Faculty Bibliography

Observational studies suggest psychosocial factors such as social support and loneliness are associated with vulnerability for frailty in older adults, but less is known about the generalizability of these putative psychosocial mechanisms in underrepresented groups. Thus, we evaluated whether better telecommunication social support and lower levels of loneliness were associated with decreased frailty and increased functional ability using a unique longitudinal cohort of rural South African older adults. We conducted generalized estimating equation and robust regression analyses using cross-sectional data from 347 participants in the HAALSI (Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa) Dementia Cohort. Social support via telecommunication and self-reported loneliness were measured using standard assessments and modeled as exposure variables. Outcomes were frailty (measured using Fried’s frailty phenotype) and functional status (measured by instrumental activities of daily living, IADLs). Lower level of telecommunication social support was associated with higher impairment in ability to perform IADLs. This association persisted after additional adjustments for depression (beta -0.007, 95 % CI -0.016, 0.001) and vascular risk factors (beta -0.012, 95 % CI -0.020, 0.003). No associations were observed in relating telecommunication social support and loneliness with frailty. Among rural South African Black older adults, lower telecommunication-based social support was associated with greater risk of impairment in functional ability. Although further validation is required for possible reverse causality, our findings suggest that future intervention studies focused on promoting telecommunication-based social support to preserve independent functioning may be merited.

PURPOSE/UNASSIGNED:To investigate the fairness of existing deep models for diabetic retinopathy (DR) detection and introduce an equitable model to reduce group performance disparities. METHODS/UNASSIGNED:We evaluated the performance and fairness of various deep learning models for DR detection using fundus images and optical coherence tomography (OCT) B-scans. A Fair Adaptive Scaling (FAS) module was developed to reduce group disparities. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), and equity across various groups was assessed by equity-scaled AUC, which accommodated both overall AUC and AUCs of individual groups. RESULTS/UNASSIGNED:Using color fundus images, the integration of FAS with EfficientNet improved the overall AUC and equity-scaled AUC from 0.88 and 0.83 to 0.90 and 0.84 (P < 0.05) by race. AUCs for Asians and Whites increased by 0.05 and 0.03, respectively (P < 0.01). For gender, both metrics improved by 0.01 (P < 0.05). Using DenseNet121 on OCT B-Scans by race, FAS improved the overall AUC and equity-scaled AUC from 0.875 and 0.81 to 0.884 and 0.82, with gains of 0.03 and 0.02 for Asians and Blacks (P < 0.01). For gender, DenseNet121's metrics rose by 0.04 and 0.03, with gains of 0.05 and 0.04 for females and males (P < 0.01). CONCLUSIONS/UNASSIGNED:Deep learning models demonstrate varying accuracies across different groups in DR detection. FAS improves equity and accuracy of deep learning models. TRANSLATIONAL RELEVANCE/UNASSIGNED:The proposed deep learning model has a potential to improve both model performance and equity of DR detection.

INTRODUCTION/UNASSIGNED:. AREAS COVERED/UNASSIGNED:The authors searched PubMed, GoogleScholar, and clinicaltrials.gov for all types of studies regarding the genetic basis of FD and recent advances in the development of disease-modifying therapies, including publications available through November 2025. EXPERT OPINION/UNASSIGNED:Experimental evidence indicates that boosting ELP1 protein levels could halt disease progression. Several small molecules and genetic therapies have shown the ability to enhance wild-type ELP1 mRNA and protein expression in animal models. An ongoing N-of-1 clinical trial is evaluating the intrathecal administration of an antisense oligonucleotide (ASO) designed to correct the splicing defect in an individual with FD. Combining small molecules, such as optimized potent oral kinetin derivatives, with intrathecal antisense oligonucleotides (ASOs) and intravitreal gene therapy using viral vectors presents a synergistic therapeutic approach to elevate ELP1 levels. Assessing the efficacy and safety of these targeted strategies will require innovative, well-designed clinical trials.

BACKGROUND/UNASSIGNED:The diagnosis of genetic hyperkinetic movement disorders has become increasingly more complex as new genes are discovered and technologies offer new diagnostic possibilities. As a result, the choice of appropriate gene testing and the interpretation of the results can become difficult to navigate for movement disorder experts and clinicians. In parallel, research is becoming crucial to pair with clinical assessments in order to explore advanced sequencing technologies and allow new genes discovery. METHODS/UNASSIGNED:Systematic review of genetic forms of hyperkinetic movement disorders and of the most relevant genetic terminology was performed. RESULTS/UNASSIGNED:Comprehensive descriptions of genetic lexicon, testing selection, and complex genetic findings related to hyperkinetic movement disorders are reported. DISCUSSION/UNASSIGNED:Here we discuss the terminology of genetic diagnosis that is now part of the clinical practice, the difficulties related to the interpretation of complex genetic results, and provide guidance and tips for gene testing selection in order not to miss important diagnosis of genetic hyperkinetic movement disorders. HIGHLIGHTS/UNASSIGNED:To review the most relevant lexicon related to genetic diagnosis, approach to gene testing, testing selection, and complex genetic findings in genetic hyperkinetic movement disorders.

