Abstract: Background: The Mano River Union (MRU) countries (Liberia, Sierra Leone, and Guinea) face persistent health-system constraints related to conflict, epidemics, underinvestment, and weak institutional capacity. Progress toward universal health coverage (UHC) requires evidence on how financing and system-strengthening strategies affect service access, equity, and resilience. This review synthesized evidence on health financing and health-system strengthening in Liberia and the wider MRU, including their implications for health outcomes, equity, and community health systems. Methods: This PRISMA 2020-compliant review was registered in PROSPERO (CRD420251243931). PubMed and African Journals Online were searched for English-language sources published from 1 January 2015 to 31 December 2025, and gray literature was sought from the World Health Organization, World Bank, UNICEF, African Development Bank, and Liberia Ministry of Health. Two reviewers independently screened records and extracted data, and primary empirical studies were appraised using the Mixed Methods Appraisal Tool 2018. Findings were integrated using narrative thematic synthesis within a health-systems framework informed by PECOS. Results: Database searches identified 1,254 records, and organizational sources identified six additional records. After 312 database duplicates were removed, 942 database records were screened; 934 were excluded, and eight reports were retrieved and assessed. All six organizational records were retrieved and assessed. No reports were excluded after full-text assessment, and all 14 reports were included, comprising six journal articles (including two reviews) and eight institutional or technical reports. Five themes emerged: chronic underfunding and low government prioritization of health; mixed, mechanism-dependent performance of financing reforms; geographic and socioeconomic disparities in maternal and child health access; central but donor-dependent community health systems; and Ebola-related disruption with uneven recovery. Governance fragmentation and donor coordination were cross-cutting concerns. Liberia's average health-budget allocation of 3.46% from 2010 to 2018 illustrates the financing gap. Conclusions: Although the evidence base is limited by heterogeneous designs, reliance on policy and technical sources, and the absence of Guinea-specific studies, evidence from the MRU indicates that underinvestment, inequity, and governance weaknesses continue to constrain health-system performance. More predictable domestic financing, equity-oriented reforms, and sustained support for integrated community health systems are priorities for advancing UHC in fragile and post-conflict settings.

Abstract: Respiratory pathogens infect children in a reproducible age order: respiratory syncytial virus (RSV) and pertussis dominate the first months of life, human bocavirus and adenovirus peak in toddlers, Mycoplasma pneumoniae pneumonia peaks at school age, rhinovirus and influenza infect all ages, and several of these pathogens resurge in older adults. Here we compile and organize the published evidence behind these patterns, treating each pathogen’s characteristic age window as a read-out of its immune mechanism within the classical age-structured tradition. Two interacting “clocks” organize the pediatric spectrum. The first is the maternal-antibody umbrella: transplacental IgG decays by infant catabolism, and the protective trough at 2–6 months is set by the distance between the starting titer and a protective threshold, measured in half-lives, rather than by any single half-life; maternal RSVpreF and Tdap vaccination and passive nirsevimab prophylaxis provide trial-level causal proof that this clock sets the infant window. The second clock is the cumulative acquisition of type-specific immunity, which closes the toddler windows of bocavirus and adenovirus but never closes for antigenically diverse rhinovirus or drifting influenza; since exposure accumulates on a similar schedule, this clock is only partially identifiable serologically. M. pneumoniae is the decisive boundary case: a single maternal clock under a constant force of infection cannot place a peak at school age—a known structural property of age-structured transmission models, no new simulations performed—so delayed first sensitization, waning partial immunity, and immunopathology on reinfection are required. For encapsulated bacteria, a “polysaccharide trap”—poorly transferred IgG2-dominated maternal antibody plus developmental T-independent unresponsiveness before age two—explains the earliest bacterial windows. We also synthesize breast-milk, innate-immune and microbiome modifiers of both clocks, and an adult “third clock” of immunosenescence. The framework yields falsifiable predictions for immunization timing and disease patterns in immunocompromised hosts.

