Search Results (239)

Latent, i.e., asymptomatic Toxoplasma gondii (T. gondii) infection might accelerate or modulate the aging process of cognitive and sensory functions involving pro-inflammatory immune responses. For evaluating a potential role of latent T. gondii infection in immunological aging, we determined T. gondii antibody levels and immunosenescence biomarkers in a cross-sectional sample of 584 volunteers aged 20–70 years from the Dortmund Vital Study (ClinicalTrials.gov Identifier NCT05155397) representing the regional population. One-hundred-sixty-one participants were seropositive, representing an overall 28% latent T. gondii seroprevalence, which did not significantly differ between males and females, but increased with age. Consequently, seropositive individuals were older than the seronegative participants. Latent T. gondii infection exhibited significant bivariate associations with the composite immune age index IMMAX pointing to accelerated immune aging in seropositive individuals. In addition, IMMAX increased with age and in males. However, associations of latent T. gondii infection with immunosenescence biomarkers disappeared when adjusting the analyses for sex and age. Moreover, the non-significant interaction between T. gondii status and age when predicting biomarker levels indicated that latent T. gondii infection did not modify the immunosenescence trend. Summarized, our results suggest that latent T. gondii infection is unlikely to modulate immune aging concerning cellular senescence in otherwise healthy working-age adults. Full article

Background: Advances in diagnosis and treatment have led to a growing population of adults with congenital heart disease (ACHD). Despite increasing life expectancy, their clinical needs—especially in older age—remain poorly defined. Cardiac and non-cardiac comorbidities are prevalent, and emerging evidence suggests accelerated biological aging compared to the general population. However, data on older patients and geriatric patients with CHD are limited. Objectives: This study aimed to characterize patients with CHD aged ≥50 years, focusing on functional status, comorbidities, sex-specific differences, and therapeutic patterns. Methods: The PATHFINDER-CHD Registry is a prospective, observational, multicenter registry enrolling patients with CHD with manifest heart failure (HF), HF history, or high HF risk. Data include anatomy, prior treatments, comorbidities, and medication use. Results: Among 1935 patients, 297 were ≥50 years old. Most had acyanotic CHD (62%); Tetralogy of Fallot (21%) was the most frequent diagnosis. A morphologic right systemic ventricle was present in 12%, and 5% had univentricular hearts. HF was manifest in 21%; 44% were classified as ACC/AHA stage B, 51% as stage C, yet 77% were in Perloff class I/II. Common cardiovascular comorbidities included aortopathy (55%), hypertension (37%), and arrhythmia (33%). Non-cardiac comorbidities included thyroid dysfunction (25%), renal impairment (18%), and neurological disease (13%). Sex-specific differences were observed. Despite HF burden, SGLT2 inhibitors and ARNIs were used in only 17% and 8.4%, respectively. Conclusions: Older patients with CHD represent a clinically complex cohort with high comorbidity burden. The findings support the concept of accelerated aging and emphasize the need for tailored interdisciplinary care strategies. Full article

Rigid wingsails are increasingly adopted for wind-assisted ship propulsion, with Symmetrically Cambered (SC) profiles identified as highly efficient for thrust generation. This study investigates installation layouts for multiple SC wingsails, focusing on aerodynamic interference that limits their performance. A fast 2D potential-flow panel method is employed and benchmarked against wind tunnel and 3D IDDES data. Two representative layouts are analyzed: triple-in-line (TL) and quad-in-parallel (QP). Layout optimization is performed using a genetic algorithm with distances between sails as design variables, constrained by the total installation span, at apparent wind angles (AWAs) of $60°$, $90°$, and $120°$. Results show that thrust generation decreases progressively from upstream to downstream sails due to interference effects, with penalties of about 4–6% in the TL and up to 28% in the QP layout. The optimization improves performance only for the TL layout at $60°$, while the QP layout shows negligible gains. Analysis of pressure distributions confirms that downstream sails suffer from reduced suction on the leading edge caused by upstream wakes. Overall, the TL layout demonstrates significantly higher aerodynamic reliability than the QP layout. These findings provide new insights into multi-sail configurations and highlight the importance of layout optimization in maximizing thrust efficiency. Full article

