After the US trauma system contracted in the 1990s with the loss of financially vulnerable trauma centers (TCs), a subsequent re-expansion took place. Many new trauma centers are for-profit (FPTCs) and may provide redundant care for affluent populations. Little is known about their role in the national trauma system. We hypothesized that FPTC catchments would provide redundant coverage to affluent populations. Data for the contiguous United States were obtained from the 2020 Decennial Census or American Community Survey. Population-weighted centroids of each census tract, as well as TC locations, were geocoded in ArcGIS Pro. FPTC status was obtained from the Centers for Medicare and Medicaid Services. Road and traffic data were obtained from Esri StreetMaps Premium. The shortest travel time from each population-weighted centroid was calculated to the nearest TC to delineate coverage areas and populations. This analysis was repeated without FPTCs to assess contributions to the trauma system. Data were exported to Stata for further analysis. In total, 83,713 population-weighted centroids and 2,044 TCs were captured. About 11% of tracts were primarily served by 223 FPTCs, representing the closest TC for 43M people. While overall transport times were similar between FPTCs and NPTCs (14.0 vs. 14.2 min, p=ns), the removal of FPTCs did not change national transport times (median 0 min; IQR, 0, 0; range, 0-98). FPTC catchment populations were associated with more urban [odds ratio (OR), 1.02, 95% CI, 1.01-1.02, p<0.001], Hispanic (OR, 1.14, 95% CI, 1.14-1.15, p<0.001), uninsured (OR, 1.65, 95% CI, 1.57-1.73, p<0.001) or Medicare covered (OR, 1.04, 95% CI, 1.02-1.07, p<0.001) populations. Most FPTCs provide redundant care to populations that are often less insured, of similar poverty levels and of different demographics as compared with nonprofit centers. However, a small subset of FPTCs provides access to care for populations who would face long transport times without them.(J Trauma Acute Care Surg. 2026;00:000-000. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). Epidemiological; Level III.
In Uganda, frequent shortages of antihypertensive medications hinder continuity of care, undermining blood pressure management. Building on preliminary ethnographic research, this study evaluates a community-led, mobile-wallet-based pooling intervention-MoPuleesa-designed to improve medication access at a rural clinic in Nakaseke District, Uganda. Over a 7-month period, 183 patients enrolled and were linked to a digital savings platform that required monthly contributions of 5000 UGX (∼USD 1.39) into a communal fund to bulk-purchase medications at a discounted cost. Using survey data, transaction logs, and clinic records, we assessed contribution behavior, risk of adverse selection, equity, changes in medication availability, and patient blood pressure levels. On average, 48% participants contributed each month. Contribution rates showed no significant differences across education levels or medication costs, suggesting minimal equity concerns or adverse selection. Government pharmacies fulfilled only 8% of total prescriptions; however, for contributors, MoPuleesa closed 84% of the remaining medication gap. However, despite improvements in medication supply, we did not observe statistically significant improvements in blood pressure. Our findings demonstrate the feasibility and effectiveness of mobile money pooling in addressing chronic medication shortages. MoPuleesa achieved broad participation and equitable outcomes in a resource-constrained setting and significantly improved medication availability. We conclude that mobile-based fund pooling for medication can significantly improve medication supply and, with improvements in eligibility assessments, could serve as a complementary or intermediate solution to structural barriers in under-resourced health systems.
Medical imaging plays a critical role in diagnosing and managing acute conditions such as Acute Respiratory Distress Syndrome (ARDS), particularly in intensive care settings. However, radiological data are often siloed across Picture Archiving and Communication Systems (PACS), with limited interoperability, traceability, and patient control. This paper proposes and validates a blockchain-enabled architecture that integrates radiological imaging data into a patient-controlled digital wallet (BioWallet) ecosystem. The system combines verifiable credentials, decentralized identifiers (DIDs), and a FHIR-compliant backend to ensure secure, auditable, and standards-based access to DICOM images and associated metadata. The ledger stores only consent and audit hashes, while clinical data remain off-chain and correctable within FHIR/EHR systems, ensuring auditability without hindering rectification. A validation scenario replicating an ICU emergency was conducted using synthetic ARDS-COVID19 cases to assess latency, consent enforceability, and user experience. Results showed a 67% reduction in image access time compared to traditional systems, 100% success in blocking unauthorized access, and high clinician satisfaction. The architecture supports FAIR-compliant reuse of annotated imaging datasets, enhances transparency in image-driven research, and aligns with GDPR and future European digital identity frameworks. This work demonstrates the feasibility and value of a decentralized, patient-centric approach to imaging data governance in high-stakes clinical environments.