Abstract: Background: Myalgic encephalomyelitis (ME) is a severely debilitating neuroimmune disease with the characteristic feature of post-exertional malaise (PEM). Whilst multiple studies have found various abnormalities, there is significant heterogeneity in findings; as such there is no consensus regarding the underlying aetiology. Mast cells are immune cells most commonly recognised for their role in allergy. The scope of biological effects mast cells have is growing in recognition, with inappropriate mast cell degranulation increasingly recognised to cause a range of symptoms and downstream effects. Hypothesis: ME may be a mast cell activation disorder variant, with exertion being the primary trigger to inappropriate mast cell degranulation, possibly due to mast cell hypersensitivity to metabolically produced reactive oxygen species. Mast cell activation releases mitochondrial components which further act as an “autopathogen”, whilst each degranulation cycle reduces mast cell metabolic flexibility. This cycle is perpetuated in those with genetic susceptibility towards Th2-dominance, which acts to both impede pathogen clearance and drive autoinflammation. The resultant chronic immune activation triggers immune and host metabolic changes resembling sickness metabolism. This causes a range of multisystemic symptoms, worsened by exertion, akin to a chronic sickness behaviour. Due to the close and bidirectional interactions between mast cells, the nervous system, and mitochondria, such a hypothesis can potentially explain various aspects of ME, such as: Why ME can be caused by a range of exposures; the core symptoms of ME; individual variances in clinical presentations; why pacing can prevent worsening; and time trends and symptoms of PEM. Several potential counterarguments are also discussed, along with methods to try and test the hypothesis. Conclusion: Several lines of evidence suggest it is at least plausible that (a subgroup of) ME could be a unique and distinct variant of a mast cell activation disorder. As the immune system and metabolism are intrinsically linked, it could be argued this is an immunometabolic mast cell disorder phenotype. However, this is one of many plausible hypotheses, requires testing and validation, and does not change the current recommendations for managing ME, nor should it be used as evidence that the aetiology of ME is established.

Abstract: A recent debate regarding the Carbohydrate-Insulin Model (CIM) and the Mass Balance Model (MBM) has raised a fundamental question: Does measuring mass rather than energy explain the pathogenesis of obesity, or does it merely quantify the excess? Gary Taubes has argued that whether we measure mass or energy, we are simply measuring a quantity, and this tells us nothing about how the system works. This commentary demonstrates that this argument rests on a fundamental category error. Mass and energy are not interchangeable currencies; energy is a scalar property of mass. The pathogenesis of obesity is a physical process – the trafficking of carbon atoms. By examining Taubes’s own analogy of a car’s fuel gauge, I show that mass accounting is not merely a quantification; it is the direct observation of the metabolic engine. The MBM does not replace the CIM’s focus on insulin; it supplies the physical language required to prove it.

Abstract: Point-of-care ultrasonography (POCUS) has emerged as a diagnostic tool in pulmonary medicine, offering real-time bedside assessment of respiratory pathologies. This narrative review examines the current applications of POCUS in pulmonary practice, evaluates its diagnostic accuracy compared to traditional imaging modalities, and explores future directions for this technology. POCUS demonstrates superior sensitivity to chest radiography for detecting pneumonia, pleural effusion, pneumothorax, and pulmonary edema, with diagnostic accuracy approaching that of computed tomography in some clinical scenarios. Key applications include evaluation of acute dyspnea, monitoring of mechanically ventilated patients, guidance of therapeutic interventions, and assessment of diaphragmatic function. Despite its advantages, POCUS requires adequate training and has limitations in some clinical contexts, particularly in ventilator-associated pneumonia and when used as a replacement rather than adjunct to standard diagnostic pathways. Emerging applications include artificial intelligence-assisted interpretation, integration into telemedicine platforms, and expanded use in outpatient pulmonary clinics. As portable ultrasound technology continues to advance and training programs become more standardized, POCUS is positioned to become one of the key components of the pulmonary physician’s diagnostic tools.

