Publications by Year: 2026

BACKGROUND: Early recurrence of atrial tachyarrhythmias (ERAT) is common after pulmonary vein isolation (PVI) and is traditionally attributed to transient post-procedural inflammation. With the introduction of pulsed field ablation (PFA), the incidence and prognostic significance of ERAT compared with thermal ablation remains unknown.

OBJECTIVE: The study aimed to compare the incidence of ERAT during the blanking period in patients undergoing PFA versus radiofrequency (RF) ablation for atrial fibrillation (AF).

METHODS: We prospectively enrolled patients undergoing first-time PVI between 2022 and 2025 at our institution. Propensity score matching was performed to address baseline imbalances and group size differences between RF and PFA PVI. The incidence of ERAT and its association with 9-month arrhythmia recurrence, defined as late recurrence of atrial tachyarrhythmias (LRAT), were analyzed.

RESULTS: A total of 962 patients were included (420 RF, 542 PFA). Patients with ERAT were more likely to be older, have persistent AF, higher CHA2DS2-VASc scores, larger atria, reduced ejection fraction, and no prior antiarrhythmic drug use. After multivariable adjustment, PFA was independently associated with a lower risk of ERAT compared with RF (hazard ratio [HR] 0.61; 95% confidence interval 0.42-0.88). ERAT was strongly associated with LRAT, with a 3-4-fold higher risk of atrial arrhythmias at 9 months (early ERAT: HR 3.78, P < .001; late ERAT: HR 4.10, P = .001), regardless of ablation modality.

CONCLUSION: PFA is associated with a significantly lower risk of ERAT compared with RF ablation. The occurrence of ERAT, irrespective of energy source, predicts a substantially higher risk of LRAT.

Loneliness affects the health and wellbeing of a substantial proportion of the global population, posing a major public health concern. Loneliness, despite being an emotional state experienced within oneself, represents a sense of isolation from other individuals beyond the self. Most contemporary psychological research on emotion, especially in adults, takes an individualistic approach and is limited in accounting for "other" minds when studying the mind of a "self." On the other hand, studies of the neurophysiology of loneliness have mostly focused on presenting the biological correlates of loneliness, not accounting for the role of loneliness in representing pre-existing or anticipated biological needs. In this article, we review interdisciplinary research on self-other representation at levels of the mind, body, and brain. We propose neurophysiological mechanisms that support self-other overlap, guided by theories of allostatic-interoceptive self-regulation and situated in a predictive processing framework. These findings suggest that self-other representation in the body and brain may form a basis for social connection, and loneliness may be associated with insufficient self-other overlap. We discuss clinical implications of this model, especially in borderline personality disorder, and end with future theoretical and methodological considerations in advancing loneliness research.

Costimulatory blockade has emerged as a promising alternative to conventional immunosuppression with the potential to reduce chronic allograft injury and minimize drug-related toxicities, including nephrotoxicity, cardiometabolic complications, and malignancies. Belatacept, the most extensively studied agent, has been associated with improved allograft function and reduced donor-specific antibody formation, although it is also associated with increased risk of acute, early graft rejection and increased risk for infections due to cytomegalovirus, Epstein-Barr virus, and Pneumocystis jirovecii. These effects may reflect the impact of costimulatory blockade on naïve T cell activation, although relatively sparing memory responses. Susceptibility to infections is, therefore, influenced by prior infectious exposures and the maintenance of immune memory in the face of diverse adjunctive immunosuppressive programs. Next-generation approaches, including Fc-silent anti-CD154 antibodies and CD28-directed therapies, are in early clinical trials with infectious complications incompletely defined. Recently, immunosuppression for clinical xenotransplantation has included costimulatory blockade as a component of generally complex immunosuppressive regimens; intensive microbiological surveillance will provide insights into any associated xenozoonotic infections. Successful integration of costimulatory blockade in allotransplantation and clinical xenotransplantation requires further prospective trials coupled with robust microbiological surveillance.