The decentralized and pseudonymous nature of cryptocurrency has facilitated its extensive use in illicit activities, including money laundering, tax evasion, and ransomware. Limiting such activities requires a well-established forensic framework. However, a dedicated methodology for examining cryptocurrency wallets remains underdeveloped. This study presents a systematic forensic analysis of Electrum wallets installed on virtual machines running Windows 10, outlining the wallet taxonomy and meticulously listing all artifacts. This study primarily focuses on memory forensics, with most of the analysis devoted to memory-based artifacts extracted from five distinct memory dump scenarios. Artifacts extraction were performed using Volatility 3 plugins, in conjunction with Python-based analysis scripts, within a Kali Linux environment. Following the memory-based analysis, a limited disk examination was conducted after wallet inactivity or system shutdown to assess whether any residual Electrum artifacts persisted beyond memory. The research examines the artifacts retrievable from wallet files, both before and after backup, and compares these results with those obtained from other methods reported in the literature. The experimental outcomes demonstrate the impact of this research on the successful extraction of private keys, wallet addresses, extended public keys, wallet files, and transaction IDs. The extracted Electrum addresses and private keys provided access to critical wallet details, and unspent Bitcoin were successfully recovered using these keys, confirming the feasibility of forensic cryptocurrency recovery and revealing data of high evidentiary value to the digital forensic community.
As Decentralized Finance (DeFi) and Non-Fungible Tokens (NFTs) expand, self-custody wallets have become the primary interface for user sovereignty. However, existing solutions suffer from critical limitations, including static authentication frameworks that compromise usability, a lack of real-time risk awareness, and inadequate key recovery mechanisms that often lead to permanent asset loss or reliance on centralized custodians. Furthermore, current wallets frequently expose transaction metadata, undermining user privacy. To address these systemic flaws, we present a modular self-custody wallet that incorporates a context-aware risk engine for real-time transaction scoring, risk-based adaptive authentication, and a dual-path decentralized key-recovery layer combining DAO-governed Shamir secret sharing with a zk-SNARK-verified fallback. The architecture further includes programmable policy enforcement and a zero-knowledge swap layer with stealth addressing to decouple front-end activity from on-chain data. The design integrates smart contracts on EVM chains and Solana through provider adapters and executes on-device ML inference to minimize latency. Experimental results demonstrate that the proposed system reduces privacy leakage probability to 5% (compared to 85% in standard architectures) and accelerates key recovery from over 24 h to approximately 8 seconds using zk-SNARKs, all while achieving 93.6% risk classification accuracy. The proposed CAPPR-Wallet advances self-custody by combining context adaptivity, privacy, and recoverability without centralized trust.
