In vertebrate adaptive immune systems, somatically diversified antigen receptors assume a central role in self/nonself discrimination. Attesting to the presence of a unique but unknown selective environment at early stages of vertebrate evolution, this facility emerged twice, in the ancestors of jawless and jawed vertebrates. Thus, the molecular structure of incomplete antigen receptor genes and their mode of assembly into functional genes are different in the two sister groups of vertebrates. It appears that adaptive immunity evolved in steps, trading immunologically favorable diversity of antigen receptor repertoires against the inherent risks of potentially destructive self recognition. Initially, the associated quality control mechanisms were largely cell-autonomous and grounded in the evolutionarily selected sequence composition of individual components available for assembly. At later stages, diversity increased in lock-step with emerging cell-nonautonomous quality control strategies: primary lymphoid organs spatially and temporally coupled repertoire development and assessment for self reactivity; regulatory cell types emerged to keep self reactive clones in check in the periphery. In this review, we discuss how comparative studies of vertebrate species situated at key positions in the phylogenetic tree have revealed traces of the evolutionary past of adaptive immune systems.
Aflatoxin (AF) contamination in tree nuts poses a serious threat to global food safety, public health, and international trade due to the potent carcinogenicity of aflatoxin B1 (AFB1). Although traditional mitigation strategies exist, their industrial implementation is constrained by a strict "technological filter," in which high detoxification efficacy must be carefully balanced against the preservation of the nutritional, structural, and sensory quality of the food matrix. This scoping review systematically mapped and critically synthesized recent scientific advances (2005-2025) in physical, chemical, and biological decontamination methods, evaluating their operational effectiveness, underlying mechanisms, and qualitative impacts on tree nuts. Guided by the question, "What physical, chemical, and biological methods are most effective for AF decontamination in tree nuts, and to what extent are they feasible regarding quality preservation and industrial applicability?", the study strictly followed the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis and was reported according to PRISMA-ScR guidelines. A total of 41 eligible original studies were selected after comprehensive screening of the PubMed, Scopus, Web of Science, and ScienceDirect databases. Physical approaches, particularly cold atmospheric plasma and UV-C radiation, achieved robust reduction rates ranging from 70% to 95%; however, these highly energetic treatments often induced lipid oxidation, evidenced by linear increases in malondialdehyde (MDA) levels in matrices such as pistachios. Among chemical methods, ozonation and the use of organic acids achieved degradation rates close to 100% for the most toxic forms, but significant technological trade-offs were identified, including up to a 29% loss of α-tocopherol in hazelnuts. Inorganic selenium emerged as a promising alternative by combining efficacy with matrix preservation. Biological strategies using microorganisms such as Bacillus subtilis, Bifidobacterium lactis, and Lactobacillus kefiri demonstrated substantial sustainable potential, with detoxification efficiencies exceeding 80% through dual mechanisms of active biosuppression and physical adsorption. No single universal method is currently sufficient to handle contamination safely. The future of commercial AF management depends on the development of "hurdle technology," integrating multi-stage synergistic interventions with automated optical sorting and intelligent packaging, supported by further technical advances, studies of practical applicability, and industrial-scale validation to ensure absolute consumer safety and commercial viability.
The escalating global demand for clean water necessitates the development of advanced membrane technologies capable of addressing complex contamination challenges and increasing the desalination efficiency. Polymeric membranes are commonly used due to their scalability and processability; however, their efficiency is limited by permeability-selectivity trade-offs and fouling. Polymer nanocomposite membranes (PNCMs) provide a promising substitute for the incorporation of functional nanofillers into polymer matrices for improving the separation efficiency. This review focuses on PNCMs for water purification and desalination, highlighting the importance of nanofillers like carbon nanotubes, graphene, and graphene oxide, metal and metal oxide nanoparticles (TiO2, ZnO, Ag), zeolites, and metal-organic frameworks. The influence of fabrication strategies, including phase inversion, electrospinning, and interfacial polymerization, on membrane structure-property relationships is systematically examined. While PNCMs demonstrate enhanced water permeability, selectivity, antifouling characteristics, and mechanical robustness compared to pristine membranes, their performance remains highly sensitive to nanofiller dispersion, interfacial compatibility, and structural stability. Key challenges, including nanoparticle agglomeration, long-term durability, and scalability constraints, are highlighted. Finally, future perspectives emphasize rational nanofiller design, controlled interface engineering, and scalable manufacturing approaches to enable the development of robust, high-performance membranes for sustainable water treatment.
