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BackgroundFrontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged

Background: Seriously injured persons with pre-existing psychiatric conditions or those injured due to violent crimes represent a particularly vulnerable treatment group. Methods: All patients with injuries from suicidal attempts (PSAs) or patients with injuries from violent offenses (PVOs) that presented to the university emergency room of a Level 1 trauma center in Germany between 1 January 2017 and 31 November 2022 were retrospectively investigated. Results: It can be seen that PVOs were significantly younger compared to PSAs (p = 0.03). Total hospital stay was significantly longer for PSAs compared to PVOs (p < 0.001). PSAs were also significantly more severely injured than PVOs (p < 0.001). Our study was able to show a significant difference between both patient groups in the region of injury (p < 0.001). PSAs had a significantly more extensive psychiatric history than PVOs (p < 0.001). Conclusion: Injuries from suicide attempts and violent offenses are a serious and growing public health problem, but one that can be addressed through timely, evidence-based, and often cost-effective interventions. It requires early interaction among multiple disciplines and a standardized approach.

SARS-CoV-2 infection was shown to induce proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma levels in sepsis. Here, we investigate the association between serum PCSK9 levels and disease severity. PCSK9 was measured in serum of 55 controls, 40 patients with moderate and 60 patients with severe COVID-19 disease. Serum PCSK9 was elevated in moderate COVID-19 compared to controls and further increased in severe cases. PCSK9 levels were not associated with C-reactive protein, bacterial superinfections, interventions, or survival in patients with severe COVID-19. PCSK9 regulates circulating cholesterol levels, and 15 cholesteryl ester (CE) species and free cholesterol (FC) were quantified by direct flow injection analysis using a high-resolution hybrid quadrupole-Orbitrap mass spectrometer. Most CE species with shorter fatty acid chains were decreased in severe compared to moderate COVID-19, and none of the CE species were correlated with PCSK9 in patients with severe COVID-19. Levels of all CE species negatively correlated with C-reactive protein in severe COVID-19 patients. Notably, FC was induced in severe compared to moderate COVID-19. The FC/CE ratio correlated positively with inflammatory markers and was associated with non-survival. The current study suggests that the imbalance between CE and FC levels is associated with disease severity and mortality in patients with COVID-19.

The degradation of different flexible polyurethane foams for molded application after thermal aging were compared. A reference sample using traditional higher emission additives and four samples of different composition using low-emission additives were compared. For the modified samples volatile organic compound (VOC) and semi-volatile organic compound (FOG/SVOC) contents fell well below the benchmarking limits, which indicates that the selected low-emission additives are incorporated into the polymer chain. To examine different material properties and for evaluating changes due to increased temperature exposure for a prolonged period of time mechanical and acoustic tests were carried out before and after dry heat aging. It was found that two low emission samples exhibited superior sound absorption compared to the reference sample along with less significant change after aging in the acoustic properties. The compressive strength was lower than the reference as a result of lower product densities. However, the change in compressive strength after aging was less than 15% (with one exception), which is acceptable according to the standard requirements. Thermogravimetric analysis was also performed and revealed that no significant difference can be observed between the examined samples due to heat degradation, indicating that the modifications made to reduce VOC content did not adversely affect the foam’s resistance to thermal degradation.

Artificial Intelligence tools have gained significant attention in recent years due to their potential to transform various sectors by automating tasks, improving efficiency, and enhancing decision-making processes. This paper explores the success of Artificial Intelligence tools, particularly ChatGPT, using the Information System-success-based framework from the perspective of users. Structural Equation Modeling techniques were applied to data collected from users of ChatGPT. The study empirically evaluated a model for measuring the success of Artificial Intelligence tools, incorporating constructs from the updated DeLone and McLean Information System success model. Four out of five hypothesized relationships between the success variables were significantly supported. The findings of this study can be used to assess the success of Artificial Intelligence tools like ChatGPT from the standpoint of their users.

