Faculty Bibliography

Patients with myotonic disorders are at risk for severe generalized muscle contraction, referred to as a "myotonic crisis." For those patients with nondystrophic myotonia (NDM), the most common trigger of a myotonic crisis is exposure to succinylcholine. In this case, a 10-year-old female patient with NDM secondary to an SCN4A pathogenic variant developed a severe myotonic crisis in the setting of an upper respiratory infection and asthma flare treated with a beta-adrenergic agonist (ß-agonist). She presented with generalized rigidity and features of hypermetabolism resembling an anesthetic-related malignant hyperthermia. Management necessitated multidisciplinary collaboration, a complex intubation strategy, and an extended course in the pediatric intensive care unit. We suspected that this crisis was precipitated in part by continuous ß-agonist use during her initial asthma management. Treatments targeting sequential steps of the myocyte activation cascade tempered the contractile apparatus leading to clinical improvement in rigidity.

BACKGROUND/UNASSIGNED:Artificial intelligence (AI) offers significant opportunities to improve the field of implementation science by supporting key activities such as evidence synthesis, contextual analysis, and decision-making to promote the adoption and sustainability of evidence-based practices. This living scoping review aims to: (1) map applications of AI in implementation research and practice; (2) identify evaluation approaches, reported outcomes, and potential risks; and (3) synthesize reported research gaps and opportunities for advancing the use of AI in implementation science. METHODS/UNASSIGNED:This scoping review will follow the Joanna Briggs Institute (JBI) methodology and the Cochrane guidance for living systematic reviews. A living scoping review is warranted to keep up with the rapid changes in AI and its growing use in implementation science. We will include empirical studies, systematic reviews, grey literature, and policy documents that describe or evaluate applications of AI to support implementation science across the steps of the Knowledge-to-Action (KTA) Model. AI methods and models of interest include machine learning, deep learning, natural language processing, large language models, and related technologies and approaches. A search strategy will be applied to bibliographic databases (MEDLINE, Embase, CINAHL, PsycINFO, IEEE Xplore, Web of Science), relevant journals, conference proceedings, and preprint servers. Two reviewers will independently screen studies and extract data on AI characteristics, specific implementation task according to the KTA Model, evaluation methods, outcome domains, risks, and research gaps. Extracted data will be analyzed descriptively and synthesized narratively using a mapping approach aligned with the KTA Model. DISCUSSION/UNASSIGNED:This living review will consolidate the evidence base on how AI is applied across the spectrum of implementation science. It will inform researchers, policymakers, and practitioners seeking to harness AI to improve the adoption, scale-up, and sustainability of evidence-based interventions, while identifying areas for methodological advancement and risk mitigation. REVIEW REGISTRATION/UNASSIGNED:Open Science Framework, May 2025: https://doi.org/10.17605/OSF.IO/2Q5DV.

BACKGROUND/UNASSIGNED:Although historical writings, anthropological accounts, and experimental studies document associations between psilocybin use and religion, no prospective experimental study has investigated how the effects of psilocybin are experienced and interpreted by religious clergy. This exploratory study evaluated the overall safety and the acute and enduring effects of psilocybin in clergy. METHODS/UNASSIGNED:= 16) at 6 months after screening using self-report measures. The effects of psilocybin were also assessed on session days and 4 and 16 months after the second psilocybin session in the 24 participants who completed both sessions. RESULTS/UNASSIGNED:The primary outcome assessment at 6 months after screening showed that, compared with the delayed control group, participants who had received psilocybin reported significantly greater positive changes in their religious practices, attitudes about their religion, and effectiveness as a religious leader, as well as in their non-religious attitudes, moods, and behavior. Follow-up assessments showed that positive changes in religious and non-religious attitudes and behavior were sustained through 16 months after the second psilocybin session. At that time, participants rated at least one of their psilocybin experiences to be among the top five most spiritually significant (96%), profoundly sacred (92%), psychologically insightful (83%), and psychologically meaningful (79%) of their lives. Furthermore, 42% rated one of their experiences to be the single most profound of their lifetime. At 16-months follow-up, most (79%) strongly endorsed that the experiences had positive effects on their religious practices (e.g., prayer or meditation) and their daily sense of the sacred, and most (71%) reported positive changes in their appreciation of religious traditions other than their own. Although no serious adverse events were reported, 46% rated a psilocybin experience as among the top five most psychologically challenging of their lives. CONCLUSIONS/UNASSIGNED:In this population of clergy, psilocybin administration was safe and increased multiple domains of overall psychological well-being including positive changes in religious attitudes and behavior as well as their vocation as a religious leader. The study was limited by a waitlist control design, homogenous sample, and the use of some unvalidated outcome measures. Further research with more rigorous control conditions and diverse samples is needed.

