Search Results (973)

[d=LE]Transitions of control between automated driving systems and human drivers remain safety-relevant and cognitively demanding moments in human–automation interaction. Recent studies show that transition performance depends not only on takeover timing or response speed but also on traffic complexity, driver readiness, automation limitations, trust calibration, and situational-awareness recovery. As in-vehicle interaction evolves toward conversational and agentic AI assistance, takeover support also becomes a problem of governing how natural-language AI systems communicate with the driver under uncertainty.Transitions of control between automated driving systems and human drivers remain safety-relevant and cognitively demanding moments in human-automation interaction. Recent studies suggest that transition performance should not be assessed only through takeover timing or response speed since control resumption quality also depends on traffic complexity, driver readiness, automation limitations, and situational awareness recovery. [d=LE]This paper proposes a digital-twin-mediated framework for human-aware takeover support in automated driving. In this framework, the companion AI is treated as an assumed LLM-based in-vehicle conversational or agentic assistant used as an advisory interaction component. The contribution is defined at the architectural level: human, vehicle, and context/road digital twins provide structured semantic state abstractions through a semantic state interface exposing confidence, freshness, provenance, and consistency metadata, while a trustworthy companion AI (TCAI) layer grounds, constrains, validates, and governs companion AI output proposals before HMI delivery.This paper motivates and defines a trustworthy companion AI (TCAI) layer for human-aware transition support in automated driving. The TCAI is conceived as a bounded, supervised, and explainable advisory agent that supports the driver without entering the safety-critical vehicle-control loop. It reasons over structured semantic state abstractions derived from a human digital twin, a vehicle digital twin, and a context/road digital twin, exposing driver readiness, automation capability, and contextual urgency in a form that supports traceable, uncertainty-aware, and degradation-aware assistance. [d=LE]Building on the research on driver-state monitoring, adaptive HMI, trust calibration, explainability, conversational assistance, and human assistance systems (HASs), the framework coordinates advisory interaction across vigilance support, contextual explanation, trust-calibrating communication, and directive handover guidance. The TCAI layer combines bounded reasoning, human-factor-derived guardrails, state-consistency management, dynamic explanation-depth control, trust-dynamics modeling, graded watchdog veto handling, mandatory access-control assumptions, and deterministic fallback. Safety-critical vehicle-control and minimum risk condition (MRC) functions remain assigned to the deterministic vehicle-control stack, while the authorized output path of the TCAI layer is validated HMI delivery.Building on the research on driver-state monitoring, adaptive HMI, trust calibration, explainability, and conversational assistance, we propose a conceptual architecture in which the TCAI coordinates multimodal assistance across different interaction conditions, including vigilance support, contextual explanation, trust-calibrating communication, and directive handover guidance. The companion does not actuate the vehicle; its outputs are constrained by runtime governance, policy enforcement, and deterministic fallback mechanisms. [d=LE]The paper concludes with a validation agenda and technical roadmap covering planned transitions, urgent handovers, degraded or adversarial conditions, temporal fusion of driver-state evidence, phase-sensitive HMI policies, trust-calibration trajectories, driver veto and partial-disabling mechanisms, and staged simulator-to-vehicle evaluation. Although motivated by SAE Level 3 automation, the framework may also inform fallback-related Level 4 scenarios in which human and automated agency must be managed under uncertainty.The paper concludes with a research roadmap for validating the proposed architecture under planned transitions, urgent handovers, and degraded or adversarial conditions. Although motivated by SAE Level 3 automation, the approach may also inform fallback-related Level 4 scenarios. Full article

