Faculty Bibliography

OBJECTIVES/OBJECTIVE:To evaluate the effect of a proprietary motion artifact correction algorithm on CBCT spatial resolution using an in vitro phantom model. STUDY DESIGN/METHODS:Fifty CBCT scans were acquired with a ProMax 3D unit using a point spread function phantom mounted on a motorized turntable. Ten protocols were tested, including no motion and induced motion up to 9 degrees, with and without activation of the correction algorithm. Spatial resolution was assessed using full width at half maximum (FWHM), surface plots, fast Fourier transforms, pairwise comparisons, and Bland-Altman analysis. RESULTS:Motion increased FWHM values and distorted the point spread function, with greater irregularity as motion magnitude increased. The correction algorithm produced partial improvement in selected motion protocols, particularly at lower motion magnitudes, but the effect was inconsistent across all motion conditions and measurement directions. In the no-motion protocol, activation of the algorithm introduced slight unsharpness and increased heterogeneity in the high-frequency domain. CONCLUSION/CONCLUSIONS:Patient motion degrades CBCT spatial resolution. The proprietary correction algorithm may provide partial improvement under selected conditions, particularly at lower motion magnitudes, but it does not replace the need for careful patient stabilization during image acquisition and should be used cautiously when motion is unlikely.

This paper introduces a novel decomposition framework to explain heterogeneity in causal effects observed across different studies, considering both observational and randomized settings. We present a formal decomposition of between-study heterogeneity, identifying sources of variability in treatment effects across studies. The proposed methodology allows for robust estimation of causal parameters under various assumptions, addressing differences in pre-treatment covariate distributions, mediating variables, and the outcome mechanism. Our approach is validated through a simulation study and applied to data from the Moving to Opportunity (MTO) study, demonstrating its practical relevance. This work contributes to the broader understanding of causal inference in multi-study environments, with potential applications in evidence synthesis and policy-making.

Variable clinical behavior is seen in oral leukoplakia, a potentially malignant illness of the mouth that may be caused by etiological factors including cigarette smoking. Therefore, it is of interest to compare the features of oral leukoplakia lesions and epithelial dysplasia in 100 individuals, all of whom were either smokers or non-smokers, using a clinico-histopathological approach. Histopathological analysis was used to ascertain the extent of epithelial dysplasia after a thorough clinical evaluation that included the location, size, shape and duration of the lesion. Smokers were more likely to have leukoplakia on the buccal mucosa, whereas non-smokers tended to have lesions on the gingiva and tongue. Regardless of smoking status, histopathological investigation showed that moderate to severe dysplasia occurred in a considerable number of patients, even though mild dysplasia predominated in both groups. Thus, we show the need of biopsy and routine monitoring of all leukoplakic lesions, even while smoking is a major etiological factor for leukoplakia formation; dysplastic alterations and possible malignant risk may occur in smokers and non-smokers alike.

BACKGROUND:Nearly half of global pregnancies are unintended. Contraceptive use is preference-sensitive, including concerns about convenience, privacy and side effects (eg, irregular bleeding, weight gain). We conducted a multi-country study examining women's preferences for attributes of current and potential future modern hormonal contraceptives using a discrete choice experiment (DCE). METHODS:Between April and October 2022, we recruited nationally representative samples of women of reproductive age from seven countries (Burkina Faso, Nigeria, Ethiopia, Kenya, Zambia, Pakistan and the USA) using multi-stage random cluster sampling from national census enumeration areas. The DCE comprised six attributes of hormonal contraceptives: format (ie, mode of administration: injection, implant, etc), dosing interval, provider-administration versus self-administration, effect on menstruation, effect on weight and time from discontinuation until return to fertility. Mixed logit models were fitted separately by country to estimate the relative preference weights (β) for each attribute level. RESULTS:Across 20 068 participants, format was the strongest driver of preferences. Injectables were most preferred in Kenya (β=0.44, 95% CI 0.25 to 0.63), Pakistan (β=0.55, 95% CI 0.29 to 0.81), Ethiopia (β=0.64, 95% CI 0.38 to 0.90) and Zambia (β=0.39, 95% CI 0.20 to 0.58). Oral pills were most preferred in the USA (β=0.78, 95% CI 0.58 to 0.98), Burkina Faso (β=0.43, 95% CI 0.27 to 0.59) and Nigeria (β=0.55, 95% CI 0.40 to 0.70). Intrauterine devices and vaginal rings were less preferred in all countries. Menstrual bleeding changes and dosing interval were secondary drivers, with longer-acting methods modestly preferred and ongoing irregular bleeding modestly non-preferred. Avoiding weight gain was significantly preferred in several countries, most strongly in Pakistan (β=0.56, 95% CI 0.44 to 0.67) and the USA (β=0.42, 95% CI 0.31 to 0.53). CONCLUSIONS:In this large, multi-country study, reproductive-age participants expressed strong, heterogeneous preferences for contraceptive format, and in some settings, avoiding weight gain side effects. These findings can support preference-aligned contraceptive product development.

