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Article
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Semun Galimam

,

Naleesha Habib

,

Madhumitha Sangeetham Krishnan Asokumar

,

Ruchir Chavada

Abstract: Background: Skin grafts including split-thickness skin grafts (SSG) and full-thickness skin grafts (FTSG) are widely used in reconstructive surgery. Infection following grafting can compromise graft take and prolong hospitalisation, yet contemporary cohort data describing incidence, microbiology and graft-specific risk factors remain limited. Methods: We conducted a retrospective observational cohort study of 977 consecutive skin graft procedures performed in 116 patients at two hospitals in New South Wales, Australia, between 1 July 2021 and 13 August 2024. Post-graft infection was defined as a clinician-diagnosed graft site infection with microbiological confirmation. Infection incidence was estimated with exact 95% confidence intervals. Associations between graft characteristics and infection were explored using chi-square testing and binomial regression to estimate relative risks. Length of stay (LOS) was assigned to the index admission corresponding to each procedure and analysed using negative binomial regression to account for overdispersion. Results: Among 977 graft procedures, 66 infections occurred, giving an overall infection incidence of 6.8% (95% CI 5.3–8.5%). Median LOS was substantially longer in infected cases than non-infected cases (34 vs 3 days, p < 0.001). Full-thickness grafts to the face (RR 0.083, 95% CI 0.008–0.827) and nose (RR 0.038, 95% CI 0.004–0.378) were associated with a reduced incidence of infection, although estimates were imprecise because of sparse data. Among infections, Staphylococcus aureus accounted for approximately 47% of cases and Pseudomonas aeruginosa for approximately 20%. In a nested antimicrobial audit cohort of 111 split-thickness skin graft procedures, peri-operative prophylaxis was common, postoperative antibiotics were frequently prescribed, and postoperative antibiotic prescribing was not associated with reduced infection, although the analysis was underpowered. Conclusions: Post-graft infection occurred in 6.8% of procedures. This rate is comparable with contemporary literature and was associated with substantial morbidity. S. aureus and P. aeruginosa predominated. These findings support consideration of targeted preventive strategies, microbiology-informed empiric therapy and antimicrobial stewardship, while highlighting the need for prospective studies with more comprehensive risk adjustment.

Article
Public Health and Healthcare
Health Policy and Services

Minoti Ganguli

,

Josue Patien Epane

,

Karl McCleary

,

Nichola Seaton Ribadu

Abstract: Background: During menopause, many women deal with a "double whammy" of hot flashes and depression. While we know each issue drives up doctor visits and costs, we still don't have a clear picture of the total financial toll when they occur together. Using nationwide U.S. data to break down this combined economic burden is an area that's wide open for more research. Methods: We conducted a retrospective cross-sectional analysis of pooled 2017–2022 Medical Expenditure Panel Survey (MEPS) data, including 22,042 U.S. women. Participants were categorized as VMS with depression, VMS without depression, or no VMS/no depression (reference). Outcomes included total annual healthcare expenditures, outpatient, emergency, and prescription expenditures, and healthcare utilization (outpatient visits, emergency department visits, inpatient hospitalizations). Survey-weighted generalized linear models with a gamma distribution and a log link were used for expenditures. In contrast, survey-weighted linear and count models were used for utilization, adjusting for demographic, socioeconomic, insurance, regional, year, and comorbidity burden. Results: Among 22,042 women, 529 (2.4%) had VMS with depression, and 268 (1.3%) had VMS without depression. The sample included 22,042 women with no VMS or depression, 529 with VMS and depression, and 268 with VMS without depression. Women with VMS and depression had the highest annual healthcare expenditures compared with women without VMS or depression. In multivariable analyses, women with VMS and depression had healthcare costs approximately 1.90 times higher than the reference group (β=0.64, SE=0.08, p< 0.0001; $11,404 vs. $6,002). Those with VMS without depression faced costs approximately 55% higher (β = 0.44, SE = 0.10, p < 0.0001; $9,303 vs. $6,002). Outpatient costs were also significantly higher among women with VMS and depression (β=0.31, SE=0.05, p< 0.0001), corresponding to approximately 36% higher outpatient costs over those with no VMS/no depression, respectively; $2,354 vs. $1,730). Women with both vasomotor symptoms (VMS) and depression had prescription drug spending that was about 2.61 times higher than those without VMS or depression (β = 0.96, SE = 0.13, p < 0.0001; $3.452 vs $1,323). Emergency department costs did not differ significantly between groups. Older age, unemployment, and higher comorbidity burden were also associated with increased healthcare costs. In utilization models, women with VMS and depression had 4.80 additional outpatient visits per year (SE = 0.50, p < 0.0001) and higher emergency department visit rates (β = 0.26, SE = 0.11, p < 0.05), corresponding to approximately 28% higher ER use, whereas inpatient hospitalizations were not significantly different. Women with VMS without depression also had more outpatient visits (β = 3.77, SE = 0.66, p < 0.0001) but no significant differences in emergency or inpatient utilization. Conclusions: VMS and depression are strong independent predictors of increased healthcare expenditures and outpatient utilization among midlife women in the United States. The excess economic burden is driven primarily by outpatient care and prescription use rather than hospitalization, suggesting that integrated menopause and mental health care may improve efficiency and reduce healthcare costs.

