The superior vena cava (SVC) is a well-recognized non-pulmonary vein (PV) focus in atrial fibrillation (AF); however, intra-SVC re-entrant atrial tachycardia (AT) is extremely rare. An 83-year-old woman with a history of PV isolation using radiofrequency ablation 1 year earlier was referred for a second ablation due to recurrent AT. Activation mapping of the AT demonstrated a re-entrant circuit involving the left atrial (LA) posterior wall. Because bilateral PVs were reconnected, pulsed-field ablation (PFA), including PV re-isolation and LA posterior wall isolation, was performed using a circular multi-electrode array PFA catheter. The initial PFA application did not terminate the tachycardia; however, the arrhythmia transitioned to a different AT. High-resolution mapping revealed a re-entrant circuit confined within the SVC sleeves, characterized by transverse re-entrant propagation. Entrainment pacing confirmed intra-SVC re-entry. Circumferential PFA was delivered to the SVC during sinus rhythm, achieving SVC isolation without sinus node dysfunction or phrenic nerve palsy. This case demonstrates effective management of intra-SVC re-entrant AT using a circular multi-electrode PFA catheter. High-resolution mapping identified a rare re-entrant circuit confined to the SVC. Owing to its tissue selectivity, PFA enables safe and effective SVC isolation while minimizing the risk of phrenic nerve injury.
Catheter ablation of ventricular tachycardia (VT) is characterized by long procedures and frequent recurrence. Personalized image-based computational models may provide noninvasive ablation target guidance but are computationally demanding and cannot localize focal arrhythmias. This study aims to clinically validate our near real-time in silico pace mapping (InSPM) approach, which rapidly localizes both focal and re-entrant arrhythmia site of origins within personalized image-based models. Personalized models incorporating scar were reconstructed from imaging data in 18 patients with structural heart disease; 12-lead electrocardiogram (ECGs) were obtained during clinical pace mapping and pacing site locations defined as ground truth. ECG templates of induced monomorphic VT were obtained. Virtual pacing was conducted in models and simulated ECGs correlated with clinical templates to produce high-resolution virtual pace-maps. Distance (d) between clinical ground truth sites and simulation predicted target areas with highest correlation quantitatively assessed InSPM accuracy for localizing focal activations. For re-entrant VT, predicted targets were compared with surrogates of VT site of origin and mapped VT circuits. Intrinsic resolution of clinical pace mapping was approximately 4 mm for similarly correlated ECGs (mean correlation coefficient >0.99). Across 270 clinical pace-mapping locations, d was 8.2 mm (6.9‒12 mm), relatively insensitive to cardiomyopathy, but with increased accuracy in right vs left ventricles. Patient-specific ECG electrodes alongside accurate scar representation, particularly in patients with ischemia, were important for optimizing InSPM accuracy. InSPM created from clinical ECG VT templates reliably identified re-entrant VT exit sites. InSPM provides a rapid and validated personalized computational modeling ablation technology to accurately localize both focal and re-entrant VTs, which may be practically integrated into clinical workflows.
UTe2 exhibits the remarkable phenomenon of re-entrant superconductivity, whereby the zero-resistance state reappears above 40 tesla after being suppressed with a field of around 10 tesla. One potential pairing mechanism, invoked in the related re-entrant superconductors UCoGe and URhGe, involves transverse fluctuations of a ferromagnetic order parameter. However, the requisite ferromagnetic order-present in both UCoGe and URhGe-is absent in UTe2, and neutron scattering shows instead that the magnetic susceptibility is peaked at an antiferromagnetic wavevector. Here, we measure the magnetotropic susceptibility of UTe2 across two field-angle planes. This quantity is sensitive to the magnetic susceptibility in a direction transverse to the applied magnetic field-a quantity that is not accessed in conventional magnetization measurements. We observe a very large decrease in the magnetotropic susceptibility over a broad range of field orientations, indicating a large increase in the transverse magnetic susceptibility. Because our technique probes the magnetic susceptibility in the long wavelength (q = 0) limit, this suggests that the strong transverse susceptibility arises from ferromagnetic spin fluctuations. These ferromagnetic fluctuations are likely important for understanding the pairing mechanism in UTe2, as all three superconducting phases of UTe2 surround this region of enhanced susceptibility in the field-angle phase diagram.