Light speckle fluctuations provide a means for noninvasive measurements of cerebral blood flow index (CBFi). While conventional Diffuse Correlation Spectroscopy (DCS) quantifies these fluctuations to provide marginal brain sensitivity for CBFi in adult humans, new techniques have emerged to improve diffuse light throughput and brain sensitivity. Here we further optimize one such approach, interferometric diffusing wave spectroscopy (iDWS), with respect to the number of independent channels, camera duty cycle and full well capacity, incident laser power, noise and artifact mitigation, and data processing. We build the system on a cart and define conditions for stable operation. We show pulsatile CBFi monitoring at 4-4.5 cm source-collector separation in adults with moderate pigmentation (Fitzpatrick 4). We also report preliminary clinical measurements of patient CBFi in the Neuro Intensive Care Unit (Neuro ICU). These results push the boundaries of iDWS CBFi monitoring performance beyond previous reports.

SIGNIFICANCE/CONCLUSIONS:The predominantly nonsignificant differences we found between head-worn (ARx) and handheld Seeing AI (artificial intelligence) implementations provide objective evidence to the ongoing debate about the relative advantages and disadvantages of form. People with vision loss must choose between these implementations based on functional needs and app accessibility, rather than form factor. PURPOSE/OBJECTIVE:To compare the functionality of AI implementations in head-worn devices versus handheld smartphones by objectively quantifying performance, usability, and acceptability when acquiring information from text and in daily activities. METHODS:A cross-sectional, counterbalanced, crossover design was employed to assess performance using Seeing AI in two formats (ARx headset and on a smartphone) and to compare two head-worn formats that utilize different AI algorithms-Seeing AI and Meta AI. Completion and timing were quantified for items in two task categories: Text and Searching & Identifying. Usability was evaluated with the System Usability Scale. Data were compared with a baseline condition with no assistive technology, and performance among AI implementations was assessed. RESULTS:There was no significant difference in the number of participants who completed tasks and timing between head-worn ARx and smartphone-based Seeing AI implementations. A comparison of two AI algorithms (Seeing AI and Meta) in wearable implementations found equivalent gains in performance but significantly faster task completion times for the Meta glasses. The timing advantage of Meta derives from its ability to provide more information about most tasks more quickly, whereas Seeing AI often requires additional prompts to gather sufficient data to complete tasks. The reported acceptability and usability were statistically similar among the three AI implementations. CONCLUSIONS:We found no evidence to demonstrate an advantage in completing tasks using either head-worn (ARx and Meta glasses) or smartphone AI implementations.

With a rising annual incidence, pancreatic cancer is now the third leading cause of cancer-related mortality in American men and women [...].

AIM/OBJECTIVE:To evaluate whether transitional circulating tumor cells (trCTCs) predict systemic recurrence of pancreatic ductal adenocarcinoma (PDAC) and assess their potential role in risk stratification for systemic treatment. BACKGROUND:The high metastatic potential of PDAC is believed to be associated with early dissemination after cancer cell reprogramming via an epithelial-to-mesenchymal transition. These cells are detectable in circulation as trCTCs and could serve as valuable biomarker capturing systemic disease involvement. METHODS:The prospective CLUSTER trial enrolled patients scheduled for PDAC resection (2016-2018). Pre- and postoperative CTCs were isolated with the Isolation-by-SizE-of-Tumor-Cells device and characterized by immunofluorescence. Cox regression with spline terms assessed associations between preoperative biomarkers and systemic recurrence, while multivariable subgroup analyses with interaction tests evaluated overall survival (OS) stratified by adjuvant chemotherapy. RESULTS:In preoperative samples, trCTCs were detected in 82 (67%) of 123 patients with a median number of two cells per ml (IQR 1-3). A linear association between preoperative trCTC counts and systemic recurrence (χ²=13.2, P=0.004) was observed, but no relevant correlation with CA19-9 levels was found (Pearson correlation=0.05, 95% CI:-0.13-0.23). Furthermore, trCTC-positivity after resection predicts recurrence and is associated with prolonged OS associated with adjuvant therapy (HR 0.21, 95%CI: 0.09-0.49) after adjustment for tumor stage and neoadjuvant chemotherapy. CONCLUSIONS:Preoperatively, higher trCTC counts are associated with increased risk of systemic recurrence, while postoperative presence reflects minimal residual disease. Integrating trCTC assessment alongside currently used biomarkers into the clinical pathway for patients with PDAC could enhance risk stratification and support more personalized treatment decisions.

