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Concept Paper
Medicine and Pharmacology
Other

Gerson Hiroshi Yoshinari Júnior

,

Luciano Magalhaes Vitorino

Abstract: Background: Large language models can support clinical work, but their use in high-stakes settings raises risks of over-reliance, opacity, and erosion of professional judgment. Objective: To present MAGI, a conceptual multipersona framework for ethical deliberation and criticality triage in clinical decision support. Approach: The proposal distinguishes constrained analytical personas from autonomous clinical agents and combines legal, personalist bioethical, and biomedical perspectives through a content-analysis-informed synthesis. No empirical implementation or validation results are reported. Proposed framework: A coordinator is intended to document relevant considerations, agreements, disagreements, evidentiary gaps, and reasons for escalation. The proposed output is an auditable deliberation report, not a treatment recommendation. Clinician review is required before any use; high-criticality cases or persistent material disagreement require escalation to the appropriate accountable human process. No convergence threshold or iteration count is established as a safety criterion. Conclusion: A multipersona architecture may help make value conflicts and automation-related risks visible before action is taken. Prospective evaluation is required to determine whether it improves issue detection, appropriate reliance, usability, or safety compared with simpler alternatives.

Article
Medicine and Pharmacology
Pathology and Pathobiology

Naveen Mekala

,

Namdev Togre

,

Sunil Kurian

,

Slava Rom

,

Uma Sriram

,

Yuri Persidsky

Abstract: Chronic exposure to ethanol (ETH) and e-cigarette vapor activates the P2X7 receptor (P2X7R) in human pulmonary alveolar epithelial cells (hPAEpiCs), promoting extracellular vesicle (EV) release. Proteomic analysis of this EVs identified enrichment of urokinase-type plasminogen activator (uPA), a key extracellular matrix remodeling enzyme. Treatment of hPAEpiCs with ETH, acetaldehyde (ALD), and e-cigarette vapor, with or without nicotine, induced NLRP3 inflammasome activation, IL-1β secretion, and increased incorporation of uPA into EVs. Exposure of human brain microvascular endothelial cells (hBMVECs) to this EVs enhanced plasmin conversion, activated MMP-9 and TGF-β1, resulting in reduced transendothelial electrical resistance (TEER), indicating blood-brain barrier (BBB) dysfunction. Pharmacological inhibition of P2X7R using ‘A804598’ significantly reduced EV-associated uPA release and attenuated endothelial injury. In vivo, chronic ETH vapor exposure increased expression of uPA, uPAR, MMP-2, and MMP-9 while decreasing SERPIN1 and TIMP1 in murine brain microvessels, changes associated with BBB disruption and IgG leakage into brain parenchyma. P2X7R inhibition normalized these effects. Collectively, these findings identify EV-associated uPA as a mediator of lung-to-brain signaling and BBB injury following ETH and e-cigarette exposure.

Article
Computer Science and Mathematics
Artificial Intelligence and Machine Learning

Robert Campbell

Abstract: Assurance for autonomous agents depends on operational evidence about policy decisions, actions, execution, effects, provenance, and enforcement. This study tests whether bounded assurance claims remain semantically admissible when that evidence is adversarially degraded. Three co-primary questions address deviation existence (B1), observable action-path reconstruction (B2), and containment/enforcement-boundary localization (B3). A deterministic mutation harness applied 14 frozen single-operator evidence-plane attacks to three known-ground-truth baselines, producing 42 adversarial cases and 126 claim evaluations. A prospectively frozen strongest-safe oracle and closed-world semantic scorer classified the 126 claim evaluations into three predefined categories: exact safe, safe conservative, and unsafe false establishment. All 42 cases were valid. Of the 126 claim evaluations, 56 were exact safe, 47 safe conservative, and 23 unsafe false establishment. The resulting Unsafe False Establishment Rate (UFER) was 23/126 = 0.18254, so the pre-specified zero-UFER target failed. Unsafe outcomes were B1 3/42, B2 19/42, and B3 1/42. Exploratory forensics classified 21 unsafe evaluations as substantive semantic incompatibilities and two as possible scorer-normalization artifacts. The dominant B2 mechanism was global ineligibility after localized evidentiary degradation. These results distinguish semantic safety from information retention: evidence defects must not induce propositions beyond the boundary justified by surviving admissible evidence.

