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    High accuracy quasi-interpolation using a new class of generalized multiquadrics
    (2024) Ortmann, Mathis; Buhmann, Martin
    A new generalization of multiquadric functions phi ( x ) = root c(2d) + || x ||(2d) , where x is an element of R-n , c is an element of R, d is an element of N, is presented to increase the accuracy of quasi -interpolation further. With the restriction to Euclidean spaces of odd dimensionality, the generalization can be used to generate a quasi -Lagrange operator that reproduces all polynomials of degree 2 d - 1. In contrast to the classical multiquadric, the convergence rate of the quasi -interpolation operator can be significantly improved by a factor h(2d -n - 1) , where h > 0 represents the grid spacing. Among other things, we compute the generalized Fourier transform of this new multiquadric function. Finally, an infinite regular grid is employed to analyse the properties of the aforementioned generalization in detail. We also present numerical results to demonstrate the advantages of our new multiquadric functions.
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    New methods for quasi-interpolation approximations: Resolution of odd-degree singularities
    (2024) Buhmann, Martin; Jäger, Janin; Jódar, Joaquín; Rodríguez, Miguel L.
    In this paper, we study functional approximations where we choose the so-called radial basis function method and more specifically, quasi-interpolation. From the various available approaches to the latter, we form new quasi-Lagrange functions when the orders of the singularities of the radial function’s Fourier transforms at zero do not match the parity of the dimension of the space, and therefore new expansions and coefficients are needed to overcome this problem. We develop explicit constructions of infinite Fourier expansions that provide these coefficients and make an extensive comparison of the approximation qualities and – with a particular focus – polynomial reproduction and uniform approximation order of the various formulae. One of the interesting observations concerns the link between algebraic conditions of expansion coefficients and analytic properties of localness and convergence.
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    Reduction of anthranilic acid to 2-aminobenzaldehyde by the white-rot fungus Bjerkandera adusta DSMZ 4708
    (2024) Babkina, Valeriia; Haiduk, Yana; Kurtash, Yuliia; Zorn, Holger; Zhuk, Tatyana
    The biocatalytic aerobic “in-water” reduction of anthranilic acid to 2-aminobenzaldehyde by growing cultures of the basidiomycetous white-rot fungus Bjerkandera adusta has been studied. The high specific activity of Bjerkandera adusta towards the carboxylic group of anthranilic acid that allows avoiding the formation of the corresponding alcohol has been demonstrated using different substrate concentrations. The presence of ethanol as co-solvent allows increasing the yield of target product. In contrast to chemical reducing agents that usually yield 2-aminobenzyl alcohol, an overreduction of anthranilic acid is completely suppressed by the fungus and gives the target flavor compound in satisfactory preparative yields. It was shown that the activity of Bjerkandera adusta towards anthranilic acid does not apply to its m- and p-isomers.
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    Unexpected reaction of antimony pentafluoride with a fluorinated propellane
    (2024) Bremer, Matthias
    While 1,3-dehydro-5,7-difluoroadamantane 11 reacts with SbF5 in super acid media (SO2ClF) to generate the 1,3-dehydroadamant-5,7-diyl dication 1, 1,3-dehydro-5-fluoroadamantane 12 fails to react analogously to produce the 1,3-dehydroadamant-5-yl cation 9; instead, the 3,5-difluoro-1-adamantylcation 13 is formed. We present a computational study that explains this surprising behavior by the initial addition of Sb2F10 to the propellane bond present in 12. This is computed to be highly exothermic and leads to a zwitterionic (or ion-pair) species, which in turn reacts autocatalytically with HF to produce the observed fluorinated cation 13, SbF3, and SbF6–.