Repetitive non-reentrant ventriculoatrial synchrony (RNRVAS) is an under-recognized pacemaker-mediated rhythm that can cause atrioventricular (AV) dyssynchrony and heart failure symptoms. A 65-year-old man with advanced nonischemic cardiomyopathy and dual-chamber implantable cardioverter-defibrillator presented with worsening heart failure symptoms. A 12-lead electrocardiogram (ECG) demonstrated ventricular pacing with retrograde atrial conduction followed by atrial pacing with functional atrial noncapture, consistent with RNRVAS. Device interrogation confirmed frequent automatic mode switching episodes. Targeted device reprogramming, including lowering the lower rate limit and shortening the AV delay restored AV synchrony and resulted in clinical improvement. RNRVAS may evade standard device detection algorithms and present with subtle but clinically significant hemodynamic compromise. Careful ECG analysis can facilitate timely diagnosis and guide simple programming adjustments, with profound symptom improvement. Careful analysis of surface ECGs can reveal RNRVAS and guide simple pacemaker reprogramming that restores AV synchrony and improves heart failure symptoms.
Ventricular tachycardia (VT) in the post-myocardial-infarction heart is sustained by re-entry arising from slow and heterogeneous impulse propagation within the infarct border zone. Seminal histological and electrophysiological studies demonstrated that re-entry is enabled by conduction corridors of surviving myocardial bundles embedded within fibrotic scar. However, growing experimental and clinical evidence indicates that this structural concept alone does not fully account for the complex electrophysiological behaviours observed in infarct-related VT. In this review, we examine the evolution of the arrhythmogenic substrate following myocardial infarction and the development of the critical slow-conducting pathway known as the 'diastolic isthmus'. Post-infarct remodelling that includes inflammatory, fibrogenic and chronic maturation phases transforms the border zone into a heterogeneous, multicellular environment, wherein surviving cardiomyocytes coexist with (myo)fibroblasts, immune cells, adipocytes and neural elements. The interactions among these cellular populations influence impulse propagation through modifications in electrotonic coupling, paracrine signalling and membrane excitability modulation. Within these constrained myocardial strands, minor alterations in intercellular coupling or ionic currents can substantially affect conduction velocity and propagation safety, leading to delayed activation while preserving the conditions necessary for re-entry. Furthermore, we discuss how these changes contribute to the three-dimensional architecture of re-entrant circuits and the implications for identifying the arrhythmogenic substrate during electroanatomical mapping, as well as the interaction between ablation energy and heterogeneous infarct tissue. Collectively, these observations challenge the traditional conception of VT corridors as passive fibrotic channels. Instead, scar-related ventricular tachycardia represents an evolving electrophysiological phenomenon resulting from progressive multicellular remodelling of the infarct border zone.