In the contemporary era of minimally invasive surgery, injectable biomaterial scaffolds have demonstrated significant potential in bone tissue engineering (BTE). Completely injectable hydrogel substratum with microscale bone graft particulates delivered through a needle-shaped orifice shifts a new paradigm for surgical interventions in clinical settings. Despite growing interest in biopolymer-based BTE systems, clinically applicable delivery platforms and a mechanistic understanding of cell-material interactions remain limited. This study developed a dual-syringe auto-mix system capable of generating an in situ cross-linking hydrogel-mineral construct composed of gelatin-hydroxyphenyl propionic acid, hyaluronic acid-tyramine, horseradish peroxidase, hydrogen peroxide, and calcium phosphate particles of varying sizes. Material distribution, rheological and mechanical properties, and swelling were characterized. Goat bone marrow-derived mesenchymal stem cells served as the basis for examining how the composite affected cell viability, morphology, proliferation, contractility, osteogenic differentiation, mineralization, and chemotactic behavior. To determine whether these biological findings were supported mechanically, an ex vivo cone-beam computed tomography model was used to evaluate volumetric stability and resistance to deformation at the graft-host interface. Cross-linking established a stable internal microarchitecture while remaining compatible with cell viability and nutrient-dependent survival. Formation of the gelatin-hyaluronan (GH) network significantly increased the storage modulus relative to gelatin (G) alone, whereas subsequent calcium phosphate incorporation (GH-CP) preserved this mechanical competence while attenuating the volumetric expansion of GH. These physical characteristics were accompanied by more organized cell morphology, enhanced osteogenic differentiation, and mineral deposition throughout a larger portion of the matrix. Heterogeneous interpenetrating gap striation (HIGS) appeared in regions of cellular aggregation and matrix deposition, and a new conceptualization of the osteogenic phenomenon, termed cling osteogenesis, has been proposed. These outcomes support an intricate relationship between early mechanical stabilization, mechanotransduction, and osteogenesis in injectable hydrogel-mineral systems.

IMPORTANCE/UNASSIGNED:Organophosphate pesticides (OPs) are established neurotoxicants; prenatal OP exposure is widespread in the US population, primarily through diet. Evidence linking prenatal OP exposure to autism spectrum disorder (ASD) and autism-related traits remains inconsistent. OBJECTIVE/UNASSIGNED:To examine the association between prenatal OP exposure and autism-related traits in childhood and to assess potential differences in the association by child sex and maternal diet. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This pooled prospective cohort study used harmonized data from mother-child pairs from 20 study sites in the Environmental influences on Child Health Outcomes (ECHO) cohort. Participants were recruited from January 1997 through December 2019, and autism-related outcomes were assessed in children ages 2 to 19 years. Data analysis was performed from April 2024 and November 2025. EXPOSURE/UNASSIGNED:Prenatal OP exposure using urinary concentrations of 3,5,6-trichloro-2-pyridinol (TCPy) and the sum of 6 dialkyl phosphate (ΣDAP) metabolites. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Parents reported autism-related traits in children using the Social Responsiveness Scale (SRS). Multivariable linear, quantile, and logistic regression models were used to estimate associations between biomarkers and SRS T scores overall and by child sex, adjusting for maternal sociodemographic and behavioral factors. We further adjusted for dietary factors in additional models and tested effect modification by maternal diet quality in exploratory analyses. RESULTS/UNASSIGNED:Among 3339 mother-child pairs examined, mean (SD) maternal age was 31 (6) years, 1665 children (49.9%) were female, and the SRS was administered at a mean (SD) age of 6.4 (3.87) years. Crude or minimally adjusted models suggested inverse associations between prenatal TCPy or ΣDAP levels and SRS scores, but these associations attenuated and lost statistical significance after full adjustment (β per doubling of TCPy concentration [ng/mL] = -0.13; 95% CI, -0.57 to 0.31; β per doubling of ΣDAP [nmol/L] = -0.42; 95% CI, -1.03 to 0.19). Results were consistent across sex-stratified models, secondary analyses using quantile and logistic regressions, various sensitivity analyses, and after adjustments for dietary confounders. There was no evidence of effect modification by diet quality. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this large, prospective cohort study among the ECHO cohort, prenatal OP exposure was not associated with autism-related traits in childhood. Given the known adverse impacts of pesticides in other contexts, further research should consider interactions with other factors, genetic susceptibility, higher exposures, or combined chemical mixtures.

