26 results on '"KRAWCZYK, M."'
Search Results
2. Post-hoc analysis of a randomized controlled trial on the impact of pre-transplant use of probiotics on outcomes after liver transplantation
- Author
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Grąt, M., Grąt, K., Krawczyk, M., Lewandowski, Z., Krasnodębski, M., Masior, Ł., Patkowski, W., and Zieniewicz, K.
- Published
- 2020
- Full Text
- View/download PDF
3. The switching of strong spin wave beams in patterned garnet films
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Gieniusz, R., primary, Gruszecki, P., additional, Krawczyk, M., additional, Guzowska, U., additional, Stognij, A., additional, and Maziewski, A., additional
- Published
- 2017
- Full Text
- View/download PDF
4. Microwave excitation of spin wave beams in thin ferromagnetic films
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Gruszecki, P., primary, Kasprzak, M., additional, Serebryannikov, A. E., additional, Krawczyk, M., additional, and Śmigaj, W., additional
- Published
- 2016
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5. Universal dependence of the spin wave band structure on the geometrical characteristics of two-dimensional magnonic crystals
- Author
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Tacchi, S., primary, Gruszecki, P., additional, Madami, M., additional, Carlotti, G., additional, Kłos, J. W., additional, Krawczyk, M., additional, Adeyeye, A., additional, and Gubbiotti, G., additional
- Published
- 2015
- Full Text
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6. Magnonic Band Engineering by Intrinsic and Extrinsic Mirror Symmetry Breaking in Antidot Spin-Wave Waveguides
- Author
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Kłos, J. W., primary, Kumar, D., additional, Krawczyk, M., additional, and Barman, A., additional
- Published
- 2013
- Full Text
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7. Goos-Hänchen shift of inelastically scattered spin-wave beams and cascade nonlinear magnon processes.
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Sobucki K, Lyubchanskii I, Krawczyk M, and Gruszecki P
- Abstract
We study, using micromagnetic simulations, the inelastic scattering of spin-wave beams on edge-localized spin-wave modes in a thin ferromagnetic film. In the splitting and confluence processes, the new spin-wave beams are generated with frequencies shifted by the edge-mode frequency. We report that inelastically scattered spin-wave beams in both processes not only change their direction of propagation but also undergo lateral shifts along the interface, analogous to the Goos-Hänchen effect known in optics. These shifts of inelastically scattered beams, for a few special cases described in the paper, can be in the range of several wavelengths, which is larger than the Goos-Hänchen shift of elastically reflected beam. Unexpectedly, at selected frequencies, we found a significant increase in the value of the lateral shifts of the scattered spin-wave beams formed in the confluence process. We show that this effect is associated with the cascading nonlinear processes taking place at the edge of the film and involving the primary edge spin wave. Our results make an important contribution to the understanding of the nonlinear nature of spin waves and provide a way to exploit it in signal processing with magnons., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)
- Published
- 2025
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8. Investigating the role of source and source trust in prebunks and debunks of misinformation in online experiments across four EU countries.
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Bruns H, Dessart FJ, Krawczyk M, Lewandowsky S, Pantazi M, Pennycook G, Schmid P, and Smillie L
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- Humans, Male, Female, Adult, Poland, Germany, Climate Change, Greece, Surveys and Questionnaires, Ireland, SARS-CoV-2, Middle Aged, Young Adult, Trust, Communication, COVID-19 epidemiology, COVID-19 prevention & control, European Union
- Abstract
Misinformation surrounding crises poses a significant challenge for public institutions. Understanding the relative effectiveness of different types of interventions to counter misinformation, and which segments of the population are most and least receptive to them, is crucial. We conducted a preregistered online experiment involving 5228 participants from Germany, Greece, Ireland, and Poland. Participants were exposed to misinformation on climate change or COVID-19. In addition, they were pre-emptively exposed to a prebunk, warning them of commonly used misleading strategies, before encountering the misinformation, or were exposed to a debunking intervention afterwards. The source of the intervention (i.e. the European Commission) was either revealed or not. The findings show that both interventions change four variables reflecting vulnerability to misinformation in the expected direction in almost all cases, with debunks being slightly more effective than prebunks. Revealing the source of the interventions did not significantly impact their overall effectiveness. One case of undesirable effect heterogeneity was observed: debunks with revealed sources were less effective in decreasing the credibility of misinformation for people with low levels of trust in the European Union (as elicited in a post-experimental questionnaire). While our results mostly suggest that the European Commission, and possibly other public institutions, can confidently debunk and prebunk misinformation regardless of the trust level of the recipients, further evidence on this is needed., (© 2024. The Author(s).)