The method for identifying the atrial entrance to the slow pathway (E-SP) during slow-fast atrioventricular nodal re-entrant tachycardia (AVNRT) remains unclear. This study examined whether the E-SP could be identified by analyzing the last entrainment response (LER) of AVNRT. The LER was analyzed at 6 intra-atrial sites-His bundle site (HB); 3 equidistantly divided sites from the HB to the coronary sinus ostium (CSOS) (sites S, M, and I); inferior-CSOS; and posteroinferior-CSOS-after manifest entrainment of AVNRT in 40 patients. We hypothesized that E-SP would be captured antidromically during entrainment and that its post-pacing interval (PPI) to the last entrained beat would equal the tachycardia cycle length (TCL). In group A (n = 27), the area from HB to site I was captured orthodromically, and inferior- and posteroinferior-CSOS were captured antidromically. PPIs from HB to site I were shorter than TCL (P < 0.0001), PPI at inferior-CSOS did not differ from TCL (389.3 ± 51.9 vs 389.2 ± 51.8 milliseconds; P = 0.3265), PPI at posteroinferior-CSOS was longer than TCL (P < 0.0001). In group B (n = 13), the area from HB to site M was captured orthodromically, and that from site I to posteroinferior-CSOS was captured antidromically. PPIs from HB to site M were shorter than TCL (P < 0.001), PPI at site I did not differ from TCL (354.7 ± 36.5 vs 354.8 ± 36.6 milliseconds; P = 0.3370), and PPIs at inferior- and posteroinferior-CSOS were longer than TCL (P < 0.001). These findings indicated that the E-SP was located at inferior-CSOS in group A and site I in group B. Successful slow pathway ablation sites matched these sites. Analysis of the LER accurately identified the E-SP in AVNRT.
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Objective　Focusing on novice public health nurses with prior work experience, this study aimed to identify the characteristics of human resource development systems related to career development, and to examine the importance of achievement levels in home visits within such systems.Methods　A web-based survey was conducted targeting all public health nurses newly employed by prefectural and municipal governments across Japan in fiscal years 2023 and 2024. In this study, we analyzed data from individuals with prior work experience. The survey items included demographic characteristics, the Comprehensive Career Development Scale for public health nurses (career score), the human resource development system, and levels of achievement during home visits for basic cases (home-visit achievement). Using hierarchical multiple regression, the career score was set as the dependent variable. In Model 1, all independent variables except home-visit achievement were entered; in Model 2, home-visit achievement was added. The adjusted coefficient of determination (R2) and its change were calculated to examine the contribution of home-visit achievement.Results　A total of 1,679 questionnaires were returned, of which 1,572 were valid, and 734 respondents had prior work experience. In the hierarchical multiple regression analysis, the adjusted R2 values were 0.095 for Model 1 and 0.114 for Model 2, indicating a significant increase of 0.02. In Model 2, variables significantly associated with the career score were workplace consultation (β＝0.19), experience in presenting at academic conferences (β＝0.08), reading journals/books purchased by the workplace (β＝0.14), self-purchased journals/books (β＝0.08), and home-visit achievement (β＝0.15).Conclusion　The adjusted R2 of Model 2 was 0.114, indicating that the career development of novice public health nurses with prior work experience could not be explained sufficiently by the variables examined in this study alone. However, workplace consultation, presentation experience, journal and book reading, and home-visit achievements were significantly associated with career score, with the inclusion of home-visit achievements further improving the explanatory power of the model. These findings suggest that, even for novice public health nurses with prior work experience, human resource development that provides systematic instruction and ensures achievement levels during home visits, together with well-developed consultation systems and learning opportunities, is important for supporting career development during the initial employment period.
Phase separation of RNA-binding proteins plays crucial roles in the cell and is modulated by RNA, including promotion and suppression at low and high RNA concentrations, respectively. In complex coacervates, suppression of phase separation is rationalized by charge inversion when increasing the concentration of one component. Here, we show that suppression of biomolecular condensates of the RNA-binding protein hnRNPA1 at high RNA concentration is driven by a different mechanism, namely the competition with formation of nano-sized protein-RNA clusters in the dilute phase. We show that the competition is modulated not only by RNA concentration, but also by the type of RNA, with specific RNA being more effective in promoting cluster formation than unspecific RNA. We further show that protein-RNA clusters convert into amyloid fibrils over a longer time-scale compared to condensates, therefore providing higher kinetic stability. The competition between clustering and phase separation reported in this study could provide a unifying framework to understand the distinct assemblies of hnRNPA1 in the nucleus and the cytoplasm, where the protein is exposed to different types and concentrations of RNA.
