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Abstract Fructosyl peptide oxidases (FPOX) are deglycating enzymes that find application as key enzymatic components in diabetes monitoring devices. Indeed, their use with blood samples can provide a measurement of the concentration of glycated hemoglobin and glycated albumin, two well-known diabetes markers. However, the FPOX currently employed in enzymatic assays cannot directly detect whole glycated proteins, making it necessary to perform a preliminary proteolytic treatment of the target protein to generate small glycated peptides that can act as viable substrates for the enzyme. This is a costly and time consuming step. In this work, we used an in silico protein engineering approach to enhance the overall thermal stability of the enzyme and to improve its catalytic activity toward large substrates. The final design shows a marked improvement in thermal stability relative to the wild type enzyme, a distinct widening of its access tunnel and significant enzymatic activity towards a range of glycated substrates.

Abstract Calculating the change in the saturated bulk modulus of a saturated rock with new fluid properties requires a priori selection of an effective bulk modulus of the solid constituents. When the rock constituents have similar mineral moduli, the theoretical bounds on the solid modulus are close to each other. However, when solid properties vary greatly, as in organic-rich shales, the actual effective solid modulus of a physical rock may vary significantly between the bounds which results in uncertainty in the predicted change in the saturated bulk modulus of the rock. We use a semi-empirical rock physics model utilizing the Brown–Korringa equation for mineralogically heterogenous rocks and introduce three parameters to estimate the pore space compressibility, the dry frame compressibility, and the fractional position of the effective solid modulus relative to the Reuss and Voigt bounds. We optimize for these three parameters in seven organic shale formations and find that the Reuss bound for the effective solid material modulus best fits the data when organic content is high. Furthermore, we use this model to fluid substitute to 100% brine saturation and find Gassmann’s equation using the Hill average predicts similar saturated moduli to the semi-empirical Brown–Korringa rock physics model when volume fraction of solid organic matter is less than 5%. However, at higher organic contents, we find that the error using the Gassmann–Hill approach increases, and the semi-empirical Brown–Korringa model better fits the data.

Abstract Chitosan was produced from Hermetia illucens pupal exuviae by heterogeneous and homogeneous deacetylation. Tomato fruits (Solanum lycopersicum), that are one of the most grown and consumed food throughout the world, were coated with 0.5 and 1% chitosan, applied by dipping or spraying, and stored at room temperature or 4 °C, for a storage period of 30 days. Statistical analysis give different results depending on the analysed parameters: heterogeneous chitosan, indeed, had a better effect than the homogenous one in maintaining more stable physico-chemical parameters, while the homogenous chitosan improved the total phenols, flavonoids and antioxidant activity. Chitosan coatings applied by spraying were more effective in all the analyses. Chitosan derived from H. illucens always performed similarly to the commercial chitosan. However, a general better performance of insect-derived chitosan on the concentration of phenolics and flavonoids, and the antioxidant activity was observed as compared to the commercial one. Chitosan coating has already been successfully used for preservation of fresh fruits, as alternative to synthetic polymers, but this is the first investigation of chitosan produced from an insect for this application. These preliminary results are encouraging regarding the validation of the insect H. illucens as a source of chitosan.

Abstract A full understanding of the characteristics of Covid-19 patients with a better chance of experiencing poor vital outcomes is critical for implementing accurate and precise treatments. In this paper, two different advanced data-driven statistical approaches along with standard statistical methods have been implemented to identify groups of patients most at-risk for death or severity of respiratory distress. First, the tree-based analysis allowed to identify profiles of patients with different risk of in-hospital death (by Survival Tree-ST analysis) and severity of respiratory distress (by Classification and Regression Tree-CART analysis), and to unravel the role on risk stratification of highly dependent covariates (i.e., demographic characteristics, admission values and comorbidities). The ST analysis identified as the most at-risk group for in-hospital death the patients with age > 65 years, creatinine $$\ge$$ ≥ 1.2 mg/dL, CRP $$\ge$$ ≥ 25 mg/L and anti-hypertensive treatment. Based on the CART analysis, the subgroups most at-risk of severity of respiratory distress were defined by patients with creatinine level $$\ge$$ ≥ 1.2 mg/dL. Furthermore, to investigate the multivariate dependence structure among the demographic characteristics, the admission values, the comorbidities and the severity of respiratory distress, the Bayesian Network analysis was applied. This analysis confirmed the influence of creatinine and CRP on the severity of respiratory distress.