Abstract: Biochar is a carbon-rich solid with potential as a fuel component, but its friability limits storage and handling. This study evaluated lignocellulosic co-materials for densifying biochar into briquettes and pellets. Briquettes contained straw/biochar ratios of 100/0, 80/20, 60/40 and 40/60; pellets contained straw/biochar/sunflower-waste ratios of 80/0/20, 60/20/20, 40/40/20 and 20/60/20. Mixture moisture was 5.88–6.81% on a wet basis. Peak compressive force was determined from five briquettes and ten pellets per formulation, and retained mass was measured during abrasion. Briquette peak force was greatest at 80/20 straw/biochar (633.02 ± 173.20 N); the formulation effect was significant by Welch ANOVA (p = 0.024) and Kruskal–Wallis testing (p = 0.004). This formulation remained 67.17% mass after 5 min. Pellet peak force was greatest at 60/20/20 straw/biochar/sunflower waste (1130.81 ± 203.69 N). Pellet data were non-normal at 60% biochar; Welch ANOVA was non-significant (p = 0.085), whereas the Kruskal–Wallis test was significant (p = 0.027). Pellet retained mass after 10 min. decreased from 96.19% without biochar to 90.84, 75.80 and 61.40% at 20, 40 and 60% biochar, respectively. A 20% biochar fraction provided the best mechanical compromise. Energy performance requires separate calorimetric and combustion verification.

Abstract: Background: The granuloma is the defining lesion of sarcoidosis, yet the internal architecture of the non-necrotising lesion — and whether the homeostatic CD10/MME+ macrophage identity enters it — is unresolved in lung.Objectives: To map the programme-level spatial anatomy of the sarcoidosis granuloma and test prespecified cross-disease predictions.Methods: We analysed 10x Visium spatial transcriptomes of three sarcoidosis lungs and one healthy control (GSE262998), four TSC1/2-deficient granuloma-model mouse lungs (GSE263088) and two validation cohorts (nine explanted sarcoidosis lungs, GSE288607; four tuberculous granuloma sections, GSE296400). Granuloma spots, partitioned into core, rim, mid and far zones, were scored for 25 macrophage modules and 49 convergence signatures.Results: A quadripartite programme — antigen presentation (core 1.48–1.80 vs 1.02–1.28), iron handling (1.30–1.45 vs 0.68–1.22), lysosomal mass (0.69–0.95 vs 0.19–0.51), cell fusion (+0.07 to +0.22 core−far in 3/3 sections) — peaked at the core in all three sarcoidosis sections, while hypoxia was flat, unlike the hypoxic-necrotic tuberculosis archetype; the gradients survived density matching, and deconvolution attributed 59–74% of core elevations to per-spot macrophage content (i.e., 26–41% of the elevations reflect per-cell state change rather than composition). The CD10/MME+ identity was not consistently recruited (core MME 0.22 versus 0.38 at far in one section; weak, inconsistent enrichment in two). All four programmes replicated across 80 sarcoidosis nodules (median Δz +0.20 to +0.52; hypoxia +0.03); tuberculous caseous cores displayed perinecrotic hypoxia cuffs with fusion depleted in the caseum (and not enriched in the viable cuff), and the prespecified foam check was falsified (sarcoidosis-strong).Conclusions: The sarcoidosis granuloma is a centripetally organised, perfusion-preserving antigen-sequestration niche without hypoxia; the homeostatic CD10+ identity is not a consistent niche component.

Abstract: Triangular Sierpiński structures have been theoretically studied for microwave applications around the lower edge of the X-band (8-12 GHz). In detail, we present electromagnetic simulations for microstrip-fed resonators on a silicon substrate, encompassing: (i) Equilateral triangles and the spectrum of high-order modes; (ii) Classical and internally stretched Sierpiński triangles; (iii) Cascaded and mixed triangular resonators. We compared analytical results with electromagnetic simulations to reconstruct the spectrum of full, non-subdivided triangles and extended them to predict the resonance modes of Sierpiński structures. For a 6 mm edge length, the analytically predicted fundamental resonance of the full triangle (9.42 GHz) agrees with the simulated one (9.58 GHz) within 2%. The first level of internal subdivision causes a coarse frequency jump of about −17% (to 7.96 GHz), while further subdivisions (C2, C3) provide a fine, nearly linear tuning of about 130 MHz. Cascading two resonators deepens the notch to −27 dB, mixing triangles of different complexity along the feed line produces multiple closely spaced resonances, and stretching the internal triangle splits the C1 resonance into two modes, enabling dual-frequency operation.

