Search Results (1,054)

Background/Objectives: Hereditary transthyretin amyloidosis (ATTRv) is a heterogeneous multisystem disease caused by pathogenic transthyretin gene (TTR) variants. Increased awareness and availability of disease-modifying therapies have resulted in increased diagnoses, even in previously nonendemic regions. The aim of this study was to update the nationwide Austrian ATTRv registry by characterizing the clinical, genetic, and regional distribution of TTR variants. Methods: This multicenter, observational analysis examined ATTRv cases diagnosed in Austria between 2014 and 2025. Individuals were included according to the presence of pathogenic or likely pathogenic variants or variants of uncertain significance (VUSs) in TTR. Results: In total, 100 individuals were identified, including symptomatic and asymptomatic carriers. Compared with our previously presented data, the number of genetically confirmed ATTRv cases has more than doubled. Twenty-three TTR variants were identified. The most frequent pathologic variants were p.His108Arg (26%), p.Ile127Phe (11%), and p.Thr69Ile (9%), while p.Val113Leu (9%) represented the most frequent VUS. Significant regional clustering of p.His108Arg was documented in Vienna and Lower Austria. Other findings included a rising number of p.Val142Ile carriers and phenotypically relevant VUSs in 20 patients. Conclusions: Our findings revealed an increasing detection rate of ATTRv in a nonendemic European region. These data underscore the importance of multidisciplinary evaluation, cascade testing, and long-term monitoring to improve early diagnosis and timely management in hereditary amyloidosis. Full article

Plastics are highly persistent materials, and their environmental degradation can potentially exacerbate, rather than alleviate, pollution. The degradation of plastic materials releases toxic monomers and additives, such as bisphenol A (BPA), styrene, and dioxins, which are more reactive, harmful, and persistent than intact plastics. With half-lives ranging from weeks to decades, they bioaccumulate in food chains, disrupt ecosystems, and contribute to endocrine disruption and mutagenicity. Natural degradation pathways, like microbial metabolism and photodegradation, are slow and incomplete, often leaving toxic intermediates such as microplastics. Artificial strategies, including bioremediation and advanced oxidation processes (AOPs), show potential to address the problems of plastic pollution but face additional challenges like secondary pollution and scalability. Sustainable alternatives, including bioplastics and renewable non-plastic substitutes, present promising solutions. However, their widespread adoption is hindered by challenges such as high production costs and the need for specific conditions to facilitate degradation, necessitating further research and development. A combined approach of reducing plastic production, advancing recycling, and implementing effective remediation strategies is critical to mitigating plastic pollution’s long-term impacts on ecosystems, biodiversity, and human health. This review provides a critical analysis of the current understanding of plastic degradation processes and the toxic byproducts they generate. It highlights the paradox wherein increased degradability may exacerbate environmental hazards. Additionally, the review assesses innovative, eco-friendly alternatives designed to mitigate plastic pollution. Full article

Background/Objectives: The transradial approach is widely used for vascular access in many disciplines. Radial artery occlusion (RAO) is a frequent sequel, and hand/arm pain affects 7.8% of patients. We aimed to elucidate whether RAO or ulnar artery occlusion (UAO) causes impaired neural blood flow and, thus, if symptoms may be attributable to claudication or nerve damage. Methods: Forty healthy volunteers (73% female), with a mean age of 38 years and without clinical or sonographic signs of carpal tunnel syndrome, were included. All underwent a standardized ultrasound examination (Aplio i800 and i22LH8 linear transducer, Canon Medical Systems) of the forearm, investigating the median nerve and its intraneural blood flow as well as the vascular status of the limb. The radial and ulnar arteries were then sequentially compressed, while changes to intraneural blood flow were noted. Thereafter, the (reverse) Barbeau test and the (inverse) modified Allen Test (MAT) were performed. Results: Simulated RAO and UAO halted intraneural blood flow in 65% and 62.5% of individuals, respectively. A total of 32.5% of participants reported discomfort in the hand/arm. Absent flow during occlusion was found at a significantly higher rate in symptomatic individuals. MAT and inverse MAT were abnormal (>10 s) in 17.5% and 7.5% of patients. Barbeau and reverse Barbeau produced type D results in 15% and 20%, respectively. Conclusions: Both simulated RAO and UAO caused the cessation of intraneural blood flow of the median nerve in two-thirds of participants, and a large proportion reported symptoms. MAT and Barbeau tests did not seem to be useful in predicting impaired neural blood flow. Full article

