Faculty Bibliography

Peptidoglycan (PG), the primary load-bearing component of bacterial cell envelopes, is a bio-derived material whose mechanical and hydration properties are central to microbial viability and their environmental responsiveness. PG has been increasingly recognized as a scalable water-responsive (WR) material, capable of converting chemical potential gradients from ambient changes in relative humidity (RH) directly into mechanical work. In this study, we leverage stress-induced PG remodeling pathways in a BB-3 Escherichia coli (E. coli) strain to modulate the architecture of its PG sacculus for enhanced WR performance. Under arabinose-deprived conditions (-Ara), BB-3 PG exhibits a twofold increase in the ratio of crosslinked-to-linear muropeptide stems and a threefold rise in the relative abundance of ③-③ (mDap-mDap) linkages relative to an arabinose-rich (+Ara) control. When responding to RH changes between 10% and 90% RH, these molecular-level modifications translated into a fivefold increase in WR actuation energy density (623.0 kJ/m³) with rapid response times on the order of seconds (τ_d: 1.8 s, τ_h: 0.7 s). The remodeled PG also displays a significant increase in stiffness (E: 8.9 GPa at 10% RH) and an 8% greater uptake of water, driving the PG matrix to generate twofold higher WR strain (ε: 30.2%). The observed increases in water retention and WR behavior of E. coli PG may also carry intriguing evolutionary implications, reflecting adaptive strategies microbes take to restructure PG layers and survive under microenvironmental nutrient scarcity. STATEMENT OF SIGNIFICANCE: Current testing of water responsive (WR) engineered living materials (ELMs) has largely overlooked bacterial species other than Bacillus subtilis. Our work addresses this gap by demonstrating that the peptidoglycan (PG) sacculus of Escherichia coli also exhibits robust WR properties. Through leveraging a combination of genetic and environmental factors during the organism's growth phase, we demonstrate that these properties can be rationally improved to yield enhanced actuator materials. By establishing a connection between PG crosslinking architecture and emergent mechanical and hydration dynamics, we present a promising approach to engineer dynamic and sustainable ELMs that can be employed as active components in high-performance actuators.

OBJECTIVE:The latest European Medicines Agency (EMA) guideline on the clinical investigation of medicines to treat epileptic disorders was adopted by the EMA Committee for Medicinal Products for Human Use in 2025. We compared this guideline with the previous version (2010), highlighting areas where significant revisions were introduced. METHODS:The 2025 and 2010 versions of the guideline were systematically analyzed to identify significant modifications. RESULTS:The latest EMA guideline incorporated terminology from the 2017 International League Against Epilepsy (ILAE) classification of seizures and epilepsy and the 2022 classification of syndromes and replaced the older term "antiepileptic drug (AED)" with "antiseizure medication (ASM)." Recommendations for add-on studies in common epilepsies have remained substantially unchanged, the main revision being the acceptability of the time-to-event design also for confirmatory trials, provided it is not the only design in the clinical development plan. A major novelty is the feasibility of extrapolating data from add-on trials to the monotherapy indication, provided specific conditions are met. Guidance on pediatric ASM development has been expanded, addressing extrapolation of efficacy from data in adults and older children and options for studies in developmental and epileptic encephalopathies and other rare epilepsies. Compared with the previous guideline, greater emphasis is placed on nonseizure outcomes, including functional, quality of life, and patient-reported outcomes. Two new sections have been introduced, addressing studies in neonates and clinical trials in status epilepticus and other seizure emergencies. Options for innovative designs, including registry-based studies, are also discussed in situations where randomized controlled trials are unfeasible. SIGNIFICANCE/CONCLUSIONS:The updated guideline reflects the changing scenario in epilepsy treatment development, with a greater focus on pediatric epilepsies, rare epilepsies, and other indications with high unmet needs. The updates also reflect the contribution during the consultation process by a wide range of stakeholders, including the ILAE Task Force on Regulatory Affairs.