Abstract: Graphical user interface (GUI) agents automate tasks in digital environments by interpreting user goals and executing interface operations. GUI grounding serves as a critical link between high-level reasoning and low-level interaction execution in GUI agents. It maps users' operation intents to specific interaction targets and their spatial parameters, enabling agents to translate high-level decisions into executable interface actions. Advances in multimodal large language models (MLLMs) have substantially improved GUI agents' capabilities in autonomous operation. However, existing surveys primarily focus on complete GUI-agent systems, leaving grounding methods, data resources, and performance limitations insufficiently synthesized. To the best of our knowledge, this is the first comprehensive survey dedicated to GUI grounding. First, we establish a unified taxonomy along three complementary dimensions—learning paradigms, inference strategies, and target representations—to systematically characterize the core mechanisms and properties of existing methods. Second, we review training datasets, evaluation benchmarks, and metrics, tracing the evolution of data resources and evaluation tasks. Third, we conduct a comparative analysis of representative methods across evaluation benchmarks, identifying their strengths and limitations across target types, instruction complexity, and interaction requirements, while examining trade-offs between accuracy and inference cost. Our analysis reveals that GUI grounding research is expanding from explicit target localization in static interfaces toward implicit intent understanding, target resolution in dynamic interfaces, and spatial-parameter prediction for complex interactions. We discuss the resulting open challenges and future research directions.

Abstract: Ischemic stroke rapidly disrupts neuronal and synaptic integrity through excitotoxicity, oxidative stress, and inflammation, yet no effective neuroprotective therapy exists. Remote ischemic conditioning (RIC) is linked to systemic protective responses, but the molecular mechanisms by which circulating blood cells (BCs) contribute to RIC-mediated neuroprotection remain poorly understood. To address this gap, we examined whether RIC is associated with changes in BC properties and whether these changes correspond to alterations in the composition and function of their secretome. RIC-treated donor BCs exhibited biochemical features consistent with reduced hemo-lysis, maintained stable glutathione levels during incubation, and showed increased catalase activity, suggesting improved redox resilience. Secretomes from RIC-treated BCs showed elevated levels of the exosome-associated tetraspanin markers CD9 and CD81. Quantitative proteomics identified 680 proteins, of which 40 were differentially abundant (DAPs) between tolerant (TS) and non-tolerant secretomes (NTS). Most DAPs were downregulated in TS. GO enrichment analysis did not identify any significantly enriched terms after FDR correction. Because no GO term passed multiple testing cor-rection, GO results were not interpreted further. Functionally, TS treatment reduced infarct volume from 62.5% to 41.6%, improved neurological scores, and significantly decreased neuronal pyknosis, degeneration, and loss in the penumbra. TS also improved systemic redox balance, lowering oxidized glutathione, reducing the oxidative stress index from 3.5% to 1.9%, and diminishing the oxidative burden, as reflected in lymphocyte DNA damage, to near-control levels. Together, these findings indicate that TS derived from RIC treated donors exhibits neuroprotective potential in an experimental stroke model and is associated with dis-tinct proteomic signatures. The results are exploratory and do not establish a definitive mechanism or therapeutic readiness.

Abstract: Retinal blood vessels form a complex branching pattern that has been shown to be fractal. Since the retinal blood vessels grow through the diffusion of angiogenic factors within the retinal plane, the Fractal Dimension (FD) of the vascular network lies between 1 and 2: This means that the branching pattern fills space more than a line, but less than a plane. In healthy human subjects, the retinal FD has been reported to be approximately 1.7, but it can be altered by the rarefaction or proliferation of blood vessels under pathological conditions. We consider Diabetic Retinopathy (DR), a retinal microvascular complication of diabetes mellitus, associated with chronic hyperglycemia. The aim of this paper is to analyze the fractal dimensions of the superficial and deep retinal vascular plexuses in Optical Coherence Tomography Angiography (OCTA) images. This could help ophthalmologists to make an early diagnosis of this pathology and reduce the risk of severe retinal complications and vision loss.