Fast-channel genetic myasthenic syndromes (FCGMSs) are caused by genetic variants in muscle nicotinic acetylcholine receptor (AChR) subunits that reduce channel open times and impair neuromuscular transmission. Among these, the CHRNE p.P141L variant (εP141L) is associated with particularly severe disease. Here, we characterized a knock-in mouse model harboring the homologous p.P141L variant in Chrne (εP141L)—C57BL/6J-Chrne^em1H/H made by the MRC GEMM program. Homozygous mutant mice fail to thrive, with early lethality (median survival of 16 days), closely recapitulating the severity observed in patients. Despite a preserved neuromuscular junction (NMJ) morphology and robust AChR expression, electrophysiological analyses revealed marked reductions in miniature and evoked endplate potential amplitudes and areas, accompanied by prolonged depolarization kinetics (contrary to expectations for AChR with reduced open times) and increased quantal content, indicative of impaired post-synaptic function with compensatory pre-synaptic adaptation. Notably, disease severity exceeded that of Chrne null mice, likely through competition with more functional g-subunit-containing fetal AChRs. Consistent with this, crossing εP141L mice with CHRNG-expressing mice provided little survival benefit. These findings demonstrate that dysfunctional AChR incorporation is more deleterious than receptor absence and highlight the critical role of subunit composition in sustaining neuromuscular transmission. Pharmacological enhancement of pre-synaptic release with 3,4-diaminopyridine partially improved synaptic parameters. In addition, the AChR-positive allosteric modulator DC-98 modestly improved neurotransmission. Thus, this mouse model provides a faithful platform for mechanistic studies and therapeutic development in FCGMS. Full article

This paper targets the air-to-ground (A2G) data backhaul scenario of UAVs and proposes a communication system based on coherent optical zero-padding orthogonal frequency division multiplexing (CO-ZP-OFDM), which unifies atmospheric turbulence scintillation, pointing errors, and Doppler frequency shift into a composite channel model. The system employs the Gamma-Gamma (GG) distribution to describe turbulence-induced intensity fluctuations, a Gaussian beam truncation model to characterize pointing errors, and a dual-pilot method to estimate and compensate the Doppler frequency offset. Furthermore, on a polarization-time-frequency (PTF) three-dimensional orthogonal grid pilot structure, we derive theoretical mean square error (MSE) expressions for the zero-forcing (ZF) and minimum mean square error (MMSE) estimators, and analyze their MSE characteristics under the proposed pilot model. Simulation results show that, under moderate turbulence, the shrinkage factor of the MMSE estimator yields only about $0.4$ dB MSE reduction over ZF at $\mathrm{SNR}=10$ dB, whereas the full receiver pipeline that combines coherence-bandwidth pilot averaging with the MMSE and maximum ratio combining (MRC) equalizer reduces the empirical MSE by approximately 15 dB. The bit error rate (BER) performance tests indicate that, under turbulence-free conditions with ideal channel estimation, the system can reduce the BER below ${10}^{-4}$ at an SNR of approximately 12 dB. Under strong turbulence conditions with MMSE channel estimation, the SNR cost required to achieve a BER of ${10}^{-3}$ is approximately 18 dB, which corresponds to a 3 to 5 dB BER gain over the ZF baseline at the same SNR. Further simulation analysis shows that the average pointing loss is highly sensitive to the angular jitter at the 1 km link distance: an angular jitter of 1 mrad incurs about 18 dB of loss, and a sub-mrad pointing stability (i.e., ${\sigma }_{\mathrm{jit}}<0.062$ mrad) is required to keep the average pointing loss below 1 dB. Full article

