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A fungal strain (FJII-L10-SW-P1) was isolated from the Mars 2020 spacecraft assembly facility and exhibited biofilm formation on spacecraft-qualified Teflon surfaces. The reconstruction of a six-loci gene tree (ITS, LSU, SSU, RPB1 and RPB2, and TEF1) using multi-locus sequence typing (MLST) analyses of the strain FJII-L10-SW-P1 supported a close relationship to other known Parengyodontium album subclade 3 isolates while being phylogenetically distinct from subclade 1 strains. The zig-zag rachides morphology of the conidiogenous cells and spindle-shaped conidia were the distinct morphological characteristics of the P. album subclade 3 strains. The MLST data and morphological analysis supported the conclusion that the P. album subclade 3 strains could be classified as a new species of the genus Parengyodontium and placed in the family Cordycipitaceae. The name Parengyodontium torokii sp. nov. is proposed to accommodate the strain, with FJII-L10-SW-P1 as the holotype. The genome of the FJII-L10-SW-P1 strain was sequenced, annotated, and the secondary metabolite clusters were identified. Genes predicted to be responsible for biofilm formation and adhesion to surfaces were identified. Homology-based assignment of gene ontologies to the predicted proteome of P. torokii revealed the presence of gene clusters responsible for synthesizing several metabolic compounds, including a cytochalasin that was also verified using traditional metabolomic analysis.

A fungal strain (FJII-L10-SW-P1) was isolated from the Mars 2020 spacecraft assembly facility and exhibited biofilm formation on spacecraft-qualified Teflon surfaces. The reconstruction of a six-loci gene tree (ITS, LSU, SSU, RPB1 and RPB2, and TEF1) using multi-locus sequence typing (MLST) analyses of the strain FJII-L10-SW-P1 supported a close relationship to other known Parengyodontium album subclade 3 isolates while being phylogenetically distinct from subclade 1 strains. The zig-zag rachides morphology of the conidiogenous cells and spindle-shaped conidia were the distinct morphological characteristics of the P. album subclade 3 strains. The MLST data and morphological analysis supported the conclusion that the P. album subclade 3 strains could be classified as a new species of the genus Parengyodontium and placed in the family Cordycipitaceae. The name Parengyodontium torokii sp. nov. is proposed to accommodate the strain, with FJII-L10-SW-P1 as the holotype. The genome of the FJII-L10-SW-P1 strain was sequenced, annotated, and the secondary metabolite clusters were identified. Genes predicted to be responsible for biofilm formation and adhesion to surfaces were identified. Homology-based assignment of gene ontologies to the predicted proteome of P. torokii revealed the presence of gene clusters responsible for synthesizing several metabolic compounds, including a cytochalasin that was also verified using traditional metabolomic analysis.

Abstract This article presents an innovative approach for real‐time allocation of weighting factor values in model predictive control of electrical drive systems. In the proposed dynamic weighting factor assignment method, the cost associated with a specific variable is determined based on its corresponding set of predictions. This approach can be employed to optimize weighting factor values for a given system or even enhance performance metrics in comparison to conventional approaches that employ fixed weighting factors. Furthermore, the method determines the optimal value of weighting factors in real‐time with low added calculation complexity. The proposed method is able to provide reliable constant weighting factors for a given working point as well. The practical application of this method is demonstrated through a case study of an LC filter equipped PMSM drive; the system encompasses six independent variables that require regulation. Experimental results utilizing both two and three level voltage source inverters and using various transient and steady‐state situations prove the feasibility of the proposed dynamic weighting factor assignment method.

Penicillin-binding proteins (PBPs) contribute to bacterial cell wall biosynthesis and are targets of antibacterial agents. Here, we investigated PBP1b inhibition by boronic acid derivatives. Chemical starting points were identified by structure-based virtual screening and aliphatic boronic acids were selected for further investigations. Structure–activity relationship studies focusing on the branching of the boron-connecting carbon and quantum mechanical/molecular mechanical simulations showed that reaction barrier free energies are compatible with fast reversible covalent binding and small or missing reaction free energies limit the inhibitory activity of the investigated boronic acid derivatives. Therefore, covalent labelling of the lysine residue of the catalytic dyad was also investigated. Compounds with a carbonyl warhead and an appropriately positioned boronic acid moiety were shown to inhibit and covalently label PBP1b. Reversible covalent labelling of the catalytic lysine by imine formation and the stabilisation of the imine by dative N–B bond is a new strategy for PBP1b inhibition.

More and more aspects of local government autonomy have been challenged in the recent years. For local authorities, which are redefining their tasks, legislative capacity is of paramount importance, especially the original legislative powers to create new legal instruments to meet the requirements of the 21st century. One of the areas in which local government is working is the development of new mechanisms for public involvement and the creation of new legal instruments to facilitate participation. However, legislation to this end is often difficult in the current legal environment. This paper illustrates the challenges faced by local legislators when trying to develop new instruments for public participation through the creation of a participatory instrument by the Municipality of Budapest. To this end, after a brief introduction to the legislative context of local legislation and the instruments of local participatory democracy, it traces the codification process, presents the resulting legal instrument and explores the dilemmas that arose during the process of public consultation, impact assessment and the incorporation of the codification into the legal environment, as presented in the legislation.

The transition from traditional petrol-based combustion engines to hydrogen-powered systems represents a promising advancement in sustainable and clean energy solutions. This review paper explores the intricacies of converting a conventional internal combustion engine to operate on hydrogen gas. Key topics include the performance limitations of hydrogen engines, the role of water injection in combustion modulation, and the investigation of direct injection and port injection systems. This review also examines challenges associated with lean and rich mixtures, risks of backfire and pre-ignition, and the conversion’s overall impact on engine performance and longevity. Additionally, this paper discusses hydrogen lubrication to prevent mechanical wear and addresses emission-related considerations.

