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Software Defined Networking (SDN) enhances network programmability and management by decoupling control and data planes. However, this logically centralized control plane introduces scalability issues and security vulnerabilities. In multi-domain SDN architectures malicious entities can compromise controllers to inject false flow rules, disrupting network integrity. Existing solutions often rely on static cryptographic authorizations, failing to monitor the real-time operational integrity of controllers. To address these limitations, this paper proposes an enhanced blockchain-based control layer security framework in multi-domain SDN (EBCS-SDN). The framework introduced a dynamic trust scoring model, an optimized dual-phase controller authentication mechanism and a decentralized behavioral-deviation hijack detection system to ensure continuous controller accountability. The empirical evaluations in a simulated multi-domain SDN environment demonstrated significant performance and security improvements over existing baselines models Voting-based, Proof-of-work (PoW)-based, DLCA_R_P, and BCS. Simulations in an emulated environment show that the proposed framework optimally reduces controller authentication latency by up to 75% and achieves a hijack detection accuracy of 96.78%. Under these simulated proof-of-concept conditions, the system demonstrated a post-attack throughput of 980 Mbps with detection and isolation times under 1.2 s. The proposed framework optimized the CPU utilization at full network nodes. Ultimately, the proposed system provides a scalable, computationally lightweight, and operationally resilient security foundation for SDN deployments.

Patient and public involvement (PPI) is increasingly promoted in health services research, yet empirical evidence remains limited on how participatory governance is operationalised in research practices. This qualitative study explored patient partners' experiences of involvement in the PaRole OncO France (PROOF) research project, a multicentre participatory action research (PAR) project aimed at adapting, implementing and evaluating a peer support intervention in oncology. Semi-structured interviews were conducted with patient partners involved in project governance. Data were analysed using inductive thematic analysis, with patient partners involved in validating analytic outputs. Seven of the eight invited patient partners (PPs) were interviewed. Three interrelated themes emerged: (1) personal invitation as recognition: a catalyst of engagement, whereby being personally solicited was experienced as recognition of experiential legitimacy; (2) securing a 'real place': relational trust, dedicated spaces and institutional frictions, capturing both the conditions enabling genuine co-governance (dedicated spaces, recognition of experiential knowledge and responsive research teams) and the administrative and temporal constraints that strained it; and (3) reciprocal transformation: perceived impacts on the research and on personal trajectories. Patient partners perceived meaningful contributions to intervention design and team cohesion, alongside personal benefits such as skills development and network building. Persistent barriers were primarily structural, including administrative constraints, research temporalities and regulatory procedures. PROOF illustrates how intentional participatory governance mechanisms can support sustained PPI in research. Addressing administrative barriers, clarifying roles and nurturing trust and communication are crucial for meaningful participation in oncology research. The qualitative data presented in this manuscript were obtained through interviews with patient partners. Patient partners co-designed governance structures, participated in all committees, co-facilitated co-construction workshops, and contributed to data interpretation and manuscript validation.

The hydrodynamic model of hydrocephalus proposes that ventriculomegaly is driven by exaggerated intraventricular pulsations rather than impaired cerebrospinal fluid (CSF) circulation alone. Under this model, endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) treats hydrocephalus by creating a pulsation absorber and by reducing a primary source of intraventricular pulsation. However, direct intraoperative human evidence supporting this two-step mechanism is lacking. This study aimed to test the hypothesis that ETV followed by CPC would produce measurable, stepwise decreases in mean intraventricular pressure (ICP) and pulsation amplitude in infants with hydrocephalus. This single-institution proof-of-concept study included infants with symptomatic hydrocephalus undergoing ETV/CPC as the first definitive treatment. A fiber-optic ICP sensor was attached to the operative ventriculoscope and passively recorded mean and pulsatile ICP (pulsation amplitude) throughout the procedure. Longitudinal brain parenchymal volume (BPV) and cerebrospinal fluid volume (CSFV) were obtained through segmentation of clinically acquired T2-weighted MRI and converted to age- and sex-matched z-scores. All patients were followed for a minimum of 6 months postoperatively. Five infants (median corrected age at ETV/CPC 8 months) were included. No surgical complications occurred, and no ETV/CPC failures were observed during follow-up. Overall, mean ICP decreased by 56-97% after the combined procedure in four patients. In three patients (Patients 1, 3, and 5), both mean ICP and pulsation amplitude decreased stepwise following ETV and then CPC, consistent with the hypothesized therapeutic mechanism. Patient 4 demonstrated a large reduction in mean ICP after ETV with minimal additional effect from CPC and no significant change in pulsation amplitude. Patient 2 demonstrated neither a reduction in mean ICP nor a meaningful change in pulsation amplitude after either procedure; this patient also had a delayed and atypical clinical response. Intracranial segmentation demonstrated BPV z-score stabilization within normal range and CSFV plateau in all patients after surgery. This proof-of-concept study provides the first direct intraoperative human evidence supporting the hydrodynamic mechanism of ETV/CPC in a subset of infant with hydrocephalus. Our findings suggest that determination of intraoperative ICP parameters is feasible, safe and might ultimately prove helpful in improving patient selection for ETV/CPC, warranting further investigation in larger cohorts.

