Faculty Bibliography

The ability to quickly learn and generalize is one of the brain's most impressive feats and recreating it remains a major challenge for modern artificial intelligence research. One of the most mysterious one-shot learning abilities displayed by humans is one-shot perceptual learning, whereby a single viewing experience drastically alters visual perception in a long-lasting manner. Where in the brain one-shot perceptual learning occurs and what mechanisms support it remain enigmatic. Combining psychophysics, 7 T fMRI, and intracranial recordings, we identify the high-level visual cortex as the most likely neural substrate wherein neural plasticity supports one-shot perceptual learning. We further develop a deep neural network model incorporating top-down feedback into a vision transformer, which recapitulates and predicts human behavior. The prior knowledge learnt by this model is highly similar to the neural code in the human high-level visual cortex. These results reveal the neurocomputational mechanisms underlying one-shot perceptual learning in humans.

BACKGROUND:Optimal emergency contraception (EC) can prevent approximately 95% of rape-related pregnancies. However, time to presentation, weight, and BMI influence efficacy of EC, and disparities in access to care, race and ethnicity, language, and socioeconomic status may modify rape-related pregnancy risk. We aimed to increase effective EC administration and eliminate potential health disparities in all sexual assault (SA) survivors managed in the emergency department (ED). METHODS:We conducted a 5-year retrospective review evaluating race and ethnicity, language, selected socioeconomic indicators, and obesity factors in EC administration. We implemented a quality improvement (QI) initiative over 2 years across three urban EDs, with interventions focused on care standardization (e.g., pharmaceutical changes, electronic health record optimizations, and checklists), multimodal and inter-disciplinary education, and sustainability of change (e.g., quality assurance reviews and bi-directional feedback). Statistical process control charts (SPCs) were used to evaluate temporal changes in EC administration to SA survivors. The Pearson Chi-squared was used to analyze differences across race and ethnicity groups in pre- and post-intervention cohorts. We estimated rape-related pregnancy preventions based on estimated pharmaceutical efficacy and previously reported marginal risks of pregnancy. RESULTS:Through two QI improvement cycles, within a pre-initiative cohort of 291 patients and post-initiative cohort of 156 patients, we increased any EC administration from 73.7% to 100% and effective EC from 44.1% to 100%, both of which were sustained for 14 months. Differences in effective EC administration across race and ethnicity groups pre-initiative (p = 0.005) were eliminated post-initiative (p = 0.840). An estimated 2.7-9.1 rape-related pregnancies were prevented in our post-initiative cohort. CONCLUSIONS:We achieved sustained effective EC administration to SA survivors and eliminated race and ethnicity disparities. Multi-modal interventions focusing on care standardization, education, and sustainability demonstrated success in patient preventative health goals and health equity.

INTRODUCTION/BACKGROUND:There has been a surge in attention to ethical controversies associated with organ donation in the USA. The Neurocritical Care Society (NCS) Ethics Committee sought to understand member experiences and attitudes related to organ donation in the USA. METHODS:We designed a survey of members who practice in the USA and have interacted with an organ procurement organization (OPO)/potential donor. The survey was disseminated by NCS from 1 June 2025 to 1 September 2025. Free-text responses were reviewed to identify themes. RESULTS:Of 2204 NCS members in the USA, there were 71 respondents who completed the survey and 37 respondents who provided free-text comments. Experiences and attitudes varied, but 59% of respondents indicated that they generally think that communication between the OPO and patient surrogates about donation after brain death/death by neurologic criteria seems appropriate, and 34% indicated that they generally think that communication between the OPO and patient surrogates regarding donation after cardiac death/death by circulatory-respiratory criteria (DCD) seems appropriate. Themes included (1) the need to improve education for the treatment team about organ donation; (2) blurred boundaries between patient care and care directed toward organ donation; (3) misalignment between OPOs and treatment team priorities; (4) loss of trust between patient surrogates and the treatment team based on interactions with OPOs; (5) suboptimal timing of communication between OPOs and patient surrogates; (6) concerns regarding a potential lack of transparency, empathy, and cultural sensitivity in communication between OPOs and patient surrogates; (7) opportunities for improvement in preoperative care before donation and palliation after extubation for DCD; and (8) changes in willingness to donate organs based on interactions with OPOs. CONCLUSIONS:Although the results from this survey reflect the experience and attitudes of a small percentage of NCS members in the USA, they indicate that there are opportunities for improvement in organ donation processes. Survey results will guide the NCS Ethics Committee in supporting members navigating ethical controversies related to organ donation.