Do the key drivers of alcohol misuse change as young adults transition from early to late stages of employee onboarding? To answer this question, a series of hypotheses were tested based on two waves of data collected from 1240 college graduates from four different universities in the United States who reported obtaining full-time employment following college graduation. Data on alcohol misuse and hypothesized mechanisms-peer drinking norms and work-related stressors-were collected during the early (i.e. first few months on the job: T1) and late (12 months following initial assessment: T2) stages of employee onboarding. Results indicate that both a key work-related stressor (role overload) and injunctive peer drinking norms (i.e. those focusing on others' approval) drive alcohol misuse in the transition from early to late stages of onboarding. However, while the relationships between injunctive peer drinking norms and alcohol misuse remain constant over the two measurement points, the mediated relationships between work-related stressors and alcohol misuse via distress is curvilinear and significantly weakens from early to late onboarding. We argue that this observed attenuation suggests that some risk factors can drive alcohol misuse in a way that is non-monotonic as well as dynamic over the course of emerging adults' career entry.
Inadequate access and timely linkage to treatment for people recently released from incarceration is a major barrier to HIV care. Differentiated service delivery models (DSDMs) that do not rely solely on clinic attendance need to be utilized, bringing HIV treatment closer to re-entrants and addressing current challenges with treatment attrition post-release from incarceration. DSDMs have demonstrated potential as alternatives to clinic-based treatment collection. We conducted a qualitative study to explore barriers to HIV care linkage and perceptions on the use of DSDMs for HIV treatment following release. We interviewed individuals, released from incarceration while on HIV treatment in Gauteng, South Africa. Participants had to be people recently released from incarceration, above the age of 18 years, living with HIV and taking Antiretroviral Therapy (ART) at their time of release from incarceration. Our results indicate that there was a high degree of enthusiasm among re-entrants for DSDMs. It is important to generate both qualitative and quantitative evidence to support DSDMs as alternatives service delivery models to clinic-based care among re-entrant populations. Based on the findings of this study, DSDM services can be part of the solution to closing the HIV treatment attrition gap among re-entrants as they transition from the prison environment to community-based care.
Interatrial connections (IACs) may act as pathways sustaining atrial fibrillation (AF), yet their role as ablation targets remains uncertain due to challenges in identifying IAC-dependent re-entrant circuits. This study tracks re-entrant activity along IACs, characterizes IAC-dependent re-entries, and assesses the impact of in silico IAC ablation on re-entry maintenance. Six patient-specific biatrial bilayer models were reconstructed from CT and MRI-derived geometries, each incorporating four IACs: Bachmann's bundle, fossa ovalis, upper posterior, and coronary sinus. The Courtemanche ionic model was used to simulate mild (M) and severe (S) AF-related electrical remodelling, with fibrosis burden ranging from 9.0% (M) to 27.6% (S). Across the 12 models, 110 sustained re-entries were induced, followed by circumferential pulmonary vein isolation. Fifteen IAC ablation strategies were tested at three different timings. Critical pathways along the six possible interatrial loops were quantified. Tachycardia cycle length (TCL) and phase singularity (PS) clusters were analysed before and after IAC ablation. Overall, 11.8% of re-entries were IAC-dependent. Larger interatrial loops were the major contributors to critical pathway formation. IAC-dependent re-entries exhibited more critical pathways, shorter TCL (194.2 vs. 201.9 ms; ΔTCL = 7.65 ms, P = 0.006), and more PS clusters in the RA body [8 (5-10) vs. 4 (2-6), P = 0.006]. Ablation timing did not influence termination rates. We present the first framework to track re-entrant activity along IACs. We identified IAC-dependent re-entry characteristics that may guide patient stratification and targeted ablation strategies in clinical practice.