Predicting responses and monitoring the severity of inflammatory bowel disease (IBD) is challenging due to a lack of specific biomarkers. This study identifies urinary hydroxyproline, a marker of collagen turnover elevated in experimental colitis, as independent of conventional biomarkers like creatinine, glomerular filtration rate, C-reactive protein, and fecal calprotectin. Among 71 IBD patients, urinary hydroxyproline levels were significantly higher compared with 36 controls, with an area under the receiver operating characteristic curve of 0.814, highlighting its potential as a diagnostic tool. No significant difference in hydroxyproline levels was observed between the 50 Crohn’s disease and 21 ulcerative colitis patients, nor was there a correlation with kidney function markers, gastrointestinal symptom severity, or stool consistency. Disease localization was not associated with urinary hydroxyproline levels. Interestingly, 14 patients with primary sclerosing cholangitis and IBD also exhibited elevated urinary hydroxyproline levels, comparable to IBD patients but higher than healthy controls. This underscores the role of urinary hydroxyproline as an independent biomarker for IBD diagnosis, without association with disease severity or established markers like fecal calprotectin.

Abstract Paneth cells (PCs), a subset of intestinal epithelial cells (IECs) found at the base of small intestinal crypts, play an essential role in maintaining intestinal homeostasis. Altered PCs function is associated with diverse intestinal pathologies, including ileal Crohn’s disease (CD). CD patients with ileal involvement have been previously demonstrated to display impairment in PCs and decreased levels of anti-microbial peptides. Although the immunosuppressive drug Azathioprine (AZA) is widely used in CD therapy, the impact of AZA on IEC differentiation remains largely elusive. In the present study, we hypothesized that the orally administered drug AZA also exerts its effect through modulation of the intestinal epithelium and specifically via modulation of PC function. AZA-treated CD patients exhibited an ileal upregulation of AMPs on both mRNA and protein levels compared to non-AZA treated patients. Upon in vitro AZA stimulation, intestinal epithelial cell line MODE-K exhibited heightened expression levels of PC marker in concert with diminished cell proliferation but boosted mitochondrial OXPHOS activity. Moreover, differentiation of IECs, including PCs differentiation, was boosted in AZA-treated murine small intestinal organoids and was associated with decreased D-glucose consumption and decreased growth rates. Of note, AZA treatment strongly decreased Lgr5 mRNA expression as well as Ki67 positive cells. Further, AZA restored dysregulated PCs associated with mitochondrial dysfunction. AZA-dependent inhibition of IEC proliferation is accompanied by boosted mitochondria function and IEC differentiation into PC.

Abstract A reduction in animal-based diets has driven market demand for alternative meat products, currently raising a new generation of plant-based meat alternatives (PBMAs). It remains unclear whether these substitutes are a short-lived trend or become established in the long term. Over the last few years, the trend of increasing sales and diversifying product range has continued, but publication activities in this field are currently limited mainly to market research and food technology topics. As their popularity increases, questions emerge about the safety and nutritional risks of these novel products. Even though all the examined products must be heated before consumption, consumers lack experience with this type of product and thus further research into product safety, is desirable. To consider these issues, we examined 32 PBMAs from Austrian supermarkets. Based on 16S rRNA gene amplicon sequencing, the majority of the products were dominated by lactic acid bacteria (either Leuconostoc or Latilactobacillus), and generally had low alpha diversity. Pseudomonadota (like Pseudomonas and Shewanella) dominated the other part of the products. In addition to LABs, a high diversity of different Bacillus, but also some Enterobacteriaceae and potentially pathogenic species were isolated with the culturing approach. We assume that especially the dominance of heterofermentative LABs has high relevance for the product stability and quality with the potential to increase shelf life of the products. The number of isolated Enterobacteriaceae and potential pathogens were low, but they still demonstrated that these products are suitable for their presence.