Background/Objectives: DNA-targeting small molecules that induce replication stress represent a promising strategy in anticancer drug development. 1,8-Naphthalimide (NI) derivatives are well-established DNA-intercalating agents, and heterocyclic annulation offers a rational approach to enhancing their potency and tumor selectivity. Here, we report the synthesis and biological evaluation of a novel series of benzofuran-containing naphthalimide derivatives, with particular focus on the lead dinitro-substituted compound 5d. Methods: Cytotoxic activity was assessed using the MTT assay in A549 (p53 wild-type), H1299 (p53-null), and MRC-5 cells. Long-term antiproliferative effects were evaluated by clonogenic survival assay. Cell cycle distribution was analyzed by propidium iodide staining and flow cytometry. Replication stress and DNA damage were quantified by EdU incorporation and γH2AX immunofluorescence, respectively. Apoptosis was assessed by Annexin V/PI staining and caspase-3/7 activation assay. p53 nuclear accumulation and autophagy induction were evaluated by immunofluorescence and Western blot, using LC3 as an autophagic marker. Results: All compounds exhibited cytotoxic activity in the nanomolar range, with 5d emerging as the most potent and selective. Clonogenic survival was significantly reduced, indicating durable suppression of proliferative capacity. Treatment with 5d induced G₁ arrest in A549 cells and the accumulation of H1299 cells in G₂/M, consistent with p53-dependent and p53-independent checkpoint activation, respectively. EdU incorporation was markedly reduced, while γH2AX intensity increased, collectively supporting a replication stress-driven mechanism of DNA damage. Apoptosis was confirmed by increased Annexin V-positive populations and caspase-3/7 activation. LC3 puncta formation and LC3-I/LC3-II conversion were increased, indicating LC3 processing and autophagosome accumulation consistent with the activation of autophagy-related processes. Conclusions: 5d induces a cellular phenotype consistent with replication stress, including reduced EdU incorporation, γH2AX accumulation, cell cycle arrest, and apoptotic cell death in a p53 status-dependent manner. These findings establish benzofuran-annulated naphthalimides as a promising scaffold for the development of anticancer agents that exploit replication stress vulnerabilities in tumor cells. Full article

The transition toward a circular economy is accelerating the development of high-performance, sustainable polymeric materials derived from renewable resources. Medium-chain-length polyhydroxyalkanoates (mcl-PHAs) represent a versatile class of biodegradable polyesters with inherent flexibility and tunable side-chain chemistry, making them attractive candidates for advanced polymer applications. Here, we report a novel class of bio-based polyurethanes (PUs) incorporating mcl-PHAs as soft segments, marking their first application in polyurethane synthesis and shifting towards greener PU synthesis. Polyurethane networks were prepared using castor oil (CO) and mcl-PHAs as polyols, with hexamethylene diisocyanate (HMDI) as a hard segment. Material properties were systematically tuned by varying the mcl-PHA/CO ratio (100/0 to 0/100), enabling precise control over structure–property relationships. Comprehensive characterization confirmed urethane bond formation and revealed predominantly amorphous materials with tunable thermal and mechanical behavior. Increasing mcl-PHA content enhanced elasticity and influenced phase organization, underscoring its role as a flexible, bio-derived soft segment. The resulting materials exhibited competitive mechanical performance alongside adjustable swelling behavior and morphology. Importantly, in vitro biocompatibility (MRC-5 fibroblasts) and eco-toxicological evaluation (Caenorhabditis elegans) confirmed the absence of toxicity. These findings highlight the potential of mcl-PHAs as sustainable building blocks for advanced polyurethane systems. Full article

Climate change and rapid urbanization increasingly threaten water security in large river basins, yet existing assessments often fail to capture the multi-scale interactions between hydroclimatic extremes and human activities. To address this gap, we developed an integrated framework combining risk assessment, multi-method driver diagnosis (Geodetector, Multi-Scale Geographically Weighted Regression (MGWR), and Structural Equation Modeling (SEM)), and Zoned Management. Using a landscape-derived Ecological Risk Index (ERI) as a proxy indicator of runoff and non-point source potential, based on established empirical linkages between landscape metrics and hydrological processes, we applied the framework to three major urban agglomerations in the Yangtze River Basin from 2000 to 2020. Our results reveal three distinct risk mechanisms: in the Chengdu–Chongqing area (CYUA), a 165.8% increase in impervious surfaces drives altered runoff; in the Middle Reaches (MRC), the q-value of the Standardized Precipitation Index (SPI) rose from 0.017 in 2000 to 0.146 in 2020, corresponding to a 759% relative increase. Although the absolute q-value of SPI remains moderate at around 0.15, its rapid rise suggests increasing hydrological sensitivity of the MRC’s river–lake system to precipitation extremes; in the Yangtze River Delta (YRD), socioeconomic activities exert overriding pressure. Based on these diagnostics, we propose tailored strategies for water environment management, adaptive planning, and disaster mitigation. This framework offers a scientific basis for differentiated water governance in large river basins facing coupled anthropogenic and hydroclimatic pressures. Full article