With the widespread adoption of cryptocurrencies, the ability to conduct continuous offline payments has increasingly become a critical technological requirement. In network-constrained scenarios, current dual-offline payment technologies are useful for single transactions. However, their limitations in continuous payment scenarios have become increasingly evident, making them unable to meet real-world application needs. This has prompted the industry to demand more urgent innovations in research on continuous offline payment capabilities. To address these challenges, this paper proposes a continuous dual-offline payment system capable of supporting multiple continuous payments. The system integrates elliptic curve cryptography (ECC) and zero-knowledge proof (ZKP) technology to generate secure asset credentials, ensuring both immutability and privacy credentials throughout the offline payment lifecycle. A dynamic credential decomposition mechanism enables the splitting of input credentials into change credentials and receipt credentials, facilitating uninterrupted dual-offline payments between hardware wallets. Additionally, it incorporates a batch verification scheme based on smart contracts, utilizing zero-balance verification and chained hash tracing to ensure payment uniqueness and prevent double-spending attacks, thereby guaranteeing the verifiability and validity of payment settlements. Experimental evaluations demonstrate that the proposed system reduces gas consumption per payment and improves execution efficiency during batch processing, combining high security with strong performance. This research provides a feasible solution for the application of digital currencies in offline scenarios, carrying significant theoretical value and practical significance for driving technological innovation and application expansion in the cryptocurrency field. In addition to cryptocurrency payments, the proposed system is also applicable to IoT and sensor network environments. Many IoT devices operate in disconnected or network-limited areas and require secure micro-transactions. Our dual-offline payment mechanism supports such scenarios, as the main cryptographic operations are lightweight enough for typical IoT hardware. This further extends the practical value of our system beyond traditional cryptocurrency payments.
Leaf-based leather is a biodegradable, negative carbon emissions, and economically suitable material compared to the conventional leather-making process. In this research, jute leaf (30 gm), cellulose (2 gm), and natural rubber latex (10 ml) composition combined composite exhibited superior tensile strength (9.58 MPa). Fourier transform infrared spectroscopy (FTIR) showed that formed aryl groups in this composite material indicated jute leaves crosslink with natural rubber latex and cellulose. Scanning electron microscopy (SEM) also represents porosity and reduced fiber pull-out. However, when thermoplastic polyurethane (TPU) was heat-compressed with this composite material, it enhanced tensile strength properties (28.9 MPa) and elongation (15.3%). Due to TPU crosslinking, FTIR confirms aryl signatures and urethane linkages formed by hydroxyl-NCO reactions, enhancing chain interactions and mechanical integrity, and SEM shows a porous microstructure supporting cohesion and interfacial adhesion. Contact-angle measurements (~ 85°) indicate the same hydrophobicity, comparable to animal leather (~ 90°). The jute leaf composite degraded within 4 months in the soil, whereas the TPU-compressed variant biodegraded within 6 months. This work presents a sustainable jute leaf bio-composite to replace leather in products such as backpacks, wallets, bags, book and file covers, automotive or home décor, creating bioeconomic opportunities in Bangladesh.
This paper explores how smart governance can reduce financial risks in the Iraqi banking industry by focusing on the adoption of the use of artificial intelligence (AI) technologies to increase financial stability and operational efficiency. The study uses a combination of quantitative indicators of the dimensions of smart governance (standards, policies, practices, information, technologies, and skills) and financial risk dimensions (market, credit, operational, and investment portfolio risks) based on the secondary data provided by the Central Bank of Iraq covering the years 2023 and 2024. The results reveal a strong progression in all aspects of smart governance during the study time in the form of the rising number of licensed electronic payment providers, the rise of the percentage of current deposits, and the further use of bank accounts and electronic wallets. Also, the human resources in the banking industry have been enhanced with expertise in professional development initiatives. In the financial risk sector, the outcomes are a decline in non-performing loans, an upward trend in the ratio of credit to deposits and an increase in total deposits and total credit facilities, hence, an indication of an improvement in the ability to handle risk. The testing of hypothesis confirms that a strong governing process, including standards, policies, practices, information management, technology adoption and development of human skills, has a positive influence on financial risk management in the AI environment. The research suggests enhancing regulatory systems, increasing digital transformation programs, investing in human-capital growth, and introducing AI-based analytical solutions to guarantee long run sustainability and stability of the financial sector.
