Faculty Bibliography

Traumatic brain injury (TBI) commonly produces persistent deficits in working memory and processing speed. This study examined whether background factors and time post-injury predict response to a 14-week auditory-based computerized cognitive remediation (CCR) program in 48 adults with chronic mild-to-severe TBI. Cognitive changes were assessed on measures of working memory and attention, processing speed, executive functions, and self-reported perceived cognitive difficulties. Multiple regression models tested age, education, premorbid intelligence, months since injury, and their interactions with group as predictors of change scores. Less time since injury significantly predicted greater gains in auditory processing speed. Higher premorbid intelligence predicted greater improvement on visual processing speed, while the inverse association on verbal attention and working memory was best interpreted as a ceiling effect. Age and education were non-significant predictors. These findings underscore the critical roles of time post-injury and cognitive reserve proxies in determining responsiveness to auditory CCR in chronic mild-to-severe TBI, supporting earlier intervention within the chronic phase and the need for personalized rehabilitation strategies tailored to premorbid cognitive capacity.Trial registration: ClinicalTrials.gov identifier: NCT02507271.

Study DesignSystematic review and meta-analysis.ObjectivesWe sought to evaluate the association between pre-treatment symptom duration and outcomes in patients undergoing radiotherapy (RT)/surgery for metastatic epidural spinal cord compression (MESCC).MethodsA systematic review included publications evaluating the association between pre-treatment symptom duration and outcomes after RT/surgery in adults with MESCC. Primary exposure was pre-treatment symptom duration. Outcomes were motor-recovery, ambulation, survival and local control. Pooled-effect-estimates were calculated.Results Of 4639 studies, 37 met the inclusion criteria (26-RT,11-surgery). RT: All studies defined symptom duration as time from motor-weakness onset to RT. Longer symptom duration was associated with improved motor-recovery (Pooled-effect-estimate=2.08, 95%CI:1.68-2.58,p<0.001) and decreased mortality-risk (improved-survival)((Pooled-effect-estimate=0.72, 95%CI:0.69-0.76,p<0.001). Although longer symptom duration was consistently associated with better ambulation and lower local recurrence, few studies precluded meta-analysis. Surgery: Symptom duration was defined as time from neurological-deficit onset to surgery in 7/11 studies; three-studies used ambulatory status, and one-study used both. Longer symptom duration was associated with increased risk-of-death (worse-survival)(Pooled-effect-estimate=1.28, 95%CI:0.54-3.03,p=0.575), though statistically insignificantly. Meta-analysis for motor-recovery wasn't feasible, but most studies found longer symptom duration worsened motor-recovery, while ambulation findings were inconsistent.ConclusionSymptom duration was associated with differing outcome patterns by treatment modality. In RT cohorts, longer symptom duration was associated with improved survival and motor recovery. In surgical cohorts, it trended toward worse survival, though this did not reach statistical significance. Most surgical studies suggested an inverse association between symptom duration and motor recovery. These findings are exploratory, and should be interpreted in context of treatment selection-bias and between-cohort heterogeneity.

Background A landmark study of 1,600 Italian-Americans in Roseto, PA, challenged the prevailing view that high saturated fat intake was a major cause of myocardial infarction (MI). Despite similar rates of cigarette smoking and obesity, and even higher levels of saturated fat consumption compared to neighboring towns, Rosetans experienced far lower MI death rates. More than 50 years later, it remains uncertain whether Roseto's residents had better heart health than the average American and, if so, what protective factors may have been responsible. Methodology We compared MI deaths in Roseto and neighboring towns to the contemporaneous Framingham Heart Study cohort matched for age and sex. Results We found no evidence that MI deaths were lower in Roseto, PA, than in Framingham, MA when controlling for age and sex. While the role of social support in health has been established in subsequent studies, methodological issues, confounding factors, and biases challenge the validity of the Roseto study. Conclusions The dramatically lower MI and MI mortality rates among males in Roseto reflect biases in sampling and comparison populations, which also impacted the contrasting Diet-Heart Hypothesis that saturated fats cause heart disease. Although social support enhances health outcomes, the Roseto study neither supported nor refuted this connection.