Communication
Public Health and Healthcare
Public Health and Health Services

Ivan Vito Ferrari

Abstract: Protein kinases play central roles in cellular signaling pathways, and their dysregulation is implicated in numerous diseases, including cancer, inflammation, and cardiovascular disorders. Natural compounds such as curcumin and polydatin have demonstrated potential in modulating kinase activity, but a systematic comparison of their interactions with protein kinases has not been extensively explored. In this study, we performed a comprehensive molecular docking analysis of curcumin and polydatin against 77 protein kinases, including receptor and non-receptor tyrosine kinases, using AutoDock Vina via the PyRx platform. Our results indicate that polydatin generally exhibits stronger binding affinities across a broad range of kinases compared to curcumin, with particularly high affinities observed for ABL1, DDR1, FGFR3, TNNI3K, JAK1, and JAK2. In contrast, curcumin shows selective strong binding primarily to KIT and DDR1. These findings highlight polydatin’s potential as a multi-target therapeutic agent, capable of modulating key kinases involved in cancer, inflammation, and cardiovascular disease. The study provides a foundation for further in vitro and in vivo investigations into polydatin as a promising candidate for targeted kinase inhibition and therapeutic development.

Review
Medicine and Pharmacology
Medicine and Pharmacology

Mi Yang

,

Li Zhang

,

Chang-Hao Luo

,

Bin-Bin Zhang

,

Jia-Nan Zhao

Abstract: Rheumatoid arthritis (RA) is sustained not only by immune activation within the synovium but also by dysfunction of the lymphatic network that normally clears interstitial fluid, inflammatory mediators, and leukocytes migrating from inflamed tissues. Functional abnormalities in lymph node stromal cells may arise before clinically apparent arthritis. After RA becomes established, the lymphatic response may shift from compensatory lymphangiogenesis to reduced collecting-vessel contraction, structural deterioration of draining lymph nodes, and impaired lymphatic drainage. This review examines how IL-33/ST2 signaling, neutrophil extracellular traps (NETs), and the lymphatic endothelial program maintained by PROX1 may influence the shift from compensatory remodeling to lymphatic dysfunction. During early inflammation, IL-33 can activate the ST2/TRAF6/PI3K/Akt/eNOS/NO pathway in lymphatic endothelial cells (LECs), while VEGF-C/VEGFR3 signaling supports lymphatic vessel growth and fluid transport. But vessel expansion does not guarantee that newly formed lymphatics mature or restore effective drainage. As inflammation persists, TNF-driven iNOS activity, occupation of lymphatic sinuses by B cells, and structural changes in draining lymph nodes can reduce lymphatic transport and prolong synovial exposure to cytokines, immune complexes, and autoantigens. NETs directly injure lymphatic endothelium in inflammatory models outside RA, but direct evidence in synovial LECs remains unavailable. NET-associated histones, proteases, myeloperoxidase, extracellular DNA, and HMGB1 should therefore be considered plausible rather than established mediators of LEC injury through junctional disruption, oxidative stress, or RAGE- and TLR9-related signaling. Reduced PROX1 activity may further weaken lymphatic endothelial identity by disrupting the expression of VEGFR3, LYVE1, PDPN, and CCL21, which support vessel maintenance and immune-cell transport. Based on these findings, we propose a stage-dependent model in which established IL-33–NET–fibroblast-like synoviocyte and IL-33–macrophage circuits increase the inflammatory burden, while declining lymphatic clearance retains the mediators that sustain these circuits. This framework separates demonstrated mechanisms from untested links and identifies synovial LEC injury, lymphatic transport, and stage-specific pathway modulation as priorities for mechanistic studies and therapeutic development.

