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Article
Biology and Life Sciences
Plant Sciences

Tatiana P. Kukina

,

Ivan A. Elshin

,

Ol’ga I. Sal’nikova

,

Svetlana V. Belenkaya

,

Evgeniia А. Kolosova

,

Ekaterina A. Volosnikova

,

Dmitry N. Shcherbakov

Abstract: The composition of low-polarity extracts obtained by sequential extraction of the aerial parts of Rhododendron adamsii Rehd. with hexane and methyl tert-butyl ether (MTBE) was investigated using GC-MS. The hexane extract was dominated by non-polar components: squalene, n-alkanes (nonacosane, hentriacontane), sesquiterpenes (trans-nerolidol, spathulenol, β-farnesene), and β-sitosterol. The subsequent MTBE extract was enriched in more polar lipids, primarily free triterpenic acids (ursolic and oleanolic acids). A critical finding was the complete absence of diterpene grayanotoxins in all tested extracts, confirming the safety of the non-polar extraction approach. In bioactivity assays, the total hexane extract demonstrated potent inhibitory activity against the SARS-CoV-2 main protease (3CLpro) with IC₅₀ values of 0.0125–0.025 mg/mL, only one order of magnitude higher than the reference inhibitor disulfiram. Fractionation revealed that the activity was distributed among free acids, bound acids, and the unsaponifiable residue, indicating a multicomponent mechanism. Importantly, none of the samples inhibited HIV-1 protease (IC₅₀ > 0.1 mg/mL), demonstrating selectivity for the cysteine protease 3CLpro over the aspartyl protease of HIV-1. These results highlight that sequential non-polar extraction of R. adamsii provides a grayanotoxin-free lipophilic complex with selective anti-SARS-CoV-2 protease activity, paving the way for bioactivity-guided identification of individual inhibitors.

Article
Social Sciences
Geography, Planning and Development

Andi Gunawan

,

Ignasia Germania M. Rada

Abstract: Waerebo Village, a UNESCO World Cultural Heritage site in Indonesia, represents a profound harmony between the Manggarai people, nature, and spirituality, yet the technical functional role of its traditional zoning remains under-researched. This study examines the Waerebo landscape model by integrating horizontal and vertical spatial patterns through literature reviews, field observations, interviews, and GIS-based analyses, including Digital Elevation Models (DEM) and multi-temporal NDVI from 2015 to 2025. Find-ings indicate that Waerebo’s landscape is organized into three concentric zone—core, uti-lization, and sacred zones—mirroring a tripartite spiritual framework of God, ancestors, and nature spirits. Geospatial data reveals a sophisticated indigenous landscape engineering system where the settlement is strategically positioned on a stable 16° terrace, while sacred forests are maintained on extreme 85° slopes to protect watersheds and mitigate landslides. Multi-temporal NDVI analysis confirms an increase in forest density from 0.47 in 2015 to 0.52 in 2025, validating the effectiveness of customary laws in maintaining ecological integrity despite tourism pressures. The study concludes that Waerebo's cosmic spiral model achieves a vital balance between culture, socio-economic survival, and environmental conservation, offering a functional blueprint for resilient cultural heritage management in challenging topographies.

Article
Physical Sciences
Astronomy and Astrophysics

Rostislav D. Nikandrov

,

Sergei B. Popov

Abstract: Robust age measurements for isolated neutron stars (NSs) are not easily available. That is why, often the characteristic age τch=P/2 is used as a proxy. Here P is the spin period of the NS and is the time derivative of P. Additional assumptions related to the initial properties and spin-down evolution are made to derive τch. As a result, it is expected that τch is an upper limit for the real age τreal. Recently, Chrimes et al. presented measurements of kinematic ages τkin for several magnetars. Surprisingly, for the majority of these sources τkin>τch. We present a simple model including a realistic approximation for the magnetic field decay in magnetars and a simple phenomenological description of the field re-emergence after an episode of fallback after the birth of a NS. We demonstrate that this simple model can explain the observed relation τkin>τch for realistic sets of parameters.