Many cancer-associated deaths result from metastases rather than primary tumors. Growing evidence suggests that DNA methylation alterations are crucial for inducing a plastic phenotype that allows cancer cells to adapt to the metastatic microenvironment. Brain metastases of melanoma (MBM) and glioblastoma (GB) share a neuroectodermal origin and the brain as tissue of residence, but their epigenetic regulation is poorly understood. Aiming at elucidating shared and tumor-distinct features, we analyzed the methylation of MGMT regulatory elements. We focused on MGMT because MGMT promoter methylation is used as a predictive marker for temozolomide response in GB, but its role in MBM has been discussed controversially. By targeting 12 CpG dinucleotides (CpGs) in the promoter, 68 CpGs in intergenic enhancers, and 31 CpGs in intragenic enhancers, we identified shared features, including an L-shaped relationship between promoter methylation and MGMT protein expression and an inverse L-shaped relationship between intragenic enhancer methylation and MGMT protein expression. GB exhibited higher methylation, particularly in promoter and intergenic enhancers, and stronger associations between methylation and overall survival than MBM. These results highlight both conserved and tumor-specific MGMT regulation, reflecting the complexity of epigenetic control in brain malignancies and emphasizing divergent evolution between MBM and GB. Full article

Background: Developing an evidence base for physiotherapy programs for patients with Cerebral Palsy (CP) requires an understanding of the microscopic and metabolic processes in striated muscle. The gracilis muscle represents a logical object of study due to the significant morphological changes in individuals with cerebral palsy. This research aims to study morphological and biochemical alterations in the gracilis muscle depending on the severity of motor impairments in CP patients. Methods: The cross-sectional study included 24 patients stratified by the severity of motor impairment. Intraoperative gracilis muscle samples were obtained during tenomyotomies. Nutritional status of patients, morphometric, and biochemical parameters were evaluated. Results: Initial body mass and Quetelet index (p = 0.02) were lower in GMFCS V patients (p = 0.01) compared to GMFCS IV and GMFCS II-III. Muscle tissue predominated in histological samples of GMFCS II-III and GMFCS V patients (p = 0.79), while connective tissue content was higher in the GMFCS IV group (p = 0.03). Strong, fast-twitch, anaerobic fibers (p = 0.761) with reduced creatine phosphokinase activity (p = 0.012) were more frequently observed in the intraoperative samples of GMFCS V patients. Low creatine phosphokinase activity was revealed in children in the GMFCS V group (p = 0.012). Conclusions: The structural and metabolic abnormalities observed in gracilis muscle of patients with spastic cerebral palsy indicates profound functional muscular dysfunction, representing one of the factors limiting children’s motor ability. The morphological and biochemical alterations in the striated muscle of CP children correlate with severity of motor dysfunction conditioned by the primary upper motor neuron disorders. Less significant changes in muscles in ambulatory children reflect favorable basis for physical therapy. Full article

Teacher shortages have become a global phenomenon, affecting educational systems across many countries. However, the strategies adopted to address it differ considerably. This study gives a first, detailed account of the reasons and effects of teacher shortages in Austria. For this purpose, a number of documents were analysed: 120 newspaper reports (to mirror the public debate), 43 parliamentary questions and ministerial responses (to mirror the policy debate), and relevant national statistics (to mirror the current situation and remedial measures by quantitative indicators). This allows a first comprehensive synthesis of public debate, policy developments, and research—comparable to country reports for other countries but currently missing for Austria. The findings of these multiple sources reveal that, following a period in the early 2000s with sufficient applicants for teaching positions, Austria gradually experienced an emerging teacher shortage. Initial responses were ad hoc, relying on measures such as increased overtime and the employment of underqualified teaching staff. More comprehensive strategies were introduced only in 2022, including a public image campaign for the teaching profession, reforms in teacher education, and new pathways for career changers. The study concludes by discussing implications for the teaching profession, school practice, and the teacher education system. Full article