Article
Physical Sciences
Mathematical Physics

Jesús M. Soledad Terrazas

Abstract: An earlier paper of mine, “Spacetime Coherence Theory,” claimed to derive the lepton and quark spectra, the CKM matrix, dark matter, dark energy, the hierarchy problem and a set of collider and gravitational-wave signatures from two ideas: that position and momentum are inseparable because spacetime is, and that matter is not primitive but a stable pattern of coherence in a field on spacetime. This paper keeps the two ideas and discards everything the two ideas do not reach. What they reach is small and exact: the first idea is the kinematic content already rebuilt in a companion paper (it yields the commutation relation and the uncertainty relation through Bargmann’s theorem, and nothing about matter); the second idea yields, through Wigner, the identity between a stable mode’s rest frequency and its mass, the identification of the earlier paper’s “coherence length” with the Compton wavelength, and a precise statement of what “crystallisation” can mean once a nonlinearity is added, namely non-topological solitons of Coleman’s type, whose spectrum is set by the potential and not by an integer. Every numerical claim of the earlier paper is checked; the lepton formula is shown to be a fit whose free parameters are the answers, and four headline numbers are off by between 24 and 70 orders of magnitude. The residue is one honest sentence: a particle is a stable, localised, frame-democratic mode of a field, and its mass is the frequency of that mode in its own frame.

Article
Computer Science and Mathematics
Mathematics

Minchul Kang

Abstract: We present a substitution-based framework for solving non-homogeneous linear ordinary differential equations by factorizing the associated differential operator into first-order factors. This reduces the original higher-order equation to a nested sequence of first-order linear equations, each solvable by an integrating factor. The method gives explicit integral representations of particular solutions and directly constructs the corresponding causal Green’s functions. For constant-coefficient second-order equations, the method recovers the standard kernels for distinct real roots, repeated roots, and complex conjugate roots. The approach also applies to variable-coefficient equations whenever a first-order factorization is available, including Cauchy-Euler equations. Finally, we show that the factorization problem for second-order variable-coefficient equations is equivalent to finding a particular solution of an associated Riccati equation.

Article
Computer Science and Mathematics
Information Systems

Julio Rives

Abstract: We investigate mechanisms by which natural systems store data across multi-dimensional spaces, integrating principles from information theory, probability, algebra, and geometry. We propose that simple Lie groups (SLGs) govern these encoding processes and act as basic information spaces. We start by showing that Euclidean space turns computationally unsolvable in higher dimensions. If we do not notice the "curse of dimensionality," it is likely because nature uses geometric positional notation at a rudimentary level. Using Benford's law, we extend the definition of radix economy to m physical dimensions. The new function measures a system's storage cost and has interesting properties. It grows as (Log_r(N))^m, rather than as N^m, providing radix r and rank m invariance, and attaining a "natural" minimum at r = e^m. This cost accommodates a homogeneous distribution of the space with a centripetal bias, avoiding the curse, and diverges when we abandon the positional system (i.e., as r->1 or r->∞) or when the dimensionality explodes (as m->∞). We review the SLGs central to modern geometry and physics. We note that they have irreducible representations of order s ≈ e^m and storage cost sorted by s, as expected. We suggest a universal notation based on balanced ternary to uniquely encode integers as the difference of two natural numbers in bijective notation. Structure and information are coupled so that the unit vectors of an s-dimensional irrep each have a label used by the radix r as an alphabetic symbol of the proposed symmetric bijective system to represent data. Finally, we examine the Weyl order of some of these SLGs, showing that Weyl divisors give rise to a logarithmic scale consistent with Benford's Law with radix r = s. This means that an SLG is autonomous to serve as an information space of non-Euclidean geometry.