Article
Biology and Life Sciences
Aquatic Science

Chao Song

,

Dongyu Song

,

Chengyao Yang

,

Yijia Li

,

Hang Li

,

Zhiqiang Ye

,

Junlin Ren

,

Sikai Wang

,

Feng Zhao

Abstract: To elucidate the characteristics of fatty acid composition in different tissues of Anguilla japonica before and after their seaward spawning migration, this study measured the fatty acid contents in the muscle, liver, and ovary of eels collected from the Yangtze River Estuary and offshore waters, and analyzed the distribution characteristics and transformation patterns of various fatty acids in different tissues. The results showed that the fatty acid composition in different tissues of eels from both the Yangtze River Estuary and offshore waters was essentially similar. Among all fatty acids, C18:1n9c had the highest proportion, accounting for over 31% of the total fatty acids in each tissue. Comparing different tissues, in eels from the Yangtze River Estuary, the muscle had the highest content of EPA, the liver had the highest content of DHA and EPA+DHA, and the ovary had the highest contents of ARA, n6-PUFA and SFA. In offshore eels, the muscle had the highest contents of C16:1, C18:1n9c and MUFA; the liver had the highest content of C16:0; and the ovary had the highest contents of C18:0, DPA, HUFA, n3-PUFA and PUFA. Comparing eels before and after seaward migration, the contents of C16:0, ARA, n6-PUFA, SFA, and the DHA/EPA ratio in the ovary of Yangtze River Estuary eels were higher than those in offshore eels. Conversely, the contents of C18:0, C16:1, C18:1n9c, EPA, DPA, DHA, EPA+DHA, HUFA, n3-PUFA, MUFA, PUFA, as well as the EPA/ARA, n3/n6 PUFA and PUFA/SFA ratios in the ovary of offshore eels were higher than those in Yangtze River Estuary eels. The ovary of Yangtze River Estuary eels mainly contained fatty acids for energy provision and precursors for long-chain fatty acid synthesis, whereas the ovary of offshore eels had preliminarily accumulated PUFA nutrients required for egg and embryonic development. Thus, the distribution patterns of different fatty acids among tissues are closely related to the seaward spawning migration process of A. japonica. Before migration, eels in the Yangtze River Estuary primarily focus on energy accumulation and liver metabolism; after entering the sea, eels gradually accumulate PUFA such as EPA, DPA+DHA and n3-PUFA as gonads develop. The selective reservation of different fatty acids in the ovary represents a physiological regulation in response to the nutritional demands of gonadal development.

Review
Biology and Life Sciences
Neuroscience and Neurology

Javonte S Thelwell

,

Aaron J Johnson

Abstract: Hypoxia is a prevalent characteristic of neurological diseases, including ischemic injury, neurodegeneration and infectious disease complications. Concurrently, hypoxia shapes both protective and pathological responses within the central nervous system (CNS). Central to this process is hypoxia-inducible factor 1α (HIF1α), a transcription factor that regu-lates cellular adaptation to reduced oxygen availability through coordinated glycolytic, inflammatory and cell survival pathways. Under hypoxic conditions, HIF1α transcriptional activity influences microglial activation, mitochondrial quality control, and cytokine production, thereby modulating neuroinflammation and neuroprotection. Preclinical evidence points toward hypoxia preconditioning being neuroprotective through HIF1α-dependent mechanisms in a context-dependent matter. This review synthesizes the current understanding of the role of HIF1α across neurological disease contexts, highlighting the intersection of hypoxia, neuroinflammation and neuronal survival. Ultimately, defining the cell-specific and context-dependent involvement of HIF1α will be critical for targeted therapeutic approaches to alleviate neuronal death and slow disease progression.

Article
Computer Science and Mathematics
Algebra and Number Theory

Gürsel Ye¸silot

Abstract: Let R be a commutative ring with a nonzero identity and M a nonzero unital R-module. We introduce the concepts of weakly n-submodules and weakly (1, n)-submodules as module-theoretic generalisations of the weakly n-ideal and weakly (1, n)-ideal. A proper submodule N of M is called a weakly n-submoduleif whenever 0 ̸= am ∈N for some a ∈R and m ∈M , then a ∈(N :R M )or m ∈Nil(M )·M , where Nil(M ) = annR(M ). Similarly, N is called a weakly (1, n)-submodule if whenever 0 ̸= abm ∈N for some nonunit elementsa, b ∈R and m ∈M , then ab ∈(N :R M ) or m ∈Nil(M )·M . Every weaklyn-submodule is a weakly (1, n)-submodule, and every weakly (1, n)-submoduleis weakly 1-absorbing primary. We provide a six-fold characterisation, provestructure theorems classifying the rings and modules over which every propersubmodule belongs to these classes in particular, we show that for faithfulnitely generated multiplication modules, every proper submodule is weakly (1, n) if and only if R is a UN-ring or a product of two elds and investigatebehaviour under homomorphisms, localisations, and quotient modules.