Objective: Long COVID (LC) has been defined as a chronic condition that occurs after SARS-CoV-2 infection and persists for more than 3 months. Dyspnea is the most common and disabling symptom with several mechanisms identified. The pathophysiology of post-COVID dyspnea is unknown. The aim of this study is to analyze the clinical profile of patients presenting with dyspnea in the context of LC and to assess its possible relation with complementary diagnostic tests. Material and Methods: This is a retrospective cohort study including adult patients diagnosed with LC attending a post-COVID outpatient clinic. Dyspnea was assessed using mMRC and Borg scales. Complementary tests included chest imaging, pulmonary function tests (PFTs) and a six-minute walk test (6MWT). These assessments were performed at several time points throughout follow-up (3, 6, and 12 months). Results: Eighty patients diagnosed with LC were included, the mean age was 60.0 ± 14.4 and 43 (54.8%) were female. Most patients were hospitalized during acute infection (97.5%) and 25 patients experienced respiratory failure. During the follow-up, chest X-rays showed persistent abnormalities in 67.5% of patients, and 6MWT was pathological in 61.3% at 277 days (IQR 176–326) after acute infection. No significant differences were observed in the prevalence of ventilatory failure across dyspnea severity categories. Reduced DLCO was observed in 20% of patients, while obstructive or restrictive patterns were infrequent. Through three follow-up visits, pulmonary function and exercise capacity remained stable, with modest improvements in DLCO and exercise-induced desaturation (p = 0.005). In multivariable analysis, obesity (adjusted OR 7.88; p = 0.023) and lower DLCO (p = 0.049) were independent predictors of more severe dyspnea, highlighting the role of non-pulmonary factors in Long COVID. Conclusions: This study describes the clinical and functional profile of a cohort of patients with LC. Although abnormal findings were frequent, only impaired DLCO and obesity were independently associated with dyspnea severity, while imaging and six-minute walk test abnormalities showed no consistent association with symptom intensity, supporting a multifactorial origin of post-COVID dyspnea. Full article

Background/Objectives: Clinical childbirth in high-income countries is increasingly shaped by standardised routines that do not always accommodate individual preferences. In Germany, approximately one in eight pregnant persons experiences clinically significant childbirth-related post-traumatic stress disorder symptoms, with pregnant persons facing language or health-literacy barriers being at particular risk of inadequate preference integration. Methods: This paper presents the conceptual foundation and proposed study design for FAIR-Birth, an interdisciplinary initiative to develop and feasibility-test a mobile application supporting Advance Birth Planning (ABP) embedded within midwifery-led antenatal care. The intervention combines four elements: transfer of the Advance Care Planning concept to antenatal care, a domain-restricted Large Language Model (LLM) supporting multilingual preference articulation, integration of the resulting ABP document into midwifery-led continuity of care, and iterative adaptation. Following the updated MRC framework, this study will employ a sequential mixed-methods design encompassing systematic review, participatory instrument development, Delphi consensus on the knowledge base, iterative technical development with usability testing, and a feasibility study across two perinatal centres in Bavaria. Results/Conclusions: FAIR-Birth is expected to generate a content-validated ABP instrument, a domain-restricted multilingual LLM dialogue system, and an evaluated application prototype. The work corresponds to the development and feasibility phases of the MRC framework; effectiveness questions are reserved for a planned subsequent randomised controlled trial. Full article