Study DesignNarrative review and conceptual framework proposal.ObjectiveTo reframe anterior cervical osteotomy (ACO) as a biomechanical continuum and propose a mechanism-based decision framework "the ACO Triad" integrating alignment, stability, and safety.MethodsA comprehensive literature review was performed across PubMed, Embase, and Web of Science to identify studies representative of distinct ACO biomechanical mechanisms. Unlike traditional hierarchical classifications based on resection volume, techniques were analyzed and synthesized into a four-tier continuum based on their dominant correction mechanism: from disc-level release to vertebral-body translation.Key Content and FindingsThe literature review suggests that sagittal alignment outcomes are governed by the mechanism of apical control (hinging vs. translation) rather than the volume of bone removed. We organized strategies into four tiers: Tier I leverages disc-level release for segmental hinging; Tier II utilizes targeted retro-corporeal decompression; Tier III encompasses traditional corpectomy, which exhibits a "correction ceiling" and stability trade-offs with longer spans; and Tier IV (e.g., VBSO, ACAF) utilizes vertebral body translation for indirect decompression. The "ACO Triad" framework explains the trade-offs: while corpectomy (Tier III) increases resection, it may compromise stability (load-sharing) and safety in adhesive disease. Conversely, translation techniques (Tier IV) decouple decompression from resection, altering the safety profile.ConclusionsAnterior cervical osteotomy is best understood as a mechanism-driven continuum. By integrating alignment, stability, and safety, the ACO Triad provides a rational foundation for surgical decision-making, shifting planning from a resection hierarchy toward biomechanical intent.
Cerebral amyloid angiopathy (CAA) is common in older adults and frequently contributes to cognitive impairment and dementia. Existing in vivo diagnostic criteria for CAA (Boston Criteria) were developed primarily in patients with intracerebral hemorrhage, and their performance in memory clinic populations remains uncertain. The updated Boston Criteria v2.0 incorporate nonhemorrhagic MRI markers intended to improve case detection. We evaluated the diagnostic accuracy of the Boston Criteria v1.5 and v2.0 against neuropathologically confirmed CAA in memory clinic patients. We performed a retrospective diagnostic accuracy study of participants from the Alzheimer's Disease Neuroimaging Initiative and National Alzheimer's Coordinating Center, selected based on availability of required brain MRI and autopsy-based neuropathology data. Patients were classified as no, possible, or probable CAA according to the Boston Criteria v1.5 and v2.0. The primary reference standard was moderate-to-severe neuropathologic CAA; analyses using any neuropathologic CAA were secondary/exploratory. Diagnostic performance was assessed using sensitivity, specificity, predictive values, likelihood ratios, F1 scores, accuracy, and area under the (receiver-operating characteristic) curve (AUC), with formal comparisons between criteria versions. Eighty patients were included (mean age: 81 years, interquartile range 74-86 years; 36.2% female, ∼80% with dementia and Alzheimer disease). Using moderate-to-severe CAA as the neuropathologic reference standard, probable CAA by Boston Criteria v1.5 had a sensitivity of 32% (95% CI 15%-50%), specificity 87% (77%-95%), and AUC 0.59 (0.49-0.69). Using the Boston Criteria v2.0, the corresponding values were 43% (25%-62%), 83% (72%-92%), and 0.63 (0.52-0.74), respectively. No overall performance measures were significantly different between the criteria versions. Secondary analyses using any neuropathologic CAA showed similar patterns. In memory clinic patients, both Boston Criteria versions showed only modest overall diagnostic performance against neuropathology. Compared with v1.5, Boston Criteria v2.0 showed a numerical shift toward greater sensitivity at the expense of specificity but no clear overall gain in accuracy. These findings support cautious, context-dependent interpretation of MRI-based CAA criteria in memory clinic settings and highlight the need for additional biomarkers to improve in vivo diagnosis in nonhemorrhagic populations. This study provides Class II evidence that, in memory clinic populations, Boston Criteria v2.0 show a trade-off between sensitivity and specificity for probable CAA diagnosis, with only modest overall diagnostic accuracy for identifying moderate-to-severe neuropathologically defined CAA.