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    MutL Activates UvrD by Interaction Between the MutL C-terminal Domain and the UvrD 2B Domain
    (2024) Storozhuk, Olha; Bruekner, Susanne R.; Paul, Ankon; Lebbink, Joyce H.G.; Sixma, Titia K.; Friedhoff, Peter
    UvrD is a helicase vital for DNA replication and quality control processes. In its monomeric state, UvrD exhibits limited helicase activity, necessitating either dimerization or assistance from an accessory protein to efficiently unwind DNA. Within the DNA mismatch repair pathway, MutL plays a pivotal role in relaying the repair signal, enabling UvrD to unwind DNA from the strand incision site up to and beyond the mismatch. Although this interdependence is well-established, the precise mechanism of activation and the specific MutL-UvrD interactions that trigger helicase activity remain elusive. To address these questions, we employed site-specific crosslinking techniques using single-cysteine variants of MutL and UvrD followed by functional assays. Our investigation unveils that the C-terminal domain of MutL not only engages with UvrD but also acts as a self-sufficient activator of UvrD helicase activity on DNA substrates with 3′-single-stranded tails. Especially when MutL is covalently attached to the 2B or 1B domain the tail length can be reduced to a minimal substrate of 5 nucleotides without affecting unwinding efficiency.
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    Clinical Characterization of Arrhythmia-Induced Cardiomyopathy in Patients With Tachyarrhythmia and Idiopathic Heart Failure
    (2024) Schach, Christian; Körtl, Thomas; Zeman, Florian; Luttenberger, Bianca; Mühleck, Franziska; Baum, Paul; Lavall, Daniel; Vosshage, Nicola H.; Resch, Markus; Ripfel, Sarah; Meindl, Christine; Ücer, Ekrem; Hamer, Okka W.; Baessler, Andrea; Arzt, Michael; Koller, Michael; Sohns, Christian; Maier, Lars S.; Wachter, Rolf; Sossalla, Samuel
    Background: Arrhythmia-induced cardiomyopathy (AIC) is a known entity, but prospective evidence for its characterization is limited. Objectives: This study aimed to: 1) determine the relative frequency of the pure form of AIC in the clinically relevant cohort of patients with newly diagnosed, otherwise unexplained left ventricular systolic dysfunction (LVSD) and tachyarrhythmia; 2) assess the time to recovery from LVSD; and 3) identify parameters for an early diagnosis of AIC. Methods: Patients were prospectively included, underwent effective rhythm restoration, and were followed-up at 2, 4, and 6 months to evaluate clinical characteristics, biomarkers, and cardiac imaging including cardiac magnetic resonance imaging. Patients with recurred arrhythmia were excluded from analysis. Results: 41 of 50 patients were diagnosed with AIC 6 months after rhythm restoration. Left ventricular (LV) ejection fraction increased 2 months after rhythm restoration from 35.4% ± 8.2% to 52.7% ± 8.0% in AIC patients vs 37.0% ± 9.5% to 43.3% ± 7.0% in non-AIC patients. From month 2 to 6, LV ejection fraction continued to increase in AIC patients (57.2% ± 6.1%; P < 0.001) but remained stable in non-AIC patients (44.0% ± 7.8%; P = 0.628). Multivariable logistic regression analysis revealed that lower LV end-diastolic diameter at baseline could be used for early diagnosis of AIC, whereas biomarkers and other morphological or functional parameters, including late LV gadolinium enhancement, did not show suitability for early diagnosis. Conclusions: We observed a high prevalence of AIC in patients with otherwise unexplained LVSD and concomitant tachyarrhythmia, suggesting that this condition may be underdiagnosed in clinical practice. Most patients recovered fast, within months, from LVSD. A low initial LV end-diastolic diameter may constitute an early marker for diagnosis of AIC.
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    Alpha- and betacoronavirus cis-acting RNA elements
    (2024) Madhugiri, Ramakanth; Nguyen, Hoang Viet; Slanina, Heiko; Ziebuhr, John
    Coronaviruses have exceptionally large RNA genomes and employ multiprotein replication/transcription complexes to orchestrate specific steps of viral RNA genome replication and expression. Most of these processes involve viral cis-acting RNA elements that are engaged in vital RNA–RNA and/or RNA–protein interactions. Over the past years, a large number of studies provided interesting new insight into the structures and, to a lesser extent, functions of specific RNA elements for representative coronaviruses, and there is evidence to suggest that (a majority of) these RNA elements are conserved across genetically divergent coronavirus genera. It is becoming increasingly clear that at least some of these elements do not function in isolation but operate through complex and highly dynamic RNA–RNA interactions. This article reviews structural and functional aspects of cis-acting RNA elements conserved in alpha- and betacoronavirus 5'- and 3'-terminal genome regions, focusing on their critical roles in viral RNA synthesis and gene expression.