Mechanical recycling of polypropylene (PP) is constrained by the heterogeneous properties of post-consumer feedstocks. Melt flow rate (MFR) is a key property relevant to processing, and it varies widely across packaging grades, which limits the quality and substitutability of recyclates. This study evaluates near-infrared hyperspectral imaging (NIR-HSI) for predicting MFR in post-consumer PP packaging. Eighty-two rigid PP samples (46 white, 36 clear) with MFR values between 2 and 108 g 10 min⁻¹ were collected from an Austrian material recovery facility. Thirteen different linear and non-linear regression models were examined using median and pixel-wise aggregated spectral representations across the samples. Tree-based models consistently achieved best performances with R² = 0.85, RMSE = 12.4 g 10 min⁻¹ on white samples and R² = 0.61, RMSE = 14.0 g 10 min⁻¹ on clear samples. On the combined sample set, R² = 0.66 and RMSE = 17.3 g 10 min⁻¹ were reached. Informative spectral regions correspond to typical bands of PP. Binary classification at different thresholds (6, 12, 30, 60 g 10 min⁻¹) were also examined and achieved balanced accuracies of 0.82–0.92. Median spectral representations consistently outperformed pixel-wise aggregation. Results demonstrate that NIR-HSI can support grade-directed sorting of post-consumer PP, particularly for opaque white samples, though heteroscedasticity at high MFR values and irreducible outliers represent inherent limitations. Full article

Introduction: Radical Antegrade Modular Pancreatosplenectomy (RAMPS) was developed to improve surgical radicality for left-sided pancreatic ductal adenocarcinoma (PDAC). Although widely accepted, the optimal surgical approach—open versus minimally invasive (MI)—is still being debated. Methods: We conducted a multicenter retrospective cohort study across three Austrian centers, including all patients undergoing RAMPS between 2016 and 2023 indicated for suspected (pre-)malignant pancreatic lesions. Patients were grouped based on the surgical approach (MI vs. open). The primary endpoints were resection margin status and lymph node yield following PDAC resection. Secondary outcomes included survival for PDAC patients and postoperative complications; non-PDAC resections were also taken into account. Results: A total of 57 patients were included, of whom 34 had PDAC. In PDAC patients, the rate of tumor-free margins and the median lymph node yield were equivalent between the MI and open approaches (R0 rate: MI 92.9% vs. open 85%, p = 0.484; median lymph node yield: MI 16 (IQR 10–23) vs. open 19 (IQR 15–25), p = 0.314). Two-year overall survival was also comparable (MI: 71.6% vs. open: 66.4%, p = 0.479). Postoperative outcomes at 90 days, like CR-POPF and major complications (Clavien–Dindo ≥ IIIa), did not differ between the two approaches. MI-RAMPS showed non-significant favorable trends in median length of stay (p = 0.093) and likelihood of receiving adjuvant chemotherapy (p = 0.075). Conclusions: In our experience, MI-RAMPS demonstrates oncologic equivalence and similar early postoperative outcomes to open RAMPS, with potential advantages such as shorter length of stay and likelihood of receiving adjuvant chemotherapy. Full article

The selection of appropriate signal labels is a central consideration in electrochemical biosensing as it directly determines the achievable detection limits, dynamic range, and overall analytical performance. Conventional electroactive labels require low operating potentials, fast electron-transfer kinetics, and reliable attachment to electrode surfaces or recognition elements. Despite their extensive use, these labels present notable challenges for point-of-care applications, particularly in the detection of small molecules where target binding does not inherently generate a measurable electrochemical output. As a result, most sensing architectures depend on externally added redox reporters, introduced either freely into solution or covalently linked to recognition structures, which increases assay complexity and limits scalability. These limitations have motivated the transition toward energy-based electrochemical signal pathways, such as the hydrogen evolution reaction (HER), oxygen reduction reaction (ORR), and water-splitting reactions. These reactions provide intrinsic electrochemical outputs that eliminate the need for synthetic redox mediators and can operate as built-in catalytic signal sources. Their integration into biosensing platforms simplifies assay design, enhances robustness, and broadens compatibility with diverse target molecules. This review outlines the mechanistic basis connecting HER/ORR/water-splitting reactions to signal generation in biosensors and highlights material design principles that enable their use as reagentless and label-free transduction strategies. Compared with traditional electroactive labels, energy-driven approaches offer simplicity, reduced cost, faster operation, and improved suitability for commercial translation. By establishing a unified framework for energy-based electro-recording mechanisms, this review aims to promote the development of next-generation bioanalytical methods that operate without electroactive labels and expand the applicability of electrochemical biosensing across various domains. Full article

