Frontiers in Physiology最新文献

{"title":"The endocannabinoid signaling system in acute and chronic pancreatitis.","authors":"Alex Mabou Tagne, Jene Jamarillo, Lance R McMahon, Daniele Piomelli","doi":"10.3389/fphys.2026.1952582","DOIUrl":"https://doi.org/10.3389/fphys.2026.1952582","url":null,"abstract":"<p><p>The endocannabinoid system (ECS) is a ubiquitous lipid signaling network that regulates tissue homeostasis. Increasing evidence indicates that the ECS undergoes profound remodeling during pancreatic injury and may influence key pathological processes underlying acute pancreatitis (AP) and chronic pancreatitis (CP). Interest in this field has grown in parallel with increasing cannabis use among individuals with pancreatic disorders and the urgent need for alternatives to opioid-based pain management. Components of the ECS, including cannabinoid receptors, the endogenous ligands, and enzymes that mobilize such ligands, are widely expressed throughout both the exocrine and endocrine pancreas, where they contribute to the regulation of pancreatic function under physiological and pathological conditions. Studies demonstrate that AP and CP are associated with distinct alterations in cannabinoid receptor expression and endocannabinoid levels, yet the functional significance of these changes remains incompletely understood. Clinical evidence, however, remains limited and often conflicting. In this narrative review, we summarize current knowledge of ECS organization and function in the pancreas, examine how endocannabinoid signaling is altered during pancreatitis, and critically evaluate the therapeutic opportunities and challenges associated with targeting ECS pathways. We discuss an emerging hypothesis in which adaptive endocannabinoid signaling may contribute to resilience following pancreatic injury and propose that progressive disruption of this response could contribute to the transition from AP to CP.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1952582"},"PeriodicalIF":4.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Physiological aspects of marathon running, volume II.","authors":"Yoshio Suzuki, Daichi Sumi, Henrique Pereira Neiva","doi":"10.3389/fphys.2026.1991611","DOIUrl":"https://doi.org/10.3389/fphys.2026.1991611","url":null,"abstract":"","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1991611"},"PeriodicalIF":4.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-fat diet accelerates pancreas pathology in the <i>Cel-HYB1</i> mouse model.","authors":"Ranveig S Brekke, Anny Gravdal, Renate V Seierstad, Xunjun K Xiao, Mark E Lowe, Caroline S Verbeke, Bente B Johansson, Anders Molven, Karianne Fjeld","doi":"10.3389/fphys.2026.1924024","DOIUrl":"https://doi.org/10.3389/fphys.2026.1924024","url":null,"abstract":"<p><strong>Introduction: </strong>The <i>CEL</i> gene encodes the pancreatic enzyme carboxyl ester lipase. The human <i>CEL-HYB1</i> allele, a hybrid variant of <i>CEL</i> and its adjacent pseudogene <i>CELP</i>, is associated with a five-fold increased risk for chronic pancreatitis in European cohorts. Humanized <i>Cel-HYB1</i> mice develop chronic pancreatitis spontaneously albeit with a relatively mild presentation. The aim of this study was to further characterize the pancreatic phenotype in <i>Cel-HYB1</i> mice.</p><p><strong>Methods: </strong>We investigated <i>Cel-HYB1</i> animals by two complementary approaches. First, we analyzed compound heterozygous <i>Cel-16R/HYB1</i> mice where the second <i>Cel</i> allele carries the 16-repeat (<i>16R</i>) VNTR of the normal human <i>CEL</i> gene. Second, heterozygous and homozygous <i>Cel-HYB1</i> animals were fed either a high-fat diet or standard chow for 3 months. All animals were characterized with respect to growth, organ weights, pancreas pathology and glucose metabolism.</p><p><strong>Results: </strong>In the <i>Cel-16R/HYB1</i> model, body weight, pancreas weight and pancreatic histology were comparable to those of heterozygous <i>Cel-HYB1</i> mice. However, within each genotype female mice generally exhibited more pronounced pancreatic histopathological changes than males. Male <i>Cel-16R/HYB1</i> mice had larger fat depots at 6 months of age, and <i>Cel-16R/HYB1</i> animals of both sexes showed slightly improved glucose tolerance relative to heterozygous <i>Cel-HYB1</i> mice. When fed a high-fat diet, increased body weights were seen across all mouse groups without genotype-dependent differences. Under this condition, <i>Cel-HYB1</i> animals displayed more pronounced pancreatic histopathology than littermate controls. Notably, no consistent genotype-dependent differences in glucose tolerance were observed in <i>Cel-HYB1</i> mice under either high-fat diet or standard chow conditions.