Abstract Global flood impacts have risen in recent decades. While increasing exposure was the dominant driver of surging impacts, counteracting vulnerability reductions have been detected, but were too weak to reverse this trend. To assess the ongoing progress on vulnerability reduction, we combine a recently available dataset of flooded areas derived from satellite imagery for 913 events with four global disaster databases and socio-economic data. Event-specific flood vulnerabilities for assets, fatalities and displacements reveal a lack of progress in reducing global flood vulnerability from 2000—2018. We examine the relationship between vulnerabilities and human development, inequality, flood exposure and local structural characteristics. We find that vulnerability levels are significantly lower in areas with good structural characteristics and significantly higher in low developed areas. However, socio-economic development was insufficient to reduce vulnerabilities over the study period. Nevertheless, the strong correlation between vulnerability and structural characteristics suggests further potential for adaptation through vulnerability reduction.

Operating in urban waters with an autonomous vessel can be challenging. The autonomous vessel must be able to react quickly and detect obstacles to avoid collisions and risky maneuvers. Exteroceptive sensors such as LiDAR and RADAR have typically been used with great success in the maritime domain, but the measurements are often too sparse to represent smaller obstacles during docking and other maritime operations. However, other sensor modalities, such as stereo cameras, can provide both appearance and dense depth information. In this paper, we present a stereo camera-based free space estimation method for the maritime domain. The mapping of navigable areas is crucial for path planning and collision avoidance systems. To robustly estimate the free space, we use vertically oriented rectangular segments known as stixels. We utilized both stereo correspondences and a recent image segmentation network trained on a large, generalized dataset to create the stixels. To validate our approach, we analyzed the estimated free space, evaluating both the accuracy and consistency in the estimated depth over time. We demonstrate the approach using a real dataset recorded with a stereo camera mounted on an autonomous ferry and compare its accuracy against measurements from a LiDAR.

Genome-wide association studies (GWASs) have identified thousands of variants for disease risk. These studies have predominantly been conducted in individuals of European ancestries, which raises questions about their transferability to individuals of other ancestries. Of particular interest are admixed populations, usually defined as populations with recent ancestry from two or more continental sources. Admixed genomes contain segments of distinct ancestries that vary in composition across individuals in the population, allowing for the same allele to induce risk for disease on different ancestral backgrounds. This mosaicism raises unique challenges for GWASs in admixed populations, such as the need to correctly adjust for population stratification. In this work we quantify the impact of differences in estimated allelic effect sizes for risk variants between ancestry backgrounds on association statistics. Specifically, while the possibility of estimated allelic effect-size heterogeneity by ancestry (HetLanc) can be modeled when performing a GWAS in admixed populations, the extent of HetLanc needed to overcome the penalty from an additional degree of freedom in the association statistic has not been thoroughly quantified. Using extensive simulations of admixed genotypes and phenotypes, we find that controlling for and conditioning effect sizes on local ancestry can reduce statistical power by up to 72%. This finding is especially pronounced in the presence of allele frequency differentiation. We replicate simulation results using 4,327 African-European admixed genomes from the UK Biobank for 12 traits to find that for most significant SNPs, HetLanc is not large enough for GWASs to benefit from modeling heterogeneity in this way.

Individuals of admixed ancestries (for example, African Americans) inherit a mosaic of ancestry segments (local ancestry) originating from multiple continental ancestral populations. This offers the unique opportunity of investigating the similarity of genetic effects on traits across ancestries within the same population. Here we introduce an approach to estimate correlation of causal genetic effects (radmix) across local ancestries and analyze 38 complex traits in African-European admixed individuals (N = 53,001) to observe very high correlations (meta-analysis radmix = 0.95, 95% credible interval 0.93-0.97), much higher than correlation of causal effects across continental ancestries. We replicate our results using regression-based methods from marginal genome-wide association study summary statistics. We also report realistic scenarios where regression-based methods yield inflated heterogeneity-by-ancestry due to ancestry-specific tagging of causal effects, and/or polygenicity. Our results motivate genetic analyses that assume minimal heterogeneity in causal effects by ancestry, with implications for the inclusion of ancestry-diverse individuals in studies.