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    The EPPO/OLAF compendium of national procedures: Romania
    (2025) Hauck, Pierre; Schneider, Jan-Martin
    This Romanian EPPO/OLAF volume comprises a collection of EU and Romanian legislation relating to EU fraud investigations. It deals with EU fraud typologies, possible EPPO/OLAF measures in Romania, and relevant Romanian precedents. The first part of this volume covers the national legal situation with regard to EPPO investigations according to Art. 26—33 of the EPPO-Regulation. The second part of the volume deals with OLAF investigations in Romania including relevant national law and co-operation with national partners.
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    Concept of a six-fold multiplex planar bioassay to distinguish endocrine agonist, antagonist, cytotoxic and false-positive responses
    (2024) Meyer, Daniel; Morlock, Gertrud E.
    To analyze a complex sample for endocrine activity, different tests must be performed to clarify androgen/estrogen agonism, antagonism, cytotoxicity, anti-cytotoxicity, and corresponding false-positive reactions. This means a large amount of work. Therefore, a six-fold planar multiplex bioassay concept was developed to evaluate up to the mentioned six endpoints or mechanisms simultaneously in the same sample analysis. Separation of active constituents from interfering matrix via high-performance thin-layer chromatography and effect differentiation via four vertical stripes (of agonists and end-products of the respective enzyme–substrate reaction) applied along each separated sample track were key to success. First, duplex endocrine bioassay versions were established. For the androgen/anti-androgen bioassay applied via piezoelectric spraying, the mean limit of biological detection of bisphenol A was 14 ng/band and its mean half maximal inhibitory concentration IC50 was 116 ng/band. Applied to trace analysis of six migrate samples from food packaging materials, 19 compound zones with agonistic or antagonistic estrogen/androgen activities were detected, with up to seven active compound zones within one migrate. For the first time, the S9 metabolism of endocrine effective compounds was studied on the same surface and revealed partial deactivation. Coupled to high-resolution mass spectrometry, molecular formulas were tentatively assigned to compounds, known to be present in packaging materials or endocrine active or previously unknown. Finally, the detection of cytotoxicity/anti-cytotoxicity and false-positives was integrated into the duplex androgen/anti-androgen bioassay. The resulting six-fold multiplex planar bioassay was evaluated with positive control standards and successfully applied to one migrate sample. The streamlined stripe concept for multiplex planar bioassays made it possible to assign different mechanisms to individual active compounds in a complex sample. The concept is generic and can be transferred to other assays.
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    The EPPO/OLAF compendium of national procedures: Poland
    (2025) Hauck, Pierre; Schneider, Jan-Martin
    Poland does not participate in the EPPO mechanism, but cooperates with OLAF. Therefore, this Polish EPPO/OLAF volume, introduced by Dominika Czerniak, discusses the specific attitude of Polish legislation towards the PIF acquis sector, Title V of the TFEU, the importance of Art. 587 (European Investigation Order) of the Polish Code of Criminal Procedure and the newly inserted Art. 615a. It also contains an analysis and compilation of the EU and Polish legislation on EU fraud offenses. These relevant laws are dealt with in the first chapter of this volume. The Anti-Fraud Office (OLAF) and its national partners carry out investigative missions, which are the subject of the second part of the book.
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    The EPPO/OLAF compendium of national procedures: Netherlands
    (2025) Hauck, Pierre; Schneider, Jan-Martin
    This Dutch EPPO/OLAF volume examines the Dutch law governing the activities of the EPPO in the Netherlands and contains references to the EPPO Regulation and the Dutch Adoption Act (Wet van 17 maart 2021). It also explores relevant legal information for OLAF's seconded national experts, its investigators and the investigative tasks of its national partners in external investigations.
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    The EPPO/OLAF compendium of national procedures: Hungary
    (2025) Hauck, Pierre; Schneider, Jan-Martin
    This Hungarian EPPO/OLAF volume focuses on criminal and administrative investigations in Hungary. As Hungary is a non-participating Member State to the EPPO, the EPPO chapter of this book discusses the relations between the EPPO countries and the Hungarian Prosecution Offices under a Working Arrangement as well as the rules of the Hungarian Prosecution Offices when investigating EU fraud and financial crime offences. It covers the material collected, co-operation with the Hungarian judicial authorities, criminal investigations into PIF-offences and compliance with the EPPO-Regulation. This volume also deals with the impact of OLAF investigations in Hungary and their significance for the Hungarian criminal justice system.