The increasing speed of transportation requires outstanding performance of energy absorbers used in passive safety systems. These absorbers must deform at approximately constant force to safely dissipate kinetic energy during a collision. Structured materials exhibit a superior energy-absorption-to-weight ratio compared to bulk materials. Auxetic structures, with a negative Poisson's ratio due to their unique internal geometry, further improve load redistribution and indentation resistance. However, their absorption capacity remains limited relative to conventional structures. Because no established method exists to systematically enhance the absorption capacity of auxetic structures, this study investigates the use of reinforcements and explains how they influence plastic hinge formation and the resulting energy dissipation mechanisms. Structures represented by reinforced re-entrant honeycomb are manufactured using Laser Powder Bed Fusion additive technology from stainless steel 316L and NiTi alloy. Complex experimental and numerical analyses show that reinforcements in re-entrant honeycomb improve absorption capacity mainly due to contact between deformed reinforcements and horizontal walls, rather than to the formation of new plastic hinges. By optimising the reinforcement placement, the unit cell can absorb three times more energy per unit mass than without reinforcements. Samples from NiTi alloy theoretically outperform those from stainless steel 316L in absorption capacity, but its practical applicability is constrained by LPBF processing challenges. Finally, a new Double Re-entrant Honeycomb structure is designed that can absorb more than 70% of energy per unit mass compared to the reference geometry, while decreasing engineering stress fluctuations by approximately 36%.
Understanding the mechanisms and anatomical substrates underlying postablation atrial tachycardia (AT) is essential for guiding targeted mapping and successful re-ablation strategies. This study analyzed patients referred for repeat ablation for AT after first-time atrial fibrillation ablation with a pentaspline pulsed field ablation (PFA) catheter. High-density electroanatomical mapping was performed to identify the mechanism of post-PFA ATs and assess lesion durability. Re-entrant circuits were analyzed according to the principles of topology (paired rotations, identification of critical boundaries, and ablation strategies). Among 4,144 patients, 236 underwent repeat ablation (160 for atrial fibrillation [3.9%] and 76 for AT [1.8%]), and this constituted the final cohort. A total of 87 ATs were mapped: 21 in the right atrium (4 focal and 17 peri-tricuspid valve re-entry) and 66 in the left atrium (1 focal and 65 re-entry). Pulmonary vein and posterior wall isolation durability were 84% and 89%, respectively. Left atrial (LA) re-entry mechanisms comprised single-loop (n = 9) and predominantly dual-loop (n = 56) re-entry, including circuits defined by anatomical boundaries (n = 32) or involving an anterior scar (n = 24). In all cases of LA re-entrant AT, sinus rhythm was restored when ablation connected the 2 critical boundaries. Topological principles accurately explained the observed activation patterns and responses to ablation. The incidence of repeat ablation for AT after pentaspline PFA was low, likely reflecting the high durability of the index lesion sets. Most post-PFA ATs manifested as dual-loop LA re-entry. Retrospective application of the topological framework provided coherent mechanistic interpretations of AT behavior and accurately predicted the response to direct and indirect critical boundary-targeted ablation.
Total hip (THA) and total knee arthroplasty (TKA) utilization has increased substantially over the past decade, highlighting the importance of understanding how operative volume is distributed among surgeons. While prior studies have focused on consolidation at the health-system level, surgeon-level procedural concentration remains incompletely characterized. A retrospective analysis of Medicare fee-for-service claims from 2013 to 2023 was performed using a national Medicare administrative claims dataset. The primary and revision THAs and TKAs were identified using Current Procedural Terminology codes, including surgeons performing ≥ 11 procedures annually. Surgeon-level case concentration was assessed using the Herfindahl-Hirschman Index (HHI), with state-level variation evaluated using change in HHI (2023 to 2013). Entrant surgeons were defined as those who had no cases in the prior two years. Temporal trends were assessed using linear regressions. Primary THA volume increased from 166,730 to 274,801 and TKA from 390,710 to 526,893 between 2013 and 2023, with corresponding increases in median annual surgeon volume (THA: 21 to 26; TKA: 27 to 31). Surgeon-level HHI declined for primary THA (2.7 to 2.0; β = -0.064/year, P < 0.001) and TKA (1.7 to 1.5; β = -0.016/year, P = 0.022), indicating decentralization. Revision THA volume decreased (5,667 to 1,814) with increasing HHI (42.4 to 132.8; β = +8.37/year, P < 0.001), while revision TKA remained persistently concentrated. Entrant surgeons accounted for 12 to 18% of annual primary arthroplasty volume. The primary THAs and TKAs have become increasingly dispersed over the last decade, whereas revision arthroplasty remained concentrated among specialist high-volume surgeons, indicating contrasting workforce patterns.
