Faculty Bibliography

A large body of evidence supports the role of the prenatal environment in shaping childhood development. The relative contributions of prenatal alcohol use (PAE), maternal socioeconomic, and nutritional status on child development vary in high- versus low-income settings. We analyzed data from a prospective cohort study among mother-infant dyads from Cape Town (CT), South Africa and the Northern Plains (NP), USA. The Mullen Scales of Early Learning were administered by trained assessors to evaluate cognitive, motor, and language development of 1-year old children. We used multiple linear regression models to assess standardized mean differences in development scores by (1) maternal prenatal factors, (2) delivery factors and (3) child factors within each study site. 1,728 infants from CT and 1,140 infants from the NP were included in the analyses. In CT, infants with moderate-to-high PAE had 0.17 SD (95% CI -0.30, -0.04) lower cognitive and 0.15 SD (-0.29, -0.2) lower expressive language scores compared to infants without PAE. In the NP, maternal obesity (BMI > 30 kg/m2) was significantly associated with -0.21 SD (-0.36, -0.06), and -0.13 SD (-0.27, -0.02) reductions in cognitive, and expressive language scores, respectively. Household crowding, lower levels of maternal educational attainment, prenatal maternal depression, low birthweight, admission to neonatal intensive care unit, and male sex had significant negative associations with cognitive and language development in both sites with effects ranging from -0.32 to -0.11 SDs. These results highlight the importance of assessing risk factors by populations across diverse social and cultural environments and emphasize the imperative to formulate intervention packages tailored to the local context.

BackgroundSex differences in Alzheimer's disease (AD) are well recognized, yet their implications for cognitive assessment remain unclear. Females often demonstrate better cognitive performance than males despite comparable levels of neurodegeneration, which may delay diagnosis.ObjectiveTo evaluate sex differences in cognitive performance across AD continuum.MethodsUsing data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we examined sex differences in total and item-level performance on the 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog-13) among cognitively normal (CN) individuals and patients with AD. Regression models were performed, adjusting for hippocampal parenchymal fraction, age, and education.ResultsThe study included 656 CN participants (59% female) and 193 AD patients (45% female). Among CN individuals, female sex was associated with lower total ADAS-Cog-13 scores (β = -2.09, p < 0.0001). CN females demonstrated superior performance on multiple verbal subdomains, including word recall, delayed word recall, naming, and word recognition. In contrast, no significant sex difference was observed in total ADAS-Cog-13 scores among AD patients, although males performed better than females on delayed word recall. Across both groups, greater hippocampal integrity was strongly associated with better global and domain-specific cognitive performance.ConclusionsSex differences in ADAS-Cog-13 performance are evident in cognitively normal individuals but largely attenuated in AD patients. Superior verbal performance in CN females, independent of hippocampal integrity, may mask early cognitive decline and contribute to delayed diagnosis. These findings highlight the importance of accounting for sex when interpreting cognitive test results, particularly in preclinical stages of AD.

AIM/OBJECTIVE:This integrative review appraises the literature on the impact of gamification on academic performance among prelicensure nursing students. BACKGROUND:Traditional classroom lectures in nursing education often rely on passive teaching strategies, limiting student engagement. Game-based learning has emerged as an innovative approach to enhance active learning and improve learning outcomes. METHOD/METHODS:Following Whittemore and Knafl's guidelines, a systematic search of the Cumulative Index to Nursing and Allied Health Literature database identified research studies published after 2000. Critical appraisal was conducted using evidence-based tools, yielding 18 quantitative studies that met the inclusion criteria. RESULTS:Four key themes were identified: enhanced academic performance, improved knowledge retention, increased student satisfaction, and strengthened clinical skills. CONCLUSION/CONCLUSIONS:Findings suggest that gamification positively influences knowledge retention in nursing didactic courses. Further research is needed to explore its impact on competency development and clinical application. Faculty development optimizing the use of gamification is needed.