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    Decoupling inert and reactive gas supply to optimize ion beam sputter deposition apparatus for a more efficient material deposition
    (2024) Benz, Sebastian L.; Müller, Isabel; Polity, Angelika; Klar, Peter J.; Becker, Martin; Chatterjee, Sangam
    For all technologies, the energy-payback time (EPBT) serves as a critical metric. As an example, we study ion beam sputter deposition (IBSD), a sputter deposition approach where plasma, target, and substrate are decoupled. We compare three different configurations for reactive gas injection in order to demonstrate how the corresponding thin-film deposition processes can be improved, i.e., via the ion source, close to the target, or close to the substrate. The latter two decouple the introduction of inert and reactive gases, thus enabling substantial additional control in the deposition process. We investigate nickel oxide (NiOx) thin films as a versatile model system which is of interest for a wide range of applications. In the growth process, we vary growth times between 5 and 205 min and examine O2/Ar flow ratios between 0.13 and 5.82 for the different gas inlet configurations. Based on detailed structural and compositional analyses of the deposited thin films, we show that the deposition mode significantly influences crystal quality, growth rate, and surface roughness. Notably, the configuration where the reactive gas is injected close to the Ni target leads to significant improvement of the crystalline quality of the deposited NiOx layers for thicknesses of 30–200 nm. Furthermore, reactive gas injection close to the substrate yields films of comparable quality for thicknesses of 800 nm and above, but at almost twice the growth rate. These findings present a promising avenue for optimizing EPBT of IBSD by yielding better films in shorter process times and at less energy consumption. Yet, for low O2/Ar ratios the formation of a secondary phase of NiAl2O4 spinel is observed.
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    Influence of different pre-treatments on the resin infiltration depth into enamel of teeth affected by molar-incisor hypomineralization (MIH)
    (2024) Amend, Stefanie; Stork, Stephan; Lücker, Susanne; Seipp, Anika; Gärtner, Ulrich; Frankenberger, Roland; Krämer, Norbert
    Objectives: This in vitro pilot study aimed to evaluate whether different pre-treatments (demineralization, deproteinization, (chemo-)mechanical reduction of the surface layer) influence the penetration depth of a resin infiltrant into MIH-affected enamel compared to initial carious lesions. Methods: Thirty extracted human permanent molars with non-cavitated initial carious lesions (n = 5) or MIH (n = 25) were chosen and randomly assigned to six experimental groups: IC: initial caries; M: MIH; MN: MIH, 5.25% sodium hypochlorite; MM: MIH, microabrasion; MA: MIH, air abrasion; MAN: MIH, air abrasion and 5.25% sodium hypochlorite. A modified indirect dual fluorescence staining method was adopted to assess the penetration depth (PD) of the resin infiltrant and the lesion depth (LD) by confocal laser scanning microscopy (CLSM). Exemplarily, scanning electron microscopic (SEM) images were captured. The relationship between group assignment and penetration/lesion depth was estimated using a linear mixed model incorporating the tooth as random effect (two observations/tooth). The significance level was set at p < 0.05. Results: For MIH-affected molars, the mean PD (in µm; median, [minimum-maximum]) were M (178.2 [32.5–748.9]), MN (275.6 [105.3–1131.0]), MM (48.7 [0.0–334.4]), MA (287.7 [239.4–491.7]), and MAN (245.4 [76.1–313.5]). Despite the observed differences in PD between the groups, these could not be statistically verified (Bonferroni, p = 0.322). The percentage penetration was significantly higher for IC than for MIH groups (Bonferroni, p < 0.05). Significance: Compared to IC, resin infiltration into MIH-affected enamel ist more variable. Different pre-treatments influence the resin penetration into developmentally hypomineralized enamel to a fluctuating level.
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    Color matching in the wild
    (2024) Gil Rodríguez, Raquel; Vazquez-Corral, Javier; Bertalmío, Marcelo; Finlayson, Graham D.