The performance of supercapacitors is often limited by conventional electrode materials, which typically necessitate a compromise between energy density, power density, and cycling stability. While two-dimensional MXenes offer high conductivity and surface area, their practical application is hindered by restacking and oxidative degradation. This study introduces a novel heterostructured composite designed to overcome these limitations. For the first time, we fabricate a porous, exfoliated network by integrating zero-dimensional SrFeO3 nanoparticles with Ti3C2Tx and V2CTx MXenes via a straightforward mechanical mixing process. In this architecture, the SrFeO3 nanoparticles fulfill a dual role: they inhibit MXene restacking and contribute significant pseudocapacitance via Faradaic reactions. The synergistic coupling between the conductive MXene scaffolds and the redox-active nanoparticles yields exceptional electrochemical performance. The optimized Ti3C2Tx@SrFeO3 and V2C@SrFeO3 electrodes achieve specific capacitances of 752 and 972 F g- 1, respectively, at 1 A g- 1, alongside excellent rate capability. Asymmetric supercapacitor devices assembled with these composites deliver high energy densities of up to 52.91 Wh kg- 1 and exhibit outstanding long-term stability, retaining over 93.9% of their initial capacitance after 5000 cycles. This work establishes the MXene/SrFeO3 heterostructure as a promising platform for high performance energy storage.
Electron-transporting layers (ETLs) are crucial in determining the performance of organic solar cells (OSCs). However, it is challenging to achieve desired efficiency and stability simultaneously for devices based on single-component ETLs. Here, we demonstrate the application of polyoxometalate (POM)-doped hybrid ETLs to achieve significantly mitigated efficiency-stability trade-off in OSCs. By tailoring the doping behaviors, hybrid ETLs exhibit cascade energy-level alignment, increased conductivity, improved electrode adhesion, strong thickness tolerance, and suppressed self-aggregation. These combined merits enable excellent efficiency (20.4%) and outstanding stability (a T93/T92 lifetime of 1500/1000 h under MPP tracking at 40°C/65°C) to be achieved for OSCs. A further elevated efficiency of 20.8% (20.4%, certified) and a T90 lifetime of 1000 h can also be achieved when PDIN-EME is used as the new organic component in the hybrid ETL, demonstrating the easy tunability of these hybrid interlayers for more efficient and robust OSCs.
Proteolysis-targeting chimaeras (PROTACs) couple target recognition to ubiquitin-dependent degradation, but their translation requires coordinated optimisation of degradation efficiency and developability. This review frames PROTAC design as a context-dependent medicinal chemistry problem rather than modular assembly of a warhead, linker and ubiquitin ligase (E3) recruiter. Linker length, rigidity, and exit vectors, together with warhead recognition topology, determine whether binary binding can form a cooperative, ubiquitination-competent ternary complex. Warhead binding mode further affects catalytic turnover and cellular degradation. Linker-free designs and disclosed clinical PROTAC structures show that beyond Rule of Five property control remains central to exposure. Conditional linkers and E3 ligase choice add biological constraints through stimulus-responsive activation, recruiter tractability, E3 expression, localisation, pathway biology, and safety liabilities. This review integrates these principles into a framework for PROTAC design. The framework aligns productive ternary complex assembly, effective exposure and biological-context compatibility within the intended therapeutic context.
The rapid growth of private equity (PE) and publicly traded corporation (PTC) ownership in hospice has raised concerns that investor-driven profit incentives may undermine care quality. Evidence on how these acquisitions affect care delivery remains limited. We linked a national PE and PTC acquisition database to Medicare claims for a beneficiary sample for the period 2010-21 and used a difference-in-differences event study to compare acquired versus nonacquired for-profit hospices on process-based quality measures and Medicare reimbursement. After PE acquisition, registered nurse, social worker, and home hospice aide minutes per thirty days declined 5.14 percent, 12.32 percent, and 6.62 percent, respectively; after PTC acquisition, registered nurse and home hospice aide minutes per thirty days declined 4.63 percent and 9.09 percent. Declines in visit minutes also were observed in the last seven days of life. Reductions in visit minutes were driven by four large acquirers. These findings highlight the need for increased transparency and oversight policies, as well as payment reforms that align reimbursement with care intensity and quality.