INTRODUCTION/BACKGROUND:Choroid plexus (ChP) enlargement is a neuroimaging biomarker of neuroinflammation and neurodegeneration. However, evidence of ChP structural and perfusion alterations in long coronavirus disease (COVID) and their clinical relevance remains limited. METHODS:This study included 86 long COVID, 67 recovered COVID, and 26 COVID-negative healthy controls (HCs). ChP volume and cerebral blood flow (CBF) were quantified, and their associations with Alzheimer's disease (AD) symptoms and plasma biomarkers were examined. RESULTS:Both patient groups showed higher ChP volume and lower CBF than HC. Relative to recovered COVID, long COVID patients had a larger ChP volume, but no significant difference in CBF. ChP volume correlated positively with glial fibrillary acidic protein (r = 0.35) and phosphorylated tau217 (p-tau217; r = 0.54), while CBF correlated negatively with p-tau217 (r = -0.56). Both ChP volume and CBF were associated with cognitive decline measured with Mini-Mental State Examination and Clinical Dementia Rating. DISCUSSION/CONCLUSIONS:These findings suggest that ChP differences in long COVID are associated with AD-related cognitive decline and increased plasma biomarkers. HIGHLIGHTS/CONCLUSIONS:Long coronavirus disease (COVID) patients show choroid plexus (ChP) enlargement and reduced cerebral blood flow. ChP alterations are associated with Alzheimer's disease (AD)-related symptoms and plasma biomarker changes. ChP alterations on magnetic resonance imaging may serve as imaging markers for tracking neurological symptoms and AD-related pathology in post-COVID patients.

BACKGROUND:Recent guidelines suggest that aspirin-ticagrelor may be considered for stroke prevention after mild acute ischemic stroke. However, it is unclear how commonly this dual antiplatelet therapy (DAPT) regimen is used in practice. METHODS:We performed a cross-sectional analysis of the Get With The Guidelines-Stroke registry 2017-2023. Patients with a non-cardioembolic mild ischemic stroke (defined as NIHSS <6) who presented within 24 hours of last known well without a contraindication to DAPT were included. The primary study outcome was the proportion of patients prescribed aspirin-ticagrelor at hospital discharge; temporal patterns of prescribing aspirin-ticagrelor and aspirin-clopidogrel over time are also described. In addition to standard tests of comparison, we used multiple logistic regression to evaluate associations between patient and facility factors and aspirin-ticagrelor use reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS:Among 1,018,736 patients meeting study criteria, 478,049 (46.9%) were female and median age was 68 (IQR: 59, 78) years. A total of 12,845 (1.3%) patients were discharged on aspirin-ticagrelor whereas 448,348 (44.0%) were discharged on aspirin-clopidogrel. Prescriptions for aspirin-ticagrelor and for aspirin-clopidogrel significantly increased over the study time-period. In regression analysis, coronary artery disease/prior myocardial infarction (OR: 2.6 [95% CI: 2.5-2.7]), Asian race (OR: 2.1 [95% CI: 1.9-2.2]), aspirin-clopidogrel prescription upon admission (OR: 2.0 [95% CI:1.9-2.1]), and history of stroke/TIA (OR: 1.98 [95% CI: (1.9-2.1)]), were substantially associated with aspirin-ticagrelor use whereas lacking insurance/self-pay (OR: 0.7 [95% CI: 0.6-0.8]), rural setting (OR: 0.8 [95% 0.7-0.9]), and primary stroke centers (OR: 0.3 [95% CI: 0.3-0.4]) were inversely associated with aspirin-ticagrelor. In the subgroup of 176,897 (17.4%) patients with NIHSS 4-5, 74,912 (50.8%) were discharged on aspirin-clopidogrel and 2,394 (1.4%) on aspirin-ticagrelor. CONCLUSION/CONCLUSIONS:Unlike aspirin-clopidogrel, aspirin-ticagrelor is infrequently administered after mild acute ischemic stroke (NIHSS <6) despite current guidelines, though the use of both DAPT regimens increased over time.

Prior expectation powerfully shapes perception, yet its effects have been notoriously difficult to characterize due to the confounding influence of attention. In this study, we systematically investigated expectation's influence on conscious visual object recognition while carefully disentangling it from attentional effects. Across three experiments, we observed that expectation's effect varied markedly depending on the experimental context. When expectation was manipulated in isolation, it enhanced recognition sensitivity, mirroring the effects of attention. However, when expectation and attention were orthogonally manipulated, a surprising interaction effect emerged whereby observers were less likely to report recognition of an expected stimulus in the unattended condition-an effect attributed to swap errors. Finally, a stronger expectation cue in both space and time reduced swap errors and increased the likelihood of observers reporting seeing the expected stimuli. These findings reveal a remarkable degree of flexibility and context dependence in expectation's influence on perception and shed new light on how attention and expectation jointly shape conscious object recognition.

