Faculty Bibliography

In a dynamic environment, sensory systems must filter out irrelevant information to construct a stable percept. Animals who rely on smell need to identify and discriminate odors despite fluctuations in concentration, yet odor receptor activation is strongly concentration dependent. Here we explored how odor signals are transformed within the mouse olfactory bulb (OB) by developing an all-optical approach to identify the connectivity between odor receptor channels (glomeruli) and the mitral and tufted cells (MTCs), while monitoring their odor responses. We found that the glomeruli and MTCs activated earliest in a sniff robustly represented odor identity across concentrations, whereas MTCs connected to later activated glomeruli were concentration dependent. Furthermore, probing the responsiveness of MTCs to glomerular input found a short temporal window of excitability at a sniff's onset, followed by prolonged odor-evoked inhibition. Our findings demonstrate, in awake animals, that the OB implements a rapid temporal filter, which is responsible for stabilizing identity across concentrations while decorrelating responses between odors.

INTRODUCTION/UNASSIGNED:We synthesized evidence on racial disparities in perinatal toxicology testing among Black and White women and their infants in the United States, including testing practices and downstream consequences such as child welfare involvement. METHODS/UNASSIGNED:We systematically searched PubMed and PsycINFO for peer-reviewed studies published before January 2023 that examined perinatal toxicology testing and reported racial outcomes. Eligible studies assessed testing practices or related consequences. A random-effects meta-analysis estimated pooled rate ratios (RRs) and 95% confidence intervals (CIs) for disparities in testing. Thematic synthesis summarized qualitative findings on downstream outcomes. Sixteen studies (1993-2023) met inclusion criteria; six contributed to the meta-analysis, encompassing over 50 000 pregnant women and/or their infants. RESULTS/UNASSIGNED:Black women and their infants were significantly more likely to be tested than their White counterparts (RR = 2.58; 95% CI: 2.03-3.29). While recent studies suggest disparities in referral to child welfare services after positive tests may be narrowing, earlier research indicates disproportionate reporting and child removal among Black and Hispanic families. CONCLUSION/UNASSIGNED:Racial inequities in perinatal and infant toxicology testing persist, with implications for maternal and child health. Future research should investigate multilevel drivers of these disparities and inform equitable policy and practice.

INTRODUCTION/BACKGROUND:We investigated the impact of racial/ethnic disparities in therapy initiation on colorectal cancer (CRC) mortality using Surveillance, Epidemiology, and End Results Program (SEER) database. METHODS:Adults aged 18-84 years with CRC were identified. Cox models for 60-month all-cause and cancer-specific mortality were adjusted for demographics, stage, tumor site, income, and rural-urban residence. RESULTS:Therapy initiation was slower for Hispanics (HR 0.85) and non-Hispanic Black (NHB) patients (HR 0.80) compared with non-Hispanic Whites (p < 0.001). Each additional month of delay was associated with a 3% increase in cancer mortality (p < 0.001). Findings were consistent across diagnosis eras, with no significant race-by-era interaction, and adjustment for socioeconomic and geographic factors resulted in minimal attenuation of racial disparities. CONCLUSION/CONCLUSIONS:Treatment delays independently contribute to all-cause and cancer-specific mortality, disproportionately affecting NHB and lower-SES patients.

BACKGROUND:Weight management strategies before total hip arthroplasty (THA) include bariatric surgery and Glucagon-like peptide-1 receptor agonists, including semaglutide. Previous studies have reported higher THA implant failure in patients who had prior bariatric surgery. This study aimed to evaluate semaglutide as a weight management alternative for patients undergoing THA and any effects on perioperative outcomes. METHODS:A retrospective review of primary, elective THAs performed between 2012 and 2024 was conducted at a single, urban, academic center. The study identified 224 patients who had a history of bariatric surgery, 202 patients who had perioperative semaglutide use, and a control group of 2,991 patients who had a body mass index (BMI) > 35. Demographic variables and clinical outcomes were compared between cohorts. RESULTS:The bariatric patients were younger (57 versus 61, P = 0.012) and more often women (65.6 versus 57.4 versus 55.4%, P < 0.001) than semaglutide and control patients. Preoperative hemoglobin A1c was lowest in semaglutide patients (6.2 versus 5.7 versus 5.8%, P < 0.001). The changes in BMI varied across groups one year before and after THA (P < 0.001). The bariatric and semaglutide groups decreased their BMI by 1.4 and 0.8, respectively, and control patients increased by 0.4. Implant survivorship was 95.5% at 10 years. There was no correlation found between any cohort and 90-day emergency department visits, readmissions, and all-time revision. Higher American Society of Anesthesiologists class and Charlson Comorbidity Index ≥ 5 conferred increased complications. CONCLUSIONS:Semaglutide appears to be a safe alternative to bariatric surgery for weight management before THA, with similar implant survival and postoperative complication rates. Further studies are warranted to understand outcomes for THA patients who use semaglutide.