Article
Public Health and Healthcare
Public, Environmental and Occupational Health

Carlos Mena

,

Yony Ormazábal

,

Eduardo Fuentes

,

Juan Carlos Cantillana

,

Victoria Villalobos

,

Nacim Molina

,

Iván Palomo

,

Diego Arauna

Abstract: Characterizing how the built environment shapes the health of aging populations is a growing priority for environmental assessment and for the spatial decision-support tools that inform age-friendly planning. Geographic information systems (GIS) allow neighborhood resources to be treated as measurable environmental exposures for older residents. We examined whether geographic information system (GIS)-derived measures of spatial accessibility to key urban resources are associated with cognitive impairment, physical and cognitive frailty subtypes, and polypharmacy in a cross-sectional study of 317 community-dwelling adults aged ≥65 years in the city of Talca, Chile. Physical frailty was assessed with the Fried phenotype, cognitive impairment with an abbreviated Mini-Mental State Examination, and polypharmacy as the daily use of ≥5 medications. A summary Urban Quality Index (UQI), a distance-based measure of spatial accessibility to neighborhood resources, was constructed from Euclidean distances and analyzed in quartiles and as a binary indicator. Cognitive impairment (25.2%), polypharmacy (49.5%), and frailty (35.0%) were highly prevalent and frequently co-occurred. In multivariable models adjusted for age, sex, education, body mass index, and nutritional risk, low UQI was not significantly associated with any outcome. Resource-specific distance patterns should be considered exploratory. These findings suggest that residence-based, straight-line accessibility may not capture the environmental exposures most relevant to healthy aging—consistent with the uncertain geographic context problem—and that richer indicators, such as walkability, public-space quality, physical barriers, and mobility-based exposure, are needed before such indices can support environmental decision-making. Given the cross-sectional design, the results are preliminary spatial associations and do not demonstrate that environmental accessibility influences these outcomes.

Review
Computer Science and Mathematics
Artificial Intelligence and Machine Learning

Ziqian Bi

,

Xin Liang Chia

,

Ye Tao

,

Junfeng Hao

,

Yue Ma

Abstract: World model has become an umbrella term for systems with very different scientific obligations. A recurrent latent con-troller, a diffusion environment, a four-dimensional driving simulator, a symbolic transition model, and a neural weatherforecaster can all predict futures, yet they expose different state, control, and uncertainty interfaces. This survey draws on 322verified sources to organize those systems by a functional contract rather than an architectural label. The contract asks whethera learned model maintains state relevant to a consumer, predicts future states or observations under admissible interventions,and makes those predictions available for evaluation or choice. A six-axis taxonomy records state semantics, transition parame-terization, intervention channel, uncertainty, temporal scope, and downstream use. It provides a common map for model-basedreinforcement learning, predictive representation learning, interactive video, robotics, driving, language environments, spatialsimulation, and scientific forecasting without treating their outputs as interchangeable. The accompanying evaluation stackseparates perceptual quality, state and transition fidelity, intervention response, decision utility, transfer, and system latency.Across these literatures, local realism has advanced faster than counterfactual reliability: a model may render a convincingfuture while forgetting hidden state, assigning the wrong consequence to a control, or becoming exploitable by its planner.The open problems that follow concern identifiable controls, persistent state, calibrated branching, causal data, compositionalabstraction, and tests in which imagined consequences are checked through real or reference-system outcomes.