The shielded pair resonator method is a useful tool in the measurement of accelerator components, such as the beam screens used in the Large Hadron Collider (LHC), the High-Luminosity (HL) LHC, or future accelerators. It can measure the resistive losses at several frequency points by separating the resistive losses on the sample from other sources of losses. We built a new resonator to be inserted into a superconducting dipole magnet (peak magnetic field of 9.5 T) and to measure the surface resistance of beam screens, such as LHC beam screens coated with amorphous carbon (a-C). The device can measure surface resistance at any temperature between 4.2 K and 300 K, in the frequency range of 400 MHz to 1600 MHz. We conducted the first surface resistance measurements of two a-C coated beam screens at 4.2 K and showed that the 200 nm to 400 nm titanium underlayer plus 50 nm a-C only has a limited effect on the surface resistance. This first result supports the choice of this coating as baseline for the HL-LHC triplets magnets upgrade. The resonator will have an important role in the characterization of next-generation beam screens, such as a beam screen with laser-engineered surface structure (LESS). Further measurements of the LHC beam screen in the presence of magnetic fields up to 9.5 T and throughout the full temperature range are going to be reported separately.

Abstract Successful sucrose replacement in cake systems requires thorough understanding of its functionality. Time-domain 1H NMR showed that water in the viscous aqueous phase isolated from cake batter by ultracentrifugation [i.e. the batter liquor (BL)] exhibits low mobility by its low T2 relaxation time (T2,D RT). This is due to its interactions with sucrose or sucrose replacers. The T2,D RT itself is positively related with the effective volumetric hydrogen bond density of sucrose or sucrose replacers. Sucrose additionally co-determines the quantity and viscosity of cake BL and thereby how much air the batter contains at the end of mixing. Like sucrose, maltitol and oligofructose provide adequate volumes of BL with low water mobility and thus sufficient air in the batter, while the rather insoluble mannitol and inulin do not. Differential scanning calorimetry and rapid viscosity analysis revealed, however, that, in contrast to sucrose and maltitol, oligofructose fails to provide appropriate timings of starch gelatinisation and protein denaturation, resulting in poor cake texture. The shortcomings of mannitol and oligofructose in terms of respectively ensuring appropriate gas content in batter and biopolymer transitions during baking can be overcome by using mixtures thereof. This work shows that successful sucrose substitutes or substitute mixtures must provide sufficient BL with low water mobility and ensure appropriate timings of starch and protein biopolymer transitions during baking.

IntroductionThe impact of the obesity pandemic on female reproductive capability is a factor that needs to be investigated. In addition, the link between endometrial thickness and in vitro fertilization (IVF) outcomes is contentious.GoalOur goal was to analyze the association among endometrium development, hormone levels, embryo quality, clinical pregnancy, anamnestic parameters, and body mass index (BMI) in women receiving IVF treatment.Patients and methods537 participants undergoing IVF/ICSI cycles with successful oocyte retrieval were enrolled. Subjects were divided into four BMI based groups: underweight (UW; n=32), normal weight (NW; n=324), overweight (OW; n= 115), obesity (OB; n=66). Anthropometric and anamnestic parameters, characteristics of stimulation, endometrial thickness on the day of hCG injection, at puncture, at embryo transfer, FSH, LH, AMH, partner’s age and the semen analysis indicators, embryo quality, clinical pregnancy, were recorded and analyzed. Support Vector Machine (SVM) was built to predict potential pregnancies based on medical data using 22 dimensions.ResultsIn accordance with BMI categories, when examining pregnant/non-pregnant division, the average age of pregnant women was significantly lower in the UW (30.9 ± 4.48 vs. 35.3 ± 5.49 years, p=0.022), NW (34.2 ± 4.25 vs. 36.3 ± 4.84 years, p

BackgroundSevere coronavirus disease 2019 (COVID-19) may require veno-venous extracorporeal membrane oxygenation (V-V ECMO). While V-V ECMO is offered in severe lung injury to COVID-19, long-term respiratory follow-up in these patients is missing. Therefore, we aimed at providing comprehensive data on the long-term respiratory effects of COVID-19 requiring V-V ECMO support during the acute phase of infection.MethodsIn prospective observational cohort study design, patients with severe COVID-19 receiving invasive mechanical ventilation and V-V ECMO (COVID group, n = 9) and healthy matched controls (n = 9) were evaluated 6 months after hospital discharge. Respiratory system resistance at 5 and 19 Hz (R5, R19), and the area under the reactance curve (AX5) was evaluated using oscillometry characterizing total and central airway resistances, and tissue elasticity, respectively. R5 and R19 difference (R5–R19) reflecting small airway function was also calculated. Forced expired volume in seconds (FEV1), forced expiratory vital capacity (FVC), functional residual capacity (FRC), carbon monoxide diffusion capacity (DLCO) and transfer coefficient (KCO) were measured.ResultsThe COVID group had a higher AX5 and R5–R19 than the healthy matched control group. However, there was no significant difference in terms of R5 or R19. The COVID group had a lower FEV1 and FVC on spirometry than the healthy matched control group. Further, the COVID group had a lower FRC on plethysmography than the healthy matched control group. Meanwhile, the COVID group had a lower DLCO than healthy matched control group. Nevertheless, its KCO was within the normal range.ConclusionSevere acute COVID-19 requiring V-V ECMO persistently impairs small airway function and reduces respiratory tissue elasticity, primarily attributed to lung restriction. These findings also suggest that even severe pulmonary pathologies of acute COVID-19 can manifest in a moderate but still persistent lung function impairment 6 months after hospital discharge.Trial registrationNCT05812196.

Cryptococcosis, a life-threatening fungal infection, frequently occurs in patients suffering from AIDS. The treatment of the disease is hampered by the limited number of the effective drugs and the increasing resistance; therefore, to find new active substances is needed. As meningitis is the most serious infection affecting the AIDS patients, effective drugs have to be capable of entering to the central nervous system. Ecdysteroids are natural bioactive molecules with considerable anabolic activity and without toxic side effects on humans. The aim of this work was to study the anti-cryptococcal activity of a natural ecdysteroid, 20E, and its three semi-synthetic derivatives obtained by structural modification of the original molecule. We established the minimum inhibitory concentration of the compounds with microdilution method and demonstrated their fungicidal activity by flow cytometry and cultivation of the drug-treated cells. The interaction of the compounds with each other and efflux transporter inhibitors was assessed by checkerboard titration method. Two derivatives, 20E-EOx and 20E-ZOx, inhibited the growth of Cryptococcus neoformans with minimum inhibitory concentration 2 mg/mL and 1 mg/mL, respectively; both compounds possess fungicidal effect. A combination of the ecdysteroids with each other and verapamil resulted in additive interaction. This study confirmed that structural modification of an originally non-antimicrobial molecule can enhance its effectiveness.

