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Various types of cellular injection have become a popular and costly treatment option for patients with knee osteoarthritis despite a paucity of literature establishing relative efficacy to each other or corticosteroid injections. Here we aimed to identify the safety and efficacy of cell injections from autologous bone marrow aspirate concentrate, autologous adipose stromal vascular fraction and allogeneic human umbilical cord tissue-derived mesenchymal stromal cells, in comparison to corticosteroid injection (CSI). The study was a phase 2/3, four-arm parallel, multicenter, single-blind, randomized, controlled clinical trial with 480 patients with a diagnosis of knee osteoarthritis (Kellgren-Lawrence II-IV). Participants were randomized to the three different arms with a 3:1 distribution. Arm 1: autologous bone marrow aspirate concentrate (n = 120), CSI (n = 40); arm 2: umbilical cord tissue-derived mesenchymal stromal cells (n = 120), CSI (n = 40); arm 3: stromal vascular fraction (n = 120), CSI (n = 40). The co-primary endpoints were the visual analog scale pain score and Knee injury and Osteoarthritis Outcome Score pain score at 12 months versus baseline. Analyses of our primary endpoints, with 440 patients, revealed that at 1 year post injection, none of the three orthobiologic injections was superior to another, or to the CSI control. In addition, none of the four groups showed a significant change in magnetic resonance imaging osteoarthritis score compared to baseline. No procedure-related serious adverse events were reported during the study period. In summary, this study shows that at 1 year post injection, there was no superior orthobiologic as compared to CSI for knee osteoarthritis. ClinicalTrials.gov Identifier: NCT03818737.

Abstract Background Infection with the Epstein-Barr virus (EBV) elicits a complex T-cell response against a broad range of viral proteins. Hence, identifying potential differences in the cellular immune response of patients with different EBV-associated diseases or different courses of the same disorder requires interrogation of a maximum number of EBV antigens. Here, we tested three novel EBV-derived antigen formulations for their ability to reactivate virus-specific T cells ex vivo in patients with EBV-associated infectious mononucleosis (IM). Methods We comparatively analyzed EBV-specific CD4+ and CD8+ T-cell responses to three EBV-derived antigen formulations in 20 pediatric patients during the early phase of IM: T-activated EBV proteins (BZLF1, EBNA3A) and EBV-like particles (EB-VLP), both able to induce CD4+ and CD8+ T-cell responses ex vivo, as well as an EBV-derived peptide pool (PP) covering 94 well-characterized CD8+ T-cell epitopes. We assessed the specificity, magnitude, kinetics, and functional characteristics of EBV-specific immune responses at two sequential time points (v1 and v2) within the first six weeks after IM symptom onset (Tonset). Results All three tested EBV-derived antigen formulations enabled the detection of EBV-reactive T cells during the early phase of IM without prior T-cell expansion in vitro. EBV-reactive CD4+ and CD8+ T cells were mainly mono-functional (CD4+: mean 64.92%, range 56.15-71.71%; CD8+: mean 58.55%, range 11.79-85.22%) within the first two weeks after symptom onset (v1) with IFN-γ and TNF-secreting cells representing the majority of mono-functional EBV-reactive T cells. By contrast, PP-reactive CD8+ T cells were primarily bi-functional (>60% at v1 and v2), produced IFN-γ and TNF and had more tri-functional than mono-functional components. We observed a moderate correlation between viral load and EBNA3A, EB-VLP, and PP-reactive CD8+ T cells (r s = 0.345, 0.418, and 0.356, respectively) within the first two weeks after Tonset, but no correlation with the number of detectable EBV-reactive CD4+ T cells. Conclusions All three EBV-derived antigen formulations represent innovative and generic recall antigens suitable for monitoring EBV-specific T-cell responses ex vivo. Their combined use facilitates a thorough analysis of EBV-specific T-cell immunity and allows the identification of functional T-cell signatures linked to disease development and severity.

Abstract Engaging young people in research is a promising approach to tackling issues like chronic disease prevention. Our involvement as youth advisors provided valuable experiences, including being at the forefront of change and learning to work within a research team. Furthermore, our experience provides greater insight and learnings for future youth engagement in research.

Efficient water treatment ideally combines ion exchange for the removal of hardness elements and toxic trace metals as well as ultrafiltration for the removal of particulate matter. Although promising for adsorption, many high‐surface‐area polymer materials cannot be easily processed into freestanding membranes or packed bed columns, due to poor solution processability and high back pressures, respectively. The preparation of hybrid membranes comprising sulfonated hypercrosslinked polymers entrapped in nanocellulose papers is described. The hybrid membranes are effective for simultaneous ultrafiltration and ion exchange. Increasing the polymer loading of the hybrid membrane produces synergy by increasing the permeance of the membranes while enhancing the ion adsorption capacity to values exceeding those of bulk hypercrosslinked polymers. The maximum ion adsorption capacity for copper is determined to be ≈100 mg g−1 outperforming that of pure polymer (71 mg g−1) and commercially available ion exchange resins. Competitive adsorption is tested in samples containing water hardness elements and trace toxic metal ions showing high ion‐exchange capacities. Even when fully loaded with water hardness elements, Ba2+ and Sr2+ are still removed from solution.