The relationships of human diversity with biomedical phenotypes are pervasive yet remain understudied, particularly in a single-cell genomics context. Here, we present the Asian Immune Diversity Atlas (AIDA), a multi-national single-cell RNA sequencing (scRNA-seq) healthy reference atlas of human immune cells. AIDA comprises 1,265,624 circulating immune cells from 619 donors, spanning 7 population groups across 5 Asian countries, and 6 controls. Though population groups are frequently compared at the continental level, we found that sub-continental diversity, age, and sex pervasively impacted cellular and molecular properties of immune cells. These included differential abundance of cell neighborhoods as well as cell populations and genes relevant to disease risk, pathogenesis, and diagnostics. We discovered functional genetic variants influencing cell-type-specific gene expression, which were under-represented in non-Asian populations, and helped contextualize disease-associated variants. AIDA enables analyses of multi-ancestry disease datasets and facilitates the development of precision medicine efforts in Asia and beyond.

Nusinersen, an antisense oligonucleotide, modulates pre-mRNA splicing to produce full length survival motor neuron protein in spinal muscular atrophy (SMA). It was approved in the US for SMA in all ages based on evidence in children. In adults, studies of nusinersen rely on real-world observational data and show stability or small improvements over time. We performed a prospective, 30 month longitudinal, observational multi-center study of adults initiating nusinersen with SMA types II/III to examine its safety, tolerability, and effectiveness. 43 participants (20 female; 14 ambulatory; 3, 17, and 23 with 2, 3, and ≥4 SMN2 copies, respectively), mean (SD) age 37.1 (11.9) years) enrolled and completed baseline assessments. Serial assessments over 30 months showed small but not significant improvements in the six minute walk test (16.1 m), Revised Upper Limb Module (0.7), Revised Hammersmith Scale (0.8), maximal inspiratory (-2.6 cm H20) and expiratory pressure (12.3 cm H20). Muscle strength and forced vital capacity did not change. The patient reported outcome Total SMA-HI improved (-11 (95% CI: -17,-5); p < 0.001)). No new safety effects were identified. This study of nusinersen in adults with SMA demonstrates stability over time in contrast to the expected decline in untreated patients, with a favorable safety profile.

OBJECTIVE:To assess variation in inpatient antepartum management strategies for placenta accreta spectrum (PAS) disorder and their association with hospitalization costs in a national sample. METHODS:This retrospective cohort study used the 2016-2021 Nationwide Readmissions Database to identify individuals aged 15-54 years who underwent cesarean hysterectomy for PAS between 23 and 35 weeks of gestation. Patients were categorized into four management groups based on whether they had a separate antepartum hospitalization and their predelivery length of stay (LOS) during the delivery hospitalization. Median total hospitalization costs (inclusive of separate antepartum and delivery hospitalization), adjusted to 2023 dollars, were analyzed as continuous and dichotomized outcomes (above the 90th percentile). Unadjusted and adjusted logistic and median regression models assessed whether inpatient management variation, postpartum LOS, demographic, and clinical factors influenced hospitalization costs. RESULTS:Among 3,237 individuals with PAS, 50.5% had no prior antepartum admission and a predelivery LOS of 2 days or less, 31.9% had no prior antepartum admission and a predelivery LOS of more than 2 days, 11.8% had a prior antepartum admission and a predelivery LOS of 2 days or less, and 5.8% had a prior antepartum admission and a predelivery LOS of more than 2 days. Median total hospitalization costs varied significantly by management group, with mean costs ranging from $21,829 to $51,039. Management variation was associated with nearly 3- to 29-times higher likelihood of high total hospitalization costs and $8,907-29,021 adjusted higher median cost depending on the specific management group. Of evaluated clinical factors, only disseminated intravascular coagulation was associated with an adjusted median cost increase of $12,921. CONCLUSION/CONCLUSIONS:Nearly one in five patients with PAS experienced an all-cause antepartum hospitalization. Variation in inpatient admission for management of PAS was evident in this national sample and was a significant driver of hospitalization costs. Although some antepartum hospitalizations and prolonged predelivery lengths of stay are unavoidable due to the complexity and severity of PAS, efforts to reduce unnecessary variations could reduce total hospitalization costs.