Azolium-derived metallates are well-established intermediates in metal–N-heterocyclic carbene chemistry; however, their potential as standalone therapeutic agents remains largely unexplored. Herein, we report the first systematic biological investigation of a diverse family of Au(I), Cu(I), Pt(II), Pd(II), and Ru(II) metallates paired with functionalized azolium cations. The complexes were synthesized quantitatively through a simple, atom-economical, and purification-free protocol under aerobic conditions in technical-grade green solvents. Structural characterization by multinuclear NMR spectroscopy and single-crystal X-ray diffraction confirmed metallate formation and enabled the first isolation and crystallographic characterization of unprecedented azolium-derived ruthenates. The antiproliferative activity of the complexes was evaluated against cisplatin-sensitive (A2780) and cisplatin-resistant (A2780cis) ovarian cancer cell lines, alongside non-cancerous MRC-5 fibroblasts. Backbone-functionalized derivatives emerged as the most potent compounds, displaying activities comparable or superior to cisplatin in A2780 cells and up to 1000-fold higher potency in the resistant A2780cis model. Notably, unlike cisplatin, the metallates retained nearly unchanged IC₅₀ values across both ovarian cancer lines, strongly suggesting resistance-evasive mechanisms of action. While benzylazido- and methyl guanosine-derived complexes generally exhibited lower overall potency, several members retained significant activity in resistant cells while showing markedly reduced toxicity toward normal fibroblasts, highlighting promising selectivity profiles. Ethoxide-functionalized derivatives and platinum-based metallates combined pronounced anticancer activity with favourable therapeutic windows. Overall, this work establishes azolium-derived metallates as a previously overlooked class of metal-based anticancer agents combining exceptional synthetic accessibility, broad structural tunability, and remarkable activity against platinum-resistant ovarian cancer. Full article

In this review, we explore the evolving role of endoscopic ultrasound (EUS) in diagnosing and managing pancretobiliary malignancies. For solid pancreatic lesions, techniques like fine-needle biopsy (FNB), contrast-enhanced EUS (CE-EUS), and macroscopic on-site evaluation (MOSE) improve sample quality and diagnostic accuracy. In cystic pancreatic lesions, fine-needle aspiration (FNA), molecular testing, and confocal laser endomicroscopy (nCLE) aid in distinguishing benign from malignant cysts. For cholangiocarcinoma, EUS guided sampling is more accurate than CT in assessing distal lesions and lymph node metastases, while combining EUS with magnetic resonance cholangiography (MRC) enhances diagnostic sensitivity. In gallbladder cancer, EUS surpasses CT and MRI in detecting lymphadenopathy and staging tumors. EUS-FNB (Fine needle biopsy) improves biopsy accuracy, especially for unresectable cases. These advancements highlight EUS as a critical tool for early cancer detection, staging, and tissue acquisition. Beyond diagnosis, EUS plays a pivotal therapeutic role in managing complications such as malignant biliary obstruction and gastric outlet obstruction, offering minimally invasive alternatives like EUS-guided biliary drainage and gastroenterostomy with high clinical success and improved patient outcomes. Full article

Cancer cell metabolism represents a critical therapeutic target, particularly under conditions of metabolic stress induced by glycolysis inhibition. Nitroglycerin (glyceryl trinitrate, GTN), a nitric oxide donor, and 2-deoxy-D-glucose (2-DG), a glycolysis inhibitor, have individually demonstrated anticancer potential through modulation of cellular metabolism and redox balance. In this study, we investigated the cytotoxic and combined effects of GTN and caffeine under 2-DG-induced metabolic stress in human cancer cell lines (HeLa, A549, HT29, and MRC-5). Cell viability was assessed using the sulforhodamine B assay after 24 and 48 h treatments, while drug interactions were evaluated using the Chou–Talalay method and combination index (CI) values. 2-DG alone reduced cell viability in a concentration- and time-dependent manner, with IC₅₀ values ranging from 2.01 to 7.05 mM depending on the cell line and exposure period. The combined treatment further enhanced cytotoxicity, particularly in A549 cells, where viability decreased to approximately 63% after 48 h and the calculated IC₅₀ value for GTN in the presence of caffeine reached 0.143 μM. CI analysis demonstrated synergistic interactions in HeLa and A549 cells (CI < 1), whereas HT29 cells predominantly exhibited antagonistic responses (CI > 1). However, strong synergistic effects were also observed in MRC-5 fibroblasts, indicating limited selectivity toward cancer cells. Molecular docking suggested favorable in silico binding of GTN to aldehyde dehydrogenase 2 (ALDH2) and caffeine to the adenosine A2A receptor. Nevertheless, these findings should be considered exploratory and hypothesis-generating because target expression, enzymatic activity, and pathway activation were not experimentally validated. Overall, the results suggest that GTN enhances caffeine-induced cytotoxicity under metabolically stressed conditions through combined metabolic and redox perturbation, although the magnitude of the response depends on cellular context and warrants further mechanistic investigation. Full article