Cascade failures in power grids occur when the failure of one component or subsystem causes a chain reaction of failures in other components or subsystems, ultimately leading to a widespread blackout or outage. Controlling cascade failures on power grids is important for many reasons like economic impact, national security, public safety and even rippled effects like troubling transportation systems. Monitoring the networks on node level has been suggested by many, either controlling all nodes of a network or by subsets. This study identifies sensitive graph elements of the weighted European power-grids (from 2016 and 2022) by two different methods. Bridges are determined between communities and “weak” nodes are selected by the lowest local synchronization of the swing equation. In the latter case we add bypasses of the same number as the bridges at weak nodes, and we compare the synchronization, cascade failure behavior by the dynamical improvement with the purely topological changes. The results are also compared if bridges are removed from networks, which results in a case similar to islanding, and with the addition of links at randomly selected places. Bypassing was found to improve synchronization the best, while the average cascade sizes are the lowest with bridge additions. However, for very large or small global couplings these network changes do not help, they seem to be useful near the synchronization transition region, where self-organization drives the power grid. Thus, we provide a demonstration for the Braess' Paradox on continent-sized power-grid simulations and uncover the limitations of this phenomenon. We also determine the cascade size distributions and justify the power-law tails near the transition point on these grids.

Abstract Purpose Selective internal radiation therapy (SIRT) requires a good liver registration of multi-modality images to obtain precise dose prediction and measurement. This study investigated the feasibility of liver registration of CT and MR images, guided by segmentation of the liver and its landmarks. The influence of the resulting lesion registration on dose estimation was evaluated. Methods The liver segmentation was done with a convolutional neural network (CNN), and the landmarks were segmented manually. Our image-based registration software and its liver-segmentation-guided extension (CNN-guided) were tuned and evaluated with 49 CT and 26 MR images from 20 SIRT patients. Each liver registration was evaluated by the root mean square distance (RMSD) of mean surface distance between manually delineated liver contours and mass center distance between manually delineated landmarks (lesions, clips, etc.). The root mean square of RMSDs (RRMSD) was used to evaluate all liver registrations. The CNN-guided registration was further extended by incorporating landmark segmentations (CNN&LM-guided) to assess the value of additional landmark guidance. To evaluate the influence of segmentation-guided registration on dose estimation, mean dose and volume percentages receiving at least 70 Gy (V70) estimated on the 99mTc-labeled macro-aggregated albumin (99mTc-MAA) SPECT were computed, either based on lesions from the reference 99mTc-MAA CT (reference lesions) or from the registered floating CT or MR images (registered lesions) using the CNN- or CNN&LM-guided algorithms. Results The RRMSD decreased for the floating CTs and MRs by 1.0 mm (11%) and 3.4 mm (34%) using CNN guidance for the image-based registration and by 2.1 mm (26%) and 1.4 mm (21%) using landmark guidance for the CNN-guided registration. The quartiles for the relative mean dose difference (the V70 difference) between the reference and registered lesions and their correlations [25th, 75th; r] are as follows: [− 5.5% (− 1.3%), 5.6% (3.4%); 0.97 (0.95)] and [− 12.3% (− 2.1%), 14.8% (2.9%); 0.96 (0.97)] for the CNN&LM- and CNN-guided CT to CT registrations, [− 7.7% (− 6.6%), 7.0% (3.1%); 0.97 (0.90)] and [− 15.1% (− 11.3%), 2.4% (2.5%); 0.91 (0.78)] for the CNN&LM- and CNN-guided MR to CT registrations. Conclusion Guidance by CNN liver segmentations and landmarks markedly improves the performance of the image-based registration. The small mean dose change between the reference and registered lesions demonstrates the feasibility of applying the CNN&LM- or CNN-guided registration to volume-level dose prediction. The CNN&LM- and CNN-guided registrations for CTs can be applied to voxel-level dose prediction according to their small V70 change for most lesions. The CNN-guided MR to CT registration still needs to incorporate landmark guidance for smaller change of voxel-level dose estimation.

Alpine bumble bees are the most important pollinators in temperate mountain ecosystems. Although they are used to encounter small-scale successions of very different climates in the mountains, many species respond sensitively to climatic changes, reflected in spatial range shifts and declining populations worldwide. Cuticular hydrocarbons (CHCs) mediate climate adaptation in some insects. However, whether they predict the elevational niche of bumble bees or their responses to climatic changes remains poorly understood. Here, we used three different approaches to study the role of bumble bees’ CHCs in the context of climate adaptation: using a 1,300 m elevational gradient, we first investigated whether the overall composition of CHCs, and two potentially climate-associated chemical traits (proportion of saturated components, mean chain length) on the cuticle of six bumble bee species were linked to the species’ elevational niches. We then analyzed intraspecific variation in CHCs of Bombus pascuorum along the elevational gradient and tested whether these traits respond to temperature. Finally, we used a field translocation experiment to test whether CHCs of Bombus lucorum workers change, when translocated from the foothill of a cool and wet mountain region to (a) higher elevations, and (b) a warm and dry region. Overall, the six species showed distinctive, species-specific CHC profiles. We found inter- and intraspecific variation in the composition of CHCs and in chemical traits along the elevational gradient, but no link to the elevational distribution of species and individuals. According to our expectations, bumble bees translocated to a warm and dry region tended to express longer CHC chains than bumble bees translocated to cool and wet foothills, which could reflect an acclimatization to regional climate. However, chain lengths did not further decrease systematically along the elevational gradient, suggesting that other factors than temperature also shape chain lengths in CHC profiles. We conclude that in alpine bumble bees, CHC profiles and traits respond at best secondarily to the climate conditions tested in this study. While the functional role of species-specific CHC profiles in bumble bees remains elusive, limited plasticity in this trait could restrict species’ ability to adapt to climatic changes.