Abstract This paper is based on a retrospective longitudinal study on people living with HIV under antiretroviral treatment (ART) where allelic variants (either heterozygous CT genotype or homozygous CC genotype) have been evaluated at position −168 of the promoter region of the protein kinase R (−168/PKR). In general, antiviral effects of interferon are partially mediated by a RNA-dependent protein kinase (PKR) that, once activated, inhibits protein synthesis. Indeed, activation of PKR response can inhibit HIV replication. To explore the role of allelic variants in shaping dynamics of commonly monitored HIV biomarkers, CD4 cells, CD8 cells and HIV-load were modelled within a latent class mixed model (LCMM) to account for participants’ heterogeneity over time. The estimated models identified two sub-groups from CD4 and HIV-load dynamics, revealing better outcomes for subgroups of participants with the heterozygous CT genotype. Heterozygous CT subjects in one of the two identified subgroups exhibited higher increase of CD4 cells and more marked decrease of HIV-load, over time, with respect to the homozygous CC subjects assigned to the same group.

Abstract A single nucleotide polymorphism in the Type 2 deiodinase (DIO2) gene (p.Thr92Ala) was found to be associated with hypertension, type 2 diabetes mellitus (T2DM), insulin resistance, and body mass index (BMI). We retrospectively evaluated 182 patients to assess whether the DIO2 p.Thr92Ala was associated with severe obesity and response to bariatric surgery. Genomic DNA was extracted from peripheral blood leukocytes before surgery. Glycemic control parameters, cardiometabolic risk biomarkers (waist circumference, lipid assessment and blood pressure) and hormonal parameters were assessed at baseline and after surgery. Based on genotype evaluation, 78/182 (42.9%) patients were homozygous wild-type (Thr/Thr), 83/182 (45.6%) heterozygous (Thr/Ala), and 21/182 (11.5%) rare homozygous (Ala/Ala). Age at the time of the first evaluation in our Unit was significantly lower in patients with DIO2 p.Thr92Ala. No significant association was observed between DIO2 p.Thr92Ala and BMI, excess weight, waist circumference, Homa Index. The prevalence of comorbidities was not associated with allele distribution except for hypertension that was more frequent in wild-type patients (p = 0.03). After bariatric surgery, excess weight loss (EWL) % and remission from comorbidities occurred without differences according to genotypes. DIO2 p.Thr92Ala does not affect the severity of obesity and its complications, but it seems to determine an earlier onset of morbid obesity. The presence of polymorphism seems not to impact on the response to bariatric surgery, both in terms of weight loss and remission of comorbidities.

Abstract Smoothness (i.e. non-intermittency) of movement is a clinically important property of the voluntary movement with accuracy and proper speed. Resting head position and head voluntary movements are impaired in cervical dystonia. The current work aims to evaluate if the smoothness of voluntary head rotations is reduced in this disease. Twenty-six cervical dystonia patients and 26 controls completed rightward and leftward head rotations. Patients’ movements were differentiated into “towards-dystonia” (rotation accentuated the torticollis) and “away-dystonia”. Smoothness was quantified by the angular jerk and arc length of the spectrum of angular speed (i.e. SPARC, arbitrary units). Movement amplitude (mean, 95% CI) on the horizontal plane was larger in controls (63.8°, 58.3°–69.2°) than patients when moving towards-dystonia (52.8°, 46.3°–59.4°; P = 0.006). Controls’ movements (49.4°/s, 41.9–56.9°/s) were faster than movements towards-dystonia (31.6°/s, 25.2–37.9°/s; P