The electrocatalytic reduction of carbon dioxide (CO2RR) is a promising technology for sustainable fuel and chemical production, offering a dual solution for climate change mitigation and carbon resource recycling. Nevertheless, the practical deployment of CO2RR is limited by some inherent bottlenecks, including low product selectivity, high overpotentials, and inadequate long-term stability. Recent investigations have demonstrated that fluorine-related modification possesses distinctive merits to boost CO2RR performance, such as tuning the electronic structure and interfacial microenvironment of catalysts. Most notably, it enables effective stabilization of high-valence active centers and regulation of catalyst dynamic reconstruction under cathodic conditions, offering advantages that can complement or, in some cases, outperform conventional modification strategies. However, fluorine modification also faces challenges, including potential trade-offs between hydrophobicity and mass transport, and limited scalability of current fluorination methods. A specialized review summarizing recent advances remains lacking. To fill this gap and provide a roadmap for rational catalyst design, this review summarizes the state-of-the-art progress of fluorine-modified CO2RR catalysts, including carbon materials, fluorine-doped metal catalysts, and organic substrate-modulated composite catalysts, aiming to clarify the structure-activity relationships. It also outlines the challenges and prospects associated with fluorine modification for CO2RR.
Despite the fact that only 2% of active sites can satisfy hydrogen oxidation reaction (HOR) activity thanks to fast kinetics, the fuel cell anode is still dependent on catalysts with large amounts of platinum (Pt). Herein, a minimal-cost ruthenium catalyst bearing ultralow quantities of Pt single atoms (RuPtSA) is developed to provide a high catalytic activity and tolerance to impurities as well as breakthrough reduction in Pt loading amounts. By introducing 1 wt.% Pt as a galvanic replacement for the Ru lattice, the active sites for the adsorption/desorption of hydrogen and CO are redefined. Ru acts both as an electron donor to Pt and as a host for OH groups, thereby accelerating the catalytic process. Using 1 wt.% Pt atoms, the HOR activity and CO resistance of Ru/C are improved, and the HOR mass activity of RuPtSA/C is 25.4-fold higher than that of Pt/C. Synergy between Ru and Pt is demonstrated by density functional theory calculations and verified using practical single-cell evaluations. Furthermore, RuPtSA/C exhibits an 18.4-fold higher mass activity than Pt/C in the HOR of an anion exchange membrane fuel cell, indicating its promise for use as a universal fuel cell anode catalyst.
Existing 3D multi-object tracking (MOT) methods often trade efficiency and generalizability for robustness, as they typically rely on complex association metrics derived from multi-modal architectures or class-specific motion priors. Challenging the common belief that greater complexity necessarily leads to stronger robustness, we propose a robust, efficient, and generalizable method for multi-modal 3D MOT, dubbed RegTrack. Inspired by Yang-Mills gauge theory, RegTrack formulates multi-modal 3D MOT as motion-compensated representation learning. Under this analogy, point-cloud object representations are viewed as matter fields, while inter-frame object motions are regarded as local variations. Geometric cues are modeled as gauge fields to adaptively compensate for such variations, and a pretrained image representation space serves as a globally invariant physical law to guide the compensation process. In this way, the resulting motion-compensated point-cloud representations, viewed as observables, are encouraged to remain consistent for the same object across frames while preserving discriminability among different objects. Their pairwise similarities thus provide a simple yet robust association metric. Specifically, RegTrack is built upon a unified tri-cue encoder (UTEnc), which consists of a local-global point cloud encoder (LG-PEnc), a mixture-of-experts-based geometry encoder (MoE-GEnc), and a frozen image encoder derived from a pretrained vision-language model. LG-PEnc efficiently encodes the spatial-structural information of object point clouds to generate foundational representations. MoE-GEnc interacts with LG-PEnc to model inter-frame geometric relationships and adaptively compensate for motion-induced representation variations without relying on class-specific priors. The frozen image encoder is used only during training to provide a stable representation space for supervising the compensation process, and is discarded during inference. As a result, RegTrack achieves robust, efficient, and generalizable inference using only point-cloud inputs, with merely 2.67 M parameters. Extensive experiments on KITTI and nuScenes demonstrate that RegTrack outperforms its thirty-five competitors.