Population control of the house mouse (Mus musculus), Norway rat (Rattus norvegicus) and black rat (Rattus rattus) is common practice worldwide. Our objective was to assess the impact on animal welfare of lethal and non-lethal control methods, including three dispatch methods. We used the Sharp and Saunders welfare assessment model with eight experts scoring eleven control methods and three dispatch methods used on the three species. We presumed the methods were performed as prescribed, only taking into account the effect on the target animal (and not, for example, on non-target catches). We did not assess population control efficacy of the methods. Methods considered to induce the least suffering to the target animal were captive-bolt traps, electrocution traps and cervical dislocation, while those with the greatest impact were anticoagulants, cholecalciferol and deprivation. Experts indicated considerable uncertainty regarding their evaluation of certain methods, which emphasises the need for further scientific research. In particular, the impact of hydrogen cyanide, chloralose and aluminium phosphide on animal welfare ought to be investigated. The experts also stressed the need to improve Standard Operating Procedures and to incorporate animal welfare assessments in Integrated Pest Management (IPM). The results of our study can help laypeople, professionals, regulatory agencies and legislators making well-informed decisions as to which methods to use when controlling commensal rodents.

Summary: Climate and land-use changes cause increasing stress to pollinators but the molecular pathways underlying stress responses are poorly understood. Here, we analyzed the transcriptomic response of Bombus lucorum workers to temperature and livestock grazing. Bumblebees sampled along an elevational gradient, and from differently managed grassland sites (livestock grazing vs unmanaged) in the German Alps did not differ in the expression of genes known for thermal stress responses. Instead, metabolic energy production pathways were upregulated in bumblebees sampled in mid- or high elevations or during cool temperatures. Extensive grazing pressure led to an upregulation of genetic pathways involved in immunoregulation and DNA-repair. We conclude that widespread bumblebees are tolerant toward temperature fluctuations in temperate mountain environments. Moderate temperature increases may even release bumblebees from metabolic stress. However, transcriptome responses to even moderate management regimes highlight the completely underestimated complexity of human influence on natural pollinators.

Abstract Affinity chromatography is the linchpin of antibody downstream processing and typically relies on bacterial immunoglobulin (Ig)-binding proteins, epitomized by staphylococcal protein A-based ligands. However, such affinity ligands are fairly costly and suffer from chemical instability, leading to ligand denaturation and leaching from chromatographic support. Innovations in this area are aimed at developing robust and highly selective antibody ligands capable of withstanding harsh column sanitization conditions. We report the development and first-stage characterization of a selective short linear peptide ligand of the IgG Fc region capable of capturing all four IgG subclasses. The ligand was discovered through in vitro directed evolution. A focused phage-display library based on a previously identified peptide lead was subjected to a single-round screen against a pool of human IgG. The hits were identified with next-generation sequencing and ranked according to the enrichment ratio relative to their frequency in the pre-screened library. The top enriched peptide GSYWYNVWF displaying highest affinity for IgG was coupled to bromohydrin-activated agarose beads via a branched linker. The resulting affinity matrix was characterized with a dynamic binding capacity of approx. 43 mg/mL, on par with commercially employed protein A-based resin.

We measured the surface resistance of titanium, amorphous carbon, and nonevaporable getter (NEG) coatings on copper samples, representative of surface treatments of beam-facing components in the High-Luminosity Large Hadron Collider at CERN. Measurements were done at room temperature as well as at liquid nitrogen temperature (77 K) by means of a novel large dielectric resonator operating at 3.4 GHz. The impact of a 100 to 400 nm titanium layer or a 50-nm amorphous carbon layer was negligible both at room temperature and down to 77 K in comparison to copper, while a thick (1140 nm) NEG layer showed a measurable increase in the surface resistance, being more significant at low temperature. The dielectric resonator proved to be a useful tool to characterize the surface resistance of flat samples with different surface treatments and sizes up to 10 cm for accelerator applications. Furthermore, its construction and operation are much simpler compared to other test devices currently in use, and it can provide accurate experimental data for the evaluation of the beam coupling impedance.

Urine is a widely available renewable source of nitrogen and phosphorous. The nitrogen in urine is present in the form of urea, which is rapidly hydrolyzed to ammonia and carbonic acid by the urease enzymes occurring in nature. In order to efficiently recover urea, the inhibition of urease must be done, usually by increasing the pH value above 11. This method, however, usually is based on external chemical dosing, limiting the sustainability of the process. In this work, the simultaneous recovery of urea and phosphorous from synthetic urine was aimed at by means of electrochemical pH modulation. Electrochemical cells were constructed and used for urea stabilization from synthetic urine by the in situ formation of OH- ions at the cathode. In addition, phosphorous precipitation with divalent cations (Ca2+, Mg2+) in the course of pH elevation was studied. Electrochemical cells equipped with commercial (Fumasep FKE) and developmental (PSEBS SU) cation exchange membranes (CEM) were used in this study to carry out urea stabilization and simultaneous P-recovery at an applied current density of 60 A m−2. The urea was successfully stabilized for a long time (more than 1 month at room temperature and nearly two months at 4 °C) at a pH of 11.5. In addition, >82% P-recovery could be achieved in the form of precipitate, which was identified as amorphous calcium magnesium phosphate (CMP) by using transmission electron microscopy (TEM).

Model Predictive Control is a promising technique for electric drive control, as it enables optimization for multiple parameters and offers reliable operation with non-linear systems. For induction machine drives it can be realized using separate cost functions for the torque and the stator flux. Although this eliminates the problem of calculating any weighting factor, the selection of the final voltage vector requires an additional sorting algorithm. By increasing the number of voltage levels or the prediction horizon, the sorting algorithm becomes more and more time-intensive, which can severely impair the performance of the control algorithm. This paper introduces a novel hybrid sorting algorithm consisting of two sorting networks and a merging step. As a case study, the described control method is applied for an induction machine with high rated frequency fed by a three-level inverter, while also discussing the implementation issues. Experimental results verify the operation of the devised sorting algorithm.