Article
Biology and Life Sciences
Animal Science, Veterinary Science and Zoology

Mohammad Zahangir Alam

,

Shin Dae-Hyun

,

You-Sam Kim

,

Myung-Hum Park

,

Yun-Mi Lee

,

Jong-Joo Kim

Abstract: The establishment of a reference population for genomic selection in Korean beef cattle is an ongoing process. There is a high likelihood of sex-specific differences in the composition of the reference and test populations. This study evaluates the accuracy of Genomic Estimated Breeding Values (GEBVs) for carcass traits in Hanwoo cattle, specifically investigating the efficacy of cow-based reference populations. The effectiveness of genomic selection (GS) is heavily dependent on the composition and size of the reference population. Utilizing genotype data from a Hanwoo 50k SNP chip and phenotypic data from 19,168 steers and 6,233 cows, the study estimated GEBV accuracies for carcass weight (CWT), eye muscle area (EMA), backfat thickness (BF), and marbling score (MS) using the GBLUP method. Results demonstrate that steer-based reference populations achieved the highest accuracy (0.64–0.88), averaging 0.78, likely due to standardized management and higher trait heritability (0.39–0.51) compared to cows. In contrast, cow-based reference populations exhibited prediction accuracies (0.55–0.75) in four traits using adjusted residual phenotype, averaging 0.64, but remained highly practical alternatives. While growth traits (CWT and EMA) showed significant bias in cross-sex predictions, fat deposition traits (BF and MS) remained stable across sexes. The study concludes that although steer-based populations provide optimal accuracy, incorporating cows into the reference population is strategically vital in Hanwoo.

Article
Engineering
Electrical and Electronic Engineering

Modou Diop

,

Adam W. Skorek

,

Mouhamadou Moustapha Diop

Abstract:

The degradation of the health state of Proton Exchange Membrane (PEM) water electrolyzer, caused by power supply variability, operating temperature changes, and other chemical factors, represents a major challenge for green hydrogen production efficiency. This paper presents an advanced hybrid system combining a digital twin and machine learning, enabling real-time anomaly detection of a PEM electrolyzer. This intelligent approach allows for the real-time prediction of operating parameters, namely current, voltage, and hydrogen flow rate, via Azure Machine Learning, and their visualization within the system's digital twin via Azure Digital Twins. Furthermore, the comparison between simulated data from the digital twin and those predicted by machine learning enables the anticipation of PEM electrolyzer anomalies. The selected prediction models rely on the Extreme Random Trees algorithm for current and voltage estimation, and on the Elastic Net algorithm for hydrogen flow rate prediction. The obtained results confirm the robustness of the proposed approach, with coefficients of determination of 0.99820, 0.99693, and 0.99665 for current, voltage, and hydrogen flow rate respectively, associated with Normalized Root Mean Square Errors (NRMSE) of 0.00870, 0.011278, and 0.11087. This high accuracy provides the digital twin with the capability to anticipate failures and extend the PEM electrolyzer's lifespan, with a view to optimizing the global efficiency of green hydrogen production.