Systemic inflammation is gaining increasing attention as a potential predictive biomarker in immune checkpoint inhibition (ICI) for head and neck squamous cell carcinoma (HNSCC). Several well-established blood-based inflammatory markers are commonly used to estimate systemic inflammatory burden. However, their utility in predicting treatment outcomes in ICI for HNSCC remains unclear. This study aimed to evaluate the predictive value of the following inflammatory indices in patients with HNSCC receiving anti-PD-1 monotherapy: C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and the systemic immune inflammation index (SII). A total of 79 patients were included in this retrospective analysis. Optimal cutoff values were determined using receiver operating characteristic curve analysis to stratify patients into high- and low-inflammation groups. Chi-square tests were used to evaluate differences in treatment response. Progression-free survival (PFS) and overall survival (OS) were assessed and compared using Kaplan–Meier analysis and log-rank testing, alongside both univariable and multivariable Cox regression models. Elevated CRP levels were associated with a reduced disease control rate. In univariable analysis, patients in the high-inflammation groups showed significantly worse OS and PFS for all assessed inflammatory indices. In multivariable analysis, CRP and combined positive score remained independently significant predictors of both OS and PFS, while PLR was an independent predictor of OS. These findings suggest that a high level of systemic inflammation is associated with poorer outcomes during anti-PD-1 therapy in HNSCC. Among the evaluated indices, CRP stood out as an independent and clinically useful biomarker, providing a simple, widely available tool that could potentially serve as a practical instrument for clinicians in the management of HNSCC during anti-PD-1 treatment. Full article

Chronic kidney disease (CKD) before treatment and renal function decline during treatment are common in elderly patients receiving hypomethylating agents (HMAs) and venetoclax (VEN). This retrospective multicenter study of 130 newly diagnosed older acute myeloid leukemia (AML) patients evaluated the prognostic impact of renal function before and during the first treatment cycle. A total of 56 patients (43%) had CKD, and 49 (38%) developed acute kidney injury (AKI) during treatment. AKI occurrence was associated with laboratory tumor lysis syndrome (LTLS). CKD before treatment showed a trend towards a lower overall response rate (ORR, OR 0.5, p = 0.07) in multivariable analysis (MVA) and inferior relapse-free survival (RFS, HR 2.16, p = 0.06) in univariate analysis (UVA), but not MVA (RFS, HR 1.93, p = 0.15). CKD did not affect overall survival (OS) or event-free survival (EFS). AKI during HMA/VEN therapy was associated with significantly higher 30-day and 60-day mortality rates and emerged as an independent prognostic factor for inferior OS (HR 1.86, p = 0.01) and EFS (HR 1.81, p = 0.007). RFS did not differ significantly by AKI status. Sepsis was a more frequent cause of death in patients with vs. without AKI (33% vs. 5%). In conclusion, kidney function is a key prognostic factor in HMA/VEN-treated patients, warranting further study on treatment adjustments and supportive care. Full article

Public–Private Partnership (PPP) procurement is a relatively new approach in Nigeria’s housing sector. This study introduces a Fuzzy Risk Allocation Decision Model (FRADM) designed to address the complex and subjective nature of risk allocation in PPP-procured Mass Housing Projects (MHPs). A structured quantitative approach involving 40 purposively selected PPP housing experts was employed. Using a fuzzy synthetic evaluation (FSE) technique, critical risk factors were assessed based on partners’ risk management capabilities and allocation criteria. Constants (Ci) normalized the risk-carrying capacity indices (RCCIs) of both public and private sectors. Results show that risk attitude ranks highest among nine allocation criteria (MIS = 6.21), with the private sector demonstrating higher overall risk management capability. For instance, the availability of finance risk is optimally shared 53.48% to the private and 46.52% to the public sector. The FRADM was validated as reliable, practical, and replicable. Implications point to enhanced transparency, equitable risk-sharing, and support for SDG 11. The model is a strategic tool for decision-makers in PPP housing delivery in Nigeria and can inform similar efforts in other emerging economies. Further research should examine applications across other infrastructure sectors. Full article

Current temperature sensors require regular recalibration to maintain reliable temperature measurement. Photonic/quantum-based approaches have the potential to radically change the practice of thermometry through provision of in situ traceability, potentially through practical primary thermometry, without the need for sensor recalibration. This article gives an overview of the European Partnership in Metrology (EPM) project: Photonic and quantum sensors for practical integrated primary thermometry (PhoQuS-T), which aims to develop sensors based on photonic ring resonators and optomechanical resonators for robust, small-scale, integrated, and wide-range temperature measurement. The different phases of the project will be presented. The development of the integrated optical practical primary thermometer operating from 4 K to 500 K will be reached by a combination of different sensing techniques: with the optomechanical sensor, quantum thermometry below 10 K will provide a quantum reference for the optical noise thermometry (operating in the range 4 K to 300 K), whilst using the high-resolution photonic (ring resonator) sensor the temperature range to be extended from 80 K to 500 K. The important issues of robust fibre-to-chip coupling will be addressed, and application case studies of the developed sensors in ion-trap monitoring and quantum-based pressure standards will be discussed. Full article