Diffuse midline gliomas, H3 K27M-mutant, World Health Organization (WHO) grade IV represent a distinct glioma entity with a predominantly paediatric presentation and remarkably poor prognosis. This report presents a case of a 73-year-old woman with a diffuse midline glioma, H3 K27M-mutant, WHO grade IV with a remarkable longitudinal extension, extending from the cervical myelon to the basal ganglia. On imaging, the lesion was predominantly suggestive of inflammatory oedema, and it was clinically associated with progressive hemi- and later tetraparesis with severe autonomic and bulbar symptoms. Laboratory examinations suggested a generalized inflammatory process; however, neither infectious nor autoimmune aetiology could be confirmed. Biopsy was deemed unfeasible given the critical localization. Presuming a seronegative autoimmune encephalomyelitis, high-dose corticosteroid therapy and plasma exchanges were conducted, resulting in a modest but transient relief. The patient passed away two months after hospitalization. Neuropathological examination of the lesion revealed a high-grade diffuse glioma with H3 K27M mutation (grade IV). Although originally considered as a paediatric entity, our case confirms reports from recent years that diffuse midline gliomas, H3 K27M-mutant, WHO grade IV can occur in adults, even among the elderly, and can mimic inflammatory alterations, posing diagnostic difficulty. Our case is one of the oldest patients reported with this pathology, the oldest with an extensive diffusely infiltrating growth pattern, and with the most extensive lesion reported in adulthood.

The Porto Metropolitan Area (Área Metropolitana do Porto, AMP) is a framework of cooperation between 17 municipalities and several districts. This metropolitan area has a specific, inter-municipal model of urban governance. In our research, we found that cooperation is significant mainly in sectors where the central legislature has essentially made this mandatory, by designing the AMP and defining its powers. In addition to AMP, only partial cooperation has been established in the field of waste management, and in the field of human public services and in the performance of public authority, there is essentially a set of autonomous organisational solutions. However, despite all this fragmentation, the above system ensures the satisfactory functioning of the metropolitan agglomeration. This also underlines the importance of transport management in urban areas, since this functioning system is based on an integrated and intermodal transport system

Abstract Background Selective internal radiation therapy (SIRT) is a promising treatment for unresectable hepatic malignancies. Predictive dose calculation based on a simulation using 99m Tc-labeled macro-aggregated albumin (99m Tc-MAA) before the treatment is considered as a potential tool for patient-specific treatment planning. Post-treatment dose measurement is mainly performed to confirm the planned absorbed dose to the tumor and non-tumor liver volumes. This study compared the predicted and measured absorbed dose distributions. Methods Thirty-one patients (67 tumors) treated by SIRT with resin microspheres were analyzed. Predicted and delivered absorbed dose was calculated using 99m Tc-MAA-SPECT and 90Y-TOF-PET imaging. The voxel-level dose distribution was derived using the local deposition model. Liver perfusion territories and tumors have been delineated on contrast-enhanced CBCT images, which have been acquired during the 99m Tc-MAA work-up. Several dose-volume histogram (DVH) parameters together with the mean dose for liver perfusion territories and non-tumoral and tumoral compartments were evaluated. Results A strong correlation between the predicted and measured mean dose for non-tumoral volume was observed (r = 0.937). The ratio of measured and predicted mean dose to this volume has a first, second, and third interquartile range of 0.83, 1.05, and 1.25. The difference between the measured and predicted mean dose did not exceed 11 Gy. The correlation between predicted and measured mean dose to the tumor was moderate (r = 0.623) with a mean difference of − 9.3 Gy. The ratio of measured and predicted tumor mean dose had a median of 1.01 with the first and third interquartile ranges of 0.58 and 1.59, respectively. Our results suggest that 99m Tc-MAA-based dosimetry could predict under or over dosing of the non-tumoral liver parenchyma for almost all cases. For more than two thirds of the tumors, a predictive absorbed dose correctly indicated either good tumor dose coverage or under-dosing of the tumor. Conclusion Our results highlight the predictive value of 99m Tc-MAA-based dose estimation to predict non-tumor liver irradiation, which can be applied to prescribe an optimized activity aiming at avoiding liver toxicity. Compared to non-tumoral tissue, a poorer agreement between predicted and measured absorbed dose is observed for tumors.

Microtransactions have become an integral part of the digital game industry. This has spurred researchers to explore the effects of this monetization strategy on players’ game enjoyment and intention to continue using the game. Hitherto, these relationships were exclusively investigated using cross-sectional survey designs. However, self-report measures tend to be only mildly correlated with actual media consumption. Moreover, cross-sectional designs do not allow for a detailed investigation into the temporal dimension of these associations. To address these issues, the current study leverages smartphone trace data to explore the longitudinal effect of in-game purchase behavior on continual mobile game use. In total, approximately 100,000 hours of mobile game activity among 6,340 subjects were analyzed. A Cox regression with time-dependent covariates was performed to examine whether performing in-game purchases affects the risk of players removing the game app from their repertoire. Results show that making an in-game purchase decreases this risk initially, prolonging the survival time of the mobile gaming app. However, this effect significantly changes over time. After the first three weeks, a reversal effect is found where previous in-game purchase behavior negatively affects the further survival of the game. Thus, mobile games without previous monetary investment are more prone to long-term continual game use if they survive the first initial weeks. Methodological and theoretical implications are discussed. As such, the current study adds to those studies that use computational methods within a traditional inferential framework to aid theory-driven inquiries.