Abstract: This study examines the incorporation of Generative Artificial Intelligence (Gen AI) into higher education through a critical analysis of the adoption of these resources in educational contexts, drawing on references such as Boa Sorte (2024), Santaella (2023, 2025), Salas-Pilco and Yang (2022), documents from UNESCO (2023), and a document from the Ministry of Education published in 2025 in Brazil. The overall objective is to critically analyze the impacts of GenAI on higher education, considering its potential, epistemological risks, and the ethical implications involved in its institutionalization. Methodologically, this is a qualitative study based on a literature review and document analysis. The results indicate that, although Gen AI contributes to the personalization of learning, the optimization of processes, and the expansion of access to information, its uncritical use can compromise the development of critical thinking, encourage practices of cognitive delegation, and undermine criteria for scientific validation. It is understood that Gen AI in higher education requires a critical approach, based on continuing teacher education, the Pedagogy of Inquiry advocated by Freire, responsible curation, and the explicit articulation of ethical and epistemological criteria. It is therefore argued that the use of Gen AI should be guided by the expansion of epistemic capital and critical awareness within the context of contemporary digital cultures.

Abstract: Background/Objectives: Generative artificial intelligence (AI) creates opportunities for dental education but challenges the validity, authenticity and governance of student assessment. This study developed international consensus on principles and assessment-specific recommendations for AI use in undergraduate dental assessment. Methods: Two international electronic Delphi rounds were followed by a separately sampled live consensus exercise at the 2026 Association for Dental Education in Europe Annual Meeting. Policy consensus required ≥70% rating 7–10; assessment classifications required ≥70% selecting the same permission category. Free-text comments underwent qualitative content analysis. Results: Round 1 included 49 participants and 34/37 policy statements reached consensus. Round 2 retained 41 participants; all 19 revised/new policy statements reached consensus and 9/19 assessment formats reached categorical consensus. Ten unresolved formats proceeded to live voting (up to n=89); only virtual reality/haptics reached consensus (51/71, 71.8%, permitted with restrictions/guidance). Comments highlighted overlapping disclosure/restriction categories, intended learning outcomes, authenticity, enforceability, equity and patient-data safeguards. Conclusions: Stakeholders agreed strongly on governance principles but not on universal permission labels for complex assessments. An outcome- and risk-based framework with explicit rules, human accountability, protected evidence of competence, data safeguards and continuing AI literacy is supported.

Abstract: Separately collected kitchen waste is a common feedstock for anaerobic digestion, but feedstock assessment often relies on a few samples whose representativeness is rarely tested. This pilot study examined the variability of the methane yield of kitchen waste (EWC 20 01 08) delivered to a municipal collection point. Nine samples were taken from three random points of same-day stockpiles in three campaigns (February–April 2026) and analysed for total and volatile solids (TS, VS), macronutrients, elemental composition and methane yield in batch assays (40 °C, inoculum-to-substrate ratio 4.3). VS/TS varied little (80.5–93.1%), whereas the methane yield ranged from 278 to 456 NmL CH₄ g⁻¹ VS (mean 362; coefficient of variation 21%). Samples from different points of the same stockpile differed significantly (nested ANOVA, p = 0.012). The between-campaign component was the largest variance estimate but was not significant with three campaigns (p = 0.070). Kitchen waste of this type was therefore highly heterogeneous when assessed from single grab samples. Neither TS nor VS/TS was related to the methane yield, whereas the composition of the dry matter was: the yield correlated with lipid content (r = 0.95), also within campaigns.