</p><p><strong>Conclusion: </strong>The humanized <i>Cel-16R</i> allele did not substantially modify the pancreatic phenotype of <i>Cel-HYB1</i> mice, although <i>Cel-16R/HYB1</i> animals exhibited somewhat improved glucose tolerance compared with heterozygous <i>Cel-HYB1</i> mice. In contrast, high-fat diet promoted exocrine pancreatic pathology, supporting a role for dietary factors as potential modifiers of disease severity in <i>CEL-HYB1</i>-associated chronic pancreatitis.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1924024"},"PeriodicalIF":4.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149171660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Added effects of dual-task water-based exercise on global cognition and physical performance in older women: a three-arm randomized controlled trial.","authors":"Camila Miranda, Lúcia Faria Borges, Andressa Martins E Silva, Katholyn Penna de Bitencourt, Mariana de Souza Strehl, Juliana Loesch, Cristine Lima Alberton, Andréa Kruger Gonçalves, Aline Nogueira Haas, Ana Carolina Kanitz","doi":"10.3389/fphys.2026.1866915","DOIUrl":"https://doi.org/10.3389/fphys.2026.1866915","url":null,"abstract":"<p><strong>Introduction: </strong>Dual-task water-based exercise has been proposed to enhance attention and executive functions and yield cognitive benefits beyond conventional aquatic aerobics exercise. However, evidence remains limited and heterogeneous, as few randomized controlled trials have directly compared dual-task aquatic interventions with conventional aquatic program of equivalent dose in older women.</p><p><strong>Methods: </strong>This three-arm, parallel-group, superiority randomized controlled trial was conducted in Porto Alegre, Brazil, at ESEFID/UFRGS. Older women were allocated to: dual-task water-based exercise (WEDT), conventional water-based exercise (WE), or a non-exercise control group (CG). The intervention lasted 14 weeks (2 sessions/week). Global cognition (MoCA total score) was the primary outcome. Secondary outcomes included specific cognitive measures, mobility (Timed Up and Go [TUG] and dual-task TUG [TUG-DT]), aerobic capacity, muscular performance, maximal voluntary isometric contraction (MVIC), and rectus femoris and vastus lateralis electromyographic activity (EMG). Outcomes were assessed at baseline and post-intervention. Intention-to-treat analyses used generalized estimating equations (GEE) with Bonferroni <i>post hoc</i> tests; per-protocol analyses (≥70% attendance) were conducted as sensitivity analyses.</p><p><strong>Results: </strong>Of 186 individuals screened, 67 were randomized (WEDT n=23; WE n=23; CG n=21). Mean attendance in ITT was 55.2% ± 10.36% (WEDT) and 65.7% ± 9.89% (WE), and no intervention-related adverse events were reported. In ITT, MoCA total score showed no main effects of time or group and no group×time interaction (p>0.05); among MoCA domains, only orientation showed a main effect of time (p=0.006). Semantic verbal fluency showed a significant group×time interaction (p=0.003), increasing in WEDT, decreasing in WE, and remaining stable in CG. TUG showed no significant effects (p>0.05), whereas TUG-DT showed a significant group×time interaction (p=0.032), driven by improvements in CG. A significant main effect of group was observed for the 6-min walk test (p=0.020). Neuromuscular outcomes showed significant group×time interactions for handgrip strength (p=0.037; increases in WE), MVIC (p=0.014), and rectus femoris activation (p=0.028).</p><p><strong>Conclusions: </strong>In older women, adding periodized dual-task demands to aquatic aerobics did not provide consistent incremental benefits for global cognition, while physical effects were modest and heterogeneous. These findings should be interpreted considering the moderate adherence and reduced intervention dose actually received; future trials should evaluate higher training doses and strategies to enhance adherence and monitoring.</p><p><strong>Trial registration: </strong>RBR-4tzrdjz.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1866915"},"PeriodicalIF":4.