Faculty Bibliography

IMPORTANCE:Although fluoride exposure at high levels during the perinatal period has been associated with socioemotional problems among children, there is limited evidence regarding potential associations at lower levels of fluoride exposure, particularly in the US. OBJECTIVE:To examine the association between prenatal exposure to public drinking water fluoride levels and children's socioemotional problems in a pooled US pediatric consortium. DESIGN, SETTING, AND PARTICIPANTS:This cohort study used observational pregnancy cohort data from January 1, 2005, to December 31, 2019, on children aged 1.5 to 17 years from the Environmental Influences on Child Health Outcomes (ECHO) Cohort, which took place at 20 prenatal pediatric cohort sites across 34 US states. Statistical analysis was conducted from December 2024 to December 2025. EXPOSURE:Area-level, time-weighted, mean fluoride concentrations in public water were estimated based on residential addresses during pregnancy. MAIN OUTCOMES AND MEASURES:Children's socioemotional problems were assessed using caregiver reports of internalizing and externalizing problems via the Child Behavior Checklist. Generalized estimating equation models evaluated the adjusted mean difference in T scores (1) across the range of exposure values in cubic spline models, (2) per 500.0-µg/L higher fluoride level in linear models, (3) across quartiles of exposure, and (4) at the US Public Health Services recommended cutoff (≤700.0 µg/L; 3998 less than the cutoff). RESULTS:The cohort comprised 5520 children (mean [SD] age, 5.8 [3.0] years; 2849 boys [51.6%]). The mean (SD) prenatal time-weighted water fluoride level was 407.9 (361.0) µg/L (range, <1.4-3272.5 µg/L). The adjusted mean difference in emotional and behavioral problem T scores per 500.0-μg/L higher exposure to prenatal public water fluoride was -0.15 (95% CI, -0.85 to 0.56) for internalizing problems and 0.06 (95% CI, -0.44 to 0.55) for externalizing problems, consistently showing no associations at the continuous level. However, some positive associations were observed only when using change point models for externalizing problems (adjusted mean difference, 1.59 [95% CI, 0.72-2.47] per 500.0-µg/L increase above the inflection point), and for some subgroups. CONCLUSIONS AND RELEVANCE:In this cohort study, prenatal exposure to fluoride levels in regulated public water was not associated with internalizing and externalizing problems among offspring. In change point models, positive associations were found for externalizing problems. The results contribute to growing evidence that could inform future policy decisions regarding fluoride in the US public water systems. Additional studies are needed to further investigate this association, especially examining other sources of fluoride that may have an association with children's emotional and behavioral problems.

OBJECTIVE:To quantify general population prevalence, and differences by sex and BMI, in ultrasound (US) features of knee osteoarthritis (KOA), patient-reported knee symptoms (Ksx), radiographic KOA (rKOA), and symptomatic KOA (sxKOA). METHODS:Participants from the Johnston County Health Study (2019-2024; n=902) provided demographic, clinical, and imaging data. Ksx was defined as self-reported pain, aching or stiffness on most days of any one month in the past 12 months. rKOA was defined as Kellgren-Lawrence grade ≥2 (or total knee replacement (TKR)), severe rKOA as grades 3-4 (or TKR), and sxKOA as rKOA and Ksx in the same knee. Standardized US scoring was performed as previously reported. Weighted prevalence estimates and 95% confidence intervals (CI) for Ksx, rKOA, sxKOA, severe rKOA, and US features were calculated overall and by sex and BMI category. RESULTS:Among 902 participants (67% female; 66% non-Hispanic white, mean age 55 years, and BMI 33 kg/m²), the weighted prevalence of Ksx, rKOA, sxKOA, and severe rKOA were 61%, 36%, 27%, and 21%, respectively, all higher (based on non-overlapping CIs) than baseline estimates from the Johnston County Osteoarthritis Project and other cohorts. Ksx, rKOA, sxKOA, and severe rKOA were higher among females and those with obesity. Compared to females with obesity, those with severe obesity had higher prevalence of all radiographic outcomes at moderate and severe grades with non-overlapping CI. US effusion and synovitis were more prevalent in males, whereas medial and lateral cartilage damage were more common in females. With increasing obesity, osteophytes and medial cartilage damage were more prevalent, while gryescale effusion was actually less frequent. CONCLUSION/CONCLUSIONS:KOA prevalence continues to increase in the population. Sex and BMI differences in KOA prevalence and US features were most pronounced among females with severe obesity. Distinguishing between sexes and by obesity levels may improve understanding of KOA mechanisms and guide tailored prevention and treatment strategies.

