Faculty Bibliography

Iron plays a vital role in early brain development, supporting critical processes such as myelination, dendritogenesis, and neurotransmitter synthesis. The perinatal period marks a crucial transition from the intrauterine to the extrauterine environment, requiring significant brain adaptation to new stimuli and metabolic demands. However, tight spatiotemporal resolution capturing the timing and sequence of brain iron changes surrounding this critical transition has yet to be achieved. Leveraging a longitudinal perinatal cohort with 147 multi-echo MRI scans spanning from 25 to 60 post-conceptual gestational weeks, we mapped brain iron growth trajectories with R2* estimation across fetal, newborn and neonatal periods. We also examined whether sex, gestational age at birth, and birth weight influence R2* developmental trajectories. We found that parietal and superior temporal regions predominately show linear growth trajectories throughout the perinatal period across birth, while the occipital cortex, the temporal pole, inferior temporal regions and a subset of frontal regions exhibit non-linear trends. For most of the non-linear trajectories, growth rates peak around 40 weeks, highlighting the critical window of birth transition for brain R2* change. These results provide the first longitudinal insights into R2* development across birth, uncovering distinct regional growth patterns that may align with different phases of neurodevelopment.

Adolescent mental health remains a critical yet under-prioritized issue in low- and middle-income countries (LMICs) like Kenya, where resource limitations, stigma, and systemic barriers hinder access to care. While policies and strategies such as Kenya's Mental Health Action Plan (2021-2025) exist on paper, their implementation is constrained by limited resources and a weak mental health service delivery infrastructure. This qualitative descriptive study examines the perspectives of mental health actors and youth advocates on the development and implementation of adolescent mental health policy in Kenya. Using a political economy analysis, we conducted 15 key informant interviews (KIIs) and analyzed observational field notes from a Google Jam board exercise to explore factors that enable or impede the prioritization of adolescent mental health policy and care. Thematic analysis was guided by Shiffman and Smith's policy framework, focusing on four domains: actor power, ideas, political context, and issue characteristics. Findings reveal significant barriers, including the exclusion of adolescents from decision-making, limited family involvement, weak policy formulation, and the destabilizing effects of government transitions. Stigma, poverty, and chronic underfunding further hinder progress, despite ongoing strategic efforts. Comparisons with other LMICs indicate that these challenges are widespread, underscoring the need for localized, inclusive, and well-coordinated approaches. Addressing these issues will require strong political commitment, increased youth-led advocacy, and sustained investment in mental health services. By prioritizing adolescent mental health, Kenya can move toward a more equitable and effective mental health system that supports the wellbeing of its youth.

OBJECTIVE:To examine associations between oxidative stress and fetal weight across pregnancy. STUDY DESIGN/METHODS:Cohort study of pregnant participants from 2016-2021 in New York City with urinary lipid, protein, and DNA oxidative stress biomarkers (<18, 18-25, >25 weeks) and estimated fetal weight from ultrasound fetal biometry with the HadlockIII formula (20, 30, 36 weeks). RESULT/RESULTS:percentile. Oxidative stress biomarkers of protein damage were associated with larger estimated fetal weight at 20 (3.4 [95% CI: 1.2, 5.7]) and 36 weeks (16.5 [95% CI: 5.2, 27.8]). CONCLUSION/CONCLUSIONS:These findings advance our understanding of different oxidative stress pathways and their potential role in fetal growth.

BACKGROUND:Adolescents in low- and middle-income countries (LMICs) face significant mental health challenges, yet their perspectives are often underrepresented in the design of preventive strategies. Co-design approaches, such as human-centered design (HCD), offer a promising way to tailor interventions and implementation strategies to adolescents’ needs and local context. In LMICs, these methods require careful adaptation to address resource constraints, limited design literacy, and cultural norms. This study documents how HCD was adapted to engage adolescents in northern Ghana as co-designers of school-based mental health preventive strategies. METHODS:Guided by the first two phases of HCD, we conducted two workshops with 24 students from 12 public senior high schools in Tamale, Ghana. Workshop 1 (Inspiration) used structured, case-based discussions informed by the Consolidated Framework for Implementation Research (CFIR) to explore adolescents’ perspectives on mental health. Workshop 2 (Ideation) used interactive choice-based activities to elicit youth-generated strategies. To align with cognitive and sociocultural factors, we incorporated scaffolded facilitation, hands-on activities, and peer-led engagement. Qualitative data from facilitator notes, artifacts, and audio-confirmed summaries were synthesized using structured rapid qualitative analysis. RESULTS:Adolescents identified key mental health concerns, including stigma, peer and family influences, and fears about confidentiality. Gender-specific discussions revealed culturally rooted concerns, such as peer pressure and substance use among boys and limited support-seeking among girls. Adolescents prioritized five school strategies: teacher training, curricular integration, mentorship programs, activities that promote positive thinking and mindfulness, and entertainment-based mental health education. Youth demonstrated a conceptual shift from viewing mental health as an individual problem to a shared responsibility across schools and communities. Formation of an Adolescent Advisory Board reflected youth interest in sustained leadership and co-design. CONCLUSIONS:Contextualized co-design methods can meaningfully engage adolescents in LMIC settings and support the development of culturally grounded, feasible, and youth-prioritized mental health strategies. Structured facilitation enhances both the inclusivity and authenticity of adolescent engagement. This study contributes to implementation science by presenting a replicable co-design framework with policy relevance and providing a foundation for multilevel intervention development in resource-constrained educational systems. SUPPLEMENTARY INFORMATION:The online version contains supplementary material available at 10.1186/s12889-025-25012-0.