BACKGROUND: Quantification of coronary sinus (CS) flow has been used with pharmacologic stress as a noninvasive surrogate of global myocardial blood flow and coronary flow reserve (CFR). Whether CS flow assessment can be extended to physiological exercise stress remains uncertain. Accurate measurement during exercise is technically challenging due to the small caliber of the CS and its rapidly varying flow dynamics, particularly under exercise conditions. In this study, we evaluated the feasibility of a high-resolution, high-frame-rate CMR approach for measuring post-exercise CS flow and CFR and compared these measures with quantitative myocardial perfusion imaging.

METHODS: We implemented a phase-contrast sequence with non-interleaved velocity-compensated and velocity-encoded k-space acquisition and truncated phase encoding. Generative artificial intelligence (AI) synthesized high-resolution images from the low-resolution inputs and interpolated intermediate frames, effectively doubling temporal resolution. In a prospective exercise CMR study, patients with stable coronary artery disease (n = 13, 50±20 years) underwent AI-enabled CS flow imaging at 1.1×1.1mm² spatial and 27 ms temporal resolution, performed twice at rest for scan/re-scan repeatability and once after exercise. Quantitative perfusion imaging was performed before and post-exercise. Scan/re-scan repeatability of rest CS flow, and inter-observer repeatability of rest and post-exercise CS flow and CS flow-derived CFR were assessed using intraclass correlation coefficients (ICC). CS flow and CFR were compared with perfusion-derived myocardial blood flow and myocardial perfusion reserve (MPR) using linear regression and Pearson correlation (r).

RESULTS: Analysis was successful in all rest and 11 of 13 stress scans; two were excluded due to ECG mis-gating. CS flow showed excellent scan/re-scan (ICC = 0.97 [0.91-0.99]) and inter-observer repeatability (ICC = 0.97 [0.92-0.99]). CS flow showed good correlation with perfusion-derived myocardial blood flow (y = 0.95×, r = 0.61, P = 0.002). CS flow-based CFR also correlated well with perfusion-derived MPR (y = 1.02×, r = 0.67, P = 0.025).

CONCLUSION: We demonstrate the feasibility of a high-resolution, high-frame-rate CMR technique for quantifying post-exercise CS flow and CFR, with excellent repeatability and good agreement with perfusion-derived measures. This approach shows promise for assessing global myocardial perfusion after physiological exercise without pharmacologic stress, warranting further validation.

OBJECTIVES: The interest in bacteriophage therapy has significantly increased due to the rising prevalence of antibiotic-resistant bacterial infections. However, the pharmacology of bacteriophage therapy has not been systematically reviewed. This scoping review aims to summarize the current state of bacteriophage pharmacokinetics and pharmacodynamics research to identify knowledge gaps and guide future research.

METHODS: Following PRISMA-ScR guidelines, we conducted a scoping review through December 18th, 2023 of MEDLINE (Ovid), PubMed, Embase (Elsevier), Web of Science Core Collection (Clarivate), and Cochrane Central. We included studies that presented original data on the pharmacokinetics and pharmacodynamics of bacteriophage therapy for in vivo infection treatment.

RESULTS: In total, 34 in vivo studies were identified varying in multiple dimensions, including model organisms, target bacteria, delivery vehicles, modes of administration, and phage type. The scoping review maps the current research landscape of in vivo bacteriophage pharmacology.

CONCLUSIONS: Bacteriophage therapy shows notable promise as a potential alternative or therapeutic adjunct to antibiotics in clinical disease settings. Several studies of phage pharmacokinetics and pharmacodynamics have been conducted; however, these studies differ in multiple dimensions, complicating attempts to develop general principles for standardized phage administration. Further, significant gaps remain in understanding the numerous intrinsic phage and host factors that might affect the pharmacokinetics and pharmacodynamics of phage therapy in vivo.

ADAPT is a nationwide initiative to transform cancer care by detecting and responding to tumor evolution in real time. Integrating multimodal data, interpretable AI, and an evolutionary clinical trial platform, ADAPT predicts emerging resistance traits and guides treatment adjustments as tumors change. A unified national infrastructure enables continuous learning across patients, linking discovery directly to care. By making therapy responsive to tumor changes, ADAPT delivers a scalable model designed to improve outcomes in precision oncology.