- Published
- 2024
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9. Existence of edge modes in periodic microstrip transmission line.
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Girich A, Ivzhenko L, Kharchenko G, Polevoy S, Tarapov S, Krawczyk M, and Kłos JW
- Abstract
The microstrip of modulated width is a realization of a one-dimensional photonic crystal operating in the microwave regime. Like any photonic crystal, the periodic microstrip is characterised by the presence of frequency bands and band gaps that enable and prohibit wave propagation, respectively. The frequency bands for microstrip of the symmetric unit cell can be distinguished by 0 or π Zak phase. The sum of these topological parameters for all bands below a given frequency gap determines the value of the surface impedance at the end of the microstrip. We demonstrate that edge modes are absent in a finite microstrip terminated at both ends in the centres of unit cells, but they can be induced by adding the defected cells. Edge modes present at both ends of the microstrip enable microwave tunneling with high transitivity in the frequency gap with or without a change in phase. This has been demonstrated experimentally and developed in detail using numerical simulations and model calculations. The investigated system, with a doublet of edge modes in the frequency gap, can be considered as a narrow passband filter of high selectivity and characterised by a significant group delay., (© 2024. The Author(s).)
- Published
- 2024
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10. The role of non-uniform magnetization texture for magnon-magnon coupling in an antidot lattice.
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Moalic M, Zelent M, Szulc K, and Krawczyk M
- Abstract
We numerically study the spin-wave dynamics in an antidot lattice based on a Co/Pd multilayer structure with reduced perpendicular magnetic anisotropy at the edges of the antidots. This structure forms a magnonic crystal with a periodic antidot pattern and a periodic magnetization configuration consisting of out-of-plane magnetized bulk and in-plane magnetized rims. Our results show a different behavior of spin waves in the bulk and in the rims under varying out-of-plane external magnetic field strength, revealing complex spin-wave spectra and hybridizations between the modes of these two subsystems. A particularly strong magnon-magnon coupling, due to exchange interactions, is found between the fundamental bulk spin-wave mode and the second-order radial rim modes. However, the dynamical coupling between the spin-wave modes at low frequencies, involving the first-order radial rim modes, is masked by the changes in the static magnetization at the bulk-rim interface with magnetic field changes. The study expands the horizons of magnonic-crystal research by combining periodic structural patterning and non-collinear magnetization texture to achieve strong magnon-magnon coupling, highlighting the significant role of exchange interactions in the hybridization., (© 2024. The Author(s).)
- Published
- 2024
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11. Author Correction: The impact of spontaneous cough on pleural pressure changes during therapeutic thoracentesis.
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Stecka AM, Grabczak EM, Michnikowski M, Zielińska-Krawczyk M, Krenke R, and Gólczewski T
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- 2023
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12. Stabilization and racetrack application of asymmetric Néel skyrmions in hybrid nanostructures.
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Zelent M, Moalic M, Mruczkiewicz M, Li X, Zhou Y, and Krawczyk M
- Abstract
Magnetic skyrmions, topological quasiparticles, are small stable magnetic textures that possess intriguing properties and potential for data storage applications. Hybrid nanostructures comprised of skyrmions and soft magnetic material can offer additional advantages for developing skyrmion-based spintronic and magnonic devices. We show that a Néel-type skyrmion confined within a nanodot placed on top of a ferromagnetic in-plane magnetized stripe produces a unique and compelling platform for exploring the mutual coupling between magnetization textures. The skyrmion induces an imprint upon the stripe, which, in turn, asymmetrically squeezes the skyrmion in the dot, increasing their size and the range of skyrmion stability at small values of Dzyaloshinskii-Moriya interaction, as well as introducing skyrmion bi-stability. Finally, by exploiting the properties of the skyrmion in a hybrid system, we demonstrate unlimited skyrmion transport along a racetrack, free of the skyrmion Hall effect., (© 2023. Springer Nature Limited.)
- Published
- 2023
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13. The impact of spontaneous cough on pleural pressure changes during therapeutic thoracentesis.