IntroductionRemote smartphone assessments of cognition, speech/language, and motor functioning in frontotemporal dementia (FTD) could enable decentralized clinical trials and improve access to research. We studied the feasibility and acceptability of remote smartphone data collection in FTD research using the ALLFTD Mobile App (ALLFTD-mApp).MethodsA diagnostically mixed sample of 214 participants with FTD or from familial FTD kindreds (asymptomatic: CDR®+NACC-FTLD = 0 [N = 101]; prodromal: 0.5 [N = 49]; symptomatic ≥1 [N = 51]; not measured [N = 13]) were asked to complete ALLFTD-mApp tests on their smartphone three times within 12 days. They completed smartphone familiarity and participation experience surveys.ResultsIt was feasible for participants to complete the ALLFTD-mApp on their own smartphones. Participants reported high smartphone familiarity, completed ∼ 70% of tasks, and considered the time commitment acceptable (98% of respondents). Greater disease severity was associated with poorer performance across several tests.DiscussionThese findings suggest that the ALLFTD-mApp study protocol is feasible and acceptable for remote FTD research.HighlightsThe ALLFTD Mobile App is a smartphone-based platform for remote, self-administered data collection.The ALLFTD Mobile App consists of a comprehensive battery of surveys and tests of executive functioning, memory, speech and language, and motor abilities.Remote digital data collection using the ALLFTD Mobile App was feasible in a multicenter research consortium that studies FTD. Data was collected in healthy controls and participants with a range of diagnoses, particularly FTD spectrum disorders.Remote digital data collection was well accepted by participants with a variety of diagnoses.

IntroductionThe use of implantable antibiotic beads has become a frequent treatment modality for the management of surgical site infections in human and veterinary medicine. The objective of this study is to describe the elution kinetics of five antibiotics from a commercially available calcium sulfate antibiotic delivery kit. A secondary goal was to compare elution concentrations with minimal inhibitory concentrations (MIC) for commonly encountered bacteria from the University of Florida’s veterinary microbiology laboratory database.MethodsCalcium sulfate powder was combined with amikacin, cefazolin, gentamicin, ampicillin/sulbactam, and meropenem. Triplicates of three antibiotic-loaded beads were immersed in 5 mL of phosphate-buffered saline (PBS) and kept at 37°C under constant agitation. Antibiotic-conditioned PBS was sampled at 14 time points from 1-h to 30 days and analyzed by liquid chromatography to determine the antibiotic concentration.ResultsAll beads eluted concentrations of antibiotics for the 30-day sampling period, except for ampicillin/sulbactam, with the most antibiotics being eluted within the first week. The concentration of antibiotics within the eluent within the first 3–9 days (3- and 5-mm beads, respectively) was greater than the MIC of common isolates. The 5 mm bead samples were superior in maintaining higher concentrations for a longer period, compared to the 3-mm beads.DiscussionCSH beads eluted antibiotics over the 30-day course of the study. Most of the antibiotic elution occurred within the first week and was maintained above the MIC of commonly encountered isolates. This information may be useful for clinical decision making for treatment of local infections encountered in practice.

Abstract Monoclonal IgG antibodies constitute the fastest growing class of therapeutics. Thus, there is an intense interest to design more potent antibody formats, where long plasma half-life is a commercially competitive differentiator affecting dosing, frequency of administration and thereby potentially patient compliance. Here, we report on an Fc-engineered variant with three amino acid substitutions Q311R/M428E/N434W (REW), that enhances plasma half-life and mucosal distribution, as well as allows for needle-free delivery across respiratory epithelial barriers in human FcRn transgenic mice. In addition, the Fc-engineered variant improves on-target complement-mediated killing of cancer cells as well as both gram-positive and gram-negative bacteria. Hence, this versatile Fc technology should be broadly applicable in antibody design aiming for long-acting prophylactic or therapeutic interventions.