Content and language integrated learning (CLIL) has expanded in Europe, favored by the large body of research, often showing positive effects of CLIL on L2 development. However, critical voices have recently questioned whether these positive findings apply to any language, given that most research focuses on English. Taking into account this concern, the present study investigated the (productive and receptive) vocabulary development in L2 English and L2 French of the same group of learners within a CLIL context. The aim was not to evaluate the benefits of CLIL over non-CLIL, but, instead, to examine whether vocabulary gains in CLIL learning are language-dependent. More specifically, this study included 75 Flemish eight-grade pupils who had CLIL lessons in both English and French. The results show that although the pupils have a larger English vocabulary, the level of improvement (from pretest to posttest) is not different across the languages. The findings indicate that within CLIL vocabulary knowledge also develops in languages other than English.

Abstract Background Bartonella spp. are vector-borne pathogens transmitted to humans via blood-sucking arthropods. Rodents such as the black rat (Rattus rattus) and Norway rat (R. norvegicus) are thought to be the main reservoirs. An infection with rodent-associated Bartonella spp. may cause severe symptoms in humans such as endocarditis and neuroretinitis. The current knowledge of Bartonella prevalence in rats from western Europe is scarce. Methods Rats and a few other rodent by-catches were trapped in the context of a rodenticide resistance study at different sites in Flanders, Belgium. During dissection, biometric data were collected, and spleen tissues were taken. DNA was extracted from spleen samples and tested for Bartonella spp. by conventional generic polymerase chain reaction (PCR). To determine the Bartonella species, a selected number of amplicons were sequenced and compared with GenBank entries. Results In total, 1123 rodents were trapped. The predominate species was R. norvegicus (99.64%). Other rodents trapped included: two water voles (Arvicola amphibius, 0.18%); one colour rat (R. norvegicus forma domestica, 0.09%); and one muskrat (Ondatra zibethicus, 0.09%). PCR analysis of 1097 rodents resulted in 410 (37.37%, 95% CI: 34.50–40.31%) Bartonella spp. DNA-positive samples. Bartonella tribocorum (94.68%, 95% CI: 88.02–98.25%) was the most frequently detected Bartonella species, followed by B. grahamii (3.19%, 95% CI: 0.66–9.04%) and B. doshiae (1.06%, 95% CI: 0.03–5.79%). An uncultured Bartonella species occurred in one water vole (1.06%, 95% CI: 0.03–5.79%). There was a significantly higher Bartonella prevalence in older rats compared to juveniles and a significant difference in Bartonella prevalence concerning the localisation of trapping sites. In contrast, there was no statistically significant difference in Bartonella prevalence regarding sex, degree of urbanisation and season. Conclusions Based on the high prevalence found, we conclude that the Norway rat seems to be a key reservoir host for zoonotic B. tribocorum in Belgium.

Despite the diverse functions of yeast, only a relatively homogenous group of Saccharomyces cerevisiae yeasts is used in the baking industry. Much of the potential of the natural diversity of yeasts has not been explored, and the sensory complexity of fermented baked foods is limited. While research on non-conventional yeast strains in bread making is increasing, it is minimal for sweet fermented bakery products. In this study, the fermentation characteristics of 23 yeasts from the bakery, beer, wine, and spirits industries were investigated in sweet dough (14% added sucrose w/w dm flour). Significant differences in invertase activity, sugar consumption (0.78–5.25% w/w dm flour), and metabolite (0.33–3.01% CO2; 0.20–1.26% ethanol; 0.17–0.80% glycerol; 0.09–0.29% organic acids) and volatile compound production were observed. A strong positive correlation (R2 = 0.76, p < 0.001) between sugar consumption and metabolite production was measured. Several non-conventional yeast strains produced more positive aroma compounds and fewer off-flavors than the reference baker’s yeast. This study shows the potential of non-conventional yeast strains in sweet dough.

This study explores the effects of child-external and child-internal factors on vocabulary skills of Vietnamese pre-schoolers. Thirty-nine Vietnamese children (54-77 months) were tested on vocabulary and cognition skills. Their parents completed a questionnaire on background information. Correlation and regression analyses were performed to explore the contribution of multiple factors to the variability in vocabulary skills. Results showed that the effects of multiple factors varied across modality and domain. Productive vocabulary was individually sensitive to more factors than receptive vocabulary; and phonologically-based vocabulary was more sensitive than semantically-based vocabulary. The strongest predictor of receptive vocabulary, productive vocabulary, semantically-based vocabulary and phonologically-based vocabulary was child intelligence, child pre-schooling length, household income and child age, respectively. The findings seem to support the multidimensional views of language with evidence that different domains or modalities of vocabulary skills respond to the effects of multiple factors differently; and components of verbal ability should be examined separately.

From early 2020, a high demand for SARS-CoV-2 tests was driven by several testing indications, including asymptomatic cases, resulting in the massive roll-out of PCR assays to combat the pandemic. Considering the dynamic of viral shedding during the course of infection, the demand to report cycle threshold (Ct) values rapidly emerged. As Ct values can be affected by a number of factors, we considered that harmonization of semi-quantitative PCR results across laboratories would avoid potential divergent interpretations, particularly in the absence of clinical or serological information. A proposal to harmonize reporting of test results was drafted by the National Reference Centre (NRC) UZ/KU Leuven, distinguishing four categories of positivity based on RNA copies/mL. Pre-quantified control material was shipped to 124 laboratories with instructions to setup a standard curve to define thresholds per assay. For each assay, the mean Ct value and corresponding standard deviation was calculated per target gene, for the three concentrations (107, 105 and 103 copies/mL) that determine the classification. The results of 17 assays are summarized. This harmonization effort allowed to ensure that all Belgian laboratories would report positive PCR results in the same semi-quantitative manner to clinicians and to the national database which feeds contact tracing interventions.