Cancer is the leading cause of disease-related deaths among children in high-income countries. Tumor heterogeneity and lack of mechanism-of-action-based therapeutic options are key challenges to overcome to improve pediatric cancer patient survival. To address these challenges, we formed the EU-IMI-2 funded public-private partnership "ITCC-Pediatric Preclinical Proof-of-Concept Platform" (ITCC-P4), which built a large repertoire of patient-derived xenograft (PDX) models representing all major high-risk solid pediatric cancer types for in vivo drug testing. A total of 353 PDX models were established from diagnostic and relapsed pediatric cancers and molecularly characterized, together with matched germline/tumor samples. Serial PDX models were also established, spanning diagnostic/posttreatment, primary/relapse, and metastasis-derived pairs. Proof-of-concept in vivo drug screening data in neuroblastoma and rhabdomyosarcoma models identified potential predictive biomarkers for targeted therapy. Molecular data from the PDX models, accessible at https://r2platform.com/itcc-p4, allowed the selection of models for preclinical testing based on oncogenic drivers and/or potential biomarkers. Operated by a non-profit entity, this sustainable platform aids academic and industrial researchers in developing and prioritizing innovative therapies for pediatric cancer.

Lyotropic liquid crystalline nanoparticles (LCNPs), including cubosomes, are increasingly investigated as antimicrobial nanomaterials because non-lamellar lipid nanoparticles can fuse with biological membranes, exchange lipids, and improve antimicrobial delivery or antibiotic combination treatment. However, prior studies have mainly addressed fusion, uptake, encapsulation, or payload stabilization, rather than testing whether retained internal curvature can be isolated as a design variable for antibacterial potentiation in a matched LCNP series. Herein, we generated lamellar vesicles, primitive cubosomes (P-cubosomes, Im3m), and diamond cubosomes (D-cubosomes, Pn3m) from the same phytantriol/DPPS lipid system. When combined with free daptomycin, rather than being used as drug-loaded carriers, these LCNPs exhibited curvature-dependent potentiation hierarchy against methicillin-resistant Staphylococcus aureus (MRSA), vesicles < P-cubosomes < D-cubosomes. Fluorescence imaging, electron microscopy, and neutron reflectometry showed progressively stronger membrane association, lipid extraction, and bilayer disruption with increasingly negative curvature. In a murine bacteremia model using a sub-optimal daptomycin regimen, the same curvature-dependent efficacy trend was retained in vivo, providing proof-of-concept support rather than therapeutic validation. This study provides direct experimental evidence, in a matched antibacterial LCNP system, that retained internal curvature modulates membrane remodeling and potentiates daptomycin against MRSA.

Complex coacervates (CCs) effectively concentrate biomolecules via liquid-liquid phase separation; however, extracting analytes for detection remains challenging because of the high ionic strength required to dissolve the CC phase. Here, we demonstrate a workflow integrating CC-based pre-concentration with nanopore sensing, which inherently operates under high-salt conditions. We investigated CCs formed by polycations (PLL, PDDA) and nucleotides (ATP, ADP) for the enrichment of microRNAs (miRNAs). While these CC components inhibited reverse-transcription polymerase chain reaction (RT-PCR), the dissolved phase was compatible with lipid bilayer-based &#x3b1;-hemolysin nanopore detection. Optimization of the polymer composition (S-PDDA/ATP) minimized pore clogging and noise. Using specific DNA probes, we successfully detected miRNA enriched in the CCs immediately after salt-induced dissolution. This study establishes a proof of concept for using phase separation as a seamless pre-concentration strategy for nanopore-based biosensing.

Thermogalvanic waste-heat harvesting offers a promising route to the productive utilization of low-grade thermal energy, but current cells remain limited by low thermopower and power output. Here, we report a thermogalvanic electrolyte that inserts the canonical Fe(CN)63-/4- redox cycle within an optimized NH4OH-CH3COOH alkaline environment. Our results show that the optimal mixture establishes differential formation energies between the hexacyanoferrate redox pair, thereby amplifying the configurational entropy difference between redox states and boosting the thermopower from 1.48 to 2.64 mV K-1 in a symmetric graphite cell, with a normalized power density of &#x223c;1.5 mW m-2 K-2 sustained across &#x394;T = 10-50 K. We show that placing the optimized electrolyte within an asymmetric copper-graphite electrode setup leads to a hybrid mechanism of galvanic-thermogalvanic (gTg), which produces a total output substantially exceeding the sum of isothermal galvanic and electrode-analogous thermogalvanic cell outputs, while also demonstrating significantly extended operational longevity over isothermal discharge. A 50-cell proof-of-concept device mounted on a PC tower produces 42 V and 160 mW total output, of which 7 V and 37.6 mW are derived from the thermal contribution.