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of endurance training on spirometric parameters in male long-distance runners.","authors":"Anna Nagórka-Bolek, Aleksandra Undrunas, Wojciech Ratkowski, Aleksandra Puch-Walczak, Łukasz Wierucki, Adam Wyszomirski, Krzysztof Kuziemski, Krzysztof Flis, Tomasz Niźnikowski, Tomasz Zdrojewski","doi":"10.3389/fphys.2026.1862024","DOIUrl":"https://doi.org/10.3389/fphys.2026.1862024","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study was to compare spirometric parameters between recreational male marathon runners (MR) and a control group (CG) representative of the male population of the Pomerania region to assess the association between endurance training and pulmonary function.</p><p><strong>Methods: </strong>A total of 31 amateur MR and 82 men in the CG aged 35-66 years participated in this study. The CG represented the male population of the Pomerania region (Poland). The analysis included basic spirometric parameters: forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), Tiffeneau index (FEV1/FVC), and the potential confounding factors: body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), smoking status, and history of obstructive lung diseases.</p><p><strong>Results: </strong>Recreational MR demonstrated significantly higher FVC and FEV1 values than the CG, both in absolute values and as percentages of predicted values (<i>p</i> < 0.001). Mean FVC was 5.24 ± 0.68 L in MR and 4.58 ± 0.95 L in controls, whilst mean FEV1 was 4.14 ± 0.55 L and 3.55 ± 0.88 L, respectively. No significant differences were observed in the Tiffeneau index (FEV1/FVC), smoking status, or prevalence of obstructive lung diseases between the groups. Although anthropometric parameters differed between groups, they were not significantly associated with spirometric outcomes.</p><p><strong>Conclusions: </strong>Recreational male MR demonstrated significantly higher FVC and FEV1 values than controls from the general male population. No significant differences were observed in the prevalence of obstructive airway disorders. Because of the relatively small sample size and cross-sectional design, the findings should be interpreted with caution. Further longitudinal studies are needed to better clarify the relationship between endurance training and pulmonary function.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1862024"},"PeriodicalIF":4.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proposal for defining the severity of environmental hypoxia.","authors":"Martin Burtscher, Ricardo Amaru, Johannes Burtscher, Katharina Hüfner, Max Gassmann","doi":"10.3389/fphys.2026.1985822","DOIUrl":"https://doi.org/10.3389/fphys.2026.1985822","url":null,"abstract":"<p><p>Every day, millions of people are exposed to environmental hypoxia, primarily due to living at or travelling to high altitudes for reasons such as work, tourism, business, or sports, e.g., mountaineering. Furthermore, hypoxic exposure at low altitudes (e.g., in hypoxia rooms or tents) is increasingly being used to pre-acclimatize individuals to high altitudes for activities such as athletic training, trekking and high-altitude climbing, as well as for preventive and therapeutic purposes. Especially for these applications a clear definition of environmental hypoxia severity is lacking, impeding risk assessment. Our proposed classification does not address the acclimatization process itself, but rather the degree of hypoxia that healthy individuals can tolerate acutely (for a few hours) without prior acclimatization and chronically (up to years) after acclimatization. Based on real-world levels of hypoxia observed in high-altitude residents and mountaineers, as well as in individuals exposed to simulated hypoxia at low altitude, we propose the following definitions: Altitudes of up to 1,000 m, corresponding to fractional inspired oxygen (FiO₂) levels above 18.5%, should be considered 'normoxia'. Altitudes ranging from 1,000 m to 3,500 m or FiO₂ levels between 18.5% and 13.5% can be classified as mild hypoxia. Altitudes between 3,500 m and 5,500 m or FiO₂ levels between 13.5% and 10.2%, represent moderate hypoxia. While people usually can acclimatize to mild and moderate hypoxia, the severe hypoxia experienced at altitudes above 5,500 m or FiO₂ levels below 10.2% poses considerable health risks to humans, where acclimatization in the long term is no longer possible.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1985822"},"PeriodicalIF":4.