Article
Biology and Life Sciences
Neuroscience and Neurology

Tahir Rahman

Abstract: Animals possess multiple executable behavioral programs but ordinarily express only a subset at any moment. The Systema Behavorum treats such programs as latent execution architectures, permitting functional comparison across species despite divergent neural implementations. Here, six systems are assigned to Drosophila melanogaster—mating, reproductive investment, competition, navigation, reward, and defense—and the female post-mating transition is used to test the framework at identified-cell resolution. Mating transfers sex peptide, reducing activity in reproductive-tract sensory neurons and the ascending SAG pathway and thereby altering reproductive-state signaling through pC1. Two circuit observations distinguish altered access from altered capacity. After mating, courtship-song responses are attenuated in vaginal-plate-opening descending neurons (vpoDNs) while remaining intact in their upstream auditory inputs. Conversely, direct activation of oviposition descending neurons (oviDNs) is equally effective in virgin and mated females despite the strong mating dependence of spontaneous egg laying. A minimal circuit model further shows that the reported equality of activation thresholds is most consistent with subtractive removal of inhibition rather than altered intrinsic gain or straightforward divisive inhibition. Consistent with this interpretation, GABAergic oviINs inhibit the oviposition pathway, making post-mating egg laying a disinhibitory release, while GABAergic input to pC1 can close the receptivity gate. The same reproductive-state signal reconfigures feeding, locomotion, search, and aggression in different directions, supporting pC1 as a candidate coordination node rather than a uniform gain controller. Comparative evidence suggests that post-mating behavioral reallocation is more conserved than its molecular implementation. No known Drosophila modulator presently satisfies the criteria for a global permissive field. Thus, the fly supports coordinated, state-dependent gating through independently addressable channels while leaving a shared permissive variable as an experimentally testable hypothesis.

Article
Public Health and Healthcare
Physical Therapy, Sports Therapy and Rehabilitation

Carlos Castellar

,

Abraham Blánquez

,

Alejandro García-Gimenez

,

Miguel Lecina

Abstract: Background: Trail running is a sport characterized by taking place in natural environ-ments and requiring constant adaptation to irregular terrain, making postural balance crucial for preventing falls and coping with the coordinative demands of these races. Objectives: This study aimed to analyse the acute effects of the elevation on dynamic and static balance in young trained trail runners. Methods: Fifteen highly trained young ath-letes (8 females, 7 males; age 16.8 ± 2.14 years) completed two similar training sessions except for the elevation gain (1000 m vs. 15 m, flat). Static Balance was evaluated using the Balance Error Scoring System (BESS), and dynamic balance was assessed with the Y Balance Test (YBT) before and after each session. Results: No statistically significant dif-ferences were found in the dynamic balance, YBT results between elevation and flat ses-sions when comparing pre- vs. post-session in the composite index (83.79 ± 7.59 vs. 83.32 ± 7.92, p = 0.763). In contrast, static balance BESS showed an average increase of 3 errors after elevation training compared with flat training (15.53 ± 1.23 vs. 12.67 ± 1.33, p < 0.001). Conclusions: These findings highlight the need for specific strategies to preserve postural balance—especially static balance—during training and after trail races, and support tak-ing elevation gain into account when programming training load in young trail runners.

Communication
Environmental and Earth Sciences
Remote Sensing

Beata Hejmanowska

Abstract: On 26 August 2026, a mass-movement and flood cascade affected the Nepal–China border region and propagated downstream through the Lende Khola–Trishuli river system. Rapid characterization of such high-mountain events is challenging because optical observations may be limited by cloud cover, while synthetic aperture radar (SAR) amplitude changes can reflect multiple surface and geometric effects. We combined pre- and post-event Landsat 8/9 imagery with multi-temporal Sentinel-1 VV observations to determine whether the 2026 disturbance produced a spatially coherent radar response. A 5.52 km2 affected-area footprint was independently delineated from Landsat imagery and used to compare Sentinel-1 changes inside and outside the mapped disturbance along a 14.4 km valley corridor. A spatially matched 2025 sequence was used to quantify reference-year spatial variability. Within the mapped footprint, median absolute VV change during the 2026 event was 2.19 dB, compared with 1.66 dB outside, while median event anomaly was 0.56 and 0.06 dB, respectively. The inside–outside anomaly contrast was positive in 27 of 29 profile segments. After adjustment for the corresponding 2025 spatial contrast, the event-specific effect remained positive in 25 of 29 segments, with a median of 0.344 dB. Over a common 14 km profile, positive effects persisted in 85.7% of 500 m units, 85.7% of 1 km units, and 100% of 2 km units. The results demonstrate that the optically mapped 2026 disturbance coincided with a robust, spatially coherent Sentinel-1 response. The proposed cross-sensor framework provides a simple approach for rapid characterization of high-mountain cascading hazards without interpreting SAR amplitude change as a direct event inventory.