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Stecka AM, Grabczak EM, Michnikowski M, Zielińska-Krawczyk M, Krenke R, and Gólczewski T
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- Aged, Cough etiology, Humans, Paracentesis, Pleura, Pleural Effusion etiology, Thoracentesis
- Abstract
Cough during therapeutic thoracentesis (TT) is considered an adverse effect. The study was aimed to evaluate the relationship between cough during TT and pleural pressure (Ppl) changes (∆P). Instantaneous Ppl was measured after withdrawal of predetermined volumes of pleural fluid. Fluid withdrawal (FW) and Ppl measurement (PplM) periods were analyzed separately using the two sample Kolmogorov-Smirnov test and the nonparametric skew to assess differences between ∆P distributions in periods with and without cough. The study involved 59 patients, median age 66 years, median withdrawn fluid volume 1800 mL (1330 ÷ 2400 mL). In total, 1265 cough episodes were recorded in 52 patients, in 24% of FW and 19% of PplM periods, respectively. Cough was associated with significant changes in ∆P distribution (p < 0.001), decreasing the left tail of ∆P distribution for FW periods (the skew = - 0.033 vs. - 0.182) and increasing the right tail for PplM periods (the skew = 0.182 vs. 0.088). Although cough was more frequent in 46 patients with normal pleural elastance (p < 0.0001), it was associated with significantly higher ∆P in patients with elevated elastance (median Ppl increase 2.9 vs. 0.2 cmH
2 O, respectively). Cough during TT is associated with small but beneficial trend in Ppl changes, particularly in patients with elevated pleural elastance, and should not be considered solely as an adverse event., (© 2022. The Author(s).)- Published
- 2022
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14. MARC1 p.A165T variant is associated with decreased markers of liver injury and enhanced antioxidant capacity in autoimmune hepatitis.
- Author
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Janik MK, Smyk W, Kruk B, Szczepankiewicz B, Górnicka B, Lebiedzińska-Arciszewska M, Potes Y, Simões ICM, Weber SN, Lammert F, Więckowski MR, Milkiewicz P, and Krawczyk M
- Subjects
- Adolescent, Adult, Aged, Child, Female, Genotype, Hepatitis, Autoimmune complications, Hepatitis, Autoimmune metabolism, Hepatitis, Autoimmune prevention & control, Humans, Liver Cirrhosis etiology, Liver Cirrhosis metabolism, Liver Cirrhosis prevention & control, Male, Middle Aged, Phenotype, Young Adult, Antioxidants metabolism, Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Hepatitis, Autoimmune genetics, Liver Cirrhosis genetics, Mitochondrial Proteins genetics, Oxidoreductases genetics, Polymorphism, Genetic genetics, Polymorphism, Genetic physiology
- Abstract
The clinical picture of autoimmune hepatitis (AIH) varies markedly between patients, potentially due to genetic modifiers. The aim of this study was to evaluate genetic variants previously associated with fatty liver as potential modulators of the AIH phenotype. The study cohort comprised 313 non-transplanted adults with AIH. In all patients, the MARC1 (rs2642438), HSD17B13 (rs72613567), PNPLA3 (rs738409), TM6SF2 (rs58542926), and MBOAT7 (rs641738) variants were genotyped using TaqMan assays. Mitochondrial damage markers in serum were analyzed in relation to the MARC1 variant. Carriers of the protective MARC1 allele had lower ALT and AST (both P < 0.05). In patients treated for AIH for ≥ 6 months, MARC1 correlated with reduced AST, ALP, GGT (all P ≤ 0.01), and lower APRI (P = 0.02). Patients carrying the protective MARC1 genotype had higher total antioxidant activity (P < 0.01) and catalase levels (P = 0.02) in serum. The PNPLA3 risk variant was associated with higher MELD (P = 0.02) in treated patients, whereas MBOAT7 increased the odds for liver cancer (OR = 3.71). None of the variants modulated the risk of death or transplantation. In conclusion, the MARC1 polymorphism has protective effects in AIH. Genotyping of MARC1, PNPLA3, and MBOAT7 polymorphisms might help to stratify patients with AIH., (© 2021. The Author(s).)
- Published
- 2021
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15. Nonresonant amplification of spin waves through interface magnetoelectric effect and spin-transfer torque.
- Author
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Graczyk P and Krawczyk M
- Abstract
We present a new mechanism for manipulation of the spin-wave amplitude through the use of the dynamic charge-mediated magnetoelectric effect in ultrathin multilayers composed of dielectric thin-film capacitors separated by a ferromagnetic bilayer. Propagating spin waves can be amplified and attenuated with rising and decreasing slopes of the oscillating voltage, respectively, locally applied to the sample. The way the spin accumulation is generated makes the interaction of the spin-transfer torque with the magnetization dynamics mode-selective and restricted to some range of spin-wave frequencies, which is contrary to known types of the spin-transfer torque effects. The interfacial nature of spin-dependent screening allows to reduce the thickness of the fixed magnetization layer to a few nanometers, thus the proposed effect significantly contributes toward realization of the magnonic devices and also miniaturization of the spintronic devices., (© 2021. The Author(s).)