Individuals of African ancestry carrying APOL1 (apolipoprotein L1) high-risk genotypes face a markedly increased risk of kidney failure, yet tools to identify those individuals likely to progress to chronic kidney disease are lacking. Here we profiled plasma proteomes of 851 Penn Medicine BioBank participants of African ancestry (285 males and 566 females) with APOL1 high-risk genotypes and preserved estimated glomerular filtration rate (eGFR) (≥60 ml min^-1 1.73 m^-2). Using elastic net Cox regression adjusted for age, sex, eGFR and albuminuria, we derived a nine-protein APOL1 Proteomic Risk Score (APRS) that predicts a composite outcome of ≥40% eGFR decline, kidney failure or death. APRS achieved a time-dependent area under the receiver operating characteristic curve (tAUC) of 86.5%, outperforming the Kidney Failure Risk Equation (66.1%) and polygenic risk scores, with 10-year event rates of 62.5% versus 3.3% across risk quintiles. External validation in Atherosclerosis Risk in Communities and UK Biobank cohorts confirmed robust accuracy (tAUC 82-85%) and consistent performance across demographic and clinical subgroups. Plasma levels of APRS component proteins correlated with kidney tissue fibrosis and tubular injury pathways, indicating strong biological plausibility. By enabling early and accurate prediction of disease progression in APOL1 high-risk individuals, APRS bridges the gap between genetic susceptibility and clinical translation. This scalable and biologically informed approach provides a precision medicine framework for early intervention and may accelerate development of APOL1-targeted therapies to reduce kidney disease disparities.

Pediatric deceased donor kidneys with acute kidney injury (ped-AKI) are at increased risk for non-utilization. To evaluate the post-transplant outcomes of ped-AKI recipients, we conducted a retrospective cohort study, comparing 17,731 adult recipients of kidneys from pediatric donors without AKI (ped-non-AKI, terminal serum creatinine (SCr)<1 mg/dL) to 1,589 ped-AKI recipients (SCr≥2 mg/dL). We used weighted logistic regression to estimate the association between ped-AKI and delayed graft function (DGF), and weighted Cox regression to estimate the association between ped-AKI and primary non-function (PNF) and all-cause graft failure (ACGF). Ped-AKI kidney recipients were at 6.0-fold (aOR=_5.325.98_6.72), 1.9-fold (aHR=_1.361.87_2.58), and 1.4-fold (aHR=_1.161.43_1.76) higher risk of DGF, PNF, and 1-year ACGF compared to ped-non-AKI recipients. En bloc ped-AKI recipients were at 5.6-fold (aOR=_3.295.57_9.43), 3.3-fold (aHR=_1.723.25_6.15), and 2.9-fold (aHR=_1.702.92_5.01) higher risk of DGF, PNF, 1-year ACGF compared to en bloc ped-non-AKI recipients. Among recipients of single kidneys from donors<20kg, ped-AKI recipients were at 8.9-fold (aOR=_4.348.87_18.12), 5-fold (aHR=_1.694.99_14.75), and 3.4-fold (aHR=_1.473.44_8.05) higher risk of DGF, PNF, 1-year ACGF compared to ped-non-AKI recipients. Ped-AKI kidney recipients have higher risks of early graft complications and failure. Risks are greatest for recipients of single kidneys from donors<20kg. Careful recipient selection and counseling are prudent when considering ped-AKI kidney offers.