Article
Environmental and Earth Sciences
Remote Sensing

Hamidreza Rahimi

,

Anselme Muzirafuti

,

Toktam Hatamisengeli

,

Yao Sun

Abstract: This study develops a probabilistic framework for forecasting coastline change on Hainan Island, China, by integrating 30 years of Landsat-derived shoreline data (1990–2019), the Digital Shoreline Analysis System (DSAS), and Gaussian Process Regression with Automatic Relevance Determination (GPR–ARD). ERA5 climatic and hydrodynamic variables were assigned to individual coastal transects as annual summary indices. Strict temporal validation demonstrated reliable shoreline-distance prediction performance (R2 = 0.781, RMSE = 11.81 m, MAE = 7.70 m, and bias = −0.66 m), while providing spatially explicit confidence intervals. Feature-importance analyses using ARD and permutation importance identified longitude, latitude, and year as the principal predictors. In contrast, annual wave, wind, temperature, and precipitation summaries showed limited independent predictive contribution, likely because annual aggregation obscures seasonal and event-scale coastal processes. Projections for 2030 and 2050 indicate contrasting shoreline responses, with substantial retreat in southern areas west of Sanya (up to approximately −70 m) and shoreline advance in the northwestern Qiongzhou Strait region (up to approximately +55 m). Projection uncertainty increases over time, reaching approximately ±32–40 m. This framework provides a business-as-usual baseline for coastal management and highlights the value of sub-annual observations and probabilistic machine-learning approaches for improving future shoreline forecasts.

Article
Social Sciences
Other

Alshaimaa Mohamed Mahmoud Hassan

,

Mona Abdulaziz Almelhem

,

Faten Mouldi Derouez

Abstract: The question of which structural levers actually enhance climate governance arises when hydrocarbon-dependent economies strive for low-carbon growth. In fact, this paper aims to analyze the impact of climate economy and ‎sustainability‎, digital transformation and ‎smart platform, economic development‎, trade openness and women's empowerment ‎and leadership on climate governance in short and long term in Saudi Arabia from 1990 to 2025 using the Autoregressive Distributed Lags (ARDL) approach. The unit root tests: Philipps-Perron (PP) and Augmented Dickey-Fuller (ADF) verify that all series are integrated of order one. The Wald test (F = 41.96) indicates the presence of long run relationships between variables. However, the Bounds test (F = 12.75) verify that long run cointegration relationships exist, and the CUSUM and CUSUMSQ plots verify parameter stability. The chosen ARDL(1,0,1,2,0,0) specification indicates that in the short term, female labor force participation (-0.122), digital transformation (-3.738 contemporaneous; -3.097 lagged), and renewable energy consumption (-1.537) all significantly lower per-capita emissions, while GDP effects cancel each other out across lags and trade openness is negligible. Long-term impacts like digital transformation (-6.955), renewable energy (-1.564), and women's empowerment (-0.125) are substantial at 1%, whereas trade openness and economic progress have no equilibrium influence. Therefore, as complementary tools of climate governance under Vision 2030, policy should prioritize expedited deployment of renewable energy, ongoing investment in e-government and smart platforms, and participation of women in the labor market.