Acute hypoxaemic respiratory failure (ARF) is the leading cause of intensive care unit (ICU) admission among immunocompromised patients. However, contemporary data regarding the epidemiology, management, and outcomes of ARF in this population remain scarce. We aimed to identify predictors of mortality and intubation in immunocompromised patients admitted to the ICU with ARF. This retrospective observational study was conducted in 103 ICUs in 26 countries. Adults (≥18 years) with ARF and immunodeficiency were eligible for inclusion. Patient data, including information on the nature of underlying immunosuppression, the cause of ARF, and the oxygenation strategy, were obtained from electronic medical records or medical charts. The primary outcome was to report 30-day mortality and identify associated factors in patients with complete data for all variables. Cox proportional hazards models were used to identify variables associated with mortality, and differences between groups were compared with χ2 tests or two-sided Wilcoxon rank-sum tests, with p values of less than 0·05 considered significant. 9854 immunocompromised patients with ARF admitted to participating ICUs between Jan 1, 2017, and Dec 31, 2023, were included in the study. The median age was 64 years (IQR 54-71); 3941 (40·0%) patients were female and 5913 (60·0%) were male. The main causes of immunodeficiency were a haematological malignancy (4759 [48·3%] of 9854 patients) or solid malignancy (3818 [38·7%] patients). Infection was the leading cause of ARF (6610 [62·0%] of 9854 patients); 5288 (53·7%) patients had more than one contributing cause of ARF, and no cause was identified in 1490 (15·1%) patients. The median partial pressure of oxygen in arterial blood (PaO2)/fractional concentration of oxygen in inspired air (FiO2) ratio was 198 [IQR 141-208]. The 30-day mortality rate was 47·3% (4662 patients). Predictors of higher mortality were older age (hazard ratio 1·01 [IQR 1·00-1·02]), higher Charlson Comorbidity Index score (1·04 [1·01-1·07]), higher Frailty Index score (1·22 [1·16-1·28]), longer time from hospital to ICU admission (1·02 [1·01-1·03]), higher respiratory rate (1·02 [1·02-1·03]), coma at ICU admission (2·04 [1·72-2·43]), invasive fungal infection as cause of ARF (1·82 [1·45-2·28]), disease-specific infiltrates (1·73 [1·32-2·26]), unidentified cause of ARF (2·16 [1·74-2·68]), and use of vasoactive drugs (2·45 [2·10-2·86]) or renal replacement therapy (2·07 [1·74-2·48]). Protective factors included receipt of a solid organ transplant (0·62 [0·49-0·79]), systemic vasculitis or connective tissue disease (0·61 (0·47-0·78]), higher PaO2/FiO2 ratio (0·78 [0·72-0·84]), receipt of high-flow nasal oxygen therapy (0·78 [0·64-0·95]), and cardiogenic pulmonary oedema (0·67 [0·51-0·89]). In this large international cohort of immunocompromised patients with ARF, we identified key risk and protective factors for mortality and intubation. These findings could improve outcomes by informing timely clinical decisions, goals-of-care discussions, and management in this vulnerable population. Kirsten and Freddy Johansen Foundation and Groupe de Recherche en Réanimation Onco-Hématologique.
Recent guidelines recommend maintenance and reliever therapy (MART) as the preferred inhaler regimen for patients with moderate to severe asthma. However, updated asthma action plans (AAPs), specifically tailored to MART, have not been developed for the US population. We sought to design a MART-specific AAP that is accessible, pictorial, and low-burden for clinicians to use during time-constrained clinical encounters. Together with health communication design experts, we used a multiphase, mixed-methods approach involving semistructured interviews with 7 adult patients with asthma and 6 clinicians at community health centers while exploring preferences for AAP content and design. Thematic analyses informed our design process, which used the 5E Design Thinking Framework. Our team ultimately developed 2 MART-specific AAPs and assessed their readability using a Flesch-Kincaid test. Patients prioritized simple visuals, concise instructions, and clear guidance for managing worsening symptoms as key to a new MART-specific AAP. Clinicians emphasized the importance of time efficiency when completing AAPs. Using this feedback, we developed a 4" × 6" wallet-sized trifold AAP with a Flesch-Kincaid grade level of 3.7 specifically tailored for MART. Because guidelines endorse MART as the preferred asthma therapy, new and updated MART-specific AAPs are important to facilitate optimal asthma care. Our team codesigned 2 MART-specific AAPs based on patient and clinician feedback.