Background: Mucosal immunity plays a pivotal role in preventing infections with SARS-CoV-2. While COVID-19 mRNA vaccines induce robust systemic immune responses in patients with inflammatory bowel disease (IBD), little is known about their efficacy in the mucosal immune compartment. In this sub-investigation of the ongoing STAR-SIGN study, we present the first analysis of mucosal immunity elicited by XBB.1.5 mRNA vaccines in immunocompromised patients with IBD. Methods: IgG and IgA antibodies targeting the receptor-binding domain of the SARS-CoV-2 JN.1 variant were quantified longitudinally in the saliva of IBD patients using the multiplex immunoassay MultiCoV-Ab. Antibody levels were quantified before and 2–4 weeks after vaccination with XBB.1.5 mRNA vaccines. All patients previously received three doses with original COVID-19 vaccines. Results: Mucosal IgG antibodies were readily induced by XBB.1.5 mRNA vaccines (p = 0.0013 comparing pre- and post-vaccination levels). However, mucosal IgA levels were comparable before and after vaccination (p = 0.8233). Consequently, mucosal IgG and IgA antibody levels correlated only moderately before and after immunization (pre-vaccination: r = 0.5294; p = 0.0239; post-vaccination: r = 0.4863; p = 0.0407). Contrary to a previous report in healthy individuals, vaccination did not induce serum IgA in patients with IBD (p = 0.5841 comparing pre- and post-vaccination levels). These data suggest that COVID-19 mRNA vaccines fail to elicit mucosal IgA in patients with IBD. Conclusions: Since mucosal IgA plays a pivotal role in infection control, the lack of IgA induction indicates that patients lack sufficient protection against SARS-CoV-2 infections which warrants the development of mucosal COVID-19 vaccines. Full article

The Adaptive Skip-gram (AdaGram) algorithm extends traditional word embeddings by learning multiple vector representations per word, enabling the capture of contextual meanings and polysemy. Originally implemented in Julia, AdaGram has seen limited adoption due to ecosystem fragmentation and the comparative scarcity of Julia’s machine learning tooling compared to Python’s mature frameworks. In this work, we present a Python-based reimplementation of AdaGram that facilitates broader integration with modern machine learning tools. Our implementation expands the model’s applicability beyond natural language, enabling the analysis of scientific notation—particularly chemical and physical formulas encoded in LaTeX. We detail the algorithmic foundations, preprocessing pipeline, and hyperparameter configurations needed for interdisciplinary corpora. Evaluations on real-world texts and LaTeX-encoded formulas demonstrate AdaGram’s effectiveness in unsupervised word sense disambiguation. Comparative analyses highlight the importance of corpus design and parameter tuning. This implementation opens new applications in formula-aware literature search engines, ambiguity reduction in automated scientific summarization, and cross-disciplinary concept alignment. Full article

Microfluidic devices have emerged as a pivotal in vitro technology for axon outgrowth studies, facilitating the separation of the cell body from the neurites by geometric constraints. However, traditional microfabrication techniques fall short in terms of scalability for large-scale production, hindering widespread application. This study presents the development of foil-based cell culture chips, made of polyethylene terephthalate and in-house formulated ultraviolet curable liquid resin by high-throughput roll-to-roll (R2R) manufacturing. Here, two microchannel designs were tested to optimize manufacturing quality and assess the neurite outgrowth behavior. The fabricated neuron-foil chips demonstrated biocompatibility and supported neurite outgrowth within microchannels under static cell culture conditions. Furthermore, fluidic flow, oriented either perpendicular or parallel to the microchannel direction, was applied to enhance the biological reproducibility within the neuron-foil chips. These findings suggest that R2R manufacturing offers a promising approach for the high-throughput production of biocompatible microfluidic devices, advancing their potential application in modeling neurological diseases within the biomedical industry. Full article

Background/Objectives: In orthopedic (diabetic) foot surgery, the serum C-reactive protein (CRP) level is frequently measured not only as a diagnostic tool, but also as a control inflammatory marker in the follow-up of postoperative surgical-site infections (SSIs) Methods: We investigated the predictive value of the post-debridement routine (control) serum CRP level in adult (diabetic) patients with an SSI in the foot. We excluded community-acquired (diabetic foot) infections and focused on the predictive accuracy of routine (control) CRP measurements in terms of ultimate therapeutic failures. Results: The median pre- and postoperative CRP levels were 25 mg/L and 8.8 mg/L, respectively. In group comparisons and multivariate assessment, neither the immediate (relative and absolute) drop in the serum CRP level, nor its values between 5 and 8 weeks and between 11 and 14 weeks predicted the failure risk of 19%. In contrast, in cases of surprisingly elevated CRP levels, this finding leads to unnecessary radiological (median costs approximatively USD 200), clinical, microbiological urinary sample (median costs USD 50), and laboratory (one CRP sample USD 10) exams. These additional exams also likely prolong the duration of hospitalization by one to two days (e.g., whilst awaiting the microbiological results) and often generate unnecessary consultations among internist and/or infectious diseases experts (USD 50). Conclusions: Routine, postoperative CRP monitoring during the treatment of established orthopedic (diabetic) foot SSIs is unnecessarily costly, and should be avoided in favor of clinical surveillance of the postoperative evolution. Full article