BACKGROUND/UNASSIGNED:Liver cancer poses a significant global health burden, characterized by substantial regional disparities. We analyzed liver cancer incidence and mortality across 204 countries and territories from 1990 to 2021 and projected trends from 2021 to 2041. MATERIALS AND METHODS/UNASSIGNED:Data from the Global Burden of Disease (GBD) Study 2021 were used to calculate age-standardized rate (ASR), average annual percentage change (AAPC), and estimated annual percentage change (EAPC). Risk factors, human development index (HDI), and sociodemographic index (SDI) were evaluated. The Nordpred and Bayesian Age-Period-Cohort (BAPC) models projected future trends. RESULTS/UNASSIGNED:Globally, according to the analysis of AAPC, the ASR of liver cancer incidence rose by 0.115% (95% CI: 0.07-0.159) annually, while the mortality ASR trend remains stable (-0.113%, 95% CI: -0.35-0.124). Viral hepatitis B and C remained primary causes, but non-alcoholic steatohepatitis (NASH) contributions increased. The summary exposure value (SEV) for drug use increased by 12% globally, with a dramatic increase of 308% in North America. High-HDI/SDI countries exhibited higher ASR than expected, which may be attributed to aging populations and the rising incidence of metabolic diseases. Projections indicated a rising number of cases but declining ASR for both males and females by 2041. CONCLUSIONS/UNASSIGNED:Tailored prevention strategies are needed to address region-specific risk factors and mitigate the growing burden of liver cancer.

BACKGROUND/AIM/OBJECTIVE:-defined 32-gene Ewing Sarcoma Specific Signature (ESS32) into a practical target atlas by integrating tumor RNA expression with normal-tissue context, protein evidence, subcellular localization, and therapeutic accessibility. MATERIALS AND METHODS/METHODS:-skeletal-muscle comparison, broad normal-organ context, EWSR1::FLI1 perturbation, tumor-only support cohorts, cell-line models, and cross-sarcoma comparison. Results were overlaid with Human Protein Atlas and published proteomic/surfaceome evidence. RESULTS:In GSE17674, the strongest tumor-enriched transcripts included NKX2-2, NPY1R, STEAP1, RBM11, RNF182, LIPI, CD99, STEAP2, LOXHD1, and DCDC2. Normal-tissue and compartment data substantially reordered RNA-only ranking. NKX2-2 showed the strongest Ewing-associated signal but encodes a nuclear transcription factor, favoring peptide-HLA/T-cell receptor (TCR) or vaccine development. RBM11 and LIPI emerged as high-interest intracellular/secretome-associated candidates, with an explicit epididymal/male reproductive caveat for LIPI. CD99 and NPY1R illustrated normal-cell reservoir and receptor-distribution constraints. CONCLUSION/CONCLUSIONS:ESS32 should be interpreted as an EWSR1::FLI1-associated RNA discovery set, not as a pre-validated target panel. Practical nomination requires integration of RNA enrichment, normal-tissue distribution, protein evidence, cellular compartment, and modality compatibility before nomination of TCR, vaccine, antibody-drug conjugate (ADC), chimeric antigen receptor (CAR), radioligand, or validation-first candidates.