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applications of single-cell transcriptomics in glaucoma research: from the aqueous humor outflow pathway to retinal ganglion cell neurodegeneration.","authors":"Xiaolu Hao, Dajiang Wang, Zhaohui Li, Shaojun Wang","doi":"10.3389/fphys.2026.1953962","DOIUrl":"10.3389/fphys.2026.1953962","url":null,"abstract":"<p><p>Glaucoma is the leading cause of irreversible blindness worldwide, driven by progressive retinal ganglion cell (RGC) degeneration. While genetic and environmental risk factors have been identified, the cell-type-specific mechanisms underlying pathogenesis remain incompletely understood. Single-cell RNA sequencing (scRNA-seq) enables high-resolution analysis of cellular heterogeneity, developmental trajectories and intercellular communication networks. This review synthesizes recent scRNA-seq advances across two critical domains in glaucoma research: (1) aqueous humor outflow pathway (AHOP) physiology and pathology; (2) primary open-angle glaucoma (POAG) pathogenesis. We identify convergent themes, including mitochondrial dysfunction as a shared mechanism across subtypes, the central role of neuroinflammation in RGC degeneration, and the therapeutic potential of metabolic interventions. We further discuss challenges in translating animal models to human disease, integrating multi-species datasets, and resolving cell-type-specific susceptibility. Finally, we highlight emerging directions in spatial transcriptomics, multi-omics integration, and precision medicine.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1953962"},"PeriodicalIF":4.3,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between in-hospital nursing workload and early functional recovery after unilateral arthroscopic rotator cuff repair: a retrospective cohort study.","authors":"Jiajie Yan, Lan Li, Yali Xu, Cuiwen Zhang, Qiang Teng, Jiamin Zhang, Xiaoxin Zhang, Meili Liu, Xiaofei Zheng, Haobo Zhong, Qiuyan Chen","doi":"10.3389/fphys.2026.1862390","DOIUrl":"10.3389/fphys.2026.1862390","url":null,"abstract":"<p><strong>Background: </strong>Early functional recovery after arthroscopic rotator cuff repair (ARCR) varies substantially among patients. Although surgical characteristics and rehabilitation strategies have been widely investigated, few studies have examined patient-level early postoperative nursing workload as an integrated indicator of care complexity after ARCR.</p><p><strong>Methods: </strong>This single-center retrospective cohort study included 202 patients who underwent unilateral ARCR between January 2022 and December 2024. Patient-level nursing workload within the first 48 hours postoperatively (NWI-48h) was quantified using structured nursing records. The primary outcome was the American Shoulder and Elbow Surgeons (ASES) score at 3 months. Multivariable linear regression and logistic regression analyses were performed with progressive adjustment for potential confounders.</p><p><strong>Results: </strong>Higher NWI-48h was associated with lower ASES scores at 3 months. In the fully adjusted model, each 1-SD increase in NWI-48h was associated with a 4.21-point decrease in ASES score (95% CI, -7.04 to -1.38; P = 0.004). Patients in the high-workload group had lower 3-month ASES scores than those in the low-workload group, with a graded association across workload tertiles. For unplanned healthcare visits or hospital readmissions, adjusted estimates were imprecise, with wide confidence intervals, and should be regarded as hypothesis-generating.</p><p><strong>Conclusion: </strong>Higher early postoperative patient-level nursing workload was associated with poorer short-term functional recovery after unilateral ARCR. NWI-48h may serve as a candidate indicator of early postoperative care complexity that warrants prospective validation before clinical application.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1862390"},"PeriodicalIF":4.3,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of acute caffeine ingestion on post-activation performance enhancement following individualized drop-jump conditioning in high-level male basketball players: a randomized, double-blind, placebo-controlled crossover trial.","authors":"Jinda Li, Mingrui Wang, Jiaxuan Sun, Chunlei Li, Junqi Wu, Adrián Rubio, Lun Chen, Zhengsheng Yang, Pengzhou Chen, Yuting Zhou, Mingze Li, Mingjia Li","doi":"10.3389/fphys.2026.1950037","DOIUrl":"10.3389/fphys.2026.1950037","url":null,"abstract":"<p><strong>Background: </strong>Post-activation performance enhancement (PAPE) is widely used as a pre-performance strategy to improve explosive performance. However, whether acute caffeine ingestion can further enhance PAPE following an individualized conditioning stimulus based on athletes' reactive strength profiles remains unclear. This study investigated the effects of acute caffeine ingestion on PAPE responses induced by a reactive strength index (RSI)-guided individualized drop-jump (DJ) protocol in high-level basketball players.