    We present a method that, given two different views of the same scene taken by two cameras with unknown settings and internal parameters, corrects the colors of one of the images making it look as if it was captured under the other camera settings. Our method is able to deal with any standard non-linear encoded images (gamma-corrected, logarithmic-encoded, or any other) without requiring any previous knowledge of the encoding. To this end, our method makes use of two important observations. First, the camera imaging pipeline from RAW to sRGB can be well approximated by considering just a per-pixel shading and a color transformation matrix, and second, for correcting the images we only need to estimate a single matrix –that will contain information from both of the original images– and an approximation of the shading term (that emulates the non-linearity). Our proposed method is fast and the results have no spurious artifacts. The method outperforms the state-of-the-art when compared with other methods that do not require knowledge of the encoding used. It is also able to compete with –and even surpass in some cases– methods that consider information about image encoding.
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    All-in-one 2LabsToGo system for analysis of ergot alkaloids in whole rye
    (2024) Jakob, Kevin; Schwack, Wolfgang; Morlock, Gertrud E.
    Ergot alkaloids, naturally occurring mycotoxins of Claviceps fungi, pose health risks. This necessitates accurate analysis methods to ensure food safety. This study explored the open-source miniaturized all-in-one 2LabsToGo system to analyze ergot alkaloids in whole rye samples. It is suited for sustainable atline analysis as it combines all planar chromatography tasks, allowing low-cost quality control in milling plants. The LOD and LOQ of ergocristine were determined to be 0.4 and 1.2 ng/zone, respectively. Detectability of ergot alkaloids was proven to be below the current maximum limit of 500 µg/kg for rye milling products. The repeatability (%RSD) was 4.1 % and the coefficient of determination of the analytical response (R2) was 0.9918 for ergocristine. The mean recovery rate of ergot alkaloids in spiked whole rye grain was close to 100 %. Results of screening whole rye for ergot alkaloids were successfully verified by comparison with those obtained by conventional status quo HPTLC instrumentation.
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    Water absorption in artificial composites: Curse or blessing?
    (2024) Niem, Thomas; Hübner, Antje; Wöstmann, Bernd
    Objectives: This study evaluated the impact of mutable water uptake on the durability of mechanical properties and the long-term reliability of artificial composites. Methods: Three resin-based CAD/CAM restorative materials (CRMs) were investigated in three-point bending tests to calculate flexural strength (FS), modulus of elasticity (ME), modulus of resilience (MR), modulus of toughness (MT), and elastic recovery (ER). All specimens (n = 180) were stored under the same conditions and tested in four subsets (n = 15 per material) that were respectively withdrawn after repeated thermocycling (5000 cycles; 5–55 °C, H2O) and repetitive drying (7 d; 37 °C, air). For every specimen, weight differences were determined per storage condition. Likewise, loss tangent data were separately recorded via dynamic mechanical analysis to reliably assess damping characteristics. Results: Repeated thermocycling always induced weight increase and a concurrent significant loss in all mechanical properties except for MT and ER of a polymethylmethacrylate-based CRM. Drying consistently provoked weight loss and raised mechanical properties to initial values. Weight increase, however, enhanced loss tangent values and accordingly distinct damping characteristics, whereas weight decrease markedly lowered damping properties. Significance: Water uptake repeatedly induced a decrease in common mechanical properties but concurrently increased damping behavior. Invertible equilibrium processes were found with no evidence for permanent material degradation.