In spite of the preeminence of Nicolas Poussin as one of the great classicist painters in seventeenth century France, some of his earlier work has not received the attention it deserves. This article turns to his Realm of Flora (c. 1631) in order to study some salient aspects that have been neglected. First, Poussin followed what I call the “Botanical Renaissance.” This study foregrounds which elements he followed and which he transformed. In conjunction with this movement, this article highlights Poussin’s uses of Platonic philosophy through the works of Marsilio Ficino. The importance of Sol in his works is replicated here in the power of the solar rays to nourish nature. Thirdly, we consider the many metamorphoses in the work and their significance. Finally, we turn to the circle in the heavens with the planets, stars and twelve constellations and contrast it with the more elongated circle of the metamorphic figures on Earth in order to highlight the relation between zodiacal signs/stars and the flowers depicted. The circular constellations contrast with an elongated, even elliptical shape of the figures on Earth, perhaps to suggest the conflict, prevalent at the time, between the Copernican heliocentric and circular system with Kepler’s elliptical view of the path of the heavenly planets. Full article

Background/Objectives: The aim of this study is to investigate how the joint, the number and the type of prior revision surgeries influence the diagnostic thresholds for synovial cell count for patients who undergo their first total hip or knee arthroplasty revision compared to re-revisions, as different cutoffs might substantially influence treatment courses. Methods: In this retrospective single-center register analysis, data from 214 revised THAs (total hip arthroplasties) and TKAs (total knee arthroplasties) were collected, of which 103 (48.1%) have so far undergone at least one revision surgery. Diagnosis was based on the EBJIS criteria, and we identified 163 (76.2%) septic and 51 (23.8%) aseptic cases. Data on synovial cell count were collected and analyzed for their diagnostic accuracy and optimal cutoffs. For re-revisions, a covariate-adjusted ROC (receiver operating characteristic) for the joint, type of previous surgery and number of surgeries was created. Results: We found no significant differences in cell counts between patients before first revision compared to those undergoing re-revision for septic (p = 0.40) and aseptic indications (p = 0.84). The overall diagnostic accuracy was high for all re-revision cases, with a sensitivity of 0.86, specificity of 0.91, AUC (area under the curve) of 0.92, at an optimal cutoff value of 2439.50 G/L. As for re-revised hip joints, the optimal cutoffs were higher compared to knee joints (2439.5 G/L vs. 2626.5 G/L, hip AUC = 0.90, knee AUC = 0.93, p = 0.14). Furthermore, the AUCs for cell count differed significantly depending on the type of previous surgery in re-revision (p = 0.03). The covariate-adjusted analysis showed no significant differences compared to the unadjusted analysis. Conclusions: Cell count remains reliable for diagnosing periprosthetic joint infection in patients with prior revisions, with minor threshold variations from the EBJIS (European Bone and Joint Infection Society) criteria. While the type of preceding revision affects accuracy, the diagnostic value remains consistently high overall. Full article

Model-Based Systems Engineering (MBSE) originated in aerospace engineering and has emerged as a promising approach in other fields for designing, analyzing, and managing complex interdisciplinary systems throughout their entire life cycle. While MBSE is applicable to various engineering domains, its applications remain closely tied to software engineering. As software becomes a critical component of physical systems, such as vehicles, appliances, and production plants, bridging the gap between software engineering and other disciplines, such as mechanical, electrical, and civil engineering, becomes essential. Despite its potential, MBSE is still in its early stages when it comes to integrating executable models of physical systems into engineering environments. The purpose of this research is to assess the present capabilities of MBSE by identifying existing missing links, thereby enabling prospective users to make well-informed decisions about its integration into organizational processes. In this analysis, it is important to have a comprehensive view of the complexity of MBSE across different disciplines to obtain an overall picture. In addition to identifying open challenges, we present three critical gaps in the MBSE practice through a comprehensive demonstration case: limited tool interoperability and model integration, modeling language limitations, and dependence on a specialized workforce. Current studies largely view MBSE as the most applicable and effective for the design phase of the system life cycle. Yet, to capture MBSE in its entirety, its principles must be applied throughout the whole system life cycle. Full article