- Published
- 2021
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16. Resonant subwavelength control of the phase of spin waves reflected from a Gires-Tournois interferometer.
- Author
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Sobucki K, Śmigaj W, Rychły J, Krawczyk M, and Gruszecki P
- Abstract
Subwavelength resonant elements are essential building blocks of metamaterials and metasurfaces, which have revolutionized photonics. Despite similarities between different wave phenomena, other types of interactions can make subwavelength coupling significantly distinct; its investigation in their context is therefore of interest both from the physics and applications perspective. In this work, we demonstrate a fully magnonic Gires-Tournois interferometer based on a subwavelength resonator made of a narrow ferromagnetic stripe lying above the edge of a ferromagnetic film. The bilayer formed by the stripe and the film underneath supports two propagative spin-wave modes, one strongly coupled with spin waves propagating in the rest of the film and another almost completely reflected at the ends of the bilayer. When the Fabry-Perot resonance conditions for this mode are satisfied, the weak coupling between both modes is sufficient to achieve high sensitivity of the phase of waves reflected from the resonator to the stripe width and, more interestingly, also to the stripe-film separation. Such spin-wave phase manipulation capabilities are a prerequisite for the design of spin-wave metasurfaces and may stimulate development of magnonic logic devices and sensors detecting magnetic nanoparticles.
- Published
- 2021
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17. Prediction of advanced fibrosis in non-alcoholic fatty liver disease using gut microbiota-based approaches compared with simple non-invasive tools.
- Author
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Lang S, Farowski F, Martin A, Wisplinghoff H, Vehreschild MJGT, Krawczyk M, Nowag A, Kretzschmar A, Scholz C, Kasper P, Roderburg C, Lammert F, Goeser T, Steffen HM, and Demir M
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- Adult, Aged, Cohort Studies, Disease Progression, Elasticity Imaging Techniques, Female, Fibrosis, Humans, Male, Middle Aged, Predictive Value of Tests, Prognosis, Risk, Sequence Analysis, RNA, Gastrointestinal Microbiome genetics, Liver pathology, Non-alcoholic Fatty Liver Disease diagnosis, RNA, Ribosomal, 16S genetics
- Abstract
Liver fibrosis is the major determinant of liver related complications in patients with non-alcoholic fatty liver disease (NAFLD). A gut microbiota signature has been explored to predict advanced fibrosis in NAFLD patients. The aim of this study was to validate and compare the diagnostic performance of gut microbiota-based approaches to simple non-invasive tools for the prediction of advanced fibrosis in NAFLD. 16S rRNA gene sequencing was performed in a cohort of 83 biopsy-proven NAFLD patients and 13 patients with non-invasively diagnosed NAFLD-cirrhosis. Random Forest models based on clinical data and sequencing results were compared with transient elastography, the NAFLD fibrosis score (NFS) and FIB-4 index. A Random Forest model containing clinical features and bacterial taxa achieved an area under the curve (AUC) of 0.87 which was only marginally superior to a model without microbiota features (AUC 0.85). The model that aimed to validate a published algorithm achieved an AUC of 0.71. AUC's for NFS and FIB-4 index were 0.86 and 0.85. Transient elastography performed best with an AUC of 0.93. Gut microbiota signatures might help to predict advanced fibrosis in NAFLD. However, transient elastography achieved the best diagnostic performance for the detection of NAFLD patients at risk for disease progression.
- Published
- 2020
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18. Genome analysis of a wild rumen bacterium Enterobacter aerogenes LU2 - a novel bio-based succinic acid producer.