Article
Biology and Life Sciences
Neuroscience and Neurology

Ayumi Matsushita

,

Maki Kimura

,

Naoko Tajima

,

Tsuyoshi Yamanaka

,

Masato Inazu

Abstract: Zinc deficiency is increasingly recognized as a risk factor for neurodegenerative diseases, yet the underlying molecular mechanisms remain incompletely understood. In this study, we investigated the impact of intracellular zinc depletion on oxidative stress and in-flammasome activation in microglial (SIM-A9) and neuronal (SH-SY5Y) cell models, and evaluated the protective effects of polyphenolic compounds. Intracellular zinc chelation with the membrane-permeable chelator TPEN markedly increased reactive oxygen species (ROS) production, reduced cell viability, and upregulated the mRNA expression of NLRP3 inflammasome–related genes and pro-inflammatory cytokines. In contrast, extracellular zinc chelation had no effect, highlighting the critical role of intracellular zinc homeostasis in maintaining redox balance. Zinc supplementation significantly attenuated these responses. Among 32 polyphenols screened by DPPH radical scavenging assay, caffeic acid derivatives—chicoric acid (ChA), rosmarinic acid (RA), and caffeic acid phenethyl ester (CAPE)—exhibited the most potent antioxidant activity, surpassing that of edaravone. These compounds suppressed ROS production and differentially protected against zinc deficiency–induced cellular damage. ChA showed the strongest ROS in-hibitory activity (IC50: 1.9 µM in SIM-A9), RA provided robust cytoprotection even at low concentrations, and CAPE most effectively suppressed inflammasome-related gene ex-pression and inhibited aggregation of both Aβ1–42 and the highly neurotoxic py-roglutamate-modified variant pEAβ3–42. These findings demonstrate that intracellular zinc deficiency drives ROS-dependent NLRP3 inflammasome activation, and suggest that caffeic acid derivative polyphenols may serve as complementary agents for mitigating neuroinflammatory and amyloidogenic processes relevant to Alzheimer's disease.

Article
Computer Science and Mathematics
Artificial Intelligence and Machine Learning

Dhadkan Shrestha

Abstract: Robots deployed in disaster environments—such as collapsed buildings, flooded tunnels, and conflict-damaged urban areas—must navigate without GPS, operate under degraded sensing conditions including dust, smoke, and darkness, and adapt rapidly to changing mission conditions. Most existing learning-based navigation approaches rely on a single policy, which often fails when the environment shifts in unexpected ways. This paper presents UC-MESL (Uncertainty-Conditioned MAP-Elites Skill Library), a framework that learns a diverse library of specialized navigation behaviors and dynamically switches between them in real time based on environmental uncertainty. Each skill is optimized for a specific operating condition and characterized by three interpretable traits: risk tolerance, exploration preference, and movement style. A lightweight selector uses live uncertainty estimates from the robot’s onboard map to choose the most appropriate skill during deployment. We evaluate UC-MESL across three simulated rescue scenarios—collapsed rubble, flooded tunnels, and war-damaged urban blocks—under four levels of sensor degradation and realistic communication outages. Compared with the strongest single-policy baseline, UC-MESL finds 18.4% more victims within the mission time budget, reaches the first victim 31.2% faster, reduces hazard exposure by 24.6%, and loses only 8.3% of performance under severe sensor noise, compared with 29.7% for a single-policy NEAT baseline. These results demonstrate that maintaining a diverse repertoire of specialized navigation skills, combined with uncertainty-aware skill selection, provides more robust and reliable autonomy for disaster-response robotics than optimizing a single general-purpose policy.

Article
Computer Science and Mathematics
Artificial Intelligence and Machine Learning

Omar Shalash

,

Esraa Khatab

,

Ahmed El-Agamy

,

Loay Elmokadem

,

Yasmin Abouelsaad

,

Jasser Zaki

,

Mohamed El-Sayed

,

Hany Said

Abstract: The YOLO (You Only Look Once) object detection models have undergone rapid evolution, with each version introducing architectural enhancements aiming to improve speed, accuracy, and deployment. Simultaneously, Single-Board Computers (SBCs) have advanced to support increasingly complex AI models in edge environments. This study presents a comprehensive benchmarking of YOLO versions 8 through 12 across a range of SBCs, including Raspberry Pi4/5, NVIDIA Jetson Nano, Jetson Orin, and LattePanda, under different power modes. Key performance metrics, including inference speed (FPS), detection accuracy (mAP), RAM usage, and computational complexity (FLOPs), are evaluated. These findings offer practical insights for developers and researchers to select optimal YOLO variants and SBC configurations for real-time edge deployment.