Background Cancer seems to have an independent adverse prognostic effect on COVID-19-related mortality, but uncertainty exists regarding its effect across different patient subgroups. We report a population-based analysis of patients hospitalised with COVID-19 with prior or current solid cancer versus those without cancer.Methods We analysed data of adult patients registered until 24 May 2020 in the Belgian nationwide database of Sciensano. The primary objective was in-hospital mortality within 30 days of COVID-19 diagnosis among patients with solid cancer versus patients without cancer. Severe event occurrence, a composite of intensive care unit admission, invasive ventilation and/or death, was a secondary objective. These endpoints were analysed across different patient subgroups. Multivariable logistic regression models were used to analyse the association between cancer and clinical characteristics (baseline analysis) and the effect of cancer on in-hospital mortality and on severe event occurrence, adjusting for clinical characteristics (in-hospital analysis).Results A total of 13 594 patients (of whom 1187 with solid cancer (8.7%)) were evaluable for the baseline analysis and 10 486 (892 with solid cancer (8.5%)) for the in-hospital analysis. Patients with cancer were older and presented with less symptoms/signs and lung imaging alterations. The 30-day in-hospital mortality was higher in patients with solid cancer compared with patients without cancer (31.7% vs 20.0%, respectively; adjusted OR (aOR) 1.34; 95% CI 1.13 to 1.58). The aOR was 3.84 (95% CI 1.94 to 7.59) among younger patients (

Abstract Purpose We have developed a multi-modal imaging approach for SIRT, combining 99mTc-MAA SPECT/CT and/or 90Y PET, 18F-FDG PET/CT, and contrast-enhanced CBCT for voxel-based dosimetry, as a tool for treatment planning and verification. For radiation dose prediction calculations, a segmentation of the total liver volume and of the liver perfusion territories is required. Method In this paper, we proposed a procedure for multi-modal image analysis to assist SIRT treatment planning. The pre-treatment 18F-FDG PET/CT, 99mTc-MAA SPECT/CT, and contrast-enhanced CBCT images were registered to a common space using an initial rigid, followed by a deformable registration. The registration was scored by an expert using Likert scores. The total liver was segmented semi-automatically based on the PET/CT and SPECT/CT images, and the liver perfusion territories were determined based on the CBCT images. The segmentations of the liver and liver lobes were compared to the manual segmentations by an expert on a CT image. Result Our methodology showed that multi-modal image analysis can be used for determination of the liver and perfusion territories using CBCT in SIRT using all pre-treatment studies. The results for image registration showed acceptable alignment with limited impact on dosimetry. The image registration performs well according to the expert reviewer (scored as perfect or with little misalignment in 94% of the cases). The semi-automatic liver segmentation agreed well with manual liver segmentation (dice coefficient of 0.92 and an average Hausdorff distance of 3.04 mm). The results showed disagreement between lobe segmentation using CBCT images compared to lobe segmentation based on CT images (average Hausdorff distance of 14.18 mm), with a high impact on the dosimetry (differences up to 9 Gy for right and 21 Gy for the left liver lobe). Conclusion This methodology can be used for pre-treatment dosimetry and for SIRT planning including the determination of the activity that should be administered to achieve the therapeutical goal. The inclusion of perfusion CBCT enables perfusion-based definition of the liver lobes, which was shown to be markedly different from the anatomical definition in some of the patients.

Fermented pastry products are produced by fermenting and baking multi-layered dough. Increasing our knowledge of the impact of the fermentation process during pastry making could offer opportunities for improving the production process or end-product quality, whereas increasing our knowledge on the sugar release and consumption dynamics by yeast could help to design sugar reduction strategies. Therefore, this study investigates the impact of yeast fermentation and different sugar concentrations on pastry dough properties and product quality characteristics. First, yeasted pastry samples were made with 8% yeast and 14% sucrose on a wheat flour dry matter base and compared to non-yeasted samples. Analysis of saccharide concentrations revealed that sucrose was almost entirely degraded by invertase in yeasted samples after mixing. Fructans were also degraded extensively, but more slowly. At least 23.6 ± 2.6% of the released glucose was consumed during fermentation. CO2 production during fermentation contributed more to product height development than water and ethanol evaporation during baking. Yeast metabolites weakened the gluten network, causing a reduction in dough strength and extensibility. However, fermentation time had a more significant impact on dough rheology parameters than the presence of yeast. In balance, yeast fermentation did not significantly affect the calculated sweetness factor of the pastry product with 14% added sucrose. Increasing the sugar content (21%) led to higher osmotic stress, resulting in reduced sugar consumption, reduced CO2 and ethanol production and a lower product volume. A darker colour and a higher sweetness factor were obtained. Reducing the sugar content (7%) had the opposite effect. Eliminating sucrose from the recipe (0%) resulted in a shortened productive fermentation time due to sugar depletion. Dough rheology was affected to a limited extent by changes in sucrose addition, although no sucrose addition or a very high sucrose level (21%) reduced the maximum dough strength. Based on the insights obtained in this study, yeast-based strategies can be developed to improve the production and quality of fermented pastry.

One way in which invasive alien species affect their environment is by acting as pathogen hosts. Pathogens limited by the availability of the native host species can profit from the presence of additional hosts. The muskrat (Ondatra zibethicus) is known to act as an intermediate host for the fox tapeworm (Echinococcus multilocularis). From 2009 to 2017, 15,402 muskrats caught in Flanders and across the border with Wallonia and France were collected and dissected with the aim of understanding the prevalence of this parasite in muskrats. Visual examination of the livers revealed 202 infected animals (1.31%). Out of the 9421 animals caught in Flanders, we found 82 individuals (0.87%) infected with E. multilocularis. No increase in prevalence was observed during this study. All of the infected animals in Flanders were found in municipalities along the Walloon border. We did not observe a northward spread of E. multilocularis infection from Wallonia to Flanders. We hypothesise that the low prevalence is the result of the reduced availability of intermediate hosts and the successful control programme which is keeping muskrat densities in the centre of the region at low levels and is preventing influx from other areas. Our results illustrate that muskrats are good sentinels for E. multilocularis and regular screening can gain valuable insight into the spread of this zoonosis.