INTRODUCTION/UNASSIGNED:Music-based interventions (MBIs) are widely used in dementia care, but objective methods for characterizing participant responses during intervention sessions remain limited. Synchronized datasets combining wearable physiological signals and behavioral observations are particularly scarce. METHODS/UNASSIGNED:We conducted a pilot feasibility study involving five individuals with Alzheimer's disease and related dementias (ADRD) who participated in 13 formal MBI sessions. Physiological signals, including photoplethysmography (PPG), electrodermal activity (EDA), skin temperature (TEMP), and accelerometry (ACC), were collected using a wrist-worn wearable sensor and synchronized with intervention playlists and time-stamped behavioral observations. Exploratory analyses examined physiological responses across intervention phases, participant-specific response patterns, time-of-day effects, and music-preference effects. RESULTS/UNASSIGNED:The dataset contains 13 intervention sessions, 99 music segments, and 248 behavioral observations. PPG, ACC, TEMP, and behavioral observations were available for all sessions, while EDA quality varied because of sensor-contact challenges. Behavioral responses were highly heterogeneous across participants, with engagement and calm behaviors observed most frequently. Physiological responses also showed substantial inter-individual variability, and case studies demonstrated that physiological and behavioral responses were not always concordant. CONCLUSION/UNASSIGNED:This study demonstrates the feasibility of collecting synchronized physiological, behavioral, and intervention-context data during MBIs in people living with dementia. The resulting publicly available multimodal dataset provides a foundation for future investigations of participant-specific responses and adaptive music-based interventions.

OBJECTIVE:To systematically review and meta-analyse the available evidence comparing perioperative outcomes between small- (≤6.3/7.5 F) and large-calibre (≥7.5/9.8 F) ureteroscopes. METHODS:A literature search of MEDLINE/PubMed, and Scopus was performed prior to March 2026 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The endpoints of interest were stone-free rates (SFRs), overall complications, and operative time. Study quality and risk of bias were evaluated using the Newcastle-Ottawa Scale and the Revised Cochrane Risk of Bias Tool for Randomised Trials for non-randomised and randomised studies. Sensitivity analyses were completed on studies reporting flexible ureteroscopes only, 7.5- vs >7.5-F ureteroscopes, and on randomised controlled trials (RCTs). RESULTS:Eight studies were included in the meta-analysis. Of those, four were RCTs while four were retrospective. Specifically, three studies compared 6.3- vs 7.5-F ureteroscopes, one 6.3- vs 8.5-F ureteroscopes, one 6- vs 7.5-F ureteroscopes, while three compared 7.5- vs >7.5-F ureteroscopes. Within the meta-analysis comparing 6.3- vs 7.5-F ureteroscopes, the small-calibre ureteroscopes were associated with a risk ratio [RR] for SFR of 0.99 (95% confidence interval [CI] 0.92-1.06), of 1.08 (95% CI 0.77-1.51) for overall complications, and a standardised mean difference in operative time of -14.5 min (95% CI -33.4 to 3.3 min). These results were virtually confirmed by all sensitivity analyses. No differences in the above outcomes were recorded for the comparison between 7.5- vs >7.5-F ureteroscopes. CONCLUSIONS:Within the present meta-analysis, the small-calibre ureteroscopes achieved comparable outcomes to large-calibre ureteroscopes. To overcome the substantial heterogeneity and residual confounding across studies, well-designed and adequately powered RCTs are required.

BACKGROUND/UNASSIGNED:Pneumatic tourniquets are routinely used in upper extremity surgery to create a bloodless operative field, often at a standard pressure of 250 mm Hg. However, high pressures may lead to complications, including tissue damage and increased pain. This study investigates whether tailoring tourniquet pressures to individual systolic blood pressure (SBP) can achieve comparable surgical field visualization while reducing inflation pressure. MATERIALS AND METHODS/UNASSIGNED:-tests. RESULTS/UNASSIGNED: = 0.27). Tourniquet adjustments were rare (2.13%, intervention only). CONCLUSION/UNASSIGNED:SBP-based tourniquet pressures effectively maintain surgical field visualization at lower pressures without compromising safety or increasing pain. These findings support wider adoption of this method and warrant further large-scale studies.