Abstract: This study introduces PCREM, a principal-component analysis/artificial neural network (PCA-ANN) framework for identifying reduced ethanol-combustion mechanism topologies from a two-dimensional OpenFOAM ethanol pool-fire analogue simulated using the 2016-12-14 San Diego Mechanism. For PCA and species ranking, 17 species are selected from the San Diego-generated fields according to the modified Millán-Merino retained-species set, with temperature included as an additional thermochemical scalar. PCA reduces the 18-dimensional thermochemical state to 10 principal components capturing 99.939% of the cumulative variance, while ANN models reconstruct temperature, species mass fractions, principal-component source terms, and diffusion information. A unity-weighted sensitivity analysis is subsequently used to rank the influence of the original thermochemical scalars on the selected quantities of interest. Based on this ranking, three candidate reduced-state mechanisms are proposed: PCREM-16, removing CH₃ CH₂O; PCREM-15, additionally removing CH₃CHOH; and PCREM-13, further removing HO₂ and C₂ H₂. Reaction-consistency analysis distinguishes directly closed pathways from those requiring ANN-based retrieval. The results establish an a priori, data-informed framework for reduced ethanol pool-fire chemistry and provide the basis for subsequent a posteriori OpenFOAM validation and computational-performance assessment.

Abstract: Metaheuristic optimisation is widely used for distribution-network operation, yet claims of superiority are often based on single cases without equal budgets, deterministic references, or reproducible seeds. This study evaluates a fuzzy-adaptive particle swarm optimiser using voltage-deviation and renewable-ramp inputs (FA-PSO-UR) for the dispatch of inverter-interfaced photovoltaic (PV) distributed generation (DG). It is compared with a genetic algorithm (GA), classical particle swarm optimisation (PSO), differential evolution (DE), a grey wolf optimiser (GWO), and time-varying PSO (TV-PSO) on the IEEE 33- and 69-bus feeders. The frozen benchmark comprises 1,080 static runs and 720 sequential 24-hour runs under smooth and cloud-driven PV profiles, with paired seeds and identical function-evaluation budgets. DE achieves the lowest static median in all six cases, whereas FA-PSO-UR is engineering-equivalent to PSO in all six and to TV-PSO in five. All sequential schedules are feasible. FA-PSO-UR achieves the lowest median objective in three of four sequential scenarios, with median gaps of 0.0056–0.0212% to the best-known deterministic references. TV-PSO ranks first for the IEEE 69-bus smooth profile, where the two methods remain engineering-equivalent. FA-PSO-UR shows practical superiority only over selected weaker baselines, not over PSO or TV-PSO. Physical-state-aware adaptation therefore provides selective dynamic benefit rather than universal dominance.

Abstract: The Belt and Road Initiative (BRI) has strengthened economic cooperation between China and its partner countries. This study examines its estimated policy effect on China’s traditional Chinese medicine (TCM) trade and the conditions shaping that effect. Using balanced panel data on China’s TCM trade with 50 partners from 2005 to 2023, we applied a difference-in-differences model and multiple robustness tests. The BRI had a significant positive estimated effect on TCM trade, which remained robust to parallel-trends, placebo, and PSM-DID tests. The trade-promoting effect was stronger at higher levels of technological innovation, logistics infrastructure, and Internet penetration. It was also strongest for crude medicinal materials, more pronounced among politically stable partners, and greater during 2013–2018 than during 2019–2023. The results identify technological innovation, logistics, and digital infrastructure as relevant facilitating factors. The estimated gains were concentrated in less-processed products, particularly Chinese medicinal materials and herbal extracts. These findings quantify the response of medical-product trade to a large-scale international cooperation policy and provide mechanism-consistent evidence relevant to sustainable resource allocation and international health cooperation.