Article
Physical Sciences
Astronomy and Astrophysics

Raheb Ali Mohammed Saleh Aoudh

Abstract:

We present a mathematically rigorous formulation of the Fundamental Speed Theory (FST), a dimensionally consistent vector–tensor theory featuring a dimensionless vector field \( \nu^{\mu} \). We introduce characteristic scales \( L_0 = 10 \) kpc and \( M_0 = \hbar/(cL_0) \) and keep \( \hbar \) and \( c \) explicit throughout. In dimensionless form, the galactic field obeys

\( \frac{d^2\tilde{\nu}}{d\xi^2} + \frac{2}{\xi}\frac{d\tilde{\nu}}{d\xi} = \beta_{\mathrm{eff}}\tilde{\nu}^3 \),\( \qquad \beta_{\mathrm{eff}} \equiv -\frac{\lambda\nu_0^2}{6c_1} = 2.0\times 10^7 \ (\lambda<0). \)

We validate the theory on the SPARC sample using three primary hierarchical levels (Levels 1–3): Level 3 (zero free parameters) fits 65.7% of galaxies with mean \( \chi_{\nu}^{2}=0.809 \); Level 2 (estimated \( M, r_d \), no fitting) reaches 93.6% with mean \( \chi_{\nu}^{2}=0.347 \) for the 160 galaxies with \( \chi_{\nu}^2<3 \); and Level 1 (fitted \( M, r_d \)) fits all 171 galaxies with mean \( \chi_{\nu}^{2}=0.170 \) (91.2% with \( \chi_{\nu}^{2}<0.5 \)). We further report two derived formulations: Level 4 (coefficient-free) and Level 5 (unified), the latter showing that the field parameters unify into a single acceleration scale

\( A_0 = \frac{(c_1+c_3)\nu_0^2 c^2}{L_0} = 2.42\times 10^{-10}\ \mathrm{m/s^2}, \)

which reproduces the full formulation identically for all galaxies. A full three-dimensional numerical experiment with disk-like (anisotropic) boundary forcing confirms that the converged 3D field profiles and rotation-curve fits remain essentially unchanged relative to the 1D quasi-spherical approximation for the tested cases. We also perform an explicit sign-convention robustness check: running the full pipeline with the alternative (negative-sign) convention yields identical fits within numerical tolerance when implemented consistently. Solar System constraints are satisfied because the relevant acceleration arises from the galactic field gradient, giving a local FST acceleration at Earth of \( \sim 8\times 10^{-15} \) of the Newtonian value. All code is archived on Zenodo, and supplementary materials (including complete fit results and both sign-convention implementations) are provided. Extension of FST to cosmological scales is left as future work.

Article
Biology and Life Sciences
Biophysics

Olga A. Snytnikova

,

Anton A. Smolentsev

,

Nataliya G. Kolosova

,

Anzhella Zh. Fursova

,

Yuri P. Tsentalovich

Abstract: This study aimed to characterize metabolomic changes in the eye lens of senescence-accelerated OXYS rats in comparison with control Wistar rats, and to identify biochemical shifts associated with genotype, age, and cataract progression. Cataract severity was clinically graded. Rats' lenses were analyzed using quantitative 1H NMR spectroscopy at 3.6 and approximately 4.5 months of age. A total of 43 metabolites were quantified. We found that at 3.6 months of age, OXYS lenses exhibited a significant accumulation of 17 metabolites, primarily amino acids, compared to Wistar rats, suggesting an imbalance between amino acid uptake and crystallin biosynthesis. However, by 4.5 months, OXYS lenses exhibited rapid metabolic changes characterized by significant decreases in amino acid, glucose, and key energy/antioxidant markers, including NAD, adenylate energy charge, and hypotaurine. Clinical cataract grade (Grade 2 vs. 3) had a negligible impact on the overall metabolomic profile. Our results indicate that profound metabolic reorganization, including an initial amino acid excess followed by energy and antioxidant depletion, precedes the morphological manifestation of cataracts in OXYS rats. We suggest that a biochemical "point of no return" occurs early in cataractogenesis, while subsequent increase in lens opacification is a secondary consequence of preexisting metabolic disturbances.