Leptospirosis remains a major public health concern in tropical regions, including Malaysia, where it is endemic. To date, evidence from remote and understudied areas remains limited. This study aims to assess the epidemiological evidence of leptospirosis among market traders in Sabah, addressing the limited available data for this potentially high-risk occupational group in this region. A cross-sectional study was conducted among 295 market traders in Kudat Town, Sabah. Sociodemographic, occupational, environmental and behavioural data were collected using a modified validated questionnaire. Venous blood samples were collected to test for Leptospira antibodies using the Microscopic Agglutination Test; a titre of 1:50 or higher was considered seropositive. Seroprevalence was estimated descriptively, while factors associated with leptospiral seropositivity were examined using univariable and multivariable logistic regression analyses. The seroprevalence of leptospirosis among market traders was 5.4% (95% CI: 3.1-8.7). Antibodies were detected against 11 Leptospira serovars/strains, mainly Lep175. In univariable analysis, predictors for seropositivity included trading frequency, rodent presence, and proximity to garbage piles. With only 16 cases, the initial multivariable model had a low EPV of 4, suggesting possible overfitting. After reducing the model (EPV = 8), proximity to garbage piles remained strongly associated (AOR = 52.61; 95% CI: 13.50-205.13; p < 0.001), while rodents at home also became significant (AOR = 5.70; 95% CI: 1.12-29.08; p = 0.037). This study provides the first empirical evidence of leptospirosis exposure among market traders in Sabah. Although the overall seroprevalence was low, the findings indicate a measurable risk and underscore the need for further large-scale studies and integrated One Health interventions to reduce exposure in this vulnerable population.
Every day, we face the opposing requirements to flexibly shift between goals and to shield them against distractions. Context-dependent adjustments of cognitive stability and flexibility are a prerequisite for adaptive behavior. A current debate centers on whether these two functions of cognitive control involve a trade-off, manifesting in reciprocal performance benefits and costs, or if cognitive stability and flexibility can be regulated independently. This study aimed to test the assumption of a stability-flexibility trade-off and investigate determinants of control regulations. We examined whether cognitive stability and flexibility can be regulated voluntarily and whether these adjustments are modulated by the task relevance of distracting information. In two task-switching paradigms with varying distractor relevance, we assessed task-switch costs and interference costs as inverse indicators of stability and flexibility. We instructed participants to either focus on the current task or switch flexibly between tasks in within-subjects designs, and monetary rewards were contingent on how well participants succeeded in implementing these instructions. Across both experiments, participants adjusted their task-switch costs but not their interference costs according to the instructions. The distractor relevance further did not moderate these adjustments. Multilevel analyses revealed no correlations between changes in task-switch costs and interference costs in both experiments. Taken together, our results provide evidence that adjustments in task-switch costs are partly under voluntary control. However, they did not provide evidence for the expected trade-off between indicators of cognitive stability and flexibility, at least in the task-switching paradigms we used. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Ion-selective membranes are among the most vital components in separation processes and electrochemical devices, such as seawater desalination and flow batteries. To overcome the permeability and selectivity trade-off of membranes, the construction of angstrom-scale transport pathways within ultrashort structures is essential. Herein, we report a novel gelation-phase separation strategy to fabricate ultrathin composite membranes with sub-nanometer pathways. The electrostatic interactions between anions of additives and dipoles of polymers drive the gelation of polymer solutions. Then, the interaction between the gel network and nonsolvent molecules induces unconventionally uniform phase separation at the molecular level, forming tunable angstrom-scale pathways within an ultrashort structure. Apart from high strength, the angstrom-scale pathways enable the membrane to achieve precise sieving of ions with slight size differences, while the ultrashort transport pathway minimizes transport resistance. The as-prepared robust free-standing 1.4 µm-thick composite membrane is demonstrated in a vanadium flow battery. It delivers a high energy efficiency exceeding 80% at a high current density of 240 mA cm-2. This work introduces a novel gelation-phase separation strategy for molecular-level precise regulation of membrane microstructures, enabling high-performance membrane design.
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A common misconception is that Antimicrobial resistance (AMR) stems solely from poor treatment management in hospitals and weak health systems. AMR is, however, driven by a multitude of factors, including environmental stressors such as contamination from industrial, agricultural, domestic, and healthcare waste, use of antibiotics in veterinary medicine and agriculture, inadequate water, sanitation, and poverty. This paper is a synthesis of stakeholder engagement to advocate for a multi-sectoral One Health approach to address the emerging global threat of AMR. The Africa One Health Network for Disease Prevention (ADAPT) led multi-sectoral stakeholder engagement at the 15th CUGH annual conference in San Francisco, USA. Up to 100 in-person attendees included medical clinicians, microbiologists, anthropologists, veterinarians, agriculturalists, crop scientists, data scientists, mathematical modellers, policy makers, and economists, among others. Stakeholders' views were audio recorded, transcribed, and analyzed manually according to pre-determined themes of (a) key achievements, (b) challenges, and (c) recommendations for multi-and inter-sectoral approaches towards antimicrobial stewardship (AMS) and AMR. Academic research institutions and governments are called to foster multi-sectoral and inter-sectoral collaborative education, research, policy, and community engagement innovations, together with the human and animal health, wildlife, agriculture, trade, tourism, urbanization, and immigration sectors, to prioritize efforts to promote AMS.