To report long-term clinical efficacy, safety, pharmacokinetics, immunogenicity and seroneutralization results of AZD7442 (monoclonal antibodies tixagevimab-cilgavimab) in patients hospitalized with COVID-19. In this phase 3, double-blind, randomized, multicentre trial, hospitalized adults with PCR-confirmed SARS-CoV-2 infection were randomly assigned 1:1 to receive AZD7442 or placebo, and followed-up until day 456, with repeated blood sample collections until day 365. Clinical endpoints included clinical status, mortality, rehospitalization, SARS-CoV-2 reinfection, and adverse events. Antidrug antibodies and serum drug concentrations were measured. Analyses were performed on the modified intention-to-treat (mITT) populations, defined as participants who actually received the intervention. Between April 28, 2021, and June 23, 2022, 237 participants were randomly assigned to AZD7442 (n = 127) or placebo (n = 110), and 123 participants actually received AZD7442. Participants were infected with pre-Omicron variants in 58.8% (133/226) of cases, versus 33.2% (75/226) of Omicron BA1, BA2, or BA5, and 8% (18/226) missing data. There was no significant difference in the distribution of the 7-point ordinal scale between the AZD7442 and placebo groups, either on day 15 (primary endpoint) (OR = 0.93 [0.54-1.61], p 0.81), or any other time point. Significantly more rehospitalizations occurred between discharge and day 456 among participants who received AZD7442 in the global mITT population (OR = 2.04 [1.03-4.05], p 0.04), but not in the antigen-positive mITT population (OR = 1.78 [0.80-3.94], p 0.15). No significant differences were observed in mortality, SARS-CoV-2 reinfection, or adverse events. In the AZD7442 group, 12 of 87 participants (13.8%) had treatment-emergent antidrug antibodies versus 5 of 69 (7.2%) in the placebo group (OR = 2.02 [0.66-6.14], p 0.21). Serum drug concentrations were detectable up to day 365 for all sampled participants (35/35). Neutralizing antibody titres were significantly higher in the AZD7442 group up to day 180. AZD7442 did not demonstrate any clinical benefit and was safe up to 15 months. This study also provides valuable data on the pharmacokinetics, immunogenicity, and neutralizing activity of AZD7442 in patients hospitalized with COVID-19.
Carbapenem-resistant Acinetobacter baumannii (CRAB) is a priority-1 critical pathogen with limited treatment options and high mortality among intensive care unit (ICU) patients. Italy reports hyperendemic levels, whereas France maintains low prevalence. Understanding cross-border differences is essential to inform infection prevention and control (IPC) and antibiotic stewardship strategies. We investigated incidence trends of CRAB infections in ICUs across the French-Italian border and assessed structural, organizational, IPC, and stewardship practices to identify factors associated with infection risk. We conducted a multi-centre observational study involving ICUs of four cross-border regions (Piemonte, Valle d'Aosta, Auvergne-Rhône-Alpes, and Provence-Alpes-Côte d'Azur). Data on ICU-acquired bloodstream infections (BSI), central-line-associated BSI, pneumonia, and ventilator-associated pneumonia with CRAB isolates were extracted from the GiViTI and Réa-Rézo surveillance systems (2019-2022). A structured survey explored ICU characteristics, IPC, and stewardship practices. Logistic regression analysis was performed to identify factors associated with CRAB infection episodes. Overall, 25 ICUs participated in data collection. Among 24,822 ICU admissions, the proportion of A. baumannii isolates that were carbapenem resistant was 18.75% (95% confidence interval [CI]: 7.97-34.98) in France and 83.56% (95% CI: 80.1-86.63) in Italy. Different approaches to IPC and antibiotic stewardship were highlighted. Structural ICU design, staffing flexibility, and resilient IPC and stewardship practices were associated with lower infection risk. The CRAB incidence was substantially higher in Italy than in France. Cross-border harmonization of surveillance and co-ordinated preventive strategies are critical to contain cross-border spread.