Article
Social Sciences
Political Science

Safran Safar Almakaty

Abstract: The field of international relations confronts significant research gaps as established theoretical frameworks struggle to address the multidimensional challenges of the twenty-first century. This study presents a comprehensive qualitative analysis of four priority research domains requiring urgent scholarly attention: artificial intelligence (AI) governance and global power dynamics, climate security and interstate conflict, digital sovereignty in the Global South, and non-state actors in hybrid warfare. Employing systematic literature review and thematic analysis grounded in interpretivist epistemology and critical realist ontology, this research identifies critical theoretical and empirical deficiencies in existing scholarship while proposing integrated frameworks for addressing them. Findings reveal that traditional international relations theories—including realism (Waltz, 1979/2010; Mearsheimer, 2001), liberalism (Keohane, 1984; Ikenberry, 2011), and constructivism (Wendt, 1999; Finnemore & Sikkink, 1998)—require substantial adaptation to address challenges posed by technological transformation, environmental change, and evolving security paradigms. The analysis identifies significant cross-domain interconnections: AI governance intersects with hybrid warfare through autonomous weapons systems and cyber operations, while climate security connects with digital sovereignty through environmental data governance. The paper concludes with evidence-based recommendations for future research agendas, emphasizing interdisciplinary collaboration, methodological innovation, and policy-relevant scholarship. This analysis contributes to advancing international relations scholarships in an era of unprecedented global complexity.

Article
Biology and Life Sciences
Cell and Developmental Biology

Marcus Hubbe

,

Robert H. Eibl

Abstract:

Leukocyte recruitment from blood into tissues involves sequential adhesive steps, including rolling and integrin-dependent arrest. The integrin VLA-4 is known to mediate firm adhesion, but can also support rolling. CD44–hyaluronan interactions have also been implicated in leukocyte rolling. Here, we used parallel-plate flow chamber assays to compare the contributions of CD44 and VLA-4 to monocyte rolling on different cellular monolayers. Monocytoid WEHI 78/24 cells rolled and adhered through CD44 on hyaluronan-presenting ECV304 monolayers, whereas VLA-4 dominated adhesion on endothelial monolayers expressing functional VCAM-1. Primary human monocytes showed similar CD44-dependent rolling on ECV304 monolayers. Blocking CD44, adding soluble hyaluronan, or removing surface hyaluronan with hyaluronidase reduced rolling and adhesion. These results show that CD44 can support monocyte rolling when VLA-4/VCAM-1 adhesion is not the dominant interaction. This cell-based flow model distinguishes CD44/hyaluronan-mediated rolling from VLA-4/VCAM-1-rolling and may help analyze monocyte rolling on hyaluronan, including tumor-derived monolayers.

Article
Computer Science and Mathematics
Artificial Intelligence and Machine Learning

Lu Wang

,

Xiaoming Ye

Abstract: Stroke, a leading cause of global disability and mortality, exhibits significant spatiotemporal associations with environmental pollutants. Predicting daily stroke admissions becomes increasingly important as the population ages. Current prediction research on stroke-related medical services mainly relies on point prediction, which lacks the ability to quantify uncertainty. In this study, we try to develop parametric probability prediction models of stroke admissions based on machine learning and deep learning algorithms. We collected stroke data and environmental data from February 11, 2019 to May 26, 2023 in Chengdu, and employed prediction models encompass negative binomial regression, natural gradient boosting (NGBoost), long short-term memory networks (LSTM), and transformer. For performance assessment, mean absolute error (MAE) is used to evaluate point prediction accuracy, while continuous ranked probability score (CRPS) is applied to assess the quality of distribution fitting.We find that models with the ability to capture and process time-series information demonstrate greater advantages in probabilistic prediction, and among the four evaluated models, the transformer model proves to be the one that delivering more reliable and precise outcomes in both point prediction of admission counts and distribution fitting performance. This probabilistic forecasting approach provides robust evidence-based decision support for healthcare administrators to optimize resource allocation and staffing arrangements, and ultimately helps elevate the quality of medical care for stroke patients.