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Szczerba H, Komoń-Janczara E, Krawczyk M, Dudziak K, Nowak A, Kuzdraliński A, Waśko A, and Targoński Z
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- Animals, Cattle, Chromosomes, Bacterial genetics, DNA, Bacterial genetics, DNA, Bacterial isolation & purification, Enterobacter aerogenes genetics, Genome, Bacterial, Genomics, Whole Genome Sequencing methods, Biosynthetic Pathways genetics, Enterobacter aerogenes metabolism, Industrial Microbiology, Rumen microbiology, Succinic Acid metabolism
- Abstract
Enterobacter aerogenes LU2 was isolated from cow rumen and recognized as a potential succinic acid producer in our previous study. Here, we present the first complete genome sequence of this new, wild strain and report its basic genetic features from a biotechnological perspective. The MinION single-molecule nanopore sequencer supported by the Illumina MiSeq platform yielded a circular 5,062,651 bp chromosome with a GC content of 55% that lacked plasmids. A total of 4,986 genes, including 4,741 protein-coding genes, 22 rRNA-, 86 tRNA-, and 10 ncRNA-encoding genes and 127 pseudogenes, were predicted. The genome features of the studied strain and other Enterobacteriaceae strains were compared. Functional studies on the genome content, metabolic pathways, growth, and carbon transport and utilization were performed. The genomic analysis indicates that succinic acid can be produced by the LU2 strain through the reductive branch of the tricarboxylic acid cycle (TCA) and the glyoxylate pathway. Antibiotic resistance genes were determined, and the potential for bacteriocin production was verified. Furthermore, one intact prophage region of length ~31,9 kb, 47 genomic islands (GIs) and many insertion sequences (ISs) as well as tandem repeats (TRs) were identified. No clustered regularly interspaced short palindromic repeats (CRISPRs) were found. Finally, comparative genome analysis with well-known succinic acid producers was conducted. The genome sequence illustrates that the LU2 strain has several desirable traits, which confirm its potential to be a highly efficient platform for the production of bulk chemicals.
- Published
- 2020
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19. Common variation in FAM155A is associated with diverticulitis but not diverticulosis.
- Author
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Reichert MC, Kupcinskas J, Schulz A, Schramm C, Weber SN, Krawczyk M, Jüngst C, Casper M, Grünhage F, Appenrodt B, Zimmer V, Tamelis A, Lukosiene JI, Pauziene N, Kiudelis G, Jonaitis L, Goeser T, Malinowski M, Glanemann M, Kupcinskas L, and Lammert F
- Subjects
- Acetylcholinesterase genetics, Aged, Cohort Studies, Collagen genetics, Female, GTPase-Activating Proteins genetics, Genetic Association Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Germany, Humans, Lithuania, Male, Middle Aged, Muscle Proteins genetics, Polymorphism, Single Nucleotide, Risk Factors, Diverticulitis, Colonic genetics, Diverticulosis, Colonic genetics, Membrane Proteins genetics
- Abstract
Colonic diverticulosis is a very common condition. Many patients develop diverticulitis or other complications of diverticular disease. Recent genome-wide association studies (GWAS) consistently identified three major genetic susceptibility factors for both conditions, but did not discriminate diverticulititis and diverticulosis in particular due the limitations of registry-based approaches. Here, we aimed to confirm the role of the identified variants for diverticulosis and diverticulitis, respectively, within a well-phenotyped cohort of patients who underwent colonoscopy. Risk variants rs4662344 in Rho GTPase-activating protein 15 (ARHGAP15), rs7609897 in collagen-like tail subunit of asymmetric acetylcholinesterase (COLQ) and rs67153654 in family with sequence similarity 155 A (FAM155A) were genotyped in 1,332 patients. Diverticulosis was assessed by colonoscopy, and diverticulitis by imaging, clinical symptoms and inflammatory markers. Risk of diverticulosis and diverticulitis was analyzed in regression models adjusted for cofactors. Overall, the variant in FAM155A was associated with diverticulitis, but not diverticulosis, when controlling for age, BMI, alcohol consumption, and smoking status (OR
adjusted 0.49 [95% CI 0.27-0.89], p = 0.002). Our results contribute to the assessment specific genetic variants identified in GWAS in the predisposition to the development of diverticulitis in patients with diverticulosis.- Published
- 2020
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20. Ischemia-reperfusion injury and the risk of hepatocellular carcinoma recurrence after deceased donor liver transplantation.