BACKGROUND:Febrile seizures occur in 3%-4% of US children aged six months to five years and are considered benign. However, sudden unexplained death in childhood is associated with 10 times increase in febrile seizures. We assessed the characteristics of children with febrile seizure and sudden death to identify factors that confer increased sudden death risk. METHODS:We conducted a case-control analysis of children with febrile seizure and subsequent sudden death versus living controls from December 2021 to June 2023 through an ∼10-minute anonymous online survey. We enrolled parents of children, living or deceased, whose child had experienced a febrile seizure from age six months to six years. Subjects were excluded if the child had an afebrile seizure or parents had not witnessed a febrile seizure. Demographic characteristics, parasomnias, and febrile seizure features were analyzed. RESULTS:A total of 381 completed surveys were received; 53 (14%) cases of febrile seizure with sudden death and 328 (86%) living controls. Cases reported febrile seizure onset >2 months earlier (P = 0.013) and reported developmental concerns (odds ratio [OR] = 2.32, 95% confidence interval [CI] [1.14, 4.71], P = 0.03), less frequent night awakenings (OR = 0.34, 95% CI [0.18, 0.65], P = 0.001), and less restless sleep (OR = 0.37, 95% CI [0.16, 0.85], P = 0.02). Cases were also less likely to drool (OR = 0.442, 95% CI [0.218, 0.900], P = 0.032) or be unresponsive for more than one minute (OR = 0.45, 95% CI [0.238, 0.854], P = 0.021). CONCLUSIONS:We report novel associations of febrile seizure and sudden death related to age, development, sleep, and observed ictal features. Anonymous survey methodology cannot exclude ascertainment bias and any related potential effect on results. Our findings suggest that impaired arousal mechanisms may increase risk of death in subjects with febrile seizure.

Pathogens have evolved to be highly adapted to their natural host. Community-associated methicillin-resistant Staphylococcus aureus USA300, for instance, is a lineage responsible for the epidemic of skin and soft tissue infections (SSTIs) in humans. Owing to its human tropism, mechanisms that enabled the rise of USA300 as a major skin pathogen remain incompletely defined. By leveraging a rodent-adapted strain of S. aureus, we developed a natural model of SSTIs. We found that LukMF', a pore-forming leukocidin homolog to the human-specific LukSF-PV toxin, drives skin pathology in mice. LukMF' lyses neutrophils via the chemokine receptor CCR1, which in turn fuels inflammatory pathology and microbial survival within the infectious nidus. Ablation of CCR1, depletion of neutrophils, or vaccination with LukMF' all protected mice from skin pathology. Thus, these data support epidemiological studies linking leukocidins with human SSTIs and highlight the power of natural models to unearth potential targets to curtail infections.

Parkinson's disease (PD) is a neurodegenerative disease characterized by motor and non-motor symptoms that progressively deteriorate and for which there is no disease-modifying pharmacological treatment. Exercise is widely recommended for individuals with PD due to its potential neuroprotective benefits. However, the mechanisms underlying these exercise-induced effects in PD remain poorly understood. Analyzing fluid biomarkers responsive to exercise could offer valuable insights into the mechanisms by which exercise impacts PD and aid in optimizing exercise prescriptions for individuals with PD. This review explores exercise-responsive biomarkers categorized into three key groups-neurotrophic, inflammatory, and neuroendocrine markers. It highlights both well-validated biomarkers and candidates with promising potential. We also highlight key biomarkers linked to PD pathology, such as α-synuclein, and their potential connection to exercise based on current evidence. Comprehensive characterization of these biomarkers will advance our understanding of the biological effects of exercise in PD, enabling mechanism-based and objective measures to evaluate exercise response in future clinical trials and its impact on PD signs and symptoms.

Naturalistic electrocorticography (ECoG) data are a rare but essential resource for studying the brain's linguistic capabilities. ECoG offers high temporal resolution suitable for investigating processes at multiple temporal timescales and frequency bands. It also provides broad spatial coverage, often along critical language areas. Here, we share a dataset of nine ECoG participants with 1,330 electrodes listening to a 30-minute audio podcast. The richness of this naturalistic stimulus can be used for various research questions, from auditory perception to narrative integration. In addition to the neural data, we extracted linguistic features of the stimulus ranging from phonetic information to large language model word embeddings. We use these linguistic features in encoding models that relate stimulus properties to neural activity. Finally, we provide detailed tutorials for preprocessing raw data, extracting stimulus features, and running encoding analyses that can serve as a pedagogical resource or a springboard for new research.

OBJECTIVE:Evaluate real-world effectiveness, patient-reported outcomes (PROs), and safety/tolerability of brivaracetam in patients (≥16 years) with focal-onset seizures currently receiving ≥ 1 antiseizure medication (ASM), and with historical or current use of levetiracetam, lamotrigine, oxcarbazepine, and/or carbamazepine. METHODS:EP0088 was a 12-month, prospective, observational study of brivaracetam in a clinical practice setting in the US. Primary study outcome was brivaracetam retention at 12 months after brivaracetam initiation. Effect of brivaracetam on patients' perceptions of their health was assessed using Patient-Reported Outcomes Measurement Information System (PROMIS) short forms and Seizure-Related Disability Assessment Scale (SERDAS). Safety outcomes included incidence of treatment-emergent adverse events (TEAEs). RESULTS:254 patients (mean age: 44.3 years; median duration of epilepsy: 17.3 years) received ≥ 1 brivaracetam dose (Safety Set; SS). Patients had a median of 3.0 historical and 2.0 concomitant ASMs (SS). For all patients (SS), including those who dropped out with unknown brivaracetam treatment status, 12-month brivaracetam retention was 57.1 % (n = 145/254); in patients with known brivaracetam treatment status (post hoc analysis), 12-month brivaracetam retention was 72.1 % (n = 145/201). Slight improvements in mean PROMIS T-scores, and improvements in mean SERDAS scores, were seen by month 1.5, and generally maintained up to 12 months (Full Analysis Set). 49.6 % of patients reported ≥ 1 TEAE, 38.2 % had drug-related TEAEs, and 16.1 % discontinued due to TEAEs (SS). CONCLUSIONS:Brivaracetam was effective in patients with difficult-to-control focal-onset seizures; as shown by brivaracetam retention at 12 months. Improvements in PROs were seen early. Brivaracetam was well-tolerated and no new safety signals were observed.