BACKGROUND:Tissue-based gene expression assays provide prognostic information in prostate cancer, but their influence on decisions regarding immediate treatment versus conservative management, including active surveillance (AS) and watchful waiting (WW), remains uncertain. METHODS:Using a linkage with the Surveillance, Epidemiology, and End Results program, we evaluated the association between a 22-gene genomic classifier (GC) and initial management among patients with low or intermediate clinical-risk prostate cancer diagnosed from 2015 through 2018. Initial management was classified as immediate therapy or AS/WW, and GC scores were grouped as low (<0.45), intermediate (0.45-0.60), or high (>0.60). Multivariable logistic regression assessed associations between GC category and immediate treatment, stratified by clinical-risk group and adjusted for demographic and clinical covariates. RESULTS:Among 2,547 patients, 286 of 1,030 (27.8%) with low- and 1,113 of 1,517 (73.4%) with intermediate clinical-risk prostate cancer received initial treatment. Use of initial treatment increased with higher GC category. Among patients with low and intermediate clinical-risk prostate cancer, respectively, 20.5% and 57.5% with low GC, 28.3% and 75.8% with intermediate GC, and 46.2% and 88.3% with high GC scores received initial treatment. Higher GC category was independently associated with greater odds of immediate treatment versus AS/WW (versus low GC: intermediate GC, odds ratio [OR] 1.98, 95% confidence interval [CI] 1.57-2.49, p < 0.001; high GC, OR 4.42, 95% CI 3.41-5.71, p < 0.001). CONCLUSIONS:Higher GC scores were associated with greater use of immediate treatment and less use of AS/WW, underscoring the need to determine whether GC testing also predicts long-term outcomes among patients managed with AS.

BACKGROUND/AIM/OBJECTIVE:Multiple measures of health and wellness have worsened for rural communities in the last two decades. Few studies have sought to characterize the rural-urban difference in 5-year cancer survival data in a nationwide sample over that time. PATIENTS AND METHODS/METHODS:We analyzed cause-specific five-year survival data for prostate, breast, colorectal, pancreatic, lung, and liver cancers diagnosed from 2000-2016 among rural and non-rural populations using the Surveillance, Epidemiology, and End Results Database. We explored the CDC Wonder Database for drug related mortality in rural and non-rural populations. Ordinary least squares regression assessed temporal survival trends, and analysis of covariance compared the statistical significance in annual change in survival between groups. RESULTS:<0.0001) of drug related mortality disparities between rural and urban populations from the years 1999 to 2015. CONCLUSION/CONCLUSIONS:From 2000 to 2016, rural-urban disparities in cancer survival widened for five of six major cancers during the same period in which national drug overdose rates increased in rural populations.

High-resolution quantitative susceptibility mapping (QSM) combined with susceptibility source decomposition provides a powerful approach for investigating the magnetic susceptibility alterations in Alzheimer's disease (AD). In this study, ex vivo three-dimensional multi-echo gradient-echo (mGRE) images of 5xFAD and