An o-phenylene-bridged di(2-anthracenyl)diamine (2) bearing two 2-anthryl units was synthesized through a two-step Buchwald-Hartwig cross-coupling strategy. Subsequent Scholl-type oxidative cyclization with FeCl3 or p-chloranil under acidic conditions proceeded with high regioselectivity, yielding a cyclic 1,1'-bianthryl derivative (1B) that incorporates an eight-membered [1,4]diazocine framework generated concurrently with intramolecular biaryl bond formation. The photophysical properties of 2 and 1B were examined using UV-vis absorption and fluorescence spectroscopy, which revealed fluorescence bands and a marked reduction in fluorescence quantum yield upon cyclization. Enantiomeric resolution of racemic 1B was accomplished by chiral high-performance liquid chromatography (HPLC), and the absolute configurations were determined through circular dichroism (CD) spectroscopy combined with time-dependent density functional theory (TD-DFT) calculations. Notably, when chiral camphorsulfonic acid served as the Br&#xf8;nsted acid additive in the p-chloranil-mediated Scholl reaction, asymmetric induction was observed, affording an enantiomeric excess (ee) of up to 10%. Although the enantioselectivity remains modest, this finding provides experimental evidence that an external chiral acid can impart stereochemical information during oxidative intramolecular biaryl bond formation. This study establishes a proof of concept for asymmetric control in Scholl-type reactions and underscores the potential of medium-sized N-bridged frameworks for constructing chiral &#x3c0;-conjugated architectures.

The increasing use of reclaimed water in Mediterranean agriculture, together with the valorization of agro-industrial by-products, has created new scenarios for potential contaminant transfer into food-derived products. Plant-based dietary supplements constitute a distinctive exposure niche because plant materials may accumulate environmental contaminants during cultivation, while downstream processing can concentrate both bioactive compounds and xenobiotics. In this preliminary case study, a targeted UHPLC-MS/MS approach was applied to BIOMEDER, a Mediterranean multi-by-product dietary supplement formulated from plant materials cultivated under conditions that included reclaimed-water irrigation, to investigate the occurrence of contaminants of emerging concern (CECs). Pharmaceuticals, pesticides, cyanotoxins, bisphenols, and a lifestyle-related marker were simultaneously evaluated. Twenty-four pharmaceuticals (&#x3a3;&#x2009;=&#x2009;167.8&#x2009;&#xb1;&#x2009;5.1&#xa0;ng g-1), sixteen pesticides (&#x3a3;&#x2009;=&#x2009;358.0&#x2009;&#xb1;&#x2009;0.8&#xa0;ng g-1), caffeine (49.5&#x2009;&#xb1;&#x2009;0.2&#xa0;ng g-1), and four cyanotoxins (&#x3a3;&#x2009;=&#x2009;0.8&#x2009;&#xb1;&#x2009;0.0&#xa0;ng g-1) were detected, whereas bisphenols were not detected above the method detection limits. Screening-level daily intake estimates, calculated assuming a supplement consumption scenario of 1&#xa0;g day-1, indicated higher body-weight-normalized exposure for children (25&#xa0;kg body weight) than adults (70&#xa0;kg body weight). Pesticides represented the dominant contaminant class, with phosmet, fluazinam, and chlorantraniliprole contributing most to the overall burden, while piroxicam and diclofenac were the principal pharmaceutical residues. Although the detected concentrations were low, the simultaneous occurrence of multiple contaminant classes highlights the relevance of mixture-based exposure assessment for plant-derived supplements. Because the study was conducted on a single supplement formulation, the results should be interpreted as a proof-of-concept dataset rather than as representative of plant-based supplements in general. To our knowledge, this is the first study reporting the concurrent occurrence of pharmaceuticals, pesticides, cyanotoxins, and a lifestyle-related chemical marker in a Mediterranean agro-industrial by-product dietary supplement, providing a baseline for future exposomic investigations and the development of monitoring strategies within a One Health framework.