Previous epidemiological studies have shown that E-cigarette and tobacco users are more likely to develop COVID-19 symptoms than non-users. To investigate the underlying mechanisms, we examined the effects of nicotine, the major component of tobacco and E-cigarette, and its major metabolite, cotinine, on the susceptibility of human respiratory epithelial cells to SARS-CoV-2 infection. We found that pre-treatment with nicotine and cotinine significantly and additively enhanced viral infection. While nicotine increased the expression of the viral receptor ACE2 and the serine protease TMPRSS2, cotinine upregulated cysteine protease cathepsin B and promoted viral spike protein cleavage. These findings suggest that nicotine and cotinine enhance SARS-CoV-2 infection at the cell entry stage through distinct mechanisms. Using a SARS-CoV-2 pseudovirus system, we further investigated the effects and mechanisms of nicotine and cotinine on viral entry. We found that both compounds enhanced pseudovirus infection, but with different time courses. Nicotine's effect correlated with the upregulation of ACE2 and TMPRSS2, whereas cotinine's effect corresponded with increased cathepsin B and viral spike protein cleavage. The cathepsin B inhibitor E64d completely abolished cotinine-enhanced viral spike protein cleavage and viral entry. In contrast, ACE2 and TMPRSS2 inhibitors (chloromethylketone and camostat) had limited effects on viral spike protein cleavage and only partially reduced the viral entry enhancement induced by nicotine and cotinine. These results indicate that nicotine promotes virus-receptor binding and cell entry, while cotinine facilitates viral entry through cathepsin B-mediated spike protein cleavage.IMPORTANCEThis study highlights the potential risks of tobacco and E-cigarette use in increasing susceptibility to COVID-19. We show that the major neurostimulant in tobacco and E-cigarette, nicotine, and its metabolite, cotinine, additively enhance SARS-CoV-2 infection in human respiratory epithelial cells by promoting viral entry. Specifically, nicotine and cotinine upregulate the expression of distinct, yet complementary sets of key cellular proteins required for viral entry. These findings suggest that both tobacco smoking and E-cigarette vaping may exacerbate COVID-19 infection rates and severity and provide new insights into how nicotine and cotinine contribute to viral susceptibility. This research underscores the need for public health measures to address the heightened risk posed by tobacco smoking and E-cigarette vaping to encounter the SARS-CoV-2 infection.

The liver-secreted protein fibrinogen-like protein 1 (FGL1) is a ligand of the coinhibitory receptor LAG3 on T cells; however, Fgl1^-/- mice exhibit autoimmune features distinct from those of Lag3^-/- mice. Here, we examined whether FGL1 acts via receptors beyond LAG3 to regulate autoimmunity. Recombinant FGL1 administration reduced autoimmune symptoms in B6/lpr lupus-like mice. This was associated with diminished antigen-specific IgM responses and B cell numbers. Genome-wide surface proteome screening identified the tumor necrosis factor receptor (TNFR) family member transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), a receptor for B cell-activating receptors BAFF and APRIL, as a receptor for FGL1. TACI bound FGL1 via an N-terminal site not required for BAFF and APRIL interaction. The impact of FGL1 administration on B cell numbers and autoimmune phenotypes was lost in Taci^-/- mice. Mechanistically, FGL1 promotes TACI internalization, thereby regulating receptor availability for activating ligands. Thus, FGL1 regulates an innate-like subset of B cells via modulating TACI availability, with implications for autoimmunity and inflammation.

OBJECTIVE:The relationship between physical activity and sleep with inflammatory arthritis (IA) is understudied, and existing research has relied largely on self-report or short-term assessments. The NIH All of Us database provides long-term accelerometry data, enabling more precise estimation of the association between lifestyle behaviors and IA. METHODS:Participants from the All of Us database who shared electronic health record and Fitbit data were included. Daily activity and sleep metrics were compared between individuals with and without IA using multiple linear regression. Cox proportional hazards regression was used to examine the association of activity and sleep patterns with incident IA in a 10-year follow-up period. RESULTS:A total of 23,855 participants were included, 200 of whom had IA. Participants with IA took fewer daily steps (P < 0.001) and had greater sleep variability (P < 0.001) compared to those without IA. 122 individuals had incident IA. Every 1,000 extra daily steps were associated with a 7% lower risk of IA (hazard ratio [HR] 0.93 [95% confidence interval (CI) 0.87-0.99], P = 0.02). Compared to those who walked <5,000 steps daily, those who walked 5,000 to 10,000 steps and 10,000+ steps had a 41% (HR 0.59 [95% CI 0.39-0.91], P = 0.02) and 50% (HR 0.50 [95% CI 0.29-0.86], P = 0.01) reduction in risk of IA. CONCLUSION/CONCLUSIONS:Individuals with IA had reduced step counts and more sleep variability compared to those without IA, highlighting how physical activity and sleep contribute to IA. Additionally, increased daily step count was associated with decreased risk of incident IA, suggesting a possible research intervention for those at high risk of IA.