</p><p><strong>Methods: </strong>Twenty-one male National Athlete Grade I basketball players (Tier 3: Highly Trained/National Level) completed a randomized, double-blind, placebo-controlled crossover trial. Participants performed two experimental conditions involving caffeine ingestion (3 mg·kg^-1 body mass) or placebo, combined with an RSI-guided individualized DJ conditioning protocol. Countermovement jump (CMJ) performance was assessed before and after conditioning at 15 s, 3 min, 6 min, 9 min, and 12 min. PAPE was defined as the change in CMJ height relative to the post-warm-up baseline.</p><p><strong>Results: </strong>Individualized DJ conditioning induced a significant time-dependent change in CMJ performance, demonstrating a transient PAPE response (time effect, p < 0.001). However, caffeine ingestion did not significantly modify the temporal profile of PAPE compared with placebo (condition × time interaction, p > 0.05). No significant differences were observed between conditions in peak CMJ height, peak enhancement magnitude, time to peak performance, or cumulative PAPE responses (all p > 0.05). Individual response analysis indicated substantial variability in caffeine-related changes, while sensitivity analysis confirmed the stability of the temporal response pattern.</p><p><strong>Conclusion: </strong>Acute caffeine ingestion at 3 mg·kg^-1 body mass did not provide additional ergogenic benefits beyond RSI-guided individualized DJ conditioning in high-level male basketball players. These findings suggest that individualized conditioning strategies may already optimize PAPE responses, with limited additional enhancement from acute caffeine supplementation under the investigated conditions.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1950037"},"PeriodicalIF":4.3,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explainable deep learning-based classification of Wolff-Parkinson-White electrocardiographic signals.","authors":"Alice Ragonesi, Stefania Fresca, Karli Gillette, Stefan Kurath-Koller, Gernot Plank, Elena Zappon","doi":"10.3389/fphys.2026.1855555","DOIUrl":"10.3389/fphys.2026.1855555","url":null,"abstract":"<p><strong>Introduction: </strong>Wolff-Parkinson-White (WPW) syndrome is a cardiac electrophysiology (EP) disorder caused by the presence of an accessory pathway (AP) that bypasses the atrioventricular node, faster ventricular activation rate, and provides a substrate for atrio-ventricular reentrant tachycardia (AVRT). Accurate localization of the AP is critical for planning and guiding catheter ablation procedures. While traditional diagnostic tree (DT) methods and more recent machine learning (ML) approaches have been proposed to predict AP location from surface electrocardiogram (ECG), they are often constrained by limited anatomical localization resolution, poor interpretability, and the use of small clinical datasets.</p><p><strong>Methods: </strong>In this preliminary patient-specific study, we present a Deep Learning (DL) model for the localization of single manifest APs across 24 cardiac regions, trained on a large, physiologically realistic database of synthetic ECGs generated using a personalized virtual heart model. We also integrate eXplainable Artificial Intelligence (XAI) methods, Guided Backpropagation, Grad-CAM, and Guided Grad-CAM, into the pipeline. This enables interpretation of DL decision-making and addresses one of the main barriers to clinical adoption: lack of transparency in ML predictions.</p><p><strong>Results: </strong>On the considered single heart geometry, our model achieves a localization accuracy above 94% and an average F1 score over 93%. XAI outputs are physiologically validated against known depolarization patterns, and a novel index is introduced to identify the most informative ECG leads for AP localization.</p><p><strong>Discussion: </strong>Results highlight lead V2 as the most critical, followed by aVR, and aVL in the left ventricle (LV) and V1 in the right ventricle (RV). This work demonstrates the potential of combining cardiac digital twins with explainable DL to enable accurate, transparent, and noninvasive AP localization.</p>","PeriodicalId":12477,"journal":{"name":"Frontiers in Physiology","volume":"17 ","pages":"1855555"},"PeriodicalIF":4.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}