Little is known about the dysbiosis of the gut microbiome in patients with mild cognitive impairment (MCI) potentially at risk for the development of Alzheimer’s disease (AD). So far, only cross-sectional differences and not longitudinal changes and their prognostic significance have been in the scope of research in MCI. Therefore, we investigated the ability of longitudinal taxonomic and functional gut microbiome data from 100 healthy controls (HC) to predict the progression from normal cognition to MCI over a 4-year follow-up period (4yFU). Logistic regression models were built with baseline features that best discriminated between the two groups using an ANOVA-type statistical analysis. The best model for the discrimination of MCI converters was based on functional data using Gene Ontology (GO), which included 14 features. This model achieved an area under the receiver operating characteristic curve (AUROC) of 0.84 at baseline, 0.78 at the 1-year follow-up (1yFU), and 0.75 at 4yFU. This functional model outperformed the taxonomic model, which included 38 genera features, in terms of descriptive performance and showed comparable efficacy to combined analyses integrating functional, taxonomic, and clinical characteristics. Thus, gut microbiome algorithms have the potential to predict MCI conversion in HCs over a 4-year period, offering a promising innovative supplement for early AD identification. Full article

Background: Defects of the foot and ankle area pose a significant challenge for both patients and surgeons. While the primary objective of microvascular free flap reconstructions of lower leg defects is limb preservation, there should be an effort to obtain the best functional and aesthetic results possible and to restore the patient’s quality of life. The aim of this study was to investigate the long-term post-operative functional outcome, health-related quality of life, scar quality, and aesthetic satisfaction in patients following microsurgical reconstructions of defects of the foot and ankle area. Methods: We conducted a monocentric, controlled cohort study of adult patients who underwent microsurgical reconstructions for defects of the foot and ankle area between 2006 and August 2022 at our department. As a control, we recruited healthy individuals. Patient-Reported Outcome Measures questionnaires were used to assess long-term results regarding functionality (LEFS: Lower Extremity Functional Scale), health-related quality of life (SF-36: Short-Form 36 Health Survey Questionnaire), scar quality (PSAS: Patient Scar Assessment Scale), aesthetic satisfaction (Aesthetic Likert Scale), pain at rest and activity (10-point Numeric Rating Scale) and usage of footwear. Results: Of the 55 potential patients who had received microvascular free flaps for reconstructions of ankle and foot defects and were eligible for study inclusion, 13 (23.6%) agreed to participate in this study. The study cohort consisted of 84.6% male subjects and the mean follow-up period was 8.6 years (±5.2). Significant moderate limitations were observed with regard to physical function of the lower extremity (LEFS: 42.5 ± 20.5, p = 0.002). Significant limitations were found in the SF-36 subscales of pain (55.8 ± 34.5, p = 0.019), physical functioning (55.0 ± 29.7, p = 0.013), and physical role functioning (38.5 ± 44.0, p = 0.006). The study yielded favorable outcomes with regard to aesthetic satisfaction (14.3 ± 4.4) and scar quality (23.5 ± 13.5). Out of all the patients, 61% were required to wear orthopedic shoes or insoles. Conclusions: Patients undergoing microsurgical reconstructions for ankle and foot defects experience moderate long-term physical limitations and persistent pain during activity. Furthermore, we observed a significant long-term impact on specific physical domains of health-related quality of life, whereas mental health seems less affected. Full article

To push the boundaries of confocal microscopy beyond its current limitations by predicting sensor responses for complex surface geometries, we build digital twins using three rigorous models, the finite element method (FEM), Fourier modal method (FMM), and boundary element method (BEM) to model light–surface interactions. Fourier optics are then used to calculate the sensor signals at the back focal plane and at the detector. A 3D illumination model is applied to 2D periodic structures for FEM and FMM modelings and to 3D aperiodic structures for BEM modeling. The lateral and vertical scanning processes of the confocal microscope are achieved through focal-point shifts of the objective, using plane-wave illuminations with varying incident and azimuthal angles. This approach reduces the need for repeated, time-intensive rigorous simulations of the scattering process when a fine scanning is desired. Furthermore, we give an in-depth description of a novel confocal microscopy method using FMM. For rectangular grating surfaces, the three models yield identical, highly accurate results, as validated by measured results. Simulations of the instrument transfer function, tilted gratings, and gratings with edge rounding offer insights into some experimentally observed effects. This research therefore provides a promising approach for correcting systematic errors in confocal microscopy. Full article