BACKGROUND:Infliximab (IFX) is commonly used in the management of acute severe ulcerative colitis (ASUC), yet up to 30% of individuals still require colectomy within 1 year. Clinical data characterizing these patients, however, are limited. AIMS/OBJECTIVE:We aimed to determine risk factors for colectomy among patients with ASUC who received in-hospital IFX treatment. METHODS:We performed a retrospective analysis of patients with ASUC who were treated with at least one dose of IFX while admitted between 2014 and 2022. Cox proportional hazards (PH) models were used to assess demographic, clinical, and laboratory risk factors for colectomy within 30 days and 1 year of IFX initiation. RESULTS:Overall, 36/170 (21.2%) patients underwent colectomy within 1 year of IFX initiation, with 22 (12.9%) individuals requiring colectomy within 30 days. On univariable analysis, concomitant Clostridioides difficile infection during admission, a ≤50% decrease in C-reactive protein (CRP) and experiencing 3 or more bowel movements per day within 48 hours after an initial IFX dose were significantly associated with 1-year colectomy. On multivariable Cox PH analysis, C. difficile infection during admission (aHR=2.92, 95% CI: 1.12-7.58) and a higher CRP/albumin ratio on admission (aHR=1.13, 95% CI: 1.01-1.27) were associated with increased colectomy risk within 1 year of IFX initiation. CONCLUSIONS:C. difficile infection and a higher CRP/albumin ratio on admission are associated with decreased time to colectomy within 1 year of IFX among patients presenting with ASUC. These factors may aid in early risk stratification to minimize delays in JAK-inhibitor initiation or surgical referral.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHI). In CTE, hyperphosphorylated tau (p-tau) aggregates are found in neurons at the depth of cortical sulci close to the gray matter/white matter (GM/WM) boundary. To date, CTE can only be diagnosed postmortem by neuropathological examination. Traumatic encephalopathy syndrome (TES) is the clinical syndrome purported to be associated with CTE pathology. The aim of this study is to investigate microstructural properties at the GM/WM boundary in individuals with a history of exposure to RHI and clinical features of CTE (i.e., TES). Diffusion magnetic resonance imaging (dMRI), TES diagnoses, and cerebrospinal fluid (CSF) biomarkers were acquired from 165 male former American football players (age: 57.29 ± 8.23 years) from the DIAGNOSE CTE Research Project, a multicenter, observational cohort study. Fractional anisotropy (FA) was measured at the GM/WM boundary of the whole brain. In addition, a widely used method (tract-based spatial statistics [TBSS]) was applied to measure FA of central WM. We used analyses of covariance to test associations between FA and TES. Furthermore, we used linear regressions to test associations between FA and nine CSF biomarkers (i.e., p-tau-181, -217, -231, total tau, amyloid β [Aβ]_1-40, Aβ_1-42, glial fibrillary acidic protein [GFAP], neurofilament light [NfL], and soluble triggering receptor expressed on myeloid cells-2 [sTREM2]). We report an association between higher FA at the GM/WM boundary and higher levels of certainty for CTE pathology (F(1, 147) = 5.781, 95% confidence interval (CI) = 0.0003-0.003, p = 0.035) as well as neurobehavioral dysregulation (F(1, 148) = 7.559, 95% CI = 0.001-0.009, p = 0.020), and functional dependence/dementia (F(1, 148) = 5.046, 95% CI = 0.0004-0.006, p = 0.039). In addition, we report an association between higher FA at the GM/WM boundary and higher CSF p-tau-181 (β = 0.272, 95% CI = 0.078-0.466, p = 0.029) and p-tau-217 (β = 0.295, 95% CI = 0.102-0.488, p = 0.027). FA of the central WM was not associated with TES diagnoses. Taken together, these findings suggest that dMRI at the GM/WM boundary could be used to investigate microstructural alterations suggestive of tau pathology-associated neurodegeneration in individuals with TES, the clinical presentation of CTE. Future studies are needed to validate this approach and to identify clinically useful cutoff values for dMRI metrics.