Phosphate-induced vascular calcification in chronic kidney disease is linked to cardiovascular mortality. This calcification process involves vascular smooth muscle cells (VSMCs), which can promote a pro-calcific environment in the vascular wall. However, the mechanisms underlying a putative phosphate sensing of VSMCs to modulate pro-calcific signaling are insufficiently clarified. In mammals, three isoforms of the inositol hexakisphosphate kinase (IP6K) exist, which have been implicated in cellular phosphate homeostasis. Therefore, each IP6K isoform was silenced in calcifying primary human aortic VSMCs. IP6K1 and IP6K2 mRNA expression were increased in calcifying VSMCs. Silencing of either IP6K1 or IP6K2 ameliorated phosphate-induced pro-calcific markers expression and VSMC calcification. IP6K3 mRNA expression was not modified during calcifying conditions, but IP6K3 silencing still resulted in some anti-calcific effects. Mechanistically, the IP6K product 5-IP7 may act as a potent inhibitor of AKT kinase signaling. Accordingly, pro-calcific conditions induced only transient AKT phosphorylation, and IP6K2 silencing increased AKT phosphorylation in calcifying VSMCs. In turn, AKT inhibition blunted the protective effects of IP6K2 knockdown, while serum- and glucocorticoid-inducible kinase 1 (SGK1) inhibition restored these effects. These observations indicate a role for IP6Ks during phosphate-induced VSMC calcification, which could be mediated by an altered balance between AKT and SGK1 signaling. Full article

This perspective provides a multidisciplinary assessment of the use of lithium-ion batteries from electric vehicles (EVs) for second-life applications, motivated by the need to improve resource efficiency, reduce environmental impacts, and support a circular battery economy. Second-life deployment requires the integrated consideration of technical performance, legal compliance, and economic viability. The analysis combines a technical evaluation of battery aging mechanisms, operational load effects, and qualification strategies with a legal assessment of the EU Batteries Regulation (EU) 2023/1542 and an economic analysis of market potential and business models (BM). From a technical perspective, the limitations of State of Health (SOH) as a standalone indicator are demonstrated, highlighting the need for multiple health indicators and degradation-aware qualification. A scalable two-step qualification approach, combining qualitative inspection with a standardized quantitative measurement protocol, is discussed. From a legal perspective, regulatory requirements and barriers related to repurposing, waste classification, and conformity assessment are analyzed. From an economic perspective, business model patterns and market dynamics are evaluated, identifying Automated Guided Vehicles (AGVs) and industrial Energy Storage Systems (ESSs) for renewable firming as particularly promising applications. The paper concludes with recommendations for action and key research needs to enable safe, economically viable, and legally compliant second-life deployment. Full article

This study investigates the geological, mineralogical, and geochemical features of the Alday ore occurrence (Central Kalba, East Kazakhstan) and aims to identify indicators of rare-metal mineralization, with lithium considered to be one of its principal components. In this study, the structural–stratigraphic position of the occurrence is refined; three series of albite–spodumene pegmatites are identified; the compositions of the ore-bearing schists and the granitoids of the Kunush and Kalba complexes are compared; and the role of metasomatic alteration in the concentration of Li, Ta, Nb, Be, and Sn is established. The plagiogranites and dikes of the Kunush complex are characterized by Li anomalies (up to 306 g/t), Ta (up to 64 g/t), and a fractionated REE spectrum (La/Yb up to 108). In addition, the following predictive criteria are formulated: the presence of tectonically disrupted dikes in the Kunush complex with Na₂O/K₂O > 4, the presence of albite and muscovite alteration zones, and the presence of ladder-type spodumene-bearing pegmatites controlled by northwest-trending faults. The ⁴⁰Ar/³⁹Ar muscovite age of the Alday pegmatites (~292 Ma) aligns with the age range of the Kalba granite complex. Based on the main principles of rare-metal pegmatite generation, it is determined that the Tochka pegmatites were formed during the fluid–magmatic fractionation of magma in large granitic reservoirs of the Kalba complex. The Karagoin–Saryozek zone—located between several large granite massifs of the Kalba complex, where host rocks function as a roof—may be promising for investigating rare-metal pegmatite mineralization. Full article