BACKGROUND:Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a transient prothrombotic process, although recent data suggests that VITT anti-platelet factor 4 (PF4) antibodies are more persistent than those in heparin-induced thrombocytopenia. OBJECTIVES/OBJECTIVE:We sought to interrogate whether anti-PF4 antibody persistence in VITT is related to the continued persistence of antibody clones from the acute phase or to the development of novel anti-PF4 antibodies due to epitope spreading. PATIENTS/METHODS/METHODS:Samples from six Ad26.COV2.S-associated VITT patients with a median time to follow-up of 244 days from acute presentation (Range, 114-664 days) were studied in antigenic/functional assays and by mass spectrometry. One ChAdOx1 nCoV-19-associated VITT patient was tested >4 years after acute presentation. RESULTS:Upon affinity-enrichment of anti-PF4 antibodies, mono/oligoclonal anti-PF4 antibodies were observed despite negative results in serum protein electrophoresis/"Mass-Fix" testing of native sera. Anti-PF4 antibody abundance decreased over time, with no evidence of novel anti-PF4 antibody production after acute presentation. Although previous studies indicate a stereotypical pairing of VITT antibodies with lambda light chains, one VITT patient produced antibodies with a kappa light chain. Long-term thrombocytopenia/thrombosis was not seen in any of these six patients, however, platelet-activating anti-PF4 antibodies were seen four years after the acute event in an additional ChAdOx1 nCoV-19-associated VITT patient with chronic low-grade thrombocytopenia. CONCLUSIONS:VITT, unlike monoclonal gammopathy of thrombotic significance, appears to be an MGUS-negative state, but needs confirmation in larger studies. VITT antibodies can be comprised of lambda or kappa light chains, and some VITT patients exhibit persistent thrombocytopenia many years after the acute event.

OBJECTIVE:Pediatric Long COVID (LC) is an infection-associated chronic condition following SARS-CoV-2 infection. While research has begun to elucidate clinical phenotypes, functional impacts are not well described. METHODS:Cross-sectional data from the NIH-funded Researching COVID to Enhance Recovery (RECOVER) pediatric observational cohort was analyzed to assess associations in school-age children (6 to 11 years) and adolescents (12 to 17 years) between LC and caregiver-reported school-related functional outcomes. LC was defined using RECOVER age group-specific symptom-based LC research indices. The primary outcome was worsening of child grades. Secondary outcomes included difficulty paying attention, limited fun with friends, and having an Individualized Education Program (IEP). Using age-stratified analyses, children with and without LC were matched based on age, sex, and dates of infection and enrollment, to estimate risk ratios (RRs) between LC and each outcome. RESULTS:The cohort included 1,976 children (406 school-age, 1,570 adolescent). 18% of school-age children and 29% of adolescents with LC had reported worsened grades, compared to 7% and 11% without LC, respectively [school-age: adjusted RR 2.18 (95% CI: 1.15-4.11); adolescent: adjusted RR 2.39 (95% CI: 1.86-3.06)]. In both age groups, children with LC were more likely to have difficulty paying attention, limited fun with friends, and IEPs. CONCLUSIONS:LC in school-age children and adolescents was negatively associated with functional school-related outcomes, including academic performance, attention, and peer interactions. As LC affects a substantial proportion of U.S. children, these findings highlight the urgent need to develop, provide, and evaluate school-related services for children and adolescents with LC.

BACKGROUND:This study compares clinical and functional outcomes between simultaneous hardware removal during total knee arthroplasty (TKA) and staged TKA after prior hardware removal. METHODS:We retrospectively reviewed 155 patients who had prior knee hardware and underwent elective primary TKA between 2012 and 2024 at an urban academic institution. Patients were categorized into "simultaneous" removal during TKA (n = 127) or "staged" TKA after removal (n = 28), and stratified by hardware type (minor/moderate/major). RESULTS:Simultaneous procedures involved significantly less "major hardware," single incisions, and tibial stem extensions than staged procedures (32.3 versus 78.6%, P < 0.001; 81.9 versus 100%, P = 0.007; and 0.8 versus 10.7%, P = 0.019, respectively). Hardware, particularly the major type, was more often retained or partially retained in the simultaneous group (48.0 versus 21.4%, P = 0.008). Reoperation, revision, and infection rates did not significantly differ based on timing or hardware location. Simultaneous patients had smaller 3-month Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity and Interference score reductions (-1.6 versus -9.9, P = 0.006 and +0.4 versus - 7.2, P = 0.007, respectively), but greater 2-year Knee Injury and Osteoarthritis Outcome Score for Joint Replacement improvements (+25.0 versus - 1.1, P = 0.006) compared to staged patients. Simultaneous major hardware removal demonstrated significantly greater 2-year Knee Injury and Osteoarthritis Outcome Score for Joint Replacement and PROMIS Pain Interference improvement (+32.0 versus -5.5, P = 0.001, and -6.2 versus +5.8, P = 0.027, respectively), but smaller 2-week PROMIS Pain Intensity score reduction (+2.2 versus -4.9, P = 0.050) compared to staged procedures. CONCLUSIONS:Simultaneous hardware removal during TKA led to higher retained major hardware rates and fewer single incisions than staged procedures, without increased reoperation or revision risks. Despite higher 3-month pain scores, simultaneous surgery achieved greater 2-year functional improvement, suggesting it offers advantages for select patients.

Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research groups, have so far yielded fragmented and sometimes inconsistent findings. Here, to help facilitate greater convergence, we conducted a 'mega-analysis' integrating 11 independent resting-state functional magnetic resonance imaging datasets across five psychedelic drugs (psilocybin, lysergic acid diethylamide, mescaline, N,N-dimethyltryptamine and ayahuasca) from research groups spanning three continents and five countries. By applying a uniform preprocessing pipeline and a Bayesian hierarchical modeling framework, we discovered several common features in the induced alterations to brain function across drugs and sites. Most prominently, we identified a core signature of increased functional connectivity between transmodal (default, frontoparietal and limbic) and unimodal networks (visual and somatomotor), with subnetwork specificity. Furthermore, key subcortical regions (thalamus, caudate and putamen) and the cerebellum exhibited altered coupling with sensorimotor networks. In contrast to several single-site reports, Bayesian modeling revealed weak-to-moderate and selective reductions in within-network functional connectivity, with substantial variability across drugs and networks. Together, these findings extend past work by demonstrating that psychedelics reconfigure large-scale cortical organization while selectively engaging subcortical circuitry. This study provides the most comprehensive synthesis of psychedelic brain action to date, helping resolve inconsistencies and offering a probabilistic map of how psychedelics alter large-scale brain organization. We hereby provide a cornerstone to benchmark and shepherd future psychedelic neuroimaging research.

Loss-of-function variants in the gene encoding angiopoietin-like protein 3 (ANGPTL3) are associated with decreased triglyceride and low-density lipoprotein cholesterol levels, as well as with lower cardiovascular risk. Here we describe a 16-week phase 1 trial of zodasiran, an ANGPTL3‑targeting small interfering RNA, in patients on lipid-lowering therapy with either hyperlipidemia (with a placebo control arm) (n = 9; 7 male and 2 female), familial hypercholesterolemia (n = 17; 9 male and 8 female) or moderate-to-severe hypertriglyceridemia (n = 6; 4 male and 2 female). Patients received zodasiran subcutaneously on days 1 and 29, followed by a 48-week open-label extension in the familial hypercholesterolemia cohort (n = 13; 7 male and 6 female) in which zodasiran was dosed every 12 weeks. No serious treatment-related adverse events, the primary endpoint of the trial, were observed. Moreover, no elevations in hepatic aminotransferases, bilirubin or glycated hemoglobin were observed, and there were no drug discontinuations. All cohorts showed reductions at week 16 (12 weeks postdosing) in serum ANGPTL3 (≤-85.4%) and triglycerides (≤-67.1%), which were secondary endpoints. Reduction in ANGPTL3 was sustained to end-of-open-label extension in the familial hypercholesterolemia cohort. These results indicate a favorable safety profile for zodasiran, with promise for correcting isolated hypercholesterolemia and moderate-to-severe hypertriglyceridemia, and support further studies of zodasiran in treating a wide spectrum of dyslipidemias. ClinicalTrials.gov registration: NCT03747224 .

The importance of rapid and accurate histologic analysis of surgical tissue in the operating room has been recognized for over a century. Our standard-of-care intraoperative pathology workflow is based on light microscopy and H&E histology, which is slow, resource-intensive, and lacks real-time digital imaging capabilities. Here, we describe an emerging and innovative method for intraoperative histologic analysis, called Intelligent Histology, that integrates artificial intelligence (AI) with stimulated Raman histology (SRH). SRH is a rapid, label-free, digital imaging method for real-time microscopic tumor tissue analysis. SRH generates high-resolution digital images of surgical specimens within seconds, enabling AI-driven tumor histologic analysis, molecular classification, and tumor infiltration detection. We review the scientific background, clinical translation, and future applications of intelligent histology in tumor neurosurgery. We focus on the major scientific and clinical studies that have demonstrated the transformative potential of intelligent histology across multiple neurosurgical specialties, including neurosurgical oncology, skull base, spine oncology, pediatric tumors, and peripheral nerve tumors. Future directions include the development of AI foundation models through multi-institutional datasets, incorporating clinical and radiologic data for multimodal learning, and predicting patient outcomes. Intelligent histology represents a transformative intraoperative workflow that can reinvent real-time tumor analysis for 21st century neurosurgery.