Abstract Oil palm trunk (OPT) is an inexpensive, abundantly available by-product of palm oil production which is typically not put to material use. Due to its comparably high cellulose content, OPT represents a suitable raw material for the preparation of cellulose nanofibrils (CNFs). Aiming for full utilization of the raw material and minimized energy demand, non-delignified and partially delignified (alkali-pretreated) OPT was subjected to mechanical fibrillation in the present study. As compared to CNFs from fully delignified OPT, the lignin-rich microfibrils obtained by this approach generally showed higher average fibril diameters, lower thermal stability as well as lower viscosity, and higher sedimentation rate in suspension. However, the combination of alkali-pretreatment and fibrillation by disc-grinding and subsequent high-pressure homogenization resulted in fibrils with properties similar to those of CNFs from fully delignified OPT. As proven by IR-spectroscopy, thermogravimetry and chemical composition analysis, alkali-treated OPT fibrils still contained substantial amounts of residual lignin which could, for instance, act as a natural coupling agent or binder in composite applications. Moreover, the facile delignification process applied herein requires far less chemicals and energy than conventional pulping and is thus beneficial from both the economic and ecological perspective.

The injection of biologic products for musculoskeletal pathologies is an emerging and promising field; however, dubious and unsafe uses for these products are often marketed. The Food and Drug Administration (FDA) has determined the need for varying degrees of regulation for these products for safety and efficacy. These regulations are frequently updated and federally enforced. As the regulatory landscape changes, clinicians using biologic products must stay informed to remain within the purview of the FDA. This article describes the current regulations of the most common products: platelet-rich plasma, bone marrow aspirate concentrate, adipose-derived products, and birth tissue products.

Abstract Carbons form critical components in biogas purification and energy storage systems and are used to modify polymer matrices. The environmental impact of producing carbons has driven research interest in biomass‐derived carbons, although these have yield, processing, and resource competition limitations. Naturally formed fungal filaments are investigated, which are abundantly available as food‐ and biotechnology‐industry by‐products and wastes as cost‐effective and sustainable templates for carbon networks. Pyrolyzed Agaricus bisporus and Pleurotus eryngii filament networks are mesoporous and microscale with a size regime close to carbon fibers. Their BET surface areas of ≈282 m2 g−1 and ≈60 m2 g−1, respectively, greatly exceed values associated with carbon fibers and non‐activated pyrolyzed bacterial cellulose and approximately on par with values for carbon black and CNTs in addition to pyrolyzed pinewood, rice husk, corn stover or olive mill waste. They also exhibit greater specific capacitance than both non‐activated and activated pyrolyzed bacterial cellulose in addition to YP‐50F (coconut shell based) commercial carbons. The high surface area and specific capacitance of fungal carbon coupled with the potential to tune these properties through species‐ and growth‐environment‐associated differences in network and filament morphology and inclusion of inorganic material through biomineralization makes them potentially useful in creating supercapacitors.

Summary: Actin cytoskeleton remodeling sustains the ability of cytotoxic T cells to search for target cells and eliminate them. We here investigated the relationship between energetic status, actin remodeling, and functional fitness in human CD8+ effector T cells. Cell spreading during migration or immunological synapse assembly mirrored cytotoxic activity. Morphological and functional fitness were boosted by interleukin-2 (IL-2), which also stimulated the transcription of glycolytic enzymes, actin isoforms, and actin-related protein (ARP)2/3 complex subunits. This molecular program scaled with F-actin content and cell spreading. Inhibiting glycolysis impaired F-actin remodeling at the lamellipodium, chemokine-driven motility, and adhesion, while mitochondrial oxidative phosphorylation blockade impacted cell elongation during confined migration. The severe morphological and functional defects of ARPC1B-deficient T cells were only partially corrected by IL-2, emphasizing ARP2/3-mediated actin polymerization as a crucial energy state integrator. The study therefore underscores the tight coordination between metabolic and actin remodeling programs to sustain the cytotoxic activity of CD8+ T cells.

In this series of papers, we present statistical maps of mirror-mode-like (MM) structures in the magnetosheaths of Mars and Venus and calculate the probability of detecting them in spacecraft data. We aim to study and compare them with the same tools and a similar payload at both planets. We consider their dependence on extreme ultraviolet (EUV) solar flux levels (high and low). The detection of these structures is done through magnetic-field-only criteria, and ambiguous determinations are checked further. In line with many previous studies at Earth, this technique has the advantage of using one instrument (a magnetometer) with good time resolution, facilitating comparisons between planetary and cometary environments. Applied to the magnetometer data of the Venus Express (VEX) spacecraft from May 2006 to November 2014, we detect structures closely resembling MMs lasting in total more than 93 000 s, corresponding to about 0.6 % of VEX's total time spent in Venus's plasma environment. We calculate MM-like occurrences normalized to the spacecraft's residence time during the course of the mission. Detection probabilities are about 10 % at most for any given controlling parameter. In general, MM-like structures appear in two main regions: one behind the shock and the other close to the induced magnetospheric boundary, as expected from theory. For solar maximum, the active region behind the bow shock is further inside the magnetosheath, near the solar minimum bow shock location. The ratios of the observations during solar minimum and maximum are slightly dependent on the depth ΔB/B of the structures; deeper structures are more prevalent at solar maximum. A dependence on solar EUV (F10.7) flux is also present, where at higher F10.7 flux the events occur at higher values than the daily-average value of the flux. The main dependence of the MM-like structures is on the condition of the bow shock: for quasi-perpendicular conditions, the MM occurrence rate is higher than for quasi-parallel conditions. However, when the shock becomes “too perpendicular” the chance of observing MM-like structures reduces again. Combining the plasma data from the Ion Mass Analyser (IMA on board Venus Express) with the magnetometer data shows that the instability criterion for MMs is reduced in the two main regions where the structures are measured, whereas it is still enhanced in the region between these two regions, implying that the generation of MMs is transferring energy from the particles to the field. With the addition of the Electron Spectrometer (ELS on board Venus Express) data, it is possible to show that there is an anti-phase between the magnetic field strength and the density for the MM-like structures. This study is Part 2 of a series of papers on the magnetosheaths of Mars and Venus.