Article
Medicine and Pharmacology
Cardiac and Cardiovascular Systems

Kavindya Fernando

,

Nilshan Fernando

,

Dilini Jayasekara

,

BKTP Dayanath

Abstract: Point-of-care testing (POCT) for cardiac troponin is increasingly used to support rapid clinical decision-making, particularly in resource-limited settings. However, while many central laboratories, including those in Sri Lanka, now use high-sensitivity cardiac troponin I (hs-cTnI) assays, commonly available POCT platforms continue to use conventional methodologies with different analytical characteristics and decision thresholds. We evaluated the analytical agreement and clinical concordance of two POCT troponin assays against a central laboratory hs-cTnI assay using paired samples obtained during routine clinical care in a Sri Lankan hospital. Both POCT devices demonstrated strong correlation with the laboratory assay (Pearson r ≈ 0.90). However, Bland–Altman analysis showed substantial positive bias and wide limits of agreement, indicating poor interchangeability at the individual sample level, with proportional bias observed in one device. Clinically relevant discordance was also identified, with 26.9% and 30.4% of samples classified as negative by POCT despite being positive by the reference assay. Regression-based recalibration did not significantly improve concordance. These findings highlight that strong correlation does not ensure diagnostic agreement, emphasizing the need for local validation before integrating POCT troponin assays into established hs-cTnI diagnostic pathways.

Article
Biology and Life Sciences
Biology and Biotechnology

Sk. Sarif Hassan

,

Kharerin Hungyo

,

Vladimir N. Uversky

Abstract: Rare diseases, though individually uncommon, collectively represent a major global health challenge, affecting millions worldwide and increasingly recognized in India as a significant contributor to pediatric and adult morbidity. Cystic fibrosis (CF), a multisystem autosomal recessive disorder caused by pathogenic variants in the Cystic Fibrosis Transmembrane Conductance Regulator (\textit{CFTR}) gene, exemplifies this burden, with delayed diagnosis and diverse mutational spectra complicating clinical management in South Asian populations. To advance rare disease genomics, quantitative analysis of CFTR sequences across multiple species is essential, as evolutionary conservation highlights residues and motifs critical for channel function, while divergence reveals lineage-specific adaptations relevant to disease mechanisms. In the present study, we performed integrative analyses encompassing amino acid composition, sequence homology, frequency-dominant residue patterns, hydropathy-based n‑gram distributions, hydropathy profile continuity, and intrinsic disorder architectures across various CFTR sequences from multiple species. The quantitative signatures derived from amino acid composition, sequence homology, hydropathy-based n‑grams, hydropathy profiles, and intrinsic disorder analyses carry significant translational impact, as they provide a unified framework for identifying conserved motifs, resolving disorder-prone domains, and guiding the precise mapping of pathogenic mutations and their functional consequences. Collectively, our findings demonstrate how cross-species quantitative protein analysis of CFTR bridges evolutionary biology with clinical investigation, providing translational insights that strengthen rare disease research and therapeutic development in cystic fibrosis.

Article
Engineering
Electrical and Electronic Engineering

Obed Muhayimana

,

Petr Toman

,

Matti Lehtonen

,

Ali Aljazaeri

,

He Li

,

Silas Tuyishime

Abstract: Accurate fault location is essential for rapid service restoration in distribution networks. How-ever, modern active distribution networks (ADNs) with high penetration of distributed energy resources (DERs) challenge conventional methods through multi-source fault contributions, bi-directional power flows, and converter-limited fault currents. This paper presents a time-domain fault-location method for both passive distribution networks (PDNs) and ADNs, based on a three-sample apparent-inductance estimator that uses local voltage and current measurements. The estimator exploits the strong correlation between line inductance and fault distance, with reduced sensitivity to fault resistance compared to classical impedance approaches. Its performance is evaluated on a 22 kV, 20 km distribution feeder, covering three fault types, four fault resistance levels (5–500 Ω), four fault locations, EN 50160 standard-compliant harmonic distortion, and DER penetration levels from 0 to 80%. Under ideal sinusoidal conditions, relative location errors remain below 2% for low-resistance faults. In ADNs, the method achieves errors be-low 5% for low-resistance faults across all fault types, with accuracy decreasing for high-resistance faults at high DER penetration. A sensitivity analysis confirms practical robustness across SNR, load current, THD, and DER penetration.

