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A three-dimensional (3D) sintering method of bulk magnetron targets has been developed recently. However, the use of bulk target had the following limitations: constrained geometry, limited chemical-phase composition, small size and cost-effectiveness. Thus a novel approach of surface sintering (2D) was arranged by a method of electromagnetic discharge evolution without applying any mechanical press. In the proposed method, the internal energy of pulsed plasma flux (~102.3 J) was dissipated at a tungsten (W) powder interface, therefore providing a form of sintered body with a density of 9.24–14.21 g/cm3 in the crystal structure of (α)-W. The morphology view indicates that, for the most part of sinters, only a subsurface (< 100 nm) was well-consolidated, which was in accordance with an almost fourfold increase in thermal diffusivity there, as showed the results of laser flash analysis. Subsequently, the decrease in mean porosity distribution (Vv) from 42.4% to 27.1% in consolidated surface was confirmed by using the microcomputed tomography (μCT) reconstruction. The (2D) sintered target was then used in the synthesis of pure metallic films by gas injection magnetron sputtering. As a result, a conductive (β)-W phase was recognized (103–405 μΩ cm), giving a promising hope for spintronic device applications.

Background & Aims: The study aimed to assess the phenomenon of achieving sustained virologic response (SVR) in patients with detectable ribonucleic acid (RNA) of hepatitis C virus (HCV) at the end of treatment (ET) with direct-acting antivirals (DAA), find how this is affected by the type of regimen, and how patients experiencing this differed from non-responders with detectable HCV RNA at the ET., Methods: The study included all consecutive patients with detectable HCV RNA at the ET selected from the EpiTer-2 database, a retrospective national multicentre project evaluating antiviral treatment in HCV-infected patients in 2015-2023., Results: Of the 16106 patients treated with IFN-free regimens with available HCV RNA assessment at the ET and at follow-up 12 weeks after treatment completion (FU), 1253 (7.8%) had detectable HCV RNA at the ET, and 1120 of them (89%) finally achieved SVR. This phenomenon was significantly more frequent in pangenotypic regimens, 10.3% vs. 4.7% in genotype-specific options (p < 0.001), and the highest proportion was documented for glecaprevir/pibrentasvir (13.7%), and velpatasvir/sofosbuvir ± ribavirin (6.9%). Patients ET + FU- treated with these two pangenotypic regimens (n = 668) had less advanced liver disease, were less frequently infected with genotype (GT) 3, and were significantly more likely to be treatment-naïve than 61 non-responders., Conclusions: We documented 7.8% rate of patients with detectable HCV RNA at the ET, of whom 89% subsequently achieved SVR, significantly more frequently in the population treated with pangenotypic regimens. Less severe liver disease, more often GT3 infection, and a higher percentage of treatment-naive patients distinguished this group from non-responders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The aim of the study was to assess the coagulation and inflammatory markers connected with severe course of COVID-19 and no clinical improvement., Material and Methods: The study population included 2590 adult patients, diagnosed with COVID-19, selected from the SARSTer national database - an ongoing project led by the Polish Association of Epidemiologists and Infectiologists and supported by the Medical Research Agency. Clinical and laboratory parameters, such as C-reactive protein (CRP), white blood cells (WBCs), neutrophil and lymphocyte count, procalcitonin, ferritin, interleukin-6 (IL-6), D-dimer concentration and platelet (PLT) count were analyzed before and after treatment (remdesivir, tocilizumab, dexamethasone, anticoagulants)., Results: Significant differences between patients with mild and severe course of the disease were observed in all examined parameters before treatment (p ​< ​0.05). After treatment only ferritin concentration did not differ significantly. In patients with pulmonary embolism, CRP concentration, neutrophil count, D-dimer and IL-6 concentration were significantly higher than in patients without embolism (p ​< ​0.05). The significant differences between the groups with and without fatal outcome were observed within all analyzed parameters. Significant differences in all examined parameters before treatment were observed between patients with and without clinical improvement (p ​< ​0.05). Multivariate logistic regression showed that no clinical improvement was associated with: IL-6>100 ​pg/ml (OR-2.14), D-dimer concentration over 1000 ​ng/ml (OR-1.62) and PLT count below 150,000/μl (OR-1.57)., Conclusions: Severe course of the disease is associated with lower PLT and lymphocyte count, higher D-dimer, CRP, neutrophil count and IL-6 concentration. The best predictors of no clinical improvement in COVID-19 are: IL-6>100 ​pg/ml, D-dimer>1000 ​ng/ml and PLT<150,000/μl., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