Economically motivated adulteration (EMA) of roasted coffee presents a critical challenge to global market integrity and consumer safety, specifically regarding the surreptitious inclusion of high-risk allergens like barley and soybeans. The detection of such contaminants is historically hindered by the Maillard reaction, a thermal convergence during roasting that renders adulterants visually and spectrally indistinguishable from the coffee matrix. To address this forensic gap, this study presents a targeted hyperspectral imaging (HSI) framework (400-1000 nm) integrated with a two-stage hierarchical Support Vector Machine (SVM) designed to decouple detection from specific biological diagnosis. A core contribution of this methodology is the implementation of Principal Component Analysis (PCA) to resolve spectral redundancy across the 128-band hypercube. By distilling the data into two primary components capturing over 92% of the cumulative variance, the framework establishes a "spectrochemical bridge" that isolates hidden chromatic and biochemical variances invisible to traditional RGB sensors. This high-significance feature space allows the SVM to overcome the "Euclidean trap" inherent in unsupervised clustering, which frequently suffers from "class collapse" in roasted materials. Experimental results demonstrate that the hierarchical pipeline achieves an optimal overall accuracy of 88.6% and a Kappa coefficient of 0.378. The system attained high reliability during the Stage-1 binary screening, achieving an F1-score of 0.922 to protect the primary coffee matrix, while the Stage-2 multi-class model successfully mapped the spatial distribution of the highly camouflaged allergens. By providing pixel-wise, automated risk assessments, this work establishes a data-driven proof-of-concept for 'Smart Food Safety' systems, highlighting the potential for forensic authentication in future industrial quality control environments.

Aging is accompanied by widespread remodeling of DNA methylation (DNAm), which can be leveraged to build epigenetic clocks. In mice, most DNAm clocks rely on internal organs or terminal tissues, limiting longitudinal studies. Here, we compared age-associated DNAm patterns in matched blood and tail-an easily accessible but underexplored tissue-and evaluated both as substrates for tissue-specific DNAm age prediction. Matched blood and tail were collected from male C57BL/6N Per2::Luc mice aged 7-103&#xa0;weeks and profiled using the Infinium Mouse Methylation BeadChip. After SeSAMe preprocessing, probe-wise regression (&#x3b2;&#x2009;~&#x2009;Age, BH-FDR&#x2009;<&#x2009;0.05) identified 78,111 age-associated CpGs in blood and 38,348 in tail. Blood showed predominantly hypomethylating changes and a later, more abrupt age shift, whereas tail exhibited a near-balanced hyper/hypomethylation pattern with smoother transitions. Segment-level analysis (BH-FDR&#x2009;<&#x2009;0.05,&#x2009;&#x2265;&#x2009;2 CpGs) identified 31,322 age-related&#xa0;differentially methylated regions (DMRs) in blood and 21,883 in tail. Direction-aware overlap yielded 6229 shared age-related DMRs, characterized by CpG island-enriched hypermethylation and Open Sea-enriched hypomethylation and linked to genes enriched for developmental, neuronal, immune, and signaling pathways. Elastic-net clocks achieved high accuracy in the training cohort (blood: &#x3b1;&#x2009;=&#x2009;0.8, 72 CpGs, MAE&#x2009;=&#x2009;2.30&#xa0;weeks, R2&#x2009;=&#x2009;0.99; tail: &#x3b1;&#x2009;=&#x2009;0.5, 192 CpGs, MAE&#x2009;=&#x2009;2.75&#xa0;weeks, R2&#x2009;=&#x2009;0.98). The blood clock generalized to an independent female blood dataset (MAE&#x2009;=&#x2009;13.48&#xa0;weeks, R2&#x2009;=&#x2009;0.76). Together, these findings provide a proof-of-concept foundation for tissue-specific epigenetic age estimation in mice using minimally invasive sampling and highlight tail as a promising substrate for longitudinal DNAm aging studies without terminal tissue collection.

A major barrier to the implementation of artificial intelligence for medical applications is automated CNNs' lack of explainability and high confidence for incorrect decisions, specifically with out-of-domain samples. We propose a generalization of image translation networks for image classification and demonstrate translation networks' potential as a more interpretable alternative to conventional black-box classifiers. We train an image-to-image network to translate an input image to class-specific hypotheticals, and then compare these with the input, both visually and quantitatively. Translation distances, the degree of alteration needed to conform to one class or another, are examined for clusters and trends, and used as a simple low-dimensional feature vector for classification. On melanoma/benign dermoscopy images, a translation distance classifier achieved 80% accuracy using only a two-dimensional feature space (versus 85% for a conventional CNN using a &#x223c; 62 , 000 -dimensional feature space). Visual inspection of rendered images revealed dataset biases, such as more scale bars in melanoma photographs than in benign lesions. Image distributions in translation distance space revealed a natural separation along the lines of dermatologist decision to biopsy, rather than between malignant and benign. On bone marrow cytology images, translation distance classifiers outperformed a conventional CNN in both 3-class (92% accuracy versus 89% for CNN) and 6-class (90% versus 86% for CNN) scenarios. This proof-of-concept shows the potential for image-to-image translation to go beyond artistic/stylistic changes and to expose dataset biases, perform dimension reduction and dataset visualization, and in some cases, potentially outperform conventional end-to-end CNN classifiers.