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Grąt M, Krawczyk M, Wronka KM, Stypułkowski J, Lewandowski Z, Wasilewicz M, Krawczyk P, Grąt K, Patkowski W, and Zieniewicz K
- Subjects
- Alanine Transaminase blood, Alanine Transaminase metabolism, Aspartate Aminotransferases blood, Aspartate Aminotransferases metabolism, Disease-Free Survival, Female, Humans, L-Lactate Dehydrogenase blood, L-Lactate Dehydrogenase metabolism, Living Donors, Male, Middle Aged, Neoplasm Recurrence, Local, Retrospective Studies, Risk Factors, Carcinoma, Hepatocellular pathology, Liver Neoplasms pathology, Liver Transplantation methods, Reperfusion Injury
- Abstract
This study aimed to evaluate the effects of ischemia-reperfusion injury (IRI) on the risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation. Data of 195 patients were retrospectively analysed. Post-reperfusion aspartate (AST), alanine transaminase, and lactate dehydrogenase (LDH) levels were the primary measures of IRI. Tumour recurrence was the primary endpoint. Post-reperfusion AST was a continuous risk factor for tumour recurrence in patients within Milan criteria (p = 0.035), with an optimal cut-off of 1896 U/L. Recurrence-free survival of patients within Milan criteria and post-reperfusion AST of <1896 and ≥1896 U/L was 96.6% and 71.9% at 5 and 3.7 years, respectively (p = 0.006). Additionally, post-reperfusion AST and LDH exceeding the upper quartile significantly increased the risk of HCC recurrence in patients within Milan criteria (p = 0.039, hazard ratio [HR] = 5.99 and p = 0.040, HR = 6.08, respectively) and to a lesser extent, in patients within Up-to-7 criteria (p = 0.028, HR = 3.58 and p = 0.039, HR = 3.33, respectively). No other significant IRI effects were found in patients beyond the Up-to-7 criteria and in analyses stratified for independent risk factors for recurrence: tumour number and differentiation, alpha-fetoprotein, and microvascular invasion. Thus, IRI exerts major negative effects on the risk of HCC recurrence after liver transplantation in patients within standard and extended criteria.
- Published
- 2018
- Full Text
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21. Polarization tunable all-dielectric color filters based on cross-shaped Si nanoantennas.
- Author
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Vashistha V, Vaidya G, Gruszecki P, Serebryannikov AE, and Krawczyk M
- Abstract
Polarization sensitive and insensitive color filters have important applications in the area of nano-spectroscopy and CCD imaging applications. Metallic nanostructures provide an efficient way to design and engineer ultrathin color filters. These nanostructures have capability to split the white light into fundamental colors and enable color filters with ultrahigh resolution but their efficiency can be restricted due to high losses in metals especially at the visible wavelengths. In this work, we demonstrate all-dielectric color filters based on Si nanoantennas, which are sensitive to incident-wave polarization and, thus, tunable with the aid of polarization angle variation. Two different information can be encoded in two different polarization states in one nanostructure. The nanoantenna based pixels are highly efficient and can provide high quality of colors, in particular, due to low losses in Si at optical frequencies. We experimentally demonstrate that a variety of colors can be achieved by changing the physical size of the nonsymmetric cross-shaped nanoantennas. The proposed devices allow to cover an extended gamut of colors on CIE-1931 chromaticity diagram owing to the existence of high-quality resonances in Si nanoantennas. Significant tunability of the suggested color filters can be achieved by varying polarization angle in both transmission and reflection mode. Additional tunability can be obtained by switching between transmission and reflection modes.
- Published
- 2017
- Full Text
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22. NOD2 gene variants confer risk for secondary sclerosing cholangitis in critically ill patients.
- Author
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Jüngst C, Stadlbauer V, Reichert MC, Zimmer V, Weber SN, Ofner-Ziegenfuß L, Voigtländer T, Spindelböck W, Fickert P, Kirchner GI, Lammert F, Lankisch TO, and Krawczyk M
- Subjects
- Genotype, Humans, Risk Factors, Cholangitis, Sclerosing genetics, Critical Illness, Genetic Predisposition to Disease, Nod2 Signaling Adaptor Protein genetics
- Abstract
Sclerosing cholangitis in critically ill patients (SC-CIP) is a progressive cholestatic disease of unknown aetiology characterized by chronic biliary infections. Hence we hypothesized that common NOD2 (nucleotide-binding oligomerisation domain containing 2) gene variants, known risk factors for Crohn's disease and bacterial translocation in liver cirrhosis, increase the odds of developing SC-CIP. Screening of 4,641 endoscopic retrograde cholangiography procedures identified 17 patients with SC-CIP, who were then genotyped for the three common NOD2 mutations (Cohort 1, discovery cohort). To validate the association, we subsequently tested these NOD2 variants in 29 patients from SC-CIP cohorts of three additional medical centers (Cohort 2, replication cohort). In Cohort 1, the NOD2 variants were present in 5 of 17 SC-CIP patients (29.4%), which is twice the frequency of the general population. These results were replicated in Cohort 2 with 8 patients (27.6%) showing NOD2 mutations. In contrast, polymorphisms of hepatocanalicular transporter genes did not have major impact on SC-CIP risk. This first study on genetic susceptibility in SC-CIP patients shows an extraordinary high frequency of NOD2 variation, pointing to a critical role of inherited impaired anti-bacterial defense in the development of this devastating biliary disease.