Measuring selective attention in a speeded task can provide valuable insight into the concentration ability of an individual, and can inform neuropsychological assessment of attention in aging, traumatic brain injury, and in various psychiatric disorders. There are only a few tools to measure selective attention that are freely available, psychometrically validated, and can be used flexibly both for in-person and remote assessment. To address this gap, we developed a self-administrable, mobile-based test called "UCancellation" (University of California Cancellation), which was designed to assess selective attention and concentration and has two stimulus sets: Letters and Pictures. UCancellation takes less than 7 minutes to complete, is automatically scored, has multiple forms to allow repeated testing, and is compatible with a variety of iOS and Android devices. Here we report the results of a study that examined parallel-test reliability and convergent validity of UCancellation in a sample of 104 college students. UCancellation Letters and Pictures showed adequate parallel test reliability (r = .71-.83, p

BackgroundFrontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged

Abstract Background Intravitreal injection (IVI) of antibody biologics is a key treatment approach in ophthalmology. Pharmaceutical compounding and storage of prefilled syringes for IVI must take place without impairing the structure and function of the biologics. This study investigated the effect of withdrawing and storing the therapeutic antibody faricimab (Vabysmo, Roche, Basel, Switzerland) in the Zero Residual silicone oil-free, 0.2-mL syringe (SJJ Solutions, The Hague, the Netherlands). Methods To assess the effect of syringe withdrawal on faricimab, we compared samples from syringes prepared at day 0 with samples taken directly from faricimab vials. To assess the effect of syringe storage on faricimab, we kept prefilled syringes in the dark at 4 oC for 7, 14, or 37 days and compared samples from these syringes with day 0. We measured protein concentration (with spectrophotometry), stability and integrity (with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), size-exclusion chromatography (SEC), and melting temperature (Tm)), as well as binding of faricimab to its cognate antigens: vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang-2) (with enzyme-linked immunosorbent assay (ELISA)). Results Faricimab migrated in line with its expected molecular mass under both reducing and non-reducing conditions for all time points when analyzed with SDS-PAGE, without any sign of degradation products or aggregation. The SEC elution profiles were identical for all time points. There were slight variations in Tm for different time points compared to day 0 but without consistent relationship with storage time. ELISA did not detect differences in VEGF-A or Ang-2 binding between time points, and faricimab did not bind the neonatal Fc receptor. Conclusions Withdrawal and storage of faricimab in syringes for up to day 37 did not impair the structure and bi-specific binding properties of the therapeutic antibody.

Extreme weather events, such as tropical cyclones, often trigger population displacement. The frequency and intensity of tropical cyclones are affected by anthropogenic climate change. However, the effect of historical climate change on displacement risk has so far not been quantified. Here, we show how displacement can be partially attributed to climate change using the example of the 2019 Tropical Cyclone Idai in Mozambique. We estimate the population exposed to high water levels following Idai's landfall using a combination of a 2D hydrodynamical storm surge model and a flood depth estimation algorithm to determine inland flood depths from remote sensing images, factual (climate change) and counterfactual (no climate change) mean sea level, and maximum wind speed conditions. Our main estimates indicate that climate change has increased displacement risk from this event by approximately 12 600–14 900 additional displaced persons, corresponding to about 2.7 % to 3.2 % of the observed displacements. The isolated effect of wind speed intensification is double that of sea level rise. These results are subject to important uncertainties related to both data and modeling assumptions, and we perform multiple sensitivity experiments to assess the range of uncertainty where possible. Besides highlighting the significant effects on humanitarian conditions already imparted by climate change, our study provides a blueprint for event-based displacement attribution.

Attila Kerényi, Professor of Geography, was born in 1943 in Sátoraljaújhely. He earned a degree as a teacher of Geography and Biology in 1967. During the 1980s, he gained national and international scientific recognition for his research on soil erosion processes, and completed his candidate dissertation in 1984. In the 1990s, he became nationally acknowledged for his publications, textbooks and scientific books on landscape and environmental protection, and earned an academic doctorate title in the topic. His scientific work was recognized with numerous awards. In 2020, he was awarded the Officer’s Cross of the Hungarian Order of Merit in recognition of his several decades of research and teaching activities which have greatly contributed to the renewal of geography education at the University of Debrecen. On the occasion of his 80th birthday, his colleagues interviewed Professor Kerényi about his family, profession, achievements and the state of global environmental systems.