At the end of 2019, the COVID-19 pandemic began, which at the time of writing continues to be a serious problem for many areas of medicine, including neurology. Since patients with multiple sclerosis (MS) often exhibit motor disability and receive disease-modifying therapy (DMT), which has an immunosuppressive effect, it is plausible that this will affect the susceptibility of MS patients to COVID-19, as well as the course of this disease. However, current data indicate that the use of DMT does not cause negative prognosis in COVID-19 sufferers, but the motor disability progression associated with MS does. In this study, we present the case reports of 4 patients with relapsing-remitting MS, who developed COVID-19, and despite the use of DMT the course of the disease was mild. Two patients were treated with dimethyl fumarate, one with Interferon β1b and one with glatiramer acetate. One of the patients using dimethyl fumarate had lymphopenia. All patients had symptoms of COVID-19 from the nervous system, the most frequent being headache, which occurred in all patients. The aim of this article is to present a case series of four patients with MS and COVID-19, and to discuss the available literature on COVID-19 in patients with MS, with particular consideration of the impact of DMT., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Since 2017 treatment-naïve patients infected with genotype 1b of hepatitis C virus and minimal or moderate fibrosis can be treated with Ombitasvir/Paritaprevir/ritonavir + Dasabuvir (OPrD) for 8 weeks according to updated Summary of Product Characteristics. The aim of our study was to assess the comparative efficacy of 8 and 12-weeks therapy with OPrD in large cohort of patients eligible for 8 weeks regimen treated in real-world setting., Materials and Methods: We analysed data of 3067 HCV genotype 1b infected patients treated with OPrD between 2015 and 2017. Final analysis included patients with none, minimal or moderate fibrosis (F0-F2)., Results: A total of 771 patients were enrolled in the study, including 197 (26%) treated for 8-weeks and 574 patients fulfilling criteria for 8-weeks but assigned to 12-weeks regimen. Majority of patients had no or minimal fibrosis (F0-F1). Longer treatment duration was more often administered in patients with moderate fibrosis, comorbidities, concomitant medications. SVR was achieved in 186 (94%) patients treated for 8 weeks and 558 (97%) for 12 weeks (p = 0.07). After exclusion of lost to follow-up patients, sustained virological response (SVR) rate reached 95% and 99%, respectively (p = 0.01). We were not able to identify factors associated with non-response., Conclusions: This real-word experience study confirmed similar, high effectiveness of 8 and 12-weeks regimens of OPrD in genotype 1b HCV infected patients with non-advanced fibrosis. Despite of reduced SVR rate after 8-weeks regimen, there is no need to extend therapy to 12-weeks in vast majority of such patients and no need to add ribavirin., Competing Interests: Declaration of competing interest Dorota Zarębska-Michaluk – Sponsored Lectures: AbbVie, Gilead, Merck; Anna Piekarska – Consultancy: AbbVie, Gilead, Merck, Roche; Jerzy Jaroszewicz – Consultancy: AbbVie, BMS, Gilead; Research funding: Merz, Roche; Jakub Klapaczyński – Sponsored Lectures Gilead; Włodzimierz Mazur – Consultancy: AbbVie, BMS, Gilead, Janssen, Merck, Roche; Research funding: AbbVie, Gilead, Merck, Roche; Rafał Krygier – Consultancy - AbbVie, Gilead, Promed; Teresa Belica-Wdowik – Consultancy: AbbVie, Gilead; Research funding: AbbVie; Barbara Baka-Ćwierz – Consultancy: AbbVie, Gilead, Roche; Research funding: AbbVie, Roche; Ewa Janczewska – Consultancy: AbbVie, BMS, Gilead, Janssen, Roche; Research funding: AbbVie, Allergan, BMS, Gilead, Janssen, Merck, Roche, Vertex, Tobira; Krzysztof Tomasiewicz – Consultancy: AbbVie, Alfa Wasserman, BMS, Gilead, Janssen, Merck, Roche; Research funding: AbbVie, BMS, Gilead, Janssen, Merck, Roche; Aleksander Garlicki – Consultancy: AbbVie, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Roche, Sanofi Pasteur; Research funding: Amgen, Janssen, Pfizer; Agnieszka Czauż-Andrzejuk – Research funding: AbbVie, Merck; Dorota Dybowska – Sponsored Lectures: Abbvie. Waldemar Halota – Consultancy: AbbVie, BMS, Gilead, Janssen, Merck, Roche; Research funding: AbbVie, Gilead, Roche; Małgorzata Pawłowska – Consultancy: AbbVie, BMS, Gilead, Janssen, Merck, Roche; Research funding: AbbVie, Gilead, Roche; Krzysztof Simon – Consultancy: AbbVie, Gilead, BMS, Merck, Janssen, Alfa-Wassermann, Baxter, Bayer, Roche; Research funding: AbbVie, Allergan, Bayer, EISAI, Gilead, Intercept, Janssen, Tobira, Pfizer; Olga Tronina – Consultancy: AbbVie; Research funding: Janssen; Robert Flisiak—Consultancy: AbbVie, Alfa Wasserman, BMS, Gilead, Janssen, Merck, Roche; Research funding: AbbVie, Gilead, Janssen, Merck, Roche; Paweł Pabjan, Beata Dobracka, Beata Lorenc, Magdalena Tudrujek-Zdunek, Marek Sitko, Jolanta Citko, Łukasz Laurans, Zbigniew Deroń, Iwona Buczyńska, Jolanta Białkowska – none declared., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The paper presents a novel approach to the production of calcium phosphate coatings of scaffolds. Mineral deposits were formed during incubation of polycaprolactone (PCL) scaffolds with bovine intestinal alkaline phosphatase in sodium glycerophosphate and calcium chloride medium. To modify hydrophobic surface of scaffolds and intensify attachment of coating, scaffolds were incubated at 50 °C (thermal activation, TA) or at 37 °C after short exposition to lipase (lipase activation, LA). Micro-computed tomography observations demonstrated that both methods resulted in deposition of mineral on the surface of external and internal walls of the scaffolds. Precipitate formed after thermal and lipase activation contained particles with average size of 200-400 nm, and the shape of donuts. In thermal activated PCL coatings X-ray diffraction disclosed peaks typical for hydroxyapatite (HAp), while after lipase activation these peaks could be precisely defined only if left for 6 days in the incubation medium. The Fourier-transform infrared spectroscopy suggested crystalline structure of HAp both after thermal and lipase activation. The adherence of bone marrow mesenchymal stem cells was initially higher on coated than pristine PCL, but during 7 days of culture the cell number increased and was similar on all tested samples. Alkaline phosphatase activity, considered as a sign of osteogenic differentiation, measured on PCL samples after 7 days was 2-3 times lower on pristine PCL than on the coated samples, but after 2 weeks increased significantly and reached similar value as on the calcium phosphate substrates., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Nowadays, the assessment of the mechanical competence of tissue engineering scaffolds based on computer simulations is a well-accepted technology. Typically, such simulations are performed by means of the Finite Element (FE) method, with the underlying structural model being created based on micro-computed tomography (microCT). Here, this analysis modality is applied to a new, ternary composite, consisting of PHBV, i.e. poly(3-hydroxybutyrate-co-3-hydroxyvalerate), PLGA, i.e. poly(lactic-co-glycolide), as well as of TCP, i.e. tricalcium phosphate hydrate. The studied scaffold structure is made up by fibers of this new composite material, manufactured by means of the rapid prototyping method. The data collected from microCT is utilized for adequately defining the mechanical properties of the FE model. In particular, the three-dimensional field of grey values is interpreted in terms of the underlying field of attenuation coefficients, taking into account the photon energy employed in microCT imaging, eventually allowing for calculation of the three-dimensionally distributed, voxel-specific composition of the studied material. For the sake of keeping the FE simulations as efficient as possible, groups of voxels are combined into one finite element; the grey value of the latter is obtained by volume averaging. Employing a two-step micromechanical homogenization scheme, the experimentally accessible stiffness of the three constituents (PHBV, PLGA, and TCP) is then, finite element by finite element, upscaled to the composition-dependent stiffness of the composite material. The plausibility and adequacy of the FE model is demonstrated by simulating the effects of uniaxial compression on the scaffold structure, in terms of resulting stress and strain fields, highlighting the importance of the fiber junctions (as they are the mechanically most stressed regions), and that neglecting the material heterogeneity would lead to a potentially significant underestimation of stresses and strains. Finally, a comparison is made of the employed analysis modality of microCT data with a previously pursued, simplified analysis strategy, highlighting the conceptual superiority of the former, and pointing out the application limits of the latter., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In vitro degradation behavior of squeeze cast (CAST) and equal channel angular pressed (ECAP) ZM21 magnesium alloy (2.0wt% Zn-0.98wt% Mn) was studied using immersion tests up to 4w in three different biological environments. Hanks' Balanced Salt