Background: MEIS proteins are essential homeobox transcription factors that play critical roles in development and have been increasingly implicated in oncogenesis, including breast cancer. Methods: In this study, we identified and characterized novel small-molecule MEIS2 inhibitors through in silico docking targeting the active region of the human MEIS2 homeobox domain. Lead candidates MEISi-2E, MEISi-3, and MEISi-4 were identified with binding energies ranging from −3.0 to −3.90 kcal/mol. The inhibitory potential of these molecules was validated in vitro using a species-conserved MEIS-Luciferase Reporter construct containing the TGACAG targeted locus. Results: Our results demonstrate that MEISi-2E, MEISi-3, and MEISi-4 significantly suppress MEIS-driven luciferase activity and downregulate the expression of Meis1, Meis2, and downstream genes such as IL17RB, CDH1, EGR2, PAX6, and SERPINE1 while upregulating negative regulator TGIF1 and SOX3. In breast cancer cell lines, these inhibitors exhibited potent growth inhibition, with MEISi-3 showing an exceptional IC50 as low as 0.1 μM in SK-BR-3 cells. Mechanistic studies using flow cytometry revealed that these inhibitors induce dose-dependent apoptosis and necrosis. Importantly, the novel inhibitors showed minimal toxicity to healthy human dermal and MRC5 fibroblasts, suggesting a favorable safety profile. Conclusions: These findings establish these small molecules as promising therapeutic candidates for targeting MEIS2-dependent pathways in breast cancer. Full article

Background/Objectives: Folate is a water-soluble B vitamin that is essential for DNA synthesis, cell division and proper growth and development, particularly during pregnancy to prevent neural tube defects (NTDs). A large, fully randomized clinical trial (RCT) from the United Kingdom in 1991 (the Medical Research Council (MRC) Vitamin Study), where participants had a prior NTD-affected pregnancy, demonstrated a 72% reduction in NTD recurrence in the folic acid treatment group. Based on this data and the high rate of unplanned pregnancies, about 90 countries fortify cereal grains with folic acid with the goal to prevent NTDs during pregnancy. This critical narrative review and policy perspective addresses the difference between folate and folic acid and between supplementation and food fortification, critically evaluates the data in three recent publications supporting mandatory fortification of food products with folic acid, and presents the case for a more personalized medicine approach to the prevention of NTDs. Methods: Relevant literature was identified through PubMed searches using the keywords “fortification”, “folic acid”, and “systematic review” or by Googe Scholar Alerts. Three studies were identified based on relevance to the topic and publication dates between January and February of 2026. Results: There is a disregard in published studies, which use pre-fortification groups as controls, for the confounding issue of changing socioeconomic factors over time. Improved socioeconomic conditions are associated with subsequent decreases in NTD prevalence regardless of fortification. Conclusions: The efficacy of folic acid supplementation for recurrent NTDs is supported by evidence-based literature, but evidence in favor of mandatory food fortification to prevent NTDs is limited. Food fortification is widely debated, raises numerous ethical issues, and has broad implications for human health. Full article