Review
Medicine and Pharmacology
Clinical Medicine

Deng Siang Lee

,

Aboubakr Hasan

Abstract: Background: Hantavirus pulmonary syndrome (HPS), also designated hantavirus cardiopulmonary syndrome, is caused by New World hantaviruses, principally Sin Nombre virus in North America and Andes virus in South America. The syndrome is characterized by rapidly progressive noncardiogenic pulmonary edema and myocardial depression, with case fatality rates of 30% to 50%. Methods: This review synthesizes peer-reviewed literature on the virological, pathophysiological, clinical, and therapeutic aspects of HPS, with emphasis on cardiopulmonary mechanisms. Sources were identified through PubMed, prioritizing original research, clinical series, and controlled trials published through 2025. Results: Pathogenic hantaviruses enter endothelial cells and platelets via αvβ3 integrins, disrupting the VEGF-VEGFR2 signaling axis and rendering endothelial cells hypersensitive to physiological VEGF concentrations. Expansion of CD8+ T cells and activated macrophages releases TNF-alpha, IFN-gamma, and nitric oxide, amplifying microvascular permeability and contributing to myocardial depression. Autopsy studies demonstrate direct hantaviral myocarditis with viral antigen in cardiac endothelium and interstitial macrophages. Transpulmonary thermodilution confirms simultaneous hypovolemia, reduced global ejection fraction, and elevated extravascular lung water. VA-ECMO initiated at the first signs of cardiopulmonary decompensation has reported survival rates approaching 80% in selected experienced centers. No antiviral has demonstrated efficacy in controlled trials during the cardiopulmonary phase. Conclusions: HPS produces a mixed shock state through increased microvascular permeability, T cell-mediated immunopathology, and direct myocarditis. Management follows a stepwise algorithm: suspected HPS triggers immediate complete blood count with peripheral blood smear and hantavirus IgM serology or RT-PCR, followed by ICU admission, conservative fluid resuscitation guided by transpulmonary thermodilution, and early contact with an ECMO-capable center at the first sign of rising lactate, falling cardiac index, refractory shock, arrhythmia, or rapid oxygenation failure.

Article
Computer Science and Mathematics
Artificial Intelligence and Machine Learning

Gabriel Axel Montes

Abstract: AGI alignment is often evaluated at a snapshot: a system is judged by its current outputs, policy profile, benchmark behavior, or apparent corrigibility. Snapshot evaluation misses a central risk of advanced deployment: a good endpoint can still be reached by a bad journey. Two trajectories may arrive in similar behavioral regions while differing in reversibility, opacity, intervention cost, memory entanglement, institutional dependency, and the quality of human judgment left available for oversight. This paper develops a path-sensitive alternative. It represents AGI development as motion through an augmented state space Z containing model and environment state, world-model structure, policy state, memory and provenance traces, governance affordances, institutional embedding, and human evaluative capacity. Cognitive integrity — the capacity of individuals, teams, or institutions to sustain calibrated attention, trust, contestability, and decision under pressure [1] — is introduced here as an alignment-relevant state variable rather than assumed as a familiar metric. The formal contribution is a scaffold of definitions: controlled transition laws over augmented state, escape cost, path-level alignment functionals, viability floors, forbidden regions, and trajectory classes distinguished by lock-in, basin structure, retargetability, and integrity preservation. The result does not supply a calibrated empirical model of deployed AGI systems. It specifies what such a model must track if alignment evidence is to cover both present behavior and the remaining possibility of legible, reversible, and cognitively intact correction.