Article
Medicine and Pharmacology
Orthopedics and Sports Medicine

Hiroaki Kimura

,

Ryoya Asaka

,

Hidenori Horigome

,

Tadashi Kobayashi

,

Hideaki Obata

Abstract: Background/Objectives: Non-specific low back pain (LBP) is multifactorial, and psychosocial factors are often important. Densified fascial tissues of the thoracolumbar and lumbogluteal fascial system, seen as “stacking fascia,” may represent one under-recognized and treatable peripheral source; routine imaging assesses the disc, vertebra and nerve root but not these tissues [1]. The release points presented are representative examples, not an exhaustive list. The objective is to present a standardized, multi-point ultrasound-guided fascia hydrorelease (US-FHR) protocol for the fascia-derived component of LBP, identified by the Fascial Pain Syndrome (FPS) criteria [2] and a stacking-fascia appearance on ultrasound, after exclusion of red-flag disease and clear radiculopathy. Methods: A Protocol Development Framework (narrative synthesis of anatomy, neurophysiology and the authors’ clinical experience; no new prospective dataset) was used to define diagnosis/evaluation, the US-FHR procedure and a region-based multi-point protocol. Results: Fifteen release points, ordered from the lower thoracic to the sacroiliac region, cover the thoracic paraspinal/latissimus–TLF continuity, serratus posterior inferior, diaphragm–quadratus lumborum interface at Th12, lumbar interfascial triangle, quadratus lumborum, psoas major at L2, lumbar plexus, posterior midline ligaments, thoracolumbar fascia, multifidus and peri-facet fascia, iliolumbar ligament, ligamentum flavum/flavum–facet point, superior cluneal nerve, gluteus medius and superior gluteal artery, and posterior sacroiliac ligament. Each point is described by anatomical rationale, referred-pain pattern, technique concept and safety, with a representative ultrasound still. Conclusions: The protocol describes a peripheral component of LBP that may be identifiable and treatable, and is offered as the methodological basis for a planned prospective study distinct from the single-site TLF pilot NCT06818175 [3].

Article
Computer Science and Mathematics
Artificial Intelligence and Machine Learning

Deepak Kumar Shukla

,

Fnu Neha

,

Deepshikha Bhati

Abstract: Self-improving artificial intelligence (AI) refers to systems that participate in identifying limitations, generating or selecting candidate modifications, evaluating their effects, and retaining validated changes that improve subsequent behavior. Existing work spans output revision, memory adaptation, synthetic-data generation, workflow optimization, parameter updates, code modification, and recursive improvement, but these directions remain fragmented in their definitions, units of analysis, and evaluation criteria. This paper introduces the SAI-V framework for characterizing and validating self-improving AI across six dimensions: target, trigger, mechanism, evaluator, persistence, and autonomy. The framework is complemented by a target-based taxonomy, a classification of improvement mechanisms, a seven-level autonomy scale, and a multidimensional evaluation model covering capability, efficiency, generalization, stability, autonomy, and safety. A controlled lifecycle based on Variation, Assessment, Verification, and Integration separates candidate modification from validated improvement and incorporates monitoring and rollback for persistent change. The framework emphasizes that modification alone does not establish improvement: retained changes must demonstrate net benefit relative to an appropriate baseline while preserving relevant operational constraints. The paper further analyzes representative application domains, technical and conceptual limitations, safety and control challenges, and open research problems involving evaluator independence, self-generated data, reproducibility, repeated improvement cycles, and recursive self-improvement.

Hypothesis
Medicine and Pharmacology
Neuroscience and Neurology

Eman Nassim Ali

,

Shahid Bashir

Abstract: Purkinje cell abnormalities, including reduced cell size and lower cell density in some postmortem series, are among the most frequently discussed cerebellar findings in autism spectrum disorder (ASD), yet their mechanistic origin and causal significance remain unresolved. We propose a circuit-based hypothesis in which developmental synaptic dysfunction or disconnection within the dentato-thalamo-cortical (DTC) network produces retrograde transneuronal changes in anatomically connected Purkinje cells, ranging from functional impairment and atrophy to cell loss. The model integrates four observations: heterogeneous Purkinje cell pathology in ASD; the participation of posterolateral cerebellar territories in non-motor cerebro-cerebellar circuits; structural and functional abnormalities reported at multiple nodes of DTC networks; and the enrichment of ASD-associated genes in pathways regulating synaptic scaffolding, maturation, pruning, and intracellular signaling. We distinguish three competing models: primary Purkinje cell pathology causing downstream network dysfunction; a shared developmental defect producing parallel abnormalities across cerebellar and cerebral structures; and our proposed model, in which distal or intermediate DTC synaptic dysfunction produces secondary retrograde Purkinje cell pathology. The hypothesis predicts circuit-topographic correspondence, temporal ordering from synaptic dysfunction to upstream neuronal change, pathway specificity, and attenuation of Purkinje cell pathology after timely restoration of synaptic or trophic support. Longitudinal multimodal imaging, postmortem connectomic-pathological correlation, and pathway-specific developmental models can directly test these predictions. Retrograde transneuronal degeneration (RTD) is proposed as a potential mechanism in a biologically defined subset of ASD, not as a universal explanation for ASD or cerebellar pathology.

