Comprehensive Cytokine Profiling of Patients with COVID-19 Receiving Tocilizumab Therapy

Coronavirus disease 2019 (COVID-19) is characterized by immune activation in response to viral spread, in severe cases leading to the development of cytokine storm syndrome (CSS) and increased mortality. Despite its importance in prognosis, the pathophysiological mechanisms of CSS in COVID-19 remain to be defined. Towards this goal, we analyzed cytokine profiles and their interrelation in regard to anti-cytokine treatment with tocilizumab in 98 hospitalized patients with COVID-19. We performed a multiplex measurement of 41 circulating cytokines in the plasma of patients on admission and 3–5 days after, during the follow-up. Then we analyzed the patient groups separated in two ways: according to the clusterization of their blood cytokines and based on the administration of tocilizumab therapy. Patients with and without CSS formed distinct clusters according to their cytokine concentration changes. However, the tocilizumab therapy, administered based on the standard clinical and laboratory criteria, did not fully correspond to those clusters of CSS. Furthermore, among all cytokines, IL-6, IL-1RA, IL-10, and G-CSF demonstrated the most prominent differences between patients with and without clinical endpoints, while only IL-1RA was prognostically significant in both groups of patients with and without tocilizumab therapy, decreasing in the former and increasing in the latter during the follow-up period. Thus, CSS in COVID-19, characterized by a correlated release of multiple cytokines, does not fully correspond to the standard parameters of disease severity. Analysis of the cytokine signature, including the IL-1RA level in addition to standard clinical and laboratory parameters may be useful to define the onset of a cytokine storm in COVID-19 as well as the indications for anti-cytokine therapy.     

Optimal image compression via block-based adaptive colour reduction with minimal contour effect

Current image acquisition devices require tremendous amounts of storage for saving the data returned. This paper overcomes the latter drawback through proposing a colour reduction technique which first subdivides the image into patches, and then makes use of fuzzy c-means and fuzzy-logic-based inference systems, in order to cluster and reduce the number of the unique colours present in each patch, iteratively. The colours available in each patch are quantised, and the emergence of false edges is checked for, by means of the Sobel edge detection algorithm, so as to minimise the contour effect. At the compression stage, a methodology taking advantage of block-based singular value decomposition and wavelet difference reduction is adopted. Considering 35000 sample images from various databases, the proposed method outperforms centre cut, moment-preserving threshold, inter-colour correlation, generic K-means and quantisation by dimensionality reduction.

     

Fibers spinning from poly(trimethylsilylpropyne) solutions

This study for the first time directs in assessment of the necessary conditions for spinning fibers from poly[1-(trimethylsilyl)1-propyne], one of the best for gas separation. It includes a search of appropriate solvents, investigation of rheological properties of solutions, a preparation of dopes with reasonable polymer content and a choice of effective coagulants based on their solubility parameters in frames of wet fiber spinning. The fibers were obtained with diameter of 7 ± 1 μm and strength of up to 200 MPa. The morphology of the surface and core of the PTMSP fibers was distinctively different: dense skin and friable core. From the viewpoint of membrane properties, it looks like asymmetrical membrane. In addition, the hollow fibers we prepared by dry spinning method. Overall, the stable fiber spinning process from PTMSP solutions was developed for the first time, and monolith and hollow PTMSP fibers of good quality were obtained. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48511.     

40-Hz Auditory Steady-State Response (ASSR) as a Biomarker of Genetic Defects in the SHANK3 Gene: A Case Report of 15-Year-Old Girl with a Rare Partial SHANK3 Duplication

SHANK3 encodes a scaffold protein involved in postsynaptic receptor density in glutamatergic synapses, including those in the parvalbumin (PV)+ inhibitory neurons—the key players in the generation of sensory gamma oscillations, such as 40-Hz auditory steady-state response (ASSR). However, 40-Hz ASSR was not studied in relation to SHANK3 functioning. Here, we present a 15-year-old girl (SH01) with previously unreported duplication of the first seven exons of the SHANK3 gene (22q13.33). SH01’s electroencephalogram (EEG) during 40-Hz click trains of 500 ms duration binaurally presented with inter-trial intervals of 500–800 ms were compared with those from typically developing children (n = 32). SH01 was diagnosed with mild mental retardation and learning disabilities (F70.88), dysgraphia, dyslexia, and smaller vocabulary than typically developing (TD) peers. Her clinical phenotype resembled the phenotype of previously described patients with 22q13.33 microduplications (≈30 reported so far). SH01 had mild autistic symptoms but below the threshold for ASD diagnosis and microcephaly. No seizures or MRI abnormalities were reported. While SH01 had relatively preserved auditory event-related potential (ERP) with slightly attenuated P1, her 40-Hz ASSR was totally absent significantly deviating from TD’s ASSR. The absence of 40-Hz ASSR in patients with microduplication, which affected the SHANK3 gene, indicates deficient temporal resolution of the auditory system, which might underlie language problems and represent a neurophysiological biomarker of SHANK3 abnormalities.     