This single-center, split-mouth, single-blind pilot randomized trial compared patient morbidity, healing and root coverage between the subepithelial connective tissue graft (SCTG) and the de-epithelialized free gingival graft (D-FGG) when combined with the modified coronally advanced tunnel (MCAT) technique in multiple adjacent gingival recessions. Sixteen systemically healthy patients with bilateral Miller Class I/II (Cairo RT1) recessions were enrolled, and contralateral sides were randomly allocated to MCAT + SCTG (control) or MCAT + D-FGG (test) by means of sequentially numbered, opaque, sealed envelopes (SNOSE). Patient-reported outcomes (pain, chewing discomfort, bleeding) and the Landry Healing Index were assessed at 1 and 2 weeks; recession depth, mean root coverage (mRC) and Root Coverage Esthetic Score (RES) were evaluated at 6 months. Both techniques achieved high mRC (test: 94.22% ± 10.28%; control: 94.60% ± 9.99%) and RES (test: 8.02 ± 0.63; control: 8.14 ± 0.77), with no statistically significant intergroup differences. Donor-site pain was significantly lower in the D-FGG group, whereas early chewing discomfort and bleeding were higher. Because the trial was not powered for equivalence or non-inferiority, these preliminary findings are hypothesis-generating and require confirmation in adequately powered trials. Full article

Background: Pre-Chronic Obstructive Pulmonary Disease (pre-COPD) and Preserved Ratio Impaired Spirometry (PRISm) phenotypes represent important components of the early obstructive lung disease spectrum, characterized by respiratory symptoms and structural lung abnormalities prior to the development of overt airflow limitation. Emphysema is considered one of the major structural phenotypes underlying airway disease and the COPD spectrum. Although cigarette smoking is the best recognized risk factor for these conditions, non-tobacco exposures may also contribute to early structural lung changes. In this study, we evaluated the radiological features, pulmonary function parameters, and dyspnea severity of CT-detected emphysema in symptomatic patients classified as having pre-COPD or PRISm, with particular attention paid to the potential influence of smoking status on disease characteristics. Methods: In this retrospective, single-center study, symptomatic patients aged 20–50 years classified as having pre-COPD or PRISm and in whom emphysema was detected on high-resolution computed tomography (HRCT) were evaluated. Only symptomatic patients who underwent HRCT for clinical indications and in whom emphysema was identified were included. Demographic characteristics, emphysema type and quantitative emphysema severity, pulmonary function parameters, and Modified Medical Research Council (mMRC) dyspnea scores were analyzed. The PRISm and pre-COPD groups were compared in terms of clinical and symptomatic characteristics. In addition, smoking-related clinical and radiological characteristics were also evaluated. Results: A total of 232 patients were included in the study. The median age was 43 years (38–48), and 84.1% of the participants were male. Among the study population, 68.5% were classified in the pre-COPD group and 31.5% in the PRISm group. The most frequently identified emphysema patterns were paraseptal (44.4%) and centrilobular (40.5%). The median total lung emphysema area was 18% (13–22). A weak negative correlation was observed between the degree of emphysema and FEV₁ (r = −0.185; p = 0.005), whereas a weak positive correlation was found between emphysema extent and the mMRC dyspnea score (r = 0.214; p = 0.001). Dyspnea severity was significantly higher in the PRISm group compared with the pre-COPD group (p < 0.001). In the smoking-status subgroup analysis, ever-smokers demonstrated significantly greater dyspnea severity and lower FEV₁ values, whereas never-smokers had a significantly higher proportion of emphysema extent > 18% (all p < 0.05). Conclusions: Radiologically detected emphysema in symptomatic patients without airflow limitation was associated with statistically significant but weak alterations in pulmonary function and dyspnea burden. Dyspnea severity was significantly higher in the PRISm phenotype. In a smoking-status subgroup analysis, ever-smokers had significantly greater dyspnea severity, whereas never-smokers showed a significantly higher proportion of extensive emphysema (>18%), despite similar functional impairment across groups. These findings underscore the importance of non-tobacco exposures in the development of emphysema within pre-obstructive spirometric phenotypes. Multicenter prospective studies incorporating healthy controls and systematic exposure documentation are needed to confirm these observations. Full article