Commissioning of a synchrotron hard X-ray nanoprobe beamline traditionally requires months of iterative alignment after hardware installation, during which operational knowledge accumulates but remains inaccessible to non-specialist users. To address this, we present a browser-based virtual commissioning platform for the Korea Light Source ID10 Hard X-ray Nanoprobe beamline (first light 2029) that allows beamline scientists to design, test and refine alignment procedures, scan plans and experimental workflows years before the first photon arrives. Specifically, the platform integrates a Monte Carlo ray-tracing engine, a standard Experimental Physics and Industrial Control System (EPICS)/Bluesky control stack, and a multilingual natural-language interface within a single deployable package, which we name HANBIT (Hybrid Agent-driven Natural-language Beamline Interactive Toolkit). Users can interactively explore parameter trade-offs, such as the effect of the secondary source aperture on beam size versus photon flux. The Monte Carlo engine reproduces the overall Shadow4 beam-profile shape and is validated against SPECTRA undulator spectra, source size and divergence. The natural language processing (NLP) agent achieves 98.2% automated action-identification accuracy across 228 test cases in Korean, English and Japanese, whereas expert review of the same responses yields an acceptance rate of 67.3%. We identify this 30.9 percentage-point gap as a central finding: automated accuracy does not guarantee operational acceptability, and closing it is the key challenge for deployment-grade natural-language beamline control. We further validate the zero-change hardware transition strategy that the beamline pursues on three real hardware subsystems, confirming that at the validated device layers the control code and scan plans operate unchanged on the real devices; the integration of the remaining parts, such as high-rate area detectors, which awaits the detector hardware, is also discussed.
Mitigation measures are essential for controlling the spread of infectious diseases during pandemics and epidemics, but they impose considerable societal, individual, and economic costs. We developed a general framework that combines simulation of disease dynamics with optimal control to determine mitigation strategies that balance infection and mitigation costs. Optimizing this trade-off, we identified three surprising effects: first, assuming a constant reproduction number [Formula: see text], the optimal response is typically "all-or-nothing": depending on disease severity, either strict mitigation or none at all is optimal, with intermediate levels emerging only in restricted regimes that we characterize analytically. Second, under seasonal variations, optimal mitigation is stricter during winter. Interestingly, a single wave of infections still arises in spring, replacing the autumn/winter waves known for classical influenza. Third, during steady vaccination campaigns, even optimal mitigation can result in transient infection waves. Finally, we quantify the cost of delayed mitigation onset and show that even short delays can substantially increase total costs-if the disease is severe. Overall, our framework is easily applicable to general and complex settings and thereby presents a versatile tool to explore optimal mitigation strategies for endemic and pandemic infectious disease.
Brugada syndrome epicardial RVOT ablation reduces VF, but procedural endpoints remain debated. Automated fractionation maps are often interpreted as scattered points, which may reflect artifacts. We propose Islands of Fractionation (IOF), a framework comparing EnSite X fractionation count settings against voltage-defined lesion-effect reference region. This case series included six Brugada syndrome patients undergoing epicardial substrate ablation. Mapping was performed in sinus rhythm using EnSite X with an Advisor HD Grid catheter. Automated fractionation maps were generated with the EnSite X CFE-count algorithm using refractory settings of 14 and 20 ms. Abnormal points were defined as fractionation count ≥3; lesion-effect reference region was defined by voltage change (pre >0.5 mV, post <0.3 mV). Island overlap was quantified using DBSCAN clustering and mesh-based area estimation. IOF revealed a consistent coverage-parsimony trade-off between refractory settings. The 14-ms setting produced broader islands with higher reference-region coverage (median overlap 84.6% [IQR 80.8-93.7]) but larger extraneous mapped area (up to 72.9 cm2). The 20-ms setting produced more compact islands with markedly reduced extraneous area (0.0-34.8 cm2) but lower coverage (59.9% [IQR 37.2-74.7]). In parallel, fractionation burden within the ablated region decreased substantially after ablation in both settings (median total burden reduction 86% vs 93%), supporting lesion-effect concordance of automated fractionation metrics. IOF provides an island-based framework for interpreting automated fractionation mapping and describing its spatial concordance with lesion-effect regions. In this retrospective series, 14 ms favored broader coverage, whereas 20 ms favored greater parsimony.