Cancer evolution is a complex and dynamic process, yet most treatment strategies remain static. Infrequent tumor sampling has limited our ability to counteract the transient adaptive states that precede resistance. To address this gap, ARPA-H launched the ADAPT program, an initiative aimed at transforming cancer care by aligning therapies with real-time tumor evolution. Within this framework, the ASCEND-CRC trial aims to uncover early adaptive mechanisms and identify biomarkers to guide therapeutic decision-making in metastatic colorectal cancer (CRC). The study moves beyond single pre-treatment biomarkers by integrating multimodal profiling to longitudinally track tumor evolution and define an actionable set of dynamic biomarkers that inform treatment decisions. Together with other ADAPT initiatives, ASCEND-CRC represents a paradigm shift in precision oncology, establishing a scalable platform to intercept resistance.

One of the largest glial populations outside the brain is in the gut. These enteric glia are involved in many functions, from intestinal peristalsis to immunity, yet it is unclear whether subtypes exist with distinct roles in homeostasis. Comparing glia from divergent microenvironments in the mouse intestine, we found that mucosal glia most resembled microglia, while muscularis glia resembled satellite glia. Tacr3, encoding the receptor for neuropeptide neurokinin B (NKB), was enriched within muscularis glia associated with neuronal soma and was undetectable in extraintestinal glia. Genetic or pharmacological manipulation of NKB-TACR3 signaling disrupted the establishment of enteric glial populations during postnatal development and dynamically modulated intestinal motor behaviors in adult mice. Collectively, we delineate spatially, transcriptionally, and functionally distinct populations of enteric glia; identify one as an unanticipated target of TACR3 antagonists in clinical use; and establish this pathway as necessary for enteric glial diversification and function.

Body functionality refers to a focus on what the body can do. Mirror exposure (ME) involves systematically looking at oneself in the mirror. Body functionality and ME interventions improve body image. In the Mirror: Functional Appreciated Bodies (IM FAB) is a digitally-deliverable micro-intervention that incorporates body functionality and ME. The current study adds to previous work by rigorously examining key body image outcomes with a randomized control study design with three groups. The present study compared 3-week (1) functionality-based ME and functionality-based text prompts ("Functionality"), to (2) non-functionality-based ME and non-body related gratitude text prompts ("Active Comparator") or (3) self-report measures only ("Assessment Only"). Measures of body image, eating disorder symptoms, body checking, body image avoidance, body appreciation and functional appreciation were administered at baseline (T1), post-intervention (T2), one- (T3) and four-month (T4) follow-ups. Analyses included 287 female-identifying undergraduates at two institutions with M(SD)AGE = 19.8(1.4) years. Using multilevel modeling, the Functionality condition demonstrated significant improvements relative to the Active Comparator condition in functionality appreciation at T2 (β = -0.38) and T4 (β = -0.24), body appreciation at T2 (β = -0.28), and eating disorder symptoms at T2 (β = 3.80). Further, the Functionality condition exhibited significant improvements compared to the Assessment Only condition in functional appreciation at T2 (β = -0.28), appearance evaluation at T3 (β = -0.21) and T4 (β = -0.21), and body checking at T3 (β = 5.54). No other comparisons were consistently significantly different. The functionality-focused ME in this study may improve positive body image.

Selective estrogen receptor degraders (SERDs) are emerging therapies for estrogen receptor-positive (ER+) breast cancer. However, certain oral SERDs, including giredestrant and camizestrant, have been associated with bradycardia in clinical trials. To elucidate the underlying molecular mechanism, we used chemical biology and genetic approaches in a zebrafish model of SERD-induced bradycardia. Giredestrant and camizestrant induced significant bradycardia in wild-type zebrafish embryos, whereas fulvestrant and amcenestrant (SERDs that do not induce bradycardia in patients) did not alter heart rate. Cotreatment with ER agonists rescued bradycardia, suggesting an ER-mediated mechanism. Mutations in gper, esr2a, and esr2b did not confer resistance to SERD-induced bradycardia, whereas esr1 mutant embryos were protected. These findings demonstrate that SERD-associated bradycardia is mediated through Esr1 signaling, supporting an on-target adverse effect.