Solution (Hanks), Earle's Balanced Salt Solution (Earle) and Eagle minimum essential medium supplemented with 10% (v/v) fetal bovine serum (E-MEM+10% FBS) were used to investigate the effect of carbonate buffer system, organic compounds and material processing on the degradation behavior of the ZM21 alloy samples. Corrosion rate of the samples was evaluated by their Mg(2+) ion release, weight loss and volume loss. In the first 24h, the corrosion rate sequence of the CAST samples was as following: Hanks>E-MEM+10% FBS>Earle. However, in longer immersion periods, the corrosion rate sequence was Earle>E-MEM+10% FBS≥Hanks. Strong buffering effect provided by carbonate buffer system helped to maintain the pH avoiding drastic increase of the corrosion rate of ZM21 in the initial stage of immersion. Organic compounds also contributed to maintain the pH of the fluid. Moreover, they adsorbed on the sample surface and formed an additional barrier on the insoluble salt layer, which was effective to retard the corrosion of CAST samples. In case of ECAP, however, this effect was overcome by the occurrence of strong localized corrosion due to the lower pH of the medium. Corrosion of ECAP samples was much greater than that of CAST, especially in Hanks, due to higher sensitivity of ECAP to localized corrosion and the presence of Cl(-). The present work demonstrates the importance of using an appropriate solution for a reliable estimation of the degradation rate of Mg-base degradable implants in biological environments, and concludes that the most appropriate solution for this purpose is E-MEM+10% FBS, which has the closest chemical composition to human blood plasma., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In the design of scaffolds for tissue engineering applications, morphological parameters such as pore size, shape, and interconnectivity, as well as transport properties, should always be tailored in view of their clinical application. In this work, we demonstrate that a regular and ordered porous texture is fundamental to achieve an even cell distribution within the scaffold under perfusion seeding. To prove our hypothesis, two sets of alginate scaffolds were fabricated using two different technological approaches of the same method: gas-in-liquid foam templating. In the first one, foam was obtained by insufflating argon in a solution of alginate and a surfactant under stirring. In the second one, foam was generated inside a flow-focusing microfluidic device under highly controlled and reproducible conditions. As a result, in the former case the derived scaffold (GF) was characterized by polydispersed pores and interconnects, while in the latter (μFL), the porous structure was highly regular both with respect to the spatial arrangement of pores and interconnects and their monodispersity. Cell seeding within perfusion bioreactors of the two scaffolds revealed that cell population inside μFL scaffolds was quantitatively higher than in GF. Furthermore, seeding efficiency data for μFL samples were characterized by a lower standard deviation, indicating higher reproducibility among replicates. Finally, these results were validated by simulation of local flow velocity (CFD) inside the scaffolds proving that μFL was around one order of magnitude more permeable than GF., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Different viral dominance patterns have been documented in coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) based on HBV DNA and HCV RNA quantification. In most cases, HCV is dominant and suppresses HBV replication. In vitro studies revealed that there is most probably no direct interference between HBV and HCV replication. We hypothesized that indirect mechanisms mediated by host immune responses might be responsible for the different dominance patterns. In this study we analysed quantitative hepatitis B surface antigen (HBsAg) as a marker for immune control of HBV and interferon γ-induced protein 10 (IP-10) as host marker for the endogenous interferon in 85 patients with HBV/HCV coinfection. Levels of HBsAg were closely associated with viral dominance patterns in 85 HBV/HCV-coinfected patients. HBsAg levels were lowest in patients with HCV dominance, even lower compared with HBV-monoinfected patients undergoing treatment with nucleos(t)ide analogues (NA) but comparable to low replicative HBsAg carriers. An increase in HCV RNA during follow up was associated with HBsAg decline. Patients with HCV dominance had significantly higher serum IP-10 levels compared with HBV-dominant patients or HBV-monoinfected patients treated with NA. Lower HBsAg and higher IP-10 levels in HCV-dominant HBV/HCV-coinfected patients suggest that HCV suppresses HBV DNA replication and also HBsAg production by immune mechanisms., (Copyright © 2015. Published by Elsevier Ltd.)

Hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. HBcrAg combines the antigenic reactivity resulting from denatured hepatitis B e antigen (HBeAg), HBV core antigen and an artificial core-related protein (p22cr). In Asian patients, high levels of HBcrAg have been suggested to be an independent risk factor for hepatocellular carcinoma, while low levels could guide safe cessation of treatment with nucleos(t)ide analogues. We here studied HBcrAg levels in different phases of HBV infection in a large European cohort predominantly infected with genotypes A and D: HBeAg-positive immune tolerance (n = 30), HBeAg-positive immune clearance (IC) (n = 60), HBeAg-negative hepatitis (ENH) (n = 50), HBeAg-negative inactive/quiescent carrier phase (c) (n = 109) and acute hepatitis B (n = 8). Median HBcrAg levels were high in the immune tolerance and immune clearance phases (8.41 and 8.11 log U/mL, respectively), lower in ENH subjects (4.82 log U/mL) but only 2.00 log U/mL in ENQ subjects. Correlation between HBcrAg and HBV DNA varied among the different phases of HBV infection, while HBcrAg moderately correlated with hepatitis B surface antigen in all phases. ENQ patients had HBcrAg levels <3 log U/mL in 79%, in contrast to only 12% in the ENH group. HBcrAg levels vary significantly during the different phases of HBV infection. HBcrAg may serve as valuable marker for virus replication and reflect the transcriptional activity of intrahepatic cccDNA. In HBeAg-negative patients, HBcrAg may help to distinguish between inactive carriers (ENQ) and those with active disease (ENH)., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: The quantifiable level of HBsAg has been suggested as a predictor of treatment response in chronic hepatitis B. However, there is limited information on HBsAg levels considering the dynamic natural course of HBV-infection. This study aimed to determine HBsAg levels in the different phases of HBV-infection in European HBsAg-positive patients., Methods: 226 HBV-monoinfected patients, not undergoing antiviral therapy, were analyzed in a cross-sectional study. Patients were categorized according to the phase of HBV-infection: HBeAg(+) immune tolerance phase (IT, n=30), immune clearance phase (IC, n=48), HBeAg(-) low-replicative phase (LR, n=68), HBeAg(-) hepatitis (ENH, n=68), and acute hepatitis B (n=12). HBsAg was quantified and correlated with HBV-DNA, HBV-genotypes and clinical parameters. In addition, 30 LR-patients were followed longitudinally., Results: HBsAg levels were higher in IT-patients and IC-patients compared to LR-patients and ENH-patients (4.96/4.37/3.09/3.87-log(10)IU/ml, p<0.001). HBsAg showed a strong correlation with HBV-DNA during acute hepatitis B (R=0.79, p<0.01). Correlation of HBsAg and HBV-DNA was weak or missing when analyzing different phases of persistent HBV-infection separately. However, associations between HBsAg and HBV-DNA were observed in patients infected with HBV-genotype D but not with HBV-genotype A. LR-patients with HBV-reactivation during follow-up (increase of HBV-DNA >2000IU/ml) showed >3-fold higher baseline HBsAg levels with a NPV of 95% for an HBsAg cut-off of 3500IU/ml., Conclusions: HBsAg levels show significant differences during the natural course of HBV-infection and between HBV-genotypes. These findings may have important implications for understanding the natural history of HBV-infection and for using quantitative HBsAg as a diagnostic tool, i.e. as a marker for predicting HBV-reactivation.

Recent studies demonstrate persistent elevation of interleukin-18 (IL-18) concentration in human immunodeficiency virus type 1 (HIV-1)-infected patients. Due to pleiotropic action of IL-18 on the immune system, dysregulation of its synthesis may lead to inappropriate immune activation. The aim of this study was to determine possible correlation between IL-18 levels and the natural stages of HIV-1 infection. IL-18 plasma concentrations were determined in 42 patients in different stages of an HIV-1 infection and in 15 healthy controls. HIV infection resulted in a more than fourfold increase of plasma IL-18 concentration compared to healthy individuals (865 +/- 87 vs. 206 +/- 32 pg/ml, P < 0.001). Moreover, a positive correlation between plasma IL-18 concentration and HIV viral load was found (r = 0.44, P < 0.01). Further analysis showed marked elevation of IL-18 levels in late-stage symptomatic patients. Plasma IL-18 concentrations in patients receiving high-activity antiretroviral treatment (HAART) were significantly lower than in those not undergoing antiretroviral treatment. Individuals who did not reach viral suppression showed higher IL-18 plasma concentration than the group with achieved viral suppression. Excessive production of IL-18 observed in our study may promote viral replication and disease progression in advanced, especially late-stage HIV-infected patients. Furthermore, reduction of IL-18 concentration can be an important step in HAART-related immune restoration.