Article
Biology and Life Sciences
Food Science and Technology

Matyas Lukacs

,

Barasa Mercy Mukite

,

Eszter Benes

,

Peter Erdelyi

,

John-Lewis Zinia Zaukuu

,

Kornel Kovacs

,

Laszlo Abranko

,

Jozsef Felfoldi

,

Zoltan Kovacs

Abstract: The agri-food industry faces increasing challenges to serve a rapidly growing population amidst intense climate change. Precision agriculture in the era of the 4th industrial revolution relies on digital data that is quickly and reliably generated. Unlike laboratory-bound wet chemistry methods, portable near infrared spectroscopy (NIRS) could provide rapid, non-destructive and on-the-spot assessment of crops with increasing regional importance, such as sweet potatoes. The present study aimed at developing an industrially feasible method by combining the NIR spectra of intact sweet potato samples and chemometrics to predict sweet potato characteristics. Samples from three sweet potato cultivars were stored at three different storage temperatures for one month with eight sampling occasions. Moisture content, total phenolic and total starch content were assessed to serve as reference. Spectra of tubers were recorded with a benchtop and a portable device with different arrangements: through-skin (intact), on cut-surface and on powdered samples. Models to differentiate between cultivars, storage conditions and predict reference parameters were built using principal component analysis (PCA), linear discriminant analysis (LDA) and partial least squares regression (PLSR) with rigorous cross- and test-set validation. Feasible regression models with up to 0.8 R2P could only be reached by using benchtop spectral data on powdered samples. Classification models, however, could reach 79.25% correct prediction to separate sweet potato cultivars by using the handheld spectral data recorded on the surface of intact tubers. The present results imply that handheld NIRS in combination with chemometrics could reach industrially feasible models to rapidly and nondestructively identify sweet potato cultivars, even those that show high physical similarities. The method presented here could be integrated into track and tracing systems where on-the-spot evaluations are necessary to ascertain product identity throughout the entire supply chain.

Article
Medicine and Pharmacology
Orthopedics and Sports Medicine

Jędrzej Tschurl

,

Tomasz Kotwicki

,

Piotr Janusz

,

Milud Shadi

Abstract: Background: Fracture of newly formed bone (the regenerate) after EF (External Fixator) removal is a serious complication of bone lengthening in Congenital Femoral Deficiency (CFD). This study aimed to determine whether prophylactic intramedullary nailing (IMN) at the time of EF removal reduces the risk of femoral fractures in CFD and to evaluate its safety. Methods: This retrospective comparative study included 53 CFD patients who underwent femoral lengthening (44 in the IMN group, 9 in the no-IMN group). We analyzed the incidence of fractures, infections, and unplanned surgeries. The predictive value of Fischgrund principles for fracture risk was evaluated. Results: The fracture rate was 11.3% (6/53). The IMN group had fewer fractures (6.8%) versus the no-IMN group (33.3%, p=0.054). Surgical treatment risk for femoral fracture was significantly lower in the IMN group (2.3% vs 33.3%, p<0.05). Despite complications in IMN group (4.5% infection rate and 4.5% nail malposition rate), the rate of unplanned surgery was lower versus the no-IMN group (11.4% vs 33.3%, p=0.12). Poor regenerate morphology (insufficient cortices) predicted femoral fractures after EF removal only in no-IMN group. Prophylactic nailing reduced the negative impact of poor regenerate morphology. Conclusions: Prophylactic intramedullary nailing is an effective strategy to prevent early femoral fractures and reduce the risk of unplanned surgery. Fischgrund principles are not useful to predict the risk of femoral fracture after prophylactic nailing.

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