Review
Social Sciences
Behavior Sciences

Alcides Chaux

Abstract: Introduction: Precision oncology has revolutionized cancer care in high-income countries, but its implementation in Latin American low-resource settings faces profound bioethical dilemmas. This study analyzes these challenges through the lens of social justice and equity. Methods: An integrative review was conducted following the Whittemore and Knafl framework. A systematic search was performed across PubMed, Scopus, SciELO, and LILACS (2015–2025). Thematic synthesis was applied to integrate empirical data with normative bioethical theories. Results: Four major analytical themes were identified: 1) The Innovation Paradox and Financial Toxicity, where prohibitive pricing (exceeding $100,000 USD/year) violates distributive justice and leads to a biological penalty in survival; 2) Infrastructure Deficits and Epistemic Injustice, highlighted by a 9.4% access rate to Next-Generation Sequencing (NGS) and the risks of applying Eurocentric genomic data to admixed LA populations; 3) Research Vulnerability, where clinical trials serve as survival strategies, compromising autonomy and informed consent; and 4) The Judicialization Dilemma, where individual court orders for high-cost drugs threaten systemic sustainability and equity. Conclusions: To prevent a genomic apartheid, Latin America must transition toward genomic sovereignty and frugal precision oncology. Bioethical frameworks in the region must prioritize protection ethics and social justice to ensure that scientific innovation does not exacerbate existing health inequities.

Article
Environmental and Earth Sciences
Atmospheric Science and Meteorology

Umberto Triacca

,

Antonello Pasini

Abstract: Recent studies have investigated whether the rate of global warming has changed since the 1970s, with particular attention to the role of natural variability and its removal from temperature time series. In particular, Foster and Rahmstorf (2026) analyzed global mean surface temperature series, adjusted for natural variability. However, their procedure might produce spurious changepoints, since it does not appropriately handle the autocorrelation present in the residuals of the models considered. In this study, we revisit the same adjusted temperature series using a different methodology (the Quandt likelihood ratio test) while properly accounting for the presence of autocorrelation. We find evidence that global temperature has departed from its previous path since around 2013-2014. Our results provide a robust proof of a clear recent increase in the temperature trend, at a rate of warming that has doubled since that date.

Review
Biology and Life Sciences
Parasitology

Ana María Fernández-Presas

,

Katia Jarquín-Yáñez

,

Adolfo Cruz-Reséndiz

,

Oscar Rodríguez-Lima

,

Jaime Zamora-Chimal

,

Blanca Esther Blancas-Luciano

Abstract: Chagas disease, caused by Trypanosoma cruzi, remains a major public health problem in Latin America and an emerging global health concern due to population mobility. Alt-hough benznidazole and nifurtimox remain the only approved antiparasitic drugs, their limited efficacy in chronic infection, prolonged treatment regimens, frequent adverse ef-fects, and variable activity across parasite strains highlight the need for new therapeutic strategies. In addition, the pathogenesis of chronic Chagas disease is driven not only by parasite persistence but also by immune-mediated tissue damage, particularly in chronic Chagas cardiomyopathy. In this review, we examine emerging therapeutic approaches that extend beyond conventional trypanocidal chemotherapy, with emphasis on plant-derived extracts, essential oils, antimicrobial peptides, and cell-based immuno-modulatory strategies. Plant compounds and essential oils have shown antiparasitic ac-tivity through mechanisms including oxidative stress induction, membrane disruption, interference with sterol biosynthesis, and mitochondrial dysfunction, while some extracts also modulate host immune responses. Antimicrobial peptides display dual potential by directly damaging parasite membranes and organelles or by reshaping infec-tion-associated inflammatory responses. In parallel, cell-based therapies such as mesen-chymal stromal cells, tolerogenic dendritic cells, and bone marrow-derived cells have demonstrated promising cardioprotective and immunoregulatory effects in experimental chronic Chagas disease. Collectively, these approaches support a multitarget therapeutic framework in which parasite-directed and host-directed interventions may complement each other. Further mechanistic studies, standardization, and translational validation will be essential to advance these candidates toward clinically useful therapies for Chagas disease.

Article
Business, Economics and Management
Finance

Nicolo Agliata

,

Tim Hasso

Abstract: Generative artificial intelligence (GAI) is increasingly embedded in personal financial, yet little is known about how models make recommendations using financial information and demographic cues. This study audits three frontier GAI models, GPT 5.5, Gemini 3.1 Pro, and Claude Opus 4.7, using a full-profile conjoint experiment in which each model evaluated the same 1,000 hypothetical investor profiles and selected among standardized conservative, balanced, and aggressive portfolios. Investor profiles systematically varied attributes, including risk tolerance, time horizon, goal type, income, and age, gender, ethnicity, marital status, and employment type. Ordered logistic regressions and matched-profile comparisons show that all three models base recommendations primarily on legitimate financial inputs, especially risk tolerance and time horizon. Gender and ethnicity do not significantly influence recommendations, although age affects all models and marital status affects ChatGPT. However, the models are not interchangeable: they differ significantly in overall risk appetite and in how they translate risk tolerance, time horizon, goal type, and age into portfolio choices, with economically meaningful differences in predicted recommendations for identical clients. These findings suggest that contemporary GAI investment advice exhibits limited evidence of conventional demographic bias but introduces a distinct form of platform risk arising from model-specific advisory logic.