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    The diverging roles of insulin-like growth factor binding proteins in pulmonary arterial hypertension
    (2024) Schlueter, Beate Christiane; Quanz, Karin; Baldauf, Julia; Petrovic, Aleksandar; Ruppert, Clemens; Guenther, Andreas; Gall, Henning; Tello, Khodr; Grimminger, Friedrich; Ghofrani, Hossein-Ardeschir; Weissmann, Norbert; Seeger, Werner; Schermuly, Ralph Theo; Weiss, Astrid
    Pulmonary hypertension (PH) is a progressive, severe and to date not curable disease of the pulmonary vasculature. Alterations of the insulin-like growth factor 1 (IGF-1) system are known to play a role in vascular pathologies and IGF-binding proteins (IGFBPs) are important regulators of the bioavailability and function of IGFs. In this study, we show that circulating plasma levels of IGFBP-1, IGFBP-2 and IGFBP-3 are increased in idiopathic pulmonary arterial hypertension (IPAH) patients compared to healthy individuals. These binding proteins inhibit the IGF-1 induced IGF-1 receptor (IGF1R) phosphorylation and exhibit diverging effects on the IGF-1 induced signaling pathways in human pulmonary arterial cells (i.e. healthy as well as IPAH-hPASMCs, and healthy hPAECs). Furthermore, IGFBPs are differentially expressed in an experimental mouse model of PH. In hypoxic mouse lungs, IGFBP-1 mRNA expression is decreased whereas the mRNA for IGFBP-2 is increased. In contrast to IGFBP-1, IGFBP-2 shows vaso-constrictive properties in the murine pulmonary vasculature. Our analyses show that IGFBP-1 and IGFBP-2 exhibit diverging effects on IGF-1 signaling and display a unique IGF1R-independent kinase activation pattern in human pulmonary arterial smooth muscle cells (hPASMCs), which represent a major contributor of PAH pathobiology. Furthermore, we could show that IGFBP-2, in contrast to IGFBP-1, induces epidermal growth factor receptor (EGFR) signaling, Stat-3 activation and expression of Stat-3 target genes. Based on our results, we conclude that the IGFBP family, especially IGFBP-1, IGFBP-2 and IGFBP-3, are deregulated in PAH, that they affect IGF signaling and thereby regulate the cellular phenotype in PH.
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    Native hepatic T1-time as a non-invasive predictor of diastolic dysfunction and a monitoring tool for disease progression and treatment response in patients with pulmonary hypertension
    (2024) Kremer, Nils; Roller, Fritz C.; Kremer, Sarah; Schäfer, Simon; Kryvenko, Vitalii; Rako, Zvonimir A.; Brito da Rocha, Bruno R.; Yogeswaran, Athiththan; Seeger, Werner; Guth, Stefan; Wiedenroth, Christoph B.; Tello, Khodr
    Aims: Hepatic T1-time derived from cardiac magnetic resonance imaging (cMRI) reflects venous congestion and may provide a simple alternative to invasive end-diastolic elastance (Eed) for assessment of right ventricular (RV) diastolic function. We investigated the association of native hepatic T1-time with single-beat Eed and the value of hepatic T1-time for longitudinal monitoring in pulmonary hypertension (PH). Methods and results: We retrospectively enrolled 85 patients with suspected PH (59% female; 78 with PH diagnosed; 7 with PH excluded) who underwent standard right heart catheterization and cMRI within 24 h between 2015 and 2020. Hepatic T1-time showed moderate to strong correlations (rho >0.3, P ≤ 0.002) with pulmonary vascular resistance, native myocardial T1-time, Eed, RV size and function, brain natriuretic peptide (BNP) level, and 6-min walk distance, and a significant association with functional class (Kruskal-Wallis P < 0.001). Eed, myocardial T1-time, and BNP were independently linked to hepatic T1-time in multivariable regression. Hepatic T1-time > 598 ms predicted elevated Eed with 72.9% sensitivity and 82.1% specificity. Hepatic T1-time was superior to Eed in predicting clinical worsening. In 16 patients with follow-up assessments, those with decreasing hepatic T1-time (7 patients) showed significant hemodynamic improvements, whereas those with increasing hepatic T1-time (9 patients) did not. In a second retrospective cohort of 27 patients with chronic thromboembolic PH undergoing balloon pulmonary angioplasty, hepatic T1-time decreased significantly and hemodynamics improved after the procedure. Conclusions: Hepatic T1-time predicts RV diastolic dysfunction and prognosis, and may be useful for monitoring disease progression and treatment response in PH.
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    The EPPO/OLAF compendium of national procedures: Finland
    (2025) Hauck, Pierre; Schneider, Jan-Martin
    This Finnish EPPO/OLAF volume provides comprehensive information for the EPPO/OLAF sector, including case law, legal sources, and relevant organizations. It also summarises the national legislation relating to Finnish EPPO investigations, with a focus on the criminal investigation procedure. The last section deals with investigative missions in connection with OLAF investigations in Finland.