BACKGROUND:The associations between different types of diabetes, characterized by distinct pathophysiology and genetic architecture, and pancreatic ductal adenocarcinoma (PDAC) risk are not understood. METHODS:We investigated associations of genetic susceptibility to type 2 diabetes (T2D), eight T2D mechanistic clusters, type 1 diabetes (T1D), and maturity-onset diabetes of the young (MODY) with PDAC risk. We used genome-wide association study (GWAS) summary-level statistics for T2D (242,283 cases, 1,569,734 controls), T1D (18,942 cases, 501,638 controls), and PDAC (10,244 cases and 360,535 controls) in individuals of European ancestry. RESULTS:Two-sample Mendelian randomization (MR) using the Robust Adjusted Profile Score (MR-RAPS) method indicated that genetically predicted T2D was associated with PDAC risk (OR = 1.10; 95% CI 1.05-1.15), particularly the T2D obesity (OR = 1.28; 95% CI 1.15-1.42) and lipodystrophy (OR = 1.25; 95% CI 1.03-1.51) clusters. No association was observed for T1D with PDAC risk (OR = 1.01; 95% CI 0.99-1.02). Pathway/gene-set analysis using the summary-based Adaptive Rank Truncated Product (sARTP) method revealed a significant association between the MODY gene-sets and PDAC risk (P = 1.5 × 10-8), which remained after excluding 20 known PDAC GWAS loci (P = 7.6 × 10-4). HNF1A, FOXA3, and HNF4A were the top contributing genes after excluding the previously identified GWAS loci regions. CONCLUSIONS:Our results from this genetic association study support that T2D, particularly the obesity and lipodystrophy mechanistic clusters, and MODY genomic susceptibility regions play a role in the etiology of PDAC.

BACKGROUND:Current CPR guidelines recommend 10 breaths/min in adult cardiac arrest patients with an advanced airway, though this is largely based on animal studies. We evaluated the association between ventilation rate and return of spontaneous circulation (ROSC) in in-hospital cardiac arrest (IHCA). METHODS:) monitoring. Patients were enrolled from 25 tertiary centers in the U.S. and U.K. A subset had intra-arrest arterial blood gases collected per routine care. RESULTS:did not differ significantly, suggesting a hemodynamic mechanism. CONCLUSIONS:monitors. Thus, more studies are needed to determine the need to re-evaluate current ventilation targets during CPR in intubated patients.

OBJECTIVE:People with migraine have a higher prevalence and severity of insomnia. We examined the relationship between insomnia severity and migraine-related disability (MIDAS) and migraine-specific quality of life (MSQv2.1). METHODS:We conducted a post-hoc analysis of a pilot randomized controlled study assessing the RELAXaHEAD application in those with insomnia and comorbid migraine. Descriptive statistics were used to summarize demographic and clinical characteristics. Linear mixed model analysis was conducted to evaluate Insomnia Severity Index (ISI) as a predictor of each MSQv2.1 domain and MIDAS. RESULTS:Forty-two participants completed baseline and at least one follow-up survey. Mean age was 43.8 years (SD 12.6) and the majority (85.7%) were female. Most participants (81.0%) had severe migraine-related disability (median baseline MIDAS, 32 (IQR 52)). Over half (54.8%) of participants had moderate clinical insomnia (mean baseline ISI, 18.5 (SD 4.6)). Baseline median MSQv2.1 scores were 44.3 (IQR 31.4) for Role Function-Restrictive (RFR), 65.0 (IQR 45.0) for Role Function-Preventive (RFP), and 46.7 (IQR 46.7) for Emotional Function (EF). The effect of ISI on MIDAS was statistically significant (rate ratio (RR)=1.10, p < 0.05, 95%CI [1.028, 1.171], meaning each one-point increase in ISI was associated with a 10% higher MIDAS score). Additionally, a 1-point increase in ISI was associated with a decrease of 1.2 points in MSQ-RFR (B=-1.205, p = 0.001),1.0 point in MSQ-RFP (B=-0.981, p = 0.020), and 1.4 points in MSQ-EF (B=-1.66, p = 0.001). CONCLUSIONS:Our study revealed significant associations between insomnia severity and migraine-related disability and quality of life, highlighting the importance of prevention and sleep intervention for patients with migraine.