Nocardiosis is a serious infection in immunosuppressed patients, especially transplant recipients. The slow-growing phenotype of the bacterium and the variety of symptoms complicate diagnosis and delay antimicrobial therapy, resulting in high mortality rates despite effective treatments. A further complication is that some nocardiosis patients test positive in fungal diagnostics that detect (1,3)-β-D-glucan (the Fungitell assay), but the basis for this cross-reactivity remains unknown. We demonstrate that nocardial cell wall arabinogalactan is a cryptic antigen responsible for cross-reactivity in the Fungitell assay and that this antigen is revealed in vivo following bacterial cell lysis. We further show that the reactivity results from a β-glucose substitution of the galactan domain, a modification specific to nocardia, and identify the optimal antigen as a tetramer of the trisaccharide repeating unit. By providing structural evidence for Fungitell cross-reactivity during nocardiosis, this work paves the way for developing specific diagnostic tools that are currently lacking.
Fiberoptic bronchoscopy in mechanically ventilated ICU patients can markedly increase airway resistance and peak inspiratory pressure (PIP), limit effective tidal volume delivery, and provoke transient hypoxemia, hypercapnia, dynamic hyperinflation, and hemodynamic instability. However, per-procedural ventilator management remains heterogeneous. This single-center trial with before-and-after design assessed the feasibility and safety of implementing a standardized low-flow ventilation protocol, and characterized its physiological effects (particularly peak inspiratory pressure), during bronchoscopy in adults intubated and ventilated in volume-assist-control mode. During the observational phase (n = 36), ventilator settings reflected usual practice (increased pressure alarm and reduced PEEP; no routine flow reduction). Following a 1-month training period, the intervention phase (n = 35) implemented an inspiratory flow rate of 20 L/min, unchanged PEEP, and a reduced respiratory rate to achieve an I:E ratio of 1:2. Physiologic and ventilator data were automatically recorded at 1-min intervals. The primary endpoint was peak inspiratory pressure (PIP), a physiological endpoint reflecting the mechanical effect of the intervention. Secondary endpoints included minute ventilation (MV), end-tidal CO2 (EtCO2), oxygenation metrics, ventilator alarms, and hypotension, feasibility and procedural safety. PIP decreased substantially (45 [35, 65] cmH2O vs. 82 [59, 93] cmH2O; p < 0.001), resulting in a reduction in the time spent with pressure alarms (3.4% vs. 24%; p < 0.0001). However, MV (5.2 [4.6, 5.9] L/min vs. 6.4 [4.1, 7.3] L/min; p = 0.2), and EtCO2 (36 [30, 40] mmHg vs. 31 [27, 39] mmHg; p = 0.4) did not differ significantly. PEEP was maintained in the intervention group (8 [6, 10] cmH2O vs. 2 [0, 5] cmH2O; p = 0.001). The protocol was demonstrated short-term procedural safety signals, as average SpO2 (98.9 [93.7, 100.0]% vs. 99.9 [96.8, 100.0], p = 0.082), and hypotension incidence (8.6% vs. 14%; p = 0.7) did not differ significantly. This protocol implementation study demonstrates that standardized low-flow ventilation with PEEP maintenance is feasible and safe during bronchoscopy in mechanically ventilated patients, with a significant reduction in peak inspiratory pressure as a robust mechanical signal. Alveolar ventilation and hemodynamic tolerance were preserved. These findings support the conduct of further research to evaluate clinical outcomes.
Wound infections remain an important medical problem, which is aggravated by the prevalence of multidrug-resistant bacteria. Among them, Enterococcus faecalis is a major pathogen of surgical site incisional and diabetic chronic wounds, but factors driving its colonization and persistence in wounds remain poorly understood. Iron, manganese, and zinc are essential cofactors in cellular processes, prompting the host to restrict their availability through mobilization of metal-sequestering proteins, a defense known as nutritional immunity. Previously, we showed that E. faecalis strains lacking key iron (Δ5Fe), manganese (Δ3Mn), or zinc (Δ2Zn) uptake systems have impaired virulence. Here, we used an excisional wound model in normoglycemic (C57Bl/6J or B6) and diabetic (C57Bl/6J lepR-/- or DB) mice to examine the role of these metal import systems in wounds. The strong upregulation of metal import genes and reduced wound colonization by Δ3Mn, Δ5Fe, and Δ2Zn strains in B6 mice indicate that iron, manganese, and zinc are limited during wound infection. While Δ2Zn and Δ3Mn strains showed no improved colonization in diabetic wounds, the Δ5Fe strain exhibited a temporary colonization advantage over non-diabetic mice. Quantifications of metal-sequestering proteins lactoferrin, transferrin, calprotectin, and psoriasin from intact skin and infected wounds indicated that nutritional immunity, especially iron restriction, is delayed in diabetes. In conclusion, this study underscores the crucial role of trace metal acquisition in E. faecalis wound colonization and suggests differences in metal bioavailability between diabetic and non-diabetic wounds, helping to explain the increased susceptibility of diabetic wounds to chronic infection.