Article
Computer Science and Mathematics
Artificial Intelligence and Machine Learning

Bocheng Xie

,

Xiaokang Guo

,

Pengwei Xiao

,

Chao Yang

Abstract: Contrastive learning–based models such as DrugCLIP have recently emerged as scalable tools for structure-based virtual screening by embedding protein structures and small molecules into a shared representation space. While these approaches demonstrate high throughput and competitive screening performance in ligand retrieval tasks, their ability to correctly identify biologically relevant ligand-binding pockets has not been systematically evaluated. Here, we construct a benchmarking dataset comprising 42 pharmacologically diverse human protein targets with experimentally validated drug-bound structures spanning multiple target families. Using this dataset, we evaluate the pocket recognition capability of DrugCLIP and compare its performance with a traditional structure-based workflow (Fpocket combined with ESSA) and a machine learning-based method (P2Rank). DrugCLIP shows robust performance for well-characterized target classes, including kinases (10/10) and nuclear receptors (5/5), but exhibits markedly reduced accuracy for ion channels (1/4), GPCRs (3/5) and transporters (3/5). Notably, pocket prediction accuracy does not strongly correlate with structural data availability, suggesting that intrinsic pocket characteristics rather than training data abundance primarily affect model performance. Across the benchmark, DrugCLIP achieves an overall success rate of 71% (95% CI: 56-83%), compared with 79% (95% CI: 64-88%) for Fpocket+ESSA and 93% (95% CI: 81-98%) for P2Rank. McNemar’s test showed no significant difference between DrugCLIP and Fpocket+ESSA (p=0.508), whereas P2Rank significantly outperformed DrugCLIP (p=0.012). Together, these results provide a quantitative evaluation of pocket recognition by contrastive learning–based models and highlight key limitations of embedding-based approaches for pocket localization.

Article
Biology and Life Sciences
Life Sciences

Sonia Terriaca

,

Maria Giovanna Scioli

,

Fabio Bertoldo

,

Paolo Nardi

,

Gian Paolo Novelli

,

Beatrice Belmonte

,

Tommaso D’Anna

,

Carmela Rita Balistreri

,

Calogera Pisano

,

Amedeo Ferlosio

+2 authors

Abstract: Background: Marfan syndrome (MFS) is a connective tissue disorder caused by FBN1 mutations, leading to elastic fiber disarray and early thoracic aortic aneurysm (TAA) formation. Currently, pharmacological treatments lack specificity and only delay progression. We previously reported a specific TGFβ-driven miR-632 up-regulation in MFS TAA tissues and blood causing smooth muscle cell dedifferentiation and aortic wall degeneration. This study evaluated the effects of three conventional antihypertensive drugs (β-blocker, ACE inhibitor and sartan) on parietal remodeling comparing them with a miR-632 inhibitor in an ex vivo TGFβ –induced model of MFS TAA. Methods and Results: Gene expression and western blot analyses demonstrated that only losartan significantly reduced miR-632 and vascular degeneration markers. Notably, combined treatment with ramipril and carvediol compromised losartan’s efficacy, highlighting the need for careful therapeutic selection. miR-632 inhibitor was the most effective strategy in this ex vivo setting, although further preclinical validation is needed to confirm its therapeutic potential in vivo. Conclusions: Our data emphasize that choosing the right treatment in MFS aortopathy requires understanding its specific impact on cellular pathways. Our findings identify losartan as the most effective standard drug while suggesting miR-632 as a promising future target to stabilize the aortic wall and delay surgery.