Security Threat Analysis of the 5G ESSENCE Platform

Wireless Personal Communications - The present paper discusses several security requirements coming from assessment of the use cases developed within the context of the original 5G-PPP “5G...     

Biomimetic gels with chemical and physical interpenetrating networks

This study aimed to create and to characterize the functional properties of gels with semi‐interpenetrating network (semi‐IPN) with focus on possible use of these composites in biomedical engineering. Polyacrylamide as a synthetic biocompatible polymer was chosen for the chemical network. The physical network comprised the gel‐forming polysaccharides xanthan gum or gellan gum. Gels were synthesized by radical polymerization of acrylamide in aqueous solutions of polysaccharides. Mechanical and electrical properties of gels with 0.2, 0.4, 0.6, 0.8 and 1.0 wt% content of polysaccharide were investigated. It was found that the inclusion of a small amount of xanthan or gellan into the polymeric network of a polyacrylamide gel significantly shifts the gel electrical potential towards the rest potential of living cells and Young's modulus towards the elasticity limits of biological soft tissues like non‐activated muscles. From the viewpoint of biomedical applications, the main advantage of the proposed composites is that the semi‐IPN structure provides a nonlinear dependence of gel tension on gel deformation, which mimics the elasticity of natural tissues. This feature opens the possibility for the promising use of the proposed gels for musculoskeletal minibioimplants or scaffolds for tissue engineering. © 2018 Society of Chemical Industry     

Generation of Liposomes to Study the Effect of Mycobacterium Tuberculosis Lipids on HIV-1 cis- and trans-Infections

Tuberculosis (TB) is the leading cause of death among HIV-1-infected individuals and Mycobacterium tuberculosis (Mtb) co-infection is an early precipitate to AIDS. We aimed to determine whether Mtb strains differentially modulate cellular susceptibility to HIV-1 infection (cis- and trans-infection), via surface receptor interaction by their cell envelope lipids. Total lipids from pathogenic (lineage 4 Mtb H37Rv, CDC1551 and lineage 2 Mtb HN878, EU127) and non-pathogenic (Mycobacterium bovis BCG and Mycobacterium smegmatis) Mycobacterium strains were integrated into liposomes mimicking the lipid distribution and antigen accessibility of the mycobacterial cell wall. The resulting liposomes were tested for modulating in vitro HIV-1 cis- and trans-infection of TZM-bl cells using single-cycle infectious virus particles. Mtb glycolipids did not affect HIV-1 direct infection however, trans-infection of both R5 and X4 tropic HIV-1 strains were impaired in the presence of glycolipids from M. bovis, Mtb H37Rv and Mtb EU127 strains when using Raji-DC-SIGN cells or immature and mature dendritic cells (DCs) to capture virus. SL1, PDIM and TDM lipids were identified to be involved in DC-SIGN recognition and impairment of HIV-1 trans-infection. These findings indicate that variant strains of Mtb have differential effect on HIV-1 trans-infection with the potential to influence HIV-1 disease course in co-infected individuals.     

Effects of Tyrosine and Tryptophan in Rats with Diet-Induced Obesity

Amino acids tyrosine (Tyr) and tryptophan (Trp) play a significant role in the regulation of energy metabolism, locomotor activity, and eating behavior. We studied the possibility of modulating these processes in obesity by increasing the pool of Tyr and Trp in the experimental diet. As a model of obesity, we used Wistar rats fed a diet with an excess specific energy value (HFCD) for 64 days. Trp led to a normalization of the rats’ body weight almost to the control level, but increased anxiety-like behavior and decreased long-term memory. The consumption of amino acids resulted in increased grip strength and impairment of short-term memory. The locomotor activity of animals decreased with age as a result of Tyr consumption, while Trp, on the contrary, prevented this. The Tyr supplementation led to the normalization of triglycerides and LDL. In the spleen cell lysates, amino acids suppressed the production of proinflammatory cytokines. The liver tissue morphology showed that the consumption of Tyr noticeably weakened the signs of fatty degeneration. The addition of Trp, on the contrary, led to an unfavorable effect, consisting of the appearance of a high number of large rounded fatty vacuoles. The data obtained indicate a more pronounced anti-inflammatory effect of Tyr as compared to Trp.