Article
Computer Science and Mathematics
Artificial Intelligence and Machine Learning

Zhisheng Tang

,

Mayank Kejriwal

Abstract: Most AI-for-science systems (agents4science) are evaluated as task-specific automation rather than persistent work environments. This leaves an important and pragmatic systems-question unresolved: what infrastructure enables scientific agents to be trustworthy, steerable, and reproducible? We present ApexClaw, a persistent workspace for human-supervised AI agents in scientific discovery. The system provisions isolated Linux environments with scientific computing libraries, a browser-based IDE, and a registry of reusable scientific skills. Rather than pursuing full autonomy, ApexClaw emphasizes human oversight through an interface that exposes agent reasoning, tool calls, and workspace files, allowing scientists to guide agents at key junctures. We validate this approach with telemetry from 81 users operating 243 workspaces across 252 conversations (March--May 2026): 87\% of users reconnected to existing workspaces, and humans intervened selectively on 3.4\% of interactions. These findings demonstrate that hybrid autonomy with persistent context is ordinary practice in real agentic science, and that durable workspaces, explicit artifacts, and auditable traces are necessary infrastructure for reproducible and steerable AI scientists.

Article
Medicine and Pharmacology
Neuroscience and Neurology

Shaoning An

,

Laura Schönfelder

,

Peter Reusch

,

Pedro M. Faustmann

,

Fatme S. Ismail

,

Timo Jendrik Faustmann

Abstract: Background: Neuroinflammation contributes to etiopathology and symptom severity in neurodegenerative and neuropsychiatric disorders. Glial cells, especially microglia and astrocytes, play a crucial role in neuroinflammation. It has been reported that ginseng and its bioactive component ginsenoside Rg1 exhibit anti-inflammatory effects and improve cognitive performance in various models. However, the exact underlying mechanisms remain unclear. Methods: An astrocyte-microglia co-culture model simulating physiological (M5, 5-10% microglia) and pathological/inflammatory (M30, 30-40% microglia) conditions was treated with different concentrations of ginsenoside Rg1 (15, 30, 45 µM), ginseng extract (derived from Korean red ginseng) at low-dose (12.5, 25, 37.5 µg/ml) or high-dose (125, 250, 375 µg/ml) for 24 hours. Cell viability was assessed by MTT assay. Microglial reactivity was examined by immunocytochemistry. Astrocytic gap-junctional coupling was investigated using scrape loading method and connexin 43 (Cx43) expression was analyzed by immunocytochemistry and Western blot. Results: Both Rg1 and low-dose ginseng extract reduced microglial activation under inflammatory conditions by promoting a phenotypic shift from activated to homeostatic (resting) microglia. Rg1 preserved astrocytic gap-junctional function by preventing the inflammation-induced downregulation of Cx43 expression and enhancing Cx43-mediated gap-junctional intercellular communication. Rg1 caused a significant reduction of glial cell viability only at high concentrations (30 and 45 µM) under inflammatory conditions. High-dose ginseng extract showed significant concentration-dependent cytotoxicity, reducing glial cell viability under physiological and pathological conditions, without comparable anti-inflammatory benefits. Conclusions: This study suggests that low-dose ginseng and its active compound Rg1 exert anti-inflammatory effects by modulation of astrocytic coupling and microglial reactivity. These results provide a novel therapeutic perspective for ginseng in the treatment of neurodegenerative and neuropsychiatric diseases related to neuroinflammation.