The topical treatment of acne vulgaris by a single therapeutic is difficult given the multifaceted causes of the disease. Treatment with photo-responsive nitric oxide (NO) donors and light represents an attractive alternative to conventional therapeutics due to the potential for multimodal therapeutic action against downstream acne processes. Herein, a topical hyaluronic acid (HA) formulation was developed to facilitate localized NO delivery from mesoporous silica nanoparticle (MSN) NO donors upon blue light exposure, while simultaneously providing anti-inflammatory activity. The NO release was tunable (0.09-0.51 µmol NO mg-1) depending on wavelength, with shorter wavelengths and greater irradiances providing more efficient photolytic liberation. Antibacterial activity and cytocompatibility were directly modulated by photolytic NO release and payload, where NO was determined to be the primary antibacterial agent and large, initial NO bursts led to preservation of cell viability. Incorporation of the MSN-based NO donors into an HA formulation afforded additional metabolic and immunomodulatory behavior in vitro, demonstrating potential to decrease sebum production and inflammation in acne vulgaris. Blue light-mediated NO release from the HA formulation presents a multifunctional therapeutic platform that addresses key contributing downstream factors of acne.
S. saprophyticus is a common pathogen of urinary tract infections, but bacteremia is rare. We report a case of S. saprophyticus infective endocarditis. A 77-year-old woman with aortic stenosis was admitted for abscessed diverticulitis: S. saprophyticus was isolated from a single blood culture and considered as contamination. Two months later, S. saprophyticus infective endocarditis was diagnosed. Very few cases are reported with a variety of sources ranging from gastrointestinal procedures, urinary tract infections, intravenous drug use and device-related infections. S. saprophyticus growth in only one blood culture does not automatically confirm a diagnosis of bacteremia, but can be significant in high-risk patients.
Enterococcus faecalis is a prolific opportunistic pathogen responsible for a range of life-threatening infections, notorious for its ability to withstand environmental stressors. Second messengers are small molecules that relay signals in response to stimuli and are thought to be crucial for bacteria like E. faecalis to modulate their adaptation to stress. The second messenger nucleotide c-di-AMP has emerged as an essential bacterial signaling molecule due to its impact on physiological processes, including adaptation to osmotic stress, cell wall homeostasis, antibiotic tolerance, and virulence. In addition, c-di-AMP is a pathogen-associated molecular pattern (PAMP) molecule that can trigger a potent stimulation of the host immune system. In previous work, we identified and characterized the enzymes responsible for the synthesis and degradation of intracellular c-di-AMP in E. faecalis, demonstrating that maintenance of c-di-AMP homeostasis is vital for its fitness and virulence. In addition to the intracellular enzymes that regulate c-di-AMP levels, a small number of bacteria encode surface-associated nucleotidases that cleave extracellular c-di-AMP and are potentially associated with immune evasion. Here, we characterize a novel and unique cell wall-anchored nucleotidase, termed EecP (E. faecalis extracellular c-di-AMP phosphodiesterase), which features duplicated catalytic domains and degrades extracellular c-di-AMP. Through competition experiments, we show that EecP likely uses c-di-GMP, and to a lesser extent AMP, as additional substrates. While a ΔeecP strain failed to display relevant phenotypes under most in vitro conditions, it exhibited increased susceptibility to killing by phagocytic cells, a phenotype at least partly associated with cGAS-STING immune signaling. NanoString analysis revealed distinct innate immune signatures in murine macrophages infected with the parent strain OG1RF or ΔeecP, uncovering differential expression of host targets known to be impacted by c-di-AMP, as well as novel targets. Using two murine infection models, we show that the impact of eecP deletion and the consequent buildup of extracellular c-di-AMP on E. faecalis pathogenesis might depend on the site of infection. Notably, disseminated infection was more severe in mice infected with ΔeecP, suggesting that extracellular c-di-AMP influences infection outcomes, likely through modulation of host immune responses.