Review
Engineering
Other

Emine Güven

,

Khalid Saad Alharbi

,

Sümeyya Arıkan Akgün

,

Ayfer Koyuncu

,

Sattam Khulaif Alenezi

,

Tariq G Alsahli

,

Muhammad Afzal

Abstract: Alzheimer's disease (AD), a leading cause of dementia worldwide, is a neurological disorder characterized by progressive cognitive decline. AD is also considered a significant socioeconomic burden. While definitive diagnostic tools such as positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) biomarker analysis offer high sensitivity and specificity, they are limited by high cost, invasiveness, and limited accessibility. Consequently, these gold standard approaches hinder their applicability for large-scale screening and longitudinal follow-up. Recent advances in blood-based biomarkers hold promise in capturing systemic molecular changes associated with AD. In particular, transcriptomic signatures derived from RNA sequencing (RNA-seq) are promising in capturing systemic molecular changes associated with AD. Gene expression profiles in peripheral blood reveal underlying pathological processes. These pathological processes can be listed as synaptic dysfunction, neuroinflammation, and metabolic dysregulation. Together with the high-dimensional datasets and AI approaches enable the identification of robust predictive models which has the assistance of estimating AD-related biomarker status. We further discussed the integration of multiple omics data, including genomics, proteomics, and metabolomics to improve biomarker robustness. We also addressed key challenges related to reproducibility, repeatibility, cohort heterogeneity, and clinical application. And we outline future directions of standardized, scalable, and clinically applicable diagnostic machineries.

Article
Medicine and Pharmacology
Transplantation

Aleksandra Stańska

,

Wojtek Karolak

,

Jacek Wojarski

Abstract: Background: Psychosocial assessment is a critical component of transplant candidate evaluation, yet its clinical utility is often limited by the descriptive nature of existing tools such as the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT). Translating multidimensional assessment data into actionable clinical insights remains a challenge in routine practice. Methods: We developed a clinical decision support application that integrates SIPAT item-level data with probabilistic risk estimation, visualization, and cohort-referenced interpretation. The application was based on a retrospective dataset of 496 lung transplant candidates evaluated at a single tertiary transplant center. Random forest–based models were used to transform SIPAT item-level data into probabilistic risk representations to estimate domain-specific risks, including depression, anxiety, nicotine-related risk, alcohol-related risk, illicit drug use, social support deficits, and non-adherence. Risk estimates were expressed as calibrated probabilities and categorized into clinically interpretable levels. Additional components included domain-level burden scoring and unsupervised clustering of multidomain risk profiles. Results: Estimated risks were predominantly low across the cohort, with high-risk subgroups identified for depression (6.5%), anxiety (2.2%), nicotine-related risk (11.3%), alcohol-related risk (4.4%), illicit drug use (2.2%), social support deficits (8.1%), and non-adherence (1.4%). Clustering analysis revealed three distinct profiles: a low-risk majority group, a subgroup characterized by elevated nicotine-related risk, and a small high-burden group with substantially elevated psychological distress, reduced social support, and increased non-adherence risk. Risk estimates showed strong and domain-consistent correlations with SIPAT scores (Spearman rho up to 0.80, p < 0.001). Feature importance analyses confirmed that risk estimation was primarily driven by clinically relevant SIPAT items. The application generated structured outputs integrating risk estimates, visualization, and intervention prioritization. Conclusions: The proposed application translates SIPAT-based psychosocial assessment into structured, multidomain risk profiles that enhance clinical interpretability and support targeted psychosocial prehabilitation. This approach provides a practical framework for translating psychosocial assessment into individualized intervention planning in lung transplant settings.

Article
Computer Science and Mathematics
Artificial Intelligence and Machine Learning

Shuyuan Wang

,

Yihui Feng

,

Xiaotian Fang

Abstract: Aiming at the core limitations of single large language models in complex task solving, including coarse task decomposition, cumulative long-chain reasoning errors, and the lack of explicit cross-agent collaboration, this paper proposes a large language model-driven multi-agent collaborative method. A hierarchical and role-based agent architecture is designed to separate task decomposition, specialized reasoning, result verification, and decision fusion, thereby enabling modular task solving and closed-loop orchestration over the full execution process. In addition, an efficient semantic communication mechanism is introduced to transmit compressed reasoning states across agents without breaking intermediate logical dependencies. A dynamic feedback iteration module is further employed to adjust routing strategy, collaboration intensity, and reasoning paths in real time according to subtask progress and verification outcomes. Comparative experiments on mathematical reasoning, multi-step planning, and complex information integration show that, relative to a single large language model, the proposed method improves the average completion rate by 21.3%, reduces the long-chain reasoning error rate by 18.7%, and reaches 92.6% cross-agent decision consistency. These results demonstrate that structured collaboration substantially improves robustness and accuracy for complex task solving and provides a practical technical path for diverse intelligent systems.

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