Electronic skin demonstrates significant potential for wearable health monitoring and human-machine interaction. However, conventional hydrogels rarely achieve a balance of high strength, fatigue resistance, sensitivity to subtle deformations, and conformability to complex curved surfaces. They often suffer from mechanical degradation, signal drift, and insufficient interfacial adhesion under repeated loading. Here, we propose a synergistic strategy integrating multibond crosslinking reinforcement with structural configuration amplification to develop a PVA/PAA/Zr4+ ion-conductive hydrogel strain sensor featuring a re-entrant honeycomb negative Poisson's ratio structure. At the material level, PVA/PAA hydrogels are fabricated via one-pot in situ photopolymerization followed by freeze-thaw-induced crystalline crosslinking. Incorporation of Zr4+ coordination, together with a high-density hydrogen-bond network, establishes a dynamic dissipation-reconstruction mechanism, thereby markedly improving strength, toughness, and fatigue durability. Structurally, the re-entrant honeycomb geometry amplifies strain and mitigates local stress concentration through unit rotation and beam bending, enhancing low-strain signal resolution and surface adaptability. The resulting hydrogel sensor delivers a maximum tensile stress of 552.9 kPa and an elongation at break of 629.4%. It provides a broad sensing range of 0.1-200% with a 0.1% resolution and a response time of 94.2 ms while maintaining stable outputs under cyclic deformation. As application demonstrations, the hydrogel sensor enables discrimination of soft gripper bending states and grasped object sizes, conforms tightly to dynamically changing curved surfaces, and supports continuous abdominal skin-contact respiratory monitoring with clear differentiation among distinct breathing patterns. Overall, this work establishes a reliable material-structure integrated design paradigm for hydrogel-based electronic skin, promoting its development toward wearable physiological monitoring.
Antibiotics lose power to kill microbes through excessive use, commonly known as antibiotic resistance, which is modeled by future cost increase from current use. The first best incorporates future cost externality due to current consumption. Resistance and consumer welfare deviate from first best in various market structures. Low prices under competition lead to high consumption and resistance. Competitive managed-care plans use rationing contracts, which partially internalize resistance cost externality by restricting use. A drug monopolist fully internalizes the externality, but sets a high price. We derive necessary and sufficient conditions for higher consumer surplus under monopoly than competition. Facing a potential entrant, an incumbent may consider entry deterrence and accommodation. To deter entry, the incumbent reduces current sales to lower future cost; this alleviates antibiotic resistance. Entry accommodation gives rise to two countervailing effects. First, incumbent and entrant will share the market. The incumbent has less incentive to internalize the cost effect, so raises production and exacerbates resistance. Second, the incumbent makes more profit when its future cost is low, so reduces production and mitigates resistance.