OBJECTIVE:To evaluate the risks of incident dyslipidemia and abnormal body mass index (BMI) during the 28-179-day post-acute phase after documented SARS-CoV-2 infection in a large pediatric sample. STUDY DESIGN/METHODS:A retrospective cohort study using the RECOVER pediatric electronic health record (EHR) datasets from 25 US children's hospitals and health institutions, from March 2020 to September 2023. This study included 384,289 COVID-19-positive patients aged 0-21 years for dyslipidemia analyses and 285,559 aged 2-21 years for BMI analyses, each with at least 6 months of follow-up. COVID-19-negative controls included 1,080,413 and 817,315 patients, respectively. SARS-CoV-2 infection was defined by a positive polymerase-chain-reaction (PCR), antigen, or serologic test; a clinical diagnosis of COVID-19; or a documented diagnosis of post-acute sequelae of SARS-CoV-2 (PASC). Incident dyslipidemia and abnormal BMI were identified using age-specific laboratory or anthropometric thresholds. Adjusted relative risks (aRRs) were estimated using propensity-score-stratified modified Poisson regression with multiple sensitivity analyses. RESULTS:During the post-acute phase, the COVID-19-positive cohort had higher rates of new-onset composite dyslipidemia (aRR 1.24; 95% CI 1.18-1.29) and abnormal BMI (aRR 1.15; 95% CI, 1.12-1.18). Results were robust to sensitivity and stratified analyses. CONCLUSION/CONCLUSIONS:Children and adolescents with documented COVID-19 infection were associated with an increased risk of new-onset dyslipidemia and abnormal BMI during the post-acute phase, highlighting the need for metabolic monitoring after infection.

Mitotic surveillance pathways monitor the duration of mitosis (M phase) in the cell cycle. Prolonged M phase, caused by spindle attachment defects or microtubule-targeting drugs, triggers formation of the ternary 'mitotic stopwatch pathway' complex (MSP) consisting of 53BP1, USP28, and p53. This complex stabilizes p53, leading to cell cycle arrest or apoptosis in daughter cells. In cancers that are resistant to paclitaxel, a microtubule-targeting agent, cells bypass mitotic surveillance activation, allowing unchecked proliferation, although the underlying mechanisms remain poorly understood. Here, we identify GMCL1 as a key negative regulator of MSP signaling. We show that 53BP1 physically interacts with GMCL1, but not its paralog GMCL2, and we map their interaction domains. CRL3^GMCL1 functions as a ubiquitin ligase that targets 53BP1 for degradation during the M phase, thereby reducing p53 accumulation in daughter cells. Depletion of GMCL1 inhibits cell cycle progression upon release from prolonged mitotic arrest, a defect that is rescued by co-silencing 53BP1 or USP28. Moreover, GMCL1 depletion sensitizes cancer cells to paclitaxel in a p53-dependent manner. Together, our findings support a model in which dysregulated CRL3^GMCL1-mediated degradation of 53BP1 prevents proper MSP function, leading to p53 degradation and continued proliferation. Targeting GMCL1 may, therefore, represent one possible avenue for addressing paclitaxel resistance in cancer cells with functional p53.

OBJECTIVES/OBJECTIVE:Cervical artery dissection (CeAD) is an important cause of ischemic stroke in young adults. Nearly 100 million annual chiropractic cervical manipulations are performed in the United States. The relationship between manipulation and CeAD remains controversial. METHODS:We analyzed patients in the multicenter STOP-CAD registry (n=4023) to identify CeAD cases diagnosed after chiropractic cervical manipulation. Demographics and clinical features were compared between manipulation-associated and nonmanipulation-associated cases using χ2 and t tests. Multivariable logistic regression identified key factors associated with manipulation-related CeAD. RESULTS:About 1 in 20 CeAD cases in this registry reported antecedent cervical manipulation. In multivariable binary logistic regression, compared with patients without prior manipulation, those with prior manipulation were younger (OR per year 0.98, 95% CI: 0.97-0.99, P=0.014), more often female (OR: 1.64, 95% CI: 1.21-2.23, P=0.001), less often diabetic (OR: 0.24, 95% CI: 0.08-0.78, P=0.018), presented with neck pain (OR: 2.80, 95% CI: 2.08-3.77, P<0.001), and had higher odds of isolated vertebral artery dissection (OR: 2.15, 95% CI: 1.57-2.94, P<0.001). Recurrent ischemic stroke rates were similar between groups. CONCLUSIONS:Given the very high number of manipulations performed annually, the absolute risk of secondary CeAD is extremely low. Manipulation-associated cases have distinct clinical features, occurring more often in younger women with vertebral dissections. Whether manipulation acts as a precipitating trigger or patients with early CeAD symptoms seek manipulation remains unresolved.