Article
Engineering
Bioengineering

Masahiro Tsutsui

,

Takumi Yoshida

,

Daisuke Naruse

,

Shingo Kunioka

,

Yuta Kikuchi

,

Naohiro Wakabayashi

,

Hiroyuki Kamiya

,

Kyohei Oyama

Abstract: Hydrophilic surface modification is widely investigated as a strategy to improve the hemocompatibility of small-diameter vascular grafts. We previously developed a polyvinyl alcohol-coated poly-ε-caprolactone nanofiber graft (PVA–PCL graft) and showed that PVA coating improved graft hydrophilicity and mechanical properties. However, whether PVA coating provides an in vivo advantage over uncoated PCL grafts remains unclear. In addition, the influence of pre-implantation surface hydration on the function of hydrophilic grafts has not been fully examined. In this study, we first compared PVA–PCL and uncoated PCL grafts in a rat abdominal aorta implantation model and found no statistically significant difference in patency rate between the graft types. We then examined whether pre-wetting enhanced the anti-fouling function of the PVA coating. In vitro whole-blood flushing assays demonstrated that pre-wetting markedly reduced blood component deposition on PVA–PCL grafts. However, this effect did not translate into detectable improvements in patency or tissue regeneration in the rat model used in this study. These findings indicate that pre-wetting effectively enhances the in vitro anti-fouling behavior of PVA–PCL grafts and may serve as a simple strategy to optimize the functional surface state of hydrophilic coatings. Further studies are needed to determine whether this in vitro improvement can be translated into meaningful enhancement of graft performance in vivo.

Article
Computer Science and Mathematics
Artificial Intelligence and Machine Learning

Ivona Velkova

,

Valentin Kisimov

Abstract: Reliable public-sector labour-market forecasting requires models that can be updated as data sources, AI tools, and labour-market signals evolve. This paper proposes a provider-independent multi-agent framework for dynamic predictive evaluation of national and regional labour markets in Bulgaria. Implemented as a Model Context Protocol (MCP) server, the system coordinates specialised agents for data ingestion, preprocessing, semantic extraction, AI-adjusted transformation modelling, automated model evaluation, and reporting through stable input-output contracts. The empirical application integrates Bulgarian Employment Agency administrative registered-unemployment indicators, Eurostat labour-market data, World Bank macroeconomic data, and text/audio/video evidence on AI, skills, and employment change. The study period covers 2015–2030, combining observed official inputs for 2015–2025 with forecast/scenario outputs for 2026–2030. For youth unemployment under 25, the semantic-enhanced model achieves the best predictive accuracy (RMSE = 0.2033; MAE = 0.1457), representing a small improvement over the structured baseline (RMSE = 0.2057; MAE = 0.1462) and a substantial RMSE reduction relative to the persistence benchmark (RMSE = 0.4750; MAE = 0.2891). Regional forecasts indicate persistent spatial inequality, with the Northwest remaining the highest-risk region and the Southwest the lowest-risk region.

Hypothesis
Medicine and Pharmacology
Pulmonary and Respiratory Medicine

Michael Eisenhut

Abstract: Localized lower respiratory tract infection including unilobar and round pneumonia can be associated with hypoxia and oxygen requirements. Previous explanations include shunting of deoxygenated blood, a systemic inflammatory response syndrome and vasoconstriction.This is unexplained.The alternative hypothesis is that spread of fluid absorption inhibiting cytokines in the alveolar spaces of the inflamed lung is cause of hypoxia in localized lower respiratory tract infection by spread of Cystic Fibrosis Transmembrane Conductance (CFTR) dysfunction in alveolar epithelial cells to more areas including those not infected. There is no evidence of pulmonary shunting to explain hypoxia in localized pneumonia. Systemic inflammatory response syndrome (SIRS) related generalized increase in alveolar capillary barrier or pulmonary vasoconstriction not visible on a chest x-ray cannot explain the hypoxia detected in most patients. Confirmation of the hypothesis could be achieved using pulmonary MRI or high resolution CT to confirm spread of alveolar fluid accumulation from the localized pneumonia focus as opposed to generalized SIRS related pulmonary oedema together with cytokine and chloride measurement in bronchoalveolar lavage samples from the lung segments near the affected lung segment and unaffected contralateral lung. Ventilation/perfusion scintigraphy could investigate for involvement of vasoconstriction or micro-emboli from intravascular coagulation.Should the posed hypothesis be confirmed adjuvant strategies including small molecule CFTR activators, CFTR activating combination of beta-agonists, phosphodiesterase inhibitors and steroids could be used to treat hypoxia and CFTR activating low-intensity ultrasound explored.