Bacterial and fungal superinfections are common in COVID-19, and early diagnosis can enable timely intervention. Serum calprotectin levels increase with bacterial, fungal, and viral infections. This study evaluated serum calprotectin as a diagnostic and prognostic tool for microbial superinfections in COVID-19. Serum samples from adult patients with moderate and severe COVID-19 were collected during hospitalization from 2020 to 2024. Calprotectin levels were measured using an enzyme-linked immunosorbent assay in 63 patients with moderate COVID-19, 60 patients with severe COVID-19, and 34 healthy individuals. Calprotectin serum levels were elevated in patients with moderate COVID-19 compared with controls, and these levels were further increased in the severe cases. Patients with severe COVID-19 and vancomycin-resistant enterococci (VRE) bacteremia had elevated calprotectin levels, but their C-reactive protein and procalcitonin levels were not increased. Fungal superinfections and herpes simplex virus reactivation did not change the calprotectin levels. A calprotectin concentration of 31.29 µg/mL can be used to diagnose VRE bloodstream infection with 60% sensitivity and 96% specificity. These data suggest that serum calprotectin may be a promising biomarker for the early detection of VRE bloodstream infections in patients with COVID-19.

Infectious diseases are associated with low iron levels and the induction of hepcidin, the primary protein regulating cellular iron export. Bone morphogenetic protein 6 (BMP6), a key regulator of hepcidin expression, has not yet been analyzed in the plasma of patients with systemic inflammatory response syndrome (SIRS) or sepsis. An analysis of 38 SIRS, 39 sepsis, and 78 septic shock patients revealed similar levels of BMP6 in sepsis and septic shock, which were lower compared to patients with SIRS and healthy controls. Plasma BMP6 levels did not correlate with procalcitonin and C-reactive protein levels in patients with SIRS or sepsis/septic shock. Neither bacterial nor SARS-CoV-2 infections affected plasma BMP6 levels. There was no difference in BMP6 levels between ventilated and non-ventilated patients, or between patients with and without dialysis. Vasopressor therapy did not alter BMP6 levels. Survivors had plasma BMP6 levels similar to non-survivors. Due to the high variability of plasma BMP6 levels, these analyses have limited clinical relevance. Iron, ferritin, and transferrin levels were known in at least 50% of patients but did not correlate with plasma BMP6 levels. In conclusion, this study showed normal BMP6 plasma levels in SIRS, which are reduced in patients with sepsis and septic shock. This suggests that the commonly observed increase in hepcidin levels and the decline in iron levels in SIRS, sepsis, and septic shock are not due to higher BMP6.

Neutrophils are critical immune cells in severe coronavirus disease 2019 (COVID-19). S100 calcium-binding protein A12 (S100A12) is highly expressed in neutrophils during acute inflammation. The aim of this study was to evaluate serum S100A12 levels as a diagnostic and prognostic tool in COVID-19. Serum samples of patients with moderate and severe COVID-19 were collected during 2020 to 2024. Enzyme-linked immunosorbent assay was used to measure serum S100A12 levels in 63 patients with moderate COVID-19, 60 patients with severe disease and 33 healthy controls. Serum S100A12 levels were elevated in moderate COVID-19 compared to controls and were even higher in severe cases. In moderate disease, serum S100A12 levels positively correlated with immune cell counts. While C-reactive protein and procalcitonin are established inflammation markers, they did not correlate with serum S100A12 levels in either patient cohort. Patients with severe COVID-19 and vancomycin-resistant enterococcus (VRE) infection had increased S100A12 levels. Elevated S100A12 levels were also observed in patients with herpes simplex reactivation. Fungal superinfections did not alter S100A12 levels. These data show that serum S100A12 increases in moderate and severe COVID-19 and is further elevated by VRE bloodstream infection and herpes simplex reactivation. Therefore, S100A12 may serve as a novel biomarker for severe COVID-19 and an early diagnostic indicator for bacterial and viral infections.