Abstract: Ori's vacuum--dust spacetime has a regular initial hypersurface whose vacuum-core portion is umbilical. The core develops a chronology horizon.Let \(\theta_0\) be the angular cutoff of the core and choose \(0<a<b\) with \(b+2\log(2+\sqrt{3})<\theta_0\). Fix a nonzero real \(p\in C_c^\infty((a,b))\) that is odd about \((a+b)/2\). We construct a smooth, nontrivial one-parameter family of finite-amplitude vacuum constraint deformations, compactly supported in a fixed annulus of the core and defined for every real \(\varepsilon\) with \(\varepsilon^2\|p^2+(p')^2\|_\infty<1\).The family satisfies both nonlinear vacuum Einstein constraints exactly within the core and extends, with Ori's unchanged dust envelope and exterior, to global Einstein--dust initial data satisfying the full constraints. We propagate its axial first variation using the established Kodama--Ishibashi formalism. Under the specified core-size and support conditions, the resulting Weyl Pontryagin first variation satisfies a logarithmic \(L^2\) lower bound as the background horizon is approached. A local hyperbolic equation and the curvature reconstruction establish finite propagation for the invariant curvature observable, even though the auxiliary master potential need not be compactly supported. A radial Wronskian gives a nonzero horizon coefficient on a set of positive spectral measure. We also compute the exact initial twist and the leading term in the initial-slice Weyl Pontryagin expansion of the finite-amplitude data. The growth estimate concerns the linearized Einstein equations, not the curvature of any fixed nonzero-amplitude development. No nonlinear chronology-protection statement is implied.

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is lethal largely because it is diagnosed after it has spread, and the only blood marker in routine use, carbohydrate antigen 19-9 (CA19-9), is a fucosylated glycan whose synthesis depends on polymorphic fucosyltransferases. Aptamers - short single-stranded oligonucleotides selected entirely in vitro - have been proposed for two decades as the recognition element that could make PDAC detectable in serum. Here we assess that proposal against the literature of the past three years. Three conclusions emerge. First, the analytical problem is largely solved: electrochemical, plasmonic, transistor-based and amplification-coupled aptasensors now reach femtomolar to attomolar limits of detection, two to four orders of magnitude below the concentration of every circulating PDAC analyte. Second, the binding problem is not solved in the place where it matters: aptamers are selected against protein epitopes, whereas the clinically validated PDAC marker is a carbohydrate, and the glycan-recognition reagents that would close this gap remain scarce. Third, the evidence problem is untouched: almost all published aptasensors stop at case-control comparison against healthy donors, a design that cannot address the benign pancreatic diseases, diabetes and jaundice that dominate the differential diagnosis, and that inflates positive predictive value in a population where prevalence is 1-2%. We set out the analyte, recognition, selection, transduction and evidence requirements for an aptamer test that could plausibly change how PDAC is found, and argue that the field’s next advance will come from assay architecture - logic-gated, multi-analyte, single-vesicle measurement - rather than from another order of magnitude in sensitivity.

Abstract: Background: To evaluate whether pupil dynamics affect the effectiveness of peripheral defocus spectacle lenses in slowing myopia progression in European Caucasian pediatric patients. Methods: This non-randomized retrospective observational study included 53 children (mean age 10±3 years) with documented progressive myopia and no ocular disease. We retrospectively reviewed the records of patients who had worn Defocus Incorporated Multiple Segments (DIMS; Hoya MiyoSmart, group A) or Highly Aspherical Lenslet Target (HALT; Stellest; EssilorLuxottica, group B) spectacle lens for at least 24 months. Cycloplegic spherical equivalent (SE) and axial length (AL), were measured at baseline and at 24 month follow- up, and myopia progression was calculated as the difference between mean SE and AL during the follow-up time. Dynamic pupillometry was measured once during the follow-up and the pupil diameter change (PDC) was calculated as the millimeters difference between scotopic and photopic diameter. Results: After 24 months, group A and B did not differ significantly in SE, AL and PDC change (p > 0.05). In group A and B the SE change was positively correlated with PDC (p < 0.05), while AL change and PDC did not show significant correlation in both groups (p > 0.05). For group A and B the PDC median was respectively 4.5 and 4.7mm.Conclusion: These findings suggest that AL change could be considered not dependent by pupil dynamics for evaluating myopia progression, and that a PDC lower than 4.5mm seems to improve the effectiveness of peripheral defocus spectacle lenses in slowing SE increase in European Caucasian pediatric patients, without significant differences between DIMS and HALT design.