at a temperature of 850 °C was investigated in a H2O or CO2 gas atmosphere. The analysis demonstrated the conversion rate of biochar obtained from pistachio shells to H2, CH4 and CO during steam gasification. The electrochemical investigations of the DC-SOFCs that were supplied with biochars obtained from pistachio shells were characterized by satisfactory values for the current and power densities at a temperature range of 700–850 °C. However, a higher power output of the DC-SOFCs was observed when CO2 was introduced to the anode chamber. Therefore, the impact of the Boudouard reaction on the performance of DC-SOFCs was confirmed. The chars that were prepared from pistachio shells were adequate for solid fuels for utilization in DC–SOFCs

Microbiome features associated with performance measures in athletic and non-athletic individuals: A case-control study.

The influence of human gut microbiota on health and disease is now commonly appreciated. Therefore, it is not surprising that microbiome research has found interest in the sports community, hoping to improve health and optimize performance. Comparative studies found new species or pathways that were more enriched in elites than sedentary controls. In addition, sport-specific and performance-level-specific microbiome features have been identified. However, the results remain inconclusive and indicate the need for further assessment. In this case-control study, we tested two athletic populations (i.e. strength athletes, endurance athletes) and a non-athletic, but physically active, control group across two acute exercise bouts, separated by a 2-week period, that measured explosive and high intensity fitness level (repeated 30-s all-out Wingate test (WT)) and cardiorespiratory fitness level (Bruce Treadmill Test). While we did not identify any group differences in alpha and beta diversity or significant differential abundance of microbiome components at baseline, one-third of the species identified were unique to each group. Longitudinal sample (pre- and post-exercise) analysis revealed an abundance of Alistipes communis in the strength group during the WT and 88 species with notable between-group differences during the Bruce Test. SparCC recognized Bifidobacterium longum and Bifidobacterium adolescentis, short-chain fatty acid producers with probiotic properties, species strongly associated with VO2max. Ultimately, we identified several taxa with different baseline abundances and longitudinal changes when comparing individuals based on their VO2max, average power, and maximal power parameters. Our results confirmed that the health status of individuals are consistent with assumptions about microbiome health. Furthermore, our findings indicate that microbiome features are associated with better performance previously identified in elite athletes