Abstract The properties of incident light play a crucial role in the mating process of diatoms, a group of ecologically important microalgae. While species-specific requirements for light intensity and photoperiod have been observed in several diatom species, little is known about the light spectrum that allows sexual reproduction. Here, we study the effects of spectral properties and light intensity on the initiation and progression of sexual reproduction in the model benthic diatom Seminavis robusta. We found that distinct stages of the mating process have different requirements for light. Vigorous mating pair formation occurred under a broad range of light intensities, ranging from 10 to 81 µE m−2 s−1, while gametogenesis and subsequent stages were strongly affected by moderate light intensities of 27 µE m−2 s−1 and up. In addition, light of blue or blue–green wavelengths was required for the formation of mating pairs. Combining flow cytometric analysis with expression profiling of the diatom-specific cyclin dsCyc2 suggests that progression through a blue light-dependent checkpoint in the G1 cell cycle phase is essential for induction of sexual reproduction. Taken together, we expand the current model of mating in benthic pennate diatoms, which relies on the interplay between light, cell cycle and sex pheromone signaling.

Abstract Head-out water immersion alters respiratory compliance which underpins defining pressure at a “Lung centroid” and the breathing “Static Lung Load”. In diving medicine as in designing dive-breathing devices a single value of lung centroid pressure is presumed as everyone’s standard. On the contrary, we considered that immersed respiratory compliance is disparate among a homogenous adult group (young, healthy, sporty). We wanted to substantiate this ample scattering for two reasons: (i) it may question the European standard used in designing dive-breathing devices; (ii) it may contribute to understand the diverse individual figures of immersed work of breathing. Resting spirometric measurements of lung volumes and the pressure–volume curve of the respiratory system were assessed for 18 subjects in two body positions (upright Up, and supine Sup). Measurements were taken in air (Air) and with subjects immersed up to the sternal notch (Imm). Compliance of the respiratory system (Crs) was calculated from pressure–volume curves for each condition. A median 60.45% reduction in Crs was recorded between Up-Air and Up-Imm (1.68 vs 0.66 L/kPa), with individual reductions ranging from 16.8 to 82.7%. We hypothesize that the previously disregarded scattering of immersion-reduced respiratory compliance might participate to substantial differences in immersed work of breathing.

Abstract Wall Shear Stress (WSS) has been demonstrated to be a biomarker of the development of atherosclerosis. In vivo assessment of WSS is still challenging, but 4D Flow MRI represents a promising tool to provide 3D velocity data from which WSS can be calculated. In this study, a system based on Laser Doppler Velocimetry (LDV) was developed to validate new improvements of 4D Flow MRI acquisitions and derived WSS computing. A hydraulic circuit was manufactured to allow both 4D Flow MRI and LDV velocity measurements. WSS profiles were calculated with one 2D and one 3D method. Results indicated an excellent agreement between MRI and LDV velocity data, and thus the set-up enabled the evaluation of the improved performances of 3D with respect to the 2D-WSS computation method. To provide a concrete example of the efficacy of this method, the influence of the spatial resolution of MRI data on derived 3D-WSS profiles was investigated. This investigation showed that, with acquisition times compatible with standard clinical conditions, a refined MRI resolution does not improve WSS assessment, if the impact of noise is unreduced. This study represents a reliable basis to validate with LDV WSS calculation methods based on 4D Flow MRI.

Abstract Raised circulating concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), have been reported in several rheumatic diseases (RDs). However, the strength of this relationship is unclear. Therefore, the aim of this systematic review and meta-analysis was to evaluate the magnitude and the robustness of the association between ADMA concentrations and RDs. We calculated standardized mean differences (SMD, with 95% confidence intervals, CI). Study heterogeneity was evaluated by meta-regressions and sensitivity analyses according to type of RDs, conventional cardiovascular risk factors, inflammatory markers, and type of ADMA assessment methodology. Thirty-seven studies with a total of 2,982 subjects (1,860 RDs patients and 1,122 healthy controls) were included in our meta-analysis. Pooled results showed that ADMA concentrations were significantly higher in patients with RDs than in healthy controls (SMD = 1.27 µmol/L, 95% CI 0.94–1.60 µmol/L; p

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.