Concept Paper
Business, Economics and Management
Marketing

Marcos Guimaraes Figueira

Abstract: The competitive ground of digital visibility has moved twice in eighteen months. The first move was from the ten blue links to the AI-generated answer; the second, still in progress, is from the answer to the autonomous action. This article develops a framework that integrates three optimization disciplines emerging in response to that shift—Answer Engine Optimization (AEO), Generative Engine Optimization (GEO), and Agentic Optimization (AgO)—under a single theoretical lens: delegated consumer–AI agency. Building on Puntoni et al.’s (2021) experiential perspective on consumer AI and Davenport et al.’s (2020) account of AI in marketing, we treat the AI assistant not as a channel but as a delegated decision-maker whose choices are governedby retrievability, attribution cost, and embedded brand associations. We argue that the central strategic risk of this transition is brand erasure—the systematic elimination of brand identity from synthesized answers and completed agentic actions—and we develop six propositions that link content and infrastructure choices to brand outcomes in this environment. We close with managerial implications for brands operating across the dual audience of human readers andmachine intermediaries, and a research agenda focused on measurement, audit methods, and governance.

Article
Biology and Life Sciences
Virology

Chi Zhang

,

Kyle Heye

,

Davide Lelli

,

Loubna Tazi

,

Stefan Rothenburg

Abstract: Poxviruses are large double-stranded DNA (dsDNA) viruses that cause important human and animal diseases, including smallpox and mpox. Poxviruses have also been identified in diverse bat populations; however, their potential for zoonotic transmission and adaptation to other mammalian hosts remains poorly understood. Poxviruses encode numerous immunomodulatory proteins that contribute to virulence, immune evasion, and host range. In this study, we performed a comparative genomic analysis of two bat-associated poxviruses belonging to the genus Vespertilionpoxvirus: hypsugopox virus (HYPV) and eptesipox virus (EPTV). We identified 24 and three previously unannotated putative open reading frames (ORFs) in HYPV, and EPTV, respectively, substantially expanding the predicted coding capacity of these viruses. Comparative analyses further revealed gene duplication and fragmentation events affecting several virulence and host range factors, as well as other unusual genomic features, including the presence of two divergent E3L homologs in EPTV. Together, our findings provide new insights into the genome evolution and potential host adaptation of bat-associated poxviruses and establish a foundation for future functional studies of Vespertilionpoxvirus biology, host-virus interactions, and zoonotic potential.

Brief Report
Medicine and Pharmacology
Pharmacology and Toxicology

Tobechi Brendan Nnanna

Abstract: In pregnancy physiologically based pharmacokinetic (PBPK) modelling within PK-Sim/Mobi, pregnancy stage is canonically parameterised on the fertilisation-age (FA) timescale, yet PK-Sim’s physiology database is indexed by chronological “Age”. The Open Systems Pharmacology (OSP) pregnancy framework therefore encodes FA on a dummy “Age” axis (30.00 years = FA 0 weeks; 30.75 years = FA 38 weeks) and generates pregnancy physiology vectors from FA 0 – 38 weeks discretised at 1-day intervals for database ingestion. Although the anchor points are publicly documented, an explicit closed-form transform and week-resolved lookup suitable for deterministic reproduction of daily physiology grids has not been routinely foregrounded in the literature or repository instructions. A unique affine mapping is derived, implied by the anchors, that provide forward and inverse equations in week- and day-space, quantifying rounding error in terms of FA-day misalignment, and supply a fertilization week (1-38) table for implementation-ready pregnancy virtual population creation in PK-Sim.

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