- Published
- 2017
- Full Text
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23. Limitations of predicting microvascular invasion in patients with hepatocellular cancer prior to liver transplantation.
- Author
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Grąt M, Stypułkowski J, Patkowski W, Bik E, Krasnodębski M, Wronka KM, Lewandowski Z, Wasilewicz M, Grąt K, Masior Ł, Ligocka J, and Krawczyk M
- Subjects
- Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular surgery, Female, Humans, Liver Neoplasms metabolism, Liver Neoplasms surgery, Male, Middle Aged, Neoplasm Invasiveness, Neoplastic Cells, Circulating pathology, Postoperative Complications epidemiology, Postoperative Complications metabolism, Predictive Value of Tests, Tumor Burden, Carcinoma, Hepatocellular pathology, Liver Neoplasms pathology, Liver Transplantation adverse effects, Microvessels pathology, Neoplasm Recurrence, Local pathology, Postoperative Complications pathology, alpha-Fetoproteins standards
- Abstract
Microvascular invasion (MVI) is well known to negatively influence outcomes following surgical treatment of hepatocellular cancer (HCC) patients. The aim of this study was to evaluate the rationale for prediction of MVI before liver transplantation (LT). Data of 200 HCC patients after LT were subject to retrospective analysis. MVI was present in 57 patients (28.5%). Tumor number (p = 0.001) and size (p = 0.009), and alpha-fetoprotein (p = 0.049) were independent predictors of MVI used to create a prediction model, defined as: 0.293x(tumor number) + 0.283x(tumor size in cm) + 0.164xlog
e (alpha-fetoprotein in ng/ml) (c statistic = 0.743). The established cut-off (≥2.24) was associated with sensitivity and specificity of 72%. MVI was not an independent risk factor for recurrence (p = 0.307), in contrast to tumor number (p = 0.047) and size (p < 0.001), alpha-fetoprotein (p < 0.001) and poor differentiation (p = 0.039). Recurrence-free survival at 5 years for patients without MVI was 85.9% as compared to 83.3% (p = 0.546) and 55.3% (p = 0.001) for patients with false negative and true positive prediction of MVI, respectively. The use of both morphological and biological tumor features enables effective pre-transplant prediction of high-risk MVI. Provided that these parameters are combined in selection of HCC patients for LT, pre-transplant identification of all patients with MVI does not appear necessary.- Published
- 2017
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24. Serum Autotaxin is a Marker of the Severity of Liver Injury and Overall Survival in Patients with Cholestatic Liver Diseases.
- Author
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Wunsch E, Krawczyk M, Milkiewicz M, Trottier J, Barbier O, Neurath MF, Lammert F, Kremer AE, and Milkiewicz P
- Subjects
- Adult, Aged, Biomarkers blood, Cholangitis, Sclerosing blood, Cholestasis blood, Cross-Sectional Studies, Female, Humans, Liver Cirrhosis, Biliary blood, Lysophospholipids blood, Male, Middle Aged, Prognosis, Proportional Hazards Models, Prospective Studies, Pruritus blood, Pruritus metabolism, Quality of Life, Severity of Illness Index, Survival Analysis, Young Adult, Cholangitis, Sclerosing metabolism, Cholestasis metabolism, Liver Cirrhosis, Biliary metabolism, Phosphoric Diester Hydrolases blood, Pruritus etiology
- Abstract
Autotaxin (ATX) is involved in the synthesis of lysophosphatidic acid. Both have recently been linked to cholestatic pruritus and liver injury. We aimed to investigate whether ATX is an indicator of cholestatic liver injury, health-related quality of life (HRQoL) and prognosis based on a group of 233 patients, 118 with primary biliary cholangitis (PBC) and 115 with primary sclerosing cholangitis (PSC). Patients were followed for 1-60 months, cumulative survival rates were calculated. ATX activity was significantly higher in both groups than in the 103 controls, particularly in patients with cirrhosis and in patients with longer disease duration. Ursodeoxycholic acid (UDCA) non-responders with PBC exhibited increased ATX activity. ATX activity was correlated with liver biochemistry, MELD, Mayo Risk scores and was associated with worse disease-specific HRQoL aspects. In both groups, Cox model analysis indicated that ATX was a negative predictor of survival. Increased ATX levels were associated with a 4-fold higher risk of death/liver transplantation in patients with PBC and a 2.6-fold higher risk in patients with PSC. We conclude that in patients with cholestatic conditions, ATX is not only associated with pruritus but also indicates impairment of other HRQoL aspects, liver dysfunction, and can serve as a predictor of survival.