Bone plates are widely used in orthopaedic surgery to stabilise fractured bones and support healing following traumatic injuries or osteotomies. However, conventional metallic bone plates suffer from stress shielding and stiffness mismatch with bone, which can hinder optimal healing. Additive manufacturing enables the incorporation of novel metamaterial architectures into polymer-based implants to enhance mechanical properties. The fatigue behaviour of these implants during the healing period is critical to ensuring their structural integrity and long-term performance. In this study, the compressive fatigue performance of fused deposition modelling (FDM)-printed carbon fibre-reinforced polylactic acid (CF-PLA) bone plates were investigated. Four metamaterial structures-tetrachiral, re-entrant, rotating square, and hexagonal-were evaluated under strain-controlled cyclic loading at 20%, 40%, 60%, and 80% of their respective yield strains. The results showed a strong dependence of fatigue behaviour on lattice geometry. Among the tested configurations, the re-entrant structured bone plate exhibited the best overall fatigue performance, sustaining up to 100,000 cycles at moderate strain levels and showing delayed stiffness degradation under high strain conditions. In contrast, rotating square and hexagonal structures showed early stiffness loss and failure at higher strain levels. These findings highlight the importance of lattice design in fatigue performance, although FDM-induced printing defects significantly influence overall fatigue behaviour.
This study aims to develop a deep learning model utilizing both surface and esophageal electrocardiogram (ECG) data to accurately differentiate types of paroxysmal supraventricular tachycardia (PSVT), including slow-fast atrioventricular nodal re-entrant tachycardia (S-F AVNRT), and orthodromic atrioventricular reentrant tachycardia with left-sided (AVRT-L) and right-sided (AVRT-R) accessory pathways. We analyzed 921 ECG cases from 775 patients from four hospitals between 2014 and 2022, segmented into 6261 ten-second ECG segments. A Residual Network (ResNet)-based model was developed. For comparison, Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) classifiers were also constructed using handcrafted time-domain and frequency-domain features. It was thoroughly evaluated using a comprehensive set of metrics. These metrics included accuracy (ACC), the area under the receiver operating characteristic curve (AUC); sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and F1-Score. The diagnostic efficacy of ECG lead configurations was robust. Among surface-only leads, the three-lead combination II+V1+aVF achieved the highest AUC (0.989). The single-lead aVF demonstrated remarkable efficiency (AUC 0.961), approaching the performance of the full 12-lead ECG (0.974). The bipolar esophageal lead (EB) alone achieved an AUC of 0.989, comparable to II+V1+aVF (AUC 0.989). The combination aVF+EB yielded the highest overall AUC of 0.996. ResNet significantly outperformed RF and XGBoost across all lead configurations (P < 0.001). This model effectively distinguishes between PSVT types, surpassing traditional diagnostics in accuracy and reliability. Future research should focus on model optimization and dataset expansion to enhance diagnostic capabilities and interpretability.
Immune responses evolve across time and tissues through coordinated programs of proliferation, differentiation, and migration, yet most single-cell measurements capture only static molecular snapshots. As a result, reconstructing how immune cells transition between alternative fates remains challenging, particularly for CD8 T cells, whose differentiation is highly dynamic and shaped by rapid expansion, contraction, and tissue trafficking. Here, we introduce an optimal transport-based fate mapping framework that reconstructs continuous CD8 T cell trajectories across time and tissues. Applied to longitudinal single-cell RNA-seq data from CD8 T cells responding to acute viral infection in mice, this approach accurately recapitulates population dynamics and resolves coherent effector and memory T cell differentiation trajectories. Extending the model to multiple tissues, we identify and experimentally validate temporally distinct waves of migration into the small intestine that give rise to divergent tissue-resident memory (Trm) fates, long-lived T cells crucial in immunosurveillance. By integrating optimal transport inference with time-resolved in vivo labeling, we demonstrate that CD52 marks recent tissue entrants and distinguishes them from Trm precursors. Finally, trajectory-guided analysis of transcription factor regulons reveals both shared and context-specific gene regulatory programs and identifies AP4 as a key regulator of circulating versus tissue-resident specification. These results establish optimal transport as a principled framework for reconstructing immune cell fate dynamics and provide a quantitative map of early events governing antiviral CD8 T cell differentiation across tissues.