OBJECTIVES/OBJECTIVE:To explore the evolution of the grief experience following Sudden Unexpected Death in Epilepsy (SUDEP) and identify factors that assist the bereaved in coping with their loss. METHODS:A survey formulated by a multidisciplinary team gathered information gathered information on decedent and respondent demographics, epilepsy details, circumstances surrounding death, postmortem experiences, descriptions of grief overtime (from 3 months to > 10 years post death), insights into coping strategies and recommendations for assisting the bereaved. RESULTS:A total of 206 participants completed the survey (predominantly middle-aged white females who were parents of the deceased). Most respondents (69.2 %) were unaware of SUDEP prior to the death and strongly desired to have had prior information. Negative impacts on relationships and mental health were highest at three months post-loss but gradually improved over time; feelings of sadness persisted while anger and guilt decreased, and acceptance increased. Interactions with understanding peers, supportive family or friends, and professional counseling were identified as most helpful, alongside clear communication and support from medical professionals and advocacy groups. CONCLUSIONS:This study highlights the profound and evolving nature of grief following SUDEP, describes the importance of SUDEP disclosure as part of comprehensive epilepsy care, and illustrates the need for ongoing and dynamic support for the bereaved. Interpretation of the findings is limited as the respondents were predominantly middle-aged white females who were parents of the deceased.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Multiple sclerosis (MS) exhibits racially disparate rates of disease progression. Black people with MS (B-PwMS) experience a more severe disease course than non-Hispanic White people with MS (NHW-PwMS). Here we investigated structural and functional connectivity as well as structure-function decoupling in the sensorimotor and default mode networks (SMN and DMN, respectively), which play a key role in determining physical and cognitive disability in people with MS. METHODS:A total of 176 participants (50 B-PwMS, 50 NHW-PwMS, 41 Black healthy controls (B-HCs), and 35 NHW-HCs) underwent 3T-MRI with T1, resting-state functional, & diffusion imaging, and clinical assessment with Expanded-Disability-Status-Scale (EDSS) & Symbol-Digit-Modalities-Test (SDMT). T1-weighted images were lesion-filled and segmented to obtain cortical, subcortical, and cerebellar structures. Diffusion and functional MRI datasets were preprocessed, and structural and functional connectivity were extracted between regions defined by the AAL3 atlas. Global and local network measures were extracted for both structural and functional connectivity, and structure-function decoupling was quantified by calculating the correlation between the strengths of the two networks, considering only edges with non-zero structural connectivity. Network measures were compared between subgroups, accounting for the impact of demographics and social determinants of health, with correction for multiple comparisons. RESULTS:Despite similar disease duration, treatment exposure, lesion load and brain volumes, B-PwMS exhibited higher EDSS and lower SDMT scores compared to NHW-PwMS, which were influenced by total income and body mass index. In both B- and NHW-PwMS, structural global efficiency and streamline density were lower in the SMN and DMN compared to their respective HCs. Structural characteristic path length in SMN was significantly higher in B-PwMS versus B-HCs, whereas no significant differences were observed in NHW groups. Extensive local rearrangements of structural and functional hubs were observed in the SMN and DMN of B-PwMS compared to B-HCs and NHW-PwMS. B-PwMS showed greater structure-function decoupling in the SMN as compared to the other groups. There was a trend towards a higher decoupling in the DMN with lower SDMT scores (ρ = -0.20, p = 0.05), and higher decoupling in the SMN with higher EDSS scores (ρ = 0.20, p = 0.06). DISCUSSION/CONCLUSIONS:Despite similar brain volumes and lesion load, B-PwMS showed a greater rearrangement of brain structural and functional connectivity within the SMN and DMN when compared with NHW-PwMS. Moreover, B-PwMS showed a higher degree of structure-function decoupling in the SMN, with a trend towards association with increased physical disability.

OBJECTIVES/OBJECTIVE:Post-acute sequelae of SARS-CoV-2 infection (PASC) can affect multiple organ systems, but the role of preinfectional body mass index (BMI) in these outcomes among children and young adults remains unclear. We aimed to evaluate the association between pre-COVID-19 BMI status and post-acute cardiovascular, gastrointestinal, and neuropsychiatric outcomes in children and young adults. METHODS:We conducted a retrospective cohort study using data from 139320 individuals aged 5 to 20 years with confirmed SARS-CoV-2 infection between March 2020 and September 2023 across 20 U.S. pediatric health systems participating in the RECOVER initiative. Pre-infection BMI was defined using measurements obtained within 18 months before the index date and categorized as healthy weight, overweight, obesity, or severe obesity; when multiple values were available, the most recent measurement was selected. We assessed incident postacute cardiovascular, gastrointestinal, and neuropsychiatric symptoms and conditions occurring 28 to 179 days post-infection. Adjusted relative risks (RRs) were estimated using modified Poisson regression models, comparing elevated BMI categories to the healthy weight. FINDINGS/RESULTS:Among 139320 participants (mean [SD] age, 13.0 [4.3] years; 51.6% female), severe obesity was associated with a higher risk of cardiovascular disorders (adjusted RR 2.56; 95% CI 1.93-3.41), particularly hypertension (adjusted RR 3.68; 95% CI 2.65-5.11). Severe obesity was also linked with increased risks of diarrhea (adjusted RR 1.34; 95% CI 1.10-1.64) and gastroesophageal reflux disease (adjusted RR 1.29; 95% CI 1.06-1.58). Associations between BMI and neuropsychiatric outcomes were heterogeneous, with inverse associations observed for some conditions, including anxiety and major depression. INTERPRETATION/CONCLUSIONS:In this cohort study, pre-COVID-19 BMI status was associated with the risk and pattern of postacute cardiovascular and gastrointestinal outcomes among children and young adults. Association between pre-infection BMI and neuropsychiatric outcomes was more variable and should be interpreted with caution. These findings suggest BMI-stratified post-COVID-19 monitoring strategies may help inform long-term care in youth.