BACKGROUND:Consensus guidelines advocate multidisciplinary care to optimise recovery following laryngectomy. However, limited evidence exists regarding the nature of the patient recovery journey or their experience accessing rehabilitation services. AIMS/OBJECTIVE:This study examined the services accessed by, and experiences of, individuals with a laryngectomy (IWL) in the first 12 months post-surgery. METHODS AND PROCEDURES/METHODS:Patient journey mapping methodology was used to explore the healthcare journey and patient experience of 12 IWL across the first 12 months of rehabilitation. Demographics and detailed service data were collated from medical records and later reviewed for accuracy with each participant. Individual interviews were used to explore issues that influenced care experiences, and participants also provided experiential ratings relating to the emotional impact of each appointment (positive/negative/neutral) and the reason for the rating. Journeys were explored collectively as a group, then 3 detailed patient journeys are presented highlighting similarities and differences in participant experiences. OUTCOMES AND RESULTS/RESULTS:Participants attended a median (Mdn) of 7 medical visits (range = 4-14), 12 allied health visits (range = 4-45), saw 13 different professionals (range = 6-22), and travelled to 6 locations (range = 2-6) for healthcare. Factors adding to the complexity of the health care journeys included preparation for surgery, nature of surgery (primary versus salvage), access to trained specialists throughout phases of care, coordinating between services, travel and funding for consumables. Despite issues, participants largely rated experiences as positive (Mdn = 77; range = 37%-100% positive). Participant perspectives on issues impacting their healthcare journey formed 6 themes: (1) Preparation for laryngectomy surgery, (2) Recovery post-surgery (3) Access to skilled and coordinated services, (4) Approach of healthcare staff, (5) Communication difficulties impacting healthcare, and (6) Accessing laryngectomy resources and costs. CONCLUSIONS AND IMPLICATIONS/CONCLUSIONS:Following laryngectomy, a wide range of multidisciplinary services are accessed to support recovery and rehabilitation. Examining patient experiences through journey mapping has highlighted challenges that can influence the care pathway. Addressing issues that impact service access and patient experience will assist in enhancing laryngectomy care pathways and improve the patient experience. WHAT THIS PAPER ADDS/CONCLUSIONS:What is already known on the subject Current care pathways advocate specialist, multidisciplinary care for optimal recovery for individuals with a laryngectomy (IWL). Although existing laryngectomy guidelines specify that a range of specialist services are required, and detail what those services should entail, what this actually looks like and means for IWL as they live this path of recovery, remains largely unexplored. What this study adds to the existing knowledge This work expands the body of evidence in laryngectomy care by exploring the healthcare journeys of a cohort of IWL to better understand the extent of medical and allied health services required in the first 12-months post-surgery and the patients' experiences of that care. This work is the first to use journey mapping, a methodology that provides detailed insights gained from both quantitative and qualitative data to elucidate the patients' care experience. Understanding the patients lived experience, and any challenges faced, is essential information needed to continue to inform future care optimisation. What are the clinical implications of this study? The collective findings from this study highlight the potential challenges IWL can face accessing care in the post-acute phase. Participants attended a high number of medical and allied health visits, from a variety of professions and services, and faced several challenges including being prepared for their recovery, accessing skilled professionals, communication with healthcare staff, and costs of necessary consumables/equipment. Healthcare providers, including speech-language pathologists, must recognise and address these issues where possible, to optimise care and reduce patient burden.

OBJECTIVE:To examine the relationship between dosage of the clinic component and child weight status in the Greenlight Plus Trial, a clinic plus digital intervention aimed to reduce early childhood obesity. STUDY DESIGN/METHODS:Longitudinal data were used from parent-child dyads (N=900) in the Greenlight Plus Trial. Clinic intervention dosage was assessed after each well child visit (WCV), as the sum of parent-reported receipt of: (1) a Greenlight booklet; (2) discussion of booklet content; and/or (3) goal setting. Multivariable models assessed the relationship between dosage and child weight-for-length (WFL). RESULTS:Across all WCVs (n=7200), parents reported not receiving any clinic intervention component at 20% of visits, receiving booklet only (dosage score=1) at 39.2% of visits, booklet receipt and discussion (dosage score=2) at 11.7% of visits, and booklet receipt, page discussion, and goal setting (dosage score=3) at 26.9% of visits. No association was detected between cumulative dosage and child WFL trajectory (p=0.31). However, we observed a statistically significant difference in the relationship of dosage to WFL in the 2 treatment arms (p=0.021). Within the clinic-only arm, there was a significant association between dosage and child WFL (p=0.005) in the first 6 months. CONCLUSIONS:Exposure to the full conceptual model of behavioral change was limited. Among those who received only the clinic intervention, dosage modestly and transiently improved infant weight. Enhancing primary care behavioral interventions with digital components, such as text messages, between visits may optimize their impact on child health outcomes including healthy growth.