Secondary use of health data is essential for advancing medical research, innovation, and public health policy across Europe. Traditional static or broad consent models are increasingly inadequate in complex, multistakeholder digital ecosystems. Dynamic consent, which enables granular, interactive, and ongoing management of individual preferences, including revocation, has emerged as a patient-centered alternative. This integrative review examines the legal feasibility and practical challenges of implementing dynamic consent for secondary health data use under the General Data Protection Regulation (GDPR) and the European Health Data Space (EHDS) Regulation. Drawing on doctrinal legal analysis, European policy documents, national derogations, and technical standards including Health Level Seven Fast Healthcare Interoperability Resources, electronic Identification, Authentication and Trust Services 2.0, European Digital Identity Wallet, and distributed ledger approaches, the study synthesizes legal, governance, and informatics perspectives. Findings indicate that while the GDPR establishes parameters supportive of specific, informed, and revocable consent, significant barriers persist due to national fragmentation, divergent lawful bases for processing, and limited cross-border revocation mechanisms. The EHDS, with provisions phasing in from 2029, shifts governance toward institutional authorization via Health Data Access Bodies and secure processing environments, reducing reliance on individual consent for many large-scale uses. Technical prerequisites, machine-readable consent artifacts, high-assurance digital identity, and policy-based enforcement remain unevenly developed. Nevertheless, integration with data altruism mechanisms under the Data Governance Act and emerging interoperability tools offers promising pathways. A 3-stage operational architecture (consent administration, decision, and enforcement) is proposed to embed dynamic consent within the hybrid EHDS-GDPR framework. However, challenges including blockchain immutability conflicts with the right to erasure, revocation propagation across systems, implementation costs, consent fatigue, and digital divides must be addressed. Dynamic consent cannot serve as a universal solution but can meaningfully enhance transparency and trust when deployed contextually alongside institutional safeguards. Coordinated EU-level harmonization, standardization, and inclusive design will be essential for its successful operationalization.
Sepsis remains a leading cause of morbidity and mortality worldwide, with survivors often following divergent trajectories: rapid recovery (RAP) or progression to chronic critical illness (CCI). CCI is characterized by persistent organ dysfunction, recurrent infections, and immune dysregulation. Myeloid-derived suppressor cells (MDSCs), which expand in number after sepsis, are implicated in this maladaptive state, yet their epigenetic regulation remains poorly understood. Here, we applied an Omni-ATAC protocol optimized to profile chromatin accessibility in CD66b + MDSCs from healthy participants (HPs) and sepsis patients across time points (day 4, day 14-21, and 6 months) and clinical outcomes (RAP, CCI, and Deceased). Dimensionality reduction analyses of genome-wide chromatin accessibility showed clear separation of sepsis and HP samples. Furthermore, these analyses revealed distinct trajectories post-sepsis diagnosis: RAP samples progressively regained HP-like chromatin states, whereas CCI samples remained epigenetically "locked" in aberrant states. Differential accessibility analysis identified thousands of promoter regions with altered accessibility, including immune checkpoint and inflammatory genes (e.g., ARG1, CD274, S100A8 / 9 ). Pathway analyses predicted global suppression of immune, metabolic, and chromatin remodeling programs in CCI, contrasting with restoration in RAP. These findings from patient-derived CD66b + MDSCs suggest that epigenetic chromatin remodeling underlies divergent recovery trajectories and highlight chromatin-modifying pathways as potential therapeutic targets to restore immune competence in sepsis patients with CCI.