The frequency and nature of neurological exams (neuro-checks) in patients with severe acquired brain injury resulting in coma or disorders of consciousness (DoC) remain variable, with limited evidence guiding practice and poor understanding of their role in predicting and preventing neurological deterioration, functional recovery and adverse effects such as delirium. This scoping review aims to explore the frequency of bedside neurological exams within the first 7 days of injury impact on clinical outcomes in adult patients with severe acquired brain injury including mortality, neurological deterioration, long-term function, and delirium. METHODS: A comprehensive literature search was conducted using the PubMed, CINAHL, Medline and EMBASE databases from 2003 to 2023. Search terms captured a range of acute brain injuries and neuro-assessment tools. Eligible studies included adult patients with severe traumatic or non-traumatic brain injury or stroke that addressed frequency of bedside neurological exams within the first 7 days of admission. RESULTS: Of 1327 studies screened, 20 met inclusion criteria, representing over 16,000 patients across 14 countries. Assessment tools varied, but use of the Glasgow Coma Scale was prevalent. Frequency of neuro-checks ranged from hourly to daily. Multiple outcome measures were utilized. Some studies found that continuing hourly neuro-checks beyond the first 48 hours did not provide additional clinical benefit. Others associated excessive assessment with increased stress or delirium. CONCLUSION: There is very low evidence supporting an association between the frequency of neuro-checks and functional outcomes, mortality, length of stay, or delirium. Although early assessments may aid prognostication, excessive exams may not improve outcomes and may contribute to harm. The heterogeneity, lack of evidence, and limited standardization of neuro-check frequency highlight the need for clinical research to guide future practice.

OBJECTIVE/UNASSIGNED:Carotid webs, first described in 1968, are increasingly recognized as a surgically treatable cause of ischemic stroke, particularly in young patients. Despite growing attention, the literature remains fragmented. We conducted the first advanced bibliometric analysis of carotid web research to map its historical foundations, identify key contributors, and illustrate emerging trends. METHODS/UNASSIGNED:The Web of Science database (inception-2025) was queried for carotid web publications. Articles and metadata were analyzed using Bibliometrix (R) and Python libraries. Reference publication year spectroscopy (RPYS) was employed to analyze the field's roots by analyzing citation frequency by publication year. RESULTS/UNASSIGNED:A total of 281 publications from 109 sources and 1,129 authors were identified. Annual publication growth averaged 6.15%, with 90% published after 2016. International collaboration was modest (9-11%), led by the U.S., China, France, and Canada. Shifts in keyword frequency reflected the field's evolution from early nosological uncertainty toward recognition of carotid webs as a distinct, high-risk lesion underlying ischemic stroke. Stroke and Journal of Vascular Surgery emerged as early key sources. Author analysis identified the most prolific contributors, though coauthorship networks remained small. RPYS revealed 19 seminal studies (1968-2021) that shaped the field's progression from early pathology descriptions to recognition of carotid webs as high-risk lesions for stroke. CONCLUSIONS/UNASSIGNED:Carotid web research has rapidly expanded, evolving into a multidisciplinary field. RPYS identified 19 seminal publications tracing the intellectual trajectory of the field. Ongoing challenges include limited collaboration, unresolved questions of pathogenesis, and variability in terminology and diagnostic criteria.

Sleep disturbances are prominent across neurodevelopmental disorders (NDDs) and may reflect specific abnormalities in brain development and function. Overnight polysomnography (PSG) allows for detailed investigation of sleep architecture, offering a unique window into neurocircuit function. Analysis of existing pediatric PSGs from clinical studies could enhance the availability of sleep studies in pediatric patients with NDDs towards a better understanding of mechanisms underlying abnormal development in NDDs. Here, we introduce and characterize a retrospective collection of 1527 clinical pediatric overnight PSGs across five different sites. We first developed an automated stager trained on independent pediatric sleep data, which yielded better performance compared to a generic stager trained primarily on adults. Using consistent staging across cohorts, we derived a panel of EEG micro-architectural features. This unbiased approach replicated broad trajectories previously described in typically developing sleep architecture. Further, we found sleep architecture disruptions in children with Down's Syndrome (DS) that were consistent across independent cohorts. Finally, we built and evaluated a model to predict age from sleep EEG metrics, which recapitulated our previous findings of younger predicted brain age in children with DS. Altogether, by creating a resource pooled from existing clinical data we expanded the available datasets and computational resources to study sleep in pediatric populations, specifically towards a better understanding of sleep in NDDs. This Retrospective Analysis of Sleep in Pediatric (RASP) cohorts dataset, including staging annotation derived from our automated stager, is deposited at https://sleepdata.org/datasets/rasp.