- Published
- 2016
- Full Text
- View/download PDF
25. Variant adiponutrin confers genetic protection against cholestatic itch.
- Author
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Krawczyk M, Milkiewicz M, Marschall HU, Bartz C, Grünhage F, Wunsch E, Milkiewicz P, and Lammert F
- Subjects
- Adult, Aged, Aged, 80 and over, Alleles, Cholestasis, Intrahepatic, Female, Genotype, Humans, Lipase metabolism, Liver metabolism, Liver pathology, Lysophospholipids genetics, Lysophospholipids metabolism, Membrane Proteins metabolism, Middle Aged, Pregnancy, Pregnancy Complications, Pruritus pathology, Genetic Association Studies, Genetic Predisposition to Disease, Lipase genetics, Membrane Proteins genetics, Pruritus genetics
- Abstract
Lysophosphatidic acid (LPA) mediates cholestatic pruritus. Recently the enzyme PNPLA3, expressed in liver and skin, was demonstrated to metabolise LPA. Here we assess the association of the PNPLA3 variant p.Ile148Met, known to be associated with (non-)alcoholic fatty liver disease (NAFLD) in genome-wide association studies, with cholestatic itch in 187 patients with primary biliary cirrhosis (PBC) and 250 PBC-free controls as well as 201 women with intrahepatic cholestasis of pregnancy (ICP) and 198 female controls without a history of ICP. Our hypothesis was that the intensity of cholestatic itch differs in carriers of distinct PNPLA3 p.Ile148Met genotypes. Patients with PBC carrying the allele p.148Met that confers an increased NAFLD risk reported less itching than carriers of the p.148Ile allele (ANOVA P = 0.048). The PNPLA3 p.148Ile allele increased the odds of requiring plasmapheresis for refractory pruritus (OR = 3.94, 95% CI = 0.91-17.00, P = 0.048). In line with these findings, the PNPLA3 p.148Met allele was underrepresented in the ICP cohort (OR = 0.66, 95% CI = 0.47-0.92, P = 0.013). Notwithstanding the need for further replication of these findings, we conclude that the PNPLA3 allele p.148Met might confer protection against cholestatic pruritus, possibly due to increased LPA-acyltransferase activity in liver and/or skin.
- Published
- 2014
- Full Text
- View/download PDF
26. SRT1720 improves survival and healthspan of obese mice.
- Author
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Minor RK, Baur JA, Gomes AP, Ward TM, Csiszar A, Mercken EM, Abdelmohsen K, Shin YK, Canto C, Scheibye-Knudsen M, Krawczyk M, Irusta PM, Martín-Montalvo A, Hubbard BP, Zhang Y, Lehrmann E, White AA, Price NL, Swindell WR, Pearson KJ, Becker KG, Bohr VA, Gorospe M, Egan JM, Talan MI, Auwerx J, Westphal CH, Ellis JL, Ungvari Z, Vlasuk GP, Elliott PJ, Sinclair DA, and de Cabo R
- Subjects
- Animals, Apoptosis drug effects, Body Composition drug effects, Dietary Fats administration & dosage, Gene Expression drug effects, Glucose metabolism, Homeostasis drug effects, Liver drug effects, Liver pathology, Male, Mice, Mice, Inbred C57BL, Pancreas drug effects, Heterocyclic Compounds, 4 or More Rings pharmacology, Longevity drug effects, Obesity physiopathology
- Abstract
Sirt1 is an NAD(+)-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet. This lifespan extension is accompanied by health benefits including reduced liver steatosis, increased insulin sensitivity, enhanced locomotor activity and normalization of gene expression profiles and markers of inflammation and apoptosis, all in the absence of any observable toxicity. Using a conditional SIRT1 knockout mouse and specific gene knockdowns we show SRT1720 affects mitochondrial respiration in a Sirt1- and PGC-1α-dependent manner. These findings indicate that SRT1720 has long-term benefits and demonstrate for the first time the feasibility of designing novel molecules that are safe and effective in promoting longevity and preventing multiple age-related diseases in mammals.
- Published
- 2011
- Full Text
- View/download PDF
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