BACKGROUND:Patients with breast cancer and limited English proficiency (LEP) experience barriers to care that may result in greater disease burden. We aim to evaluate breast cancer presentation and pathologic characteristics of patients with LEP compared with patients with English proficiency (EP). PATIENTS AND METHODS/METHODS:We performed an institutional review board (IRB)-approved, retrospective review of prospectively collected patient-reported data among a multilingual population evaluated within a New York City safety-net health system between 2018 and 2025. Comparative analysis and logistic regression were used. RESULTS:) compared with EP (31.2% versus 18.5%; p = 0.012) and was significantly associated with completion axillary lymph node dissection compared with EP (12.8% versus 3.6%; p = 0.0041). Patients with LEP had significantly longer time-to-therapy intervals from biopsy to first therapy compared with EP (52 versus 49 days; p = 0.041). On multivariate analysis, both LEP and delays to first therapy were significantly associated with axillary nodal metastasis. CONCLUSIONS:Patients with breast cancer and LEP were significantly more likely to have axillary nodal metastasis compared with patients with EP. Increased axillary nodal metastasis in this population may, in part, be due to lack of screening and delays to breast cancer treatment.

OBJECTIVE:Epidemiologic estimates for age of systemic lupus erythematosus (SLE) diagnosis are limited, particularly for men and racial and ethnic subpopulations in the United States. Leveraging the Centers for Disease Control and Prevention (CDC) National Lupus Registry network of population-based SLE registries, meta-analyses were performed estimating age-specific incidence of SLE by sex, race, and ethnicity. METHODS:The CDC network of SLE registries includes five state-based registries, plus a sixth Indian Health Service registry. Incidence periods spanned calendar years 2002-2018. Registries provided age-specific incidence of SLE, fulfilling the American College of Rheumatology (ACR) SLE classification criteria, per 100,000 person-years, stratified by sex, race, and ethnicity for the meta-analyses. RESULTS:Incidence rates among women were highest for those aged 30-39 (12.7, 95%CI: 9.5-16.8), while rates among men were highest for those aged 60-69 (2.1, 95%CI: 1.3-3.4). Black women aged 20-39 had the highest SLE incidence rates (23.6, 95%CI: 20.7-26.8). Among women diagnosed with SLE before age 20, incidence was highest among Asian (6.5, 95%CI: 2.8-15.2) individuals. Among women diagnosed with SLE after age 60, incidence was highest among American Indian/Alaska Native (9.4, 95%CI: 3.4-15.4) individuals. Weighted percentages show 10.0% of those with SLE were diagnosed before age 20, while 15.1% were diagnosed after age 60. The largest proportion of individuals with SLE, 22.1%, were diagnosed between 30-39 years. CONCLUSIONS:This study provides comprehensive sex- and race-specific estimates of age at SLE diagnosis. The substantial later in life SLE incidence among men and disease burden in pediatric and older populations should raise awareness in considering SLE in the differential diagnosis in previously underrecognized groups.

Brain arteriovenous malformations (bAVMs) are vascular anomalies characterized by direct arterial to venous shunting without an intervening capillary bed, predisposing patients to intracranial hemorrhage and subsequent neurological morbidity and mortality. Evidence suggests that development and evolution of bAVMs are influenced by ongoing molecular and inflammatory processes. Chronic inflammation within the AVM microenvironment has emerged as a key driver of dysregulated angiogenesis, vascular instability, and hemorrhage risk. The objective of this review is to examine the molecular and cellular mechanisms through which inflammatory pathways contribute to AVM development, rupture, and treatment response. A comprehensive search of the Web of Science database was performed from database inception through September 2024. Following removal of duplicate articles, titles and abstracts were screened and full texts were reviewed for relevance. Experimental, translational, and clinical studies investigating inflammatory signaling pathways, immune cell involvement, molecular biomarkers, and therapeutic implications in AVMs were included. A total of 342 studies were included in the final review. Current evidence demonstrates that inflammatory signaling plays a central role in AVM pathobiology. Pro-inflammatory cytokines including interleukin-1β, interleukin-6, and tumor necrosis factor-α promote endothelial activation, leukocyte recruitment, and abnormal angiogenesis within the AVM nidus. Dysregulation of signaling pathways such as VEGF, TGF-β/BMP, NF-κB, Notch, and KRAS/MAPK-ERK contributes to extracellular matrix degradation, vascular remodeling, and vessel fragility. Infiltration by macrophages and neutrophils further amplifies inflammatory cascades through the release of matrix metalloproteinases and reactive oxygen species, increasing rupture risk. In addition to its pathogenic role, inflammation also contributes to success of AVM obliteration using stereotactic radiosurgery through radiation-induced endothelial injury, immune cell recruitment, and progressive vascular fibrosis. Inflammation is a fundamental component of AVM formation, progression, and therapeutic response. Targeting these pathways, in combination with surgical or radiosurgical interventions, may offer new opportunities for improving AVM management and improving approaches in cerebrovascular neurosurgery.