Abstract Background In epilepsy patients, SISCOM or subtraction ictal single photon emission computed tomography co-registered to magnetic resonance imaging has become a routinely used, non-invasive technique to localize the ictal onset zone (IOZ). Thresholding of clusters with a predefined number of standard deviations from normality (z-score) is generally accepted to localize the IOZ. In this study, we aimed to assess the robustness of this parameter in a group of patients with well-characterized drug-resistant epilepsy in whom the exact location of the IOZ was known after successful epilepsy surgery. Eighty patients underwent preoperative SISCOM and were seizure free in a postoperative period of minimum 1 year. SISCOMs with z-threshold 2 and 1.5 were analyzed by two experienced readers separately, blinded from the clinical ground truth data. Their reported location of the IOZ was compared with the operative resection zone. Furthermore, confidence scores of the SISCOM IOZ were compared for the two thresholds. Results Visual reporting with a z-score threshold of 1.5 and 2 showed no statistically significant difference in localizing correspondence with the ground truth (70 vs. 72% respectively, p = 0.17). Interrater agreement was moderate (κ = 0.65) at the threshold of 1.5, but high (κ = 0.84) at a threshold of 2, where also reviewers were significantly more confident (p

Abstract Objective Diterpene alkaloids are secondary plant metabolites and chemotaxonomical markers with a strong biological activity. These compounds are characteristic for the Ranunculaceae family, while their occurrence in other taxa is rare. Several species of the Spiraea genus (Rosaceae) are examples of this rarity. Screening Spiraea species for alkaloid content is a chemotaxonomical approach to clarify the classification and phylogeny of the genus. Novel pharmacological findings make further investigations of Spiraea diterpene alkaloids promising. Results Seven Spiraea species were screened for diterpene alkaloids. Phytochemical and pharmacological investigations were performed on Spiraea chamaedryfolia, the species found to contain diterpene alkaloids. Its alkaloid-rich fractions were found to exert a remarkable xanthine-oxidase inhibitory activity and a moderate antibacterial activity. The alkaloid distribution within the root was clarified by microscopic techniques.

Abstract Background Antibiotics are frequently used in intensive care units (ICUs), and their use is associated with the emergence of bacterial resistance to antibiotics. The aim of this study was to investigate the association between the emergence of Pseudomonas aeruginosa resistance and the duration of antibiotic exposure or mode of administration in an ICU unit. Methods A 4-year cohort study of intensive care unit was performed in patients with P. aeruginosa isolates from clinical specimens, initially susceptible to the investigated antibiotics (piperacillin/tazobactam, ceftazidime, ciprofloxacin, meropenem and amikacin). Odds ratios (ORs) with 95% confidence interval (95% CI) of emergence of resistance were calculated using logistic regression analysis for various exposure periods to antibiotics (1–3, 4–7, 8–15 and >15 days) relative to no exposure with adjustment for age, sex, Simplified Acute Physiology Score 3 (SAPS 3) and length of stay. ORs on the emergence of P. aeruginosa resistance were also calculated for the various modes of administration. Results Included were 187 patients [mean age 61 years, 69% male, mean SAPS 3 score (SD): 59 (12.3)]. None of the antibiotics investigated showed the emergence of resistance within 1–3 days. Significant meropenem resistance emerged within 8–15 days [OR 79.1 (14.9–421.0)] after antibiotic exposure unlike other antibiotics (>15 days). No difference was observed between intermittent and extended administration of meropenem and between beta-lactam mono- or combined therapy. Conclusions Use of meropenem was associated with the emergence of resistance as soon as 8 days after exposure to the antibiotic.

BACKGROUND:How dental education influences students' dental and dentofacial esthetic perception has been studied for some time, given the importance of esthetics in dentistry. However, no study before has studied this question in a large sample of students from all grades of dental school. This study sought to fill that gap. The aim was to assess if students' dentofacial esthetic autoperception and heteroperception are associated with their actual stage of studies (grade) and if autoperception has any effect on heteroperception. METHODS:Between October 2018 and August 2019, a questionnaire was distributed to 919 dental students of all 5 grades of dental school at all four dental schools in Hungary. The questionnaire consisted of the following parts (see also the supplementary material): 1. Demographic data (3 items), Self-Esthetics I (11 multiple- choice items regarding the respondents' perception of their own dentofacial esthetics), Self-Esthetics II (6 Likert-type items regarding the respondents' perception of their own dentofacial esthetics), and Image rating (10 items, 5 images each, of which the respondents have to choose the one they find the most attractive). Both the self-esthetics and the photo rating items were aimed at the assessment of mini- and microesthetic features. RESULTS:The response rate was 93.7% (861 students). The self-perception of the respondents was highly favorable, regardless of grade or gender. Grade and heteroperception were significantly associated regarding maxillary midline shift (p < 0.01) and the relative visibility of the arches behind the lips (p < 0.01). Detailed analysis showed a characteristic pattern of preference changes across grades for both esthetic aspects. The third year of studies appeared to be a dividing line in both cases, after which a real preference order was established. Association between autoperception and heteroperception could not be verified for statistical reasons. CONCLUSION:Our findings corroborate the results of most previous studies regarding the effect of dental education on the dentofacial esthetic perception of students. We have shown that the effect can be demonstrated on the grade level, which we attribute to the specific curricular contents. We found no gender effect, which, in the light of the literature, suggests that the gender effect in dentofacial esthetic perception is highly culture dependent. The results allow no conclusion regarding the relation between autoperception and heteroperception.

In the second language acquisition literature, data of naturally occurring language use are considered the most ideal data to make statements about second-language (L2) development. This study examines to what extent experimentally elicited data can provide an equally valid basis for determining L2 development, by testing predictions derived from Processability Theory regarding the L2 acquisition of the German case system. Using naturally occurring language data, previous research on L2 German case acquisition has uncovered three developmental stages. The present cross-sectional study investigates whether the same stages occur in data obtained from an experimental task (i.e., a computer oral elicited imitation task (OEIT). Thirty-six university L2 learners of German participated in the study. The results show that the elicited data prove comparable to the naturally occurring data. As such, this study corroborates a previous validation study on developmental stages in L2 English, which demonstrated the comparability of naturally occurring and experimentally elicited data. In addition, concerning methodological advancement of the OEIT design, the present study proposes to include a direct measure of comprehension.