Legacy Health

Abstract Background: Latin American (LA) women are more likely to be diagnosed with aggressive early-stage breast cancer (EBC) compared to Non-Hispanic White (NHW) women, yet population-specific tumor biology remains underexplored. Previously, we reported elevated immune gene expression in BluePrint® (BP) Luminal B tumors in LA patients (pts) with EBC and obesity compared to Black and NHW cohorts. Here, we present updated clinical comparisons between LA, NHW and Black pts with EBC and whole transcriptome analysis (WTA) between BP Luminal B and Basal BC in pts with obesity. Methods: Clinical and WT data were analyzed from 15,577 EBC pts self-identified as LA, Black, or NHW enrolled in FLEX (NCT03053193), a prospective observational study with MammaPrint® risk of recurrence and BP molecular subtyping assays, and WT profiles. ImPrint, 53-gene immune signature, results (+/-) were generated for pts with hormone receptor positive (HR+) EBC. Chi-square and t-tests were conducted on clinical groups using arsenal R package. For WT comparisons, 215 obese LA pts with BP Luminal B and 77 with BP Basal EBC were matched to corresponding NHW and Black pts by age, T and N status. Differentially expressed genes (DEGs) were evaluated using limma, and pathway enrichment was performed using gene set enrichment analysis with Hallmark gene sets. Significant results were reported with adjusted p < 0.05. Results: Compared to Black and NHW pts, LA pts were younger and more often premenopausal (Table). Both LA and Black pts had statistically significantly higher rates of obesity compared to NHW pts. Significantly higher rates of MP High Risk 2, BP Basal and ImPrint+ tumors were observed in LA and Black pts vs NHW. WT comparisons among the obese subpopulations revealed that metabolic pathways, including adipogenesis, angiogenesis, epithelial-mesenchymal transition, and oxidative phosphorylation were significantly downregulated in EBC in LA pts vs NHW and Black cohorts. Conversely, immune-related pathways such as allograft rejection and interferon gamma response were enriched among LA pts with Basal cancers compared to NHW and Black groups. These coordinated pathway alterations suggest unique metabolic and immune profiles in LA EBC subtypes with a median absolute fold change of 1.3 among DEGs. Conclusion: The data suggest that signals from metabolic pathway alterations from modest immune-related gene upregulation may contribute to more aggressive tumor behavior in obese LA pts with EBC. Clinical and transcriptomic analyses demonstrated differences in Luminal B and Basal EBC biology among self-identified LA pts compared to NHW and Black cohorts, consistent with prior research. With further research, these findings may offer treatment targets which may enhance outcomes and reflect the importance of including racially and ethnically diverse pts in clinical trials to characterize population-specific differences in EBC outcomes. Citation Format: M. Mazo Canola, A. Santillan, J. Alberty-Oller, E. Dias, V. Kaklamani, A. Elkhanany, K. Hoskins, M. Habibi, R. Hampton, J. L. Barone, N. M. Johnson, N. Gordon, N. Sookhan, T. Bah, P. John, E. Aponte, S. Diab, V. Klimberg, N. Stivers, C. Page, S. Uygun, W. Audeh, J. O'Shaughnessy. Distinct Immune and Metabolic profiles in Latin American breast cancer patients with obesity enrolled in FLEX [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-09-09.

PurposeThe purpose of this study was to test whether loss of functional microvascular (MV) or large vessel (LV) volume exceeds loss of retinal nerve fiber layer (RNFL) and optic nerve head (ONH) rim tissue volume in a nonhuman primate (NHP) model of experimental glaucoma (EG).MethodsRhesus macaques (N = 28) were imaged by optical coherence tomography (OCT) and OCT angiography (OCTA) during baseline and after induction of unilateral EG. ONH and RNFL tissue volume were compared to MV and LV vascular volume (the same voxels weighted by their OCTA signal). Linear regression was used to compare rates of change between EG and fellow control eyes for each parameter after normalization to their pre-EG baseline average values, and mixed-effects models were used to compare baseline average values to those at the onset of significant change of ONH minimum rim width, RNFL thickness, and the final time point.ResultsONH rim volume, the LV proportion of rim volume, and RNFL volume significantly declined in EG eyes compared to control eyes (P < 0.0001). The MV proportion of non-vascular rim tissue remained constant (P = 0.053), but the MV proportion of non-vascular RNFL significantly declined in EG eyes only (P < 0.0001). Cross-sectional analysis demonstrated significant reductions in MV proportion of the RNFL but not the ONH rim at the onset of structural change in EG eyes.ConclusionsProgressive loss of functional microvasculature (adequately perfused capillaries) within the RNFL, occurring early and in excess of the neuroglial tissue it supplies, supports future investigation of therapeutic strategies that target vascular function.

Human T-lymphotropic virus (HTLV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) each have the propensity for infection as well as the development of latency in humans. As many ocular tissue report forms provided by Eye Bank Association of America (EBAA) member eye banks list serological testing results for these viruses, the EBAA Policy and Position Review Subcommittee (PPRS) sought to investigate and clarify the implications of these results. Current EBAA policies regarding HTLV, CMV, and EBV were reviewed. Additionally, a search of articles written in or translated into the English language regarding the aforementioned viruses with a focus on ocular infection and ocular tissue transplantation was performed on PubMed. Current EBAA policies indicate that ocular tissues from donors with seropositivity to HTLV, CMV, and/or EBV can be used for transplantation. The risk of transmission of HTLV was felt to be the most consequential, given its low seroprevalence and its association with adult T-cell lymphoma/leukemia. However, as corneal and limbal tissue are not leukocyte-rich, the risk of transmitting HTLV is low. Despite reports of the isolation of all 3 viruses in ocular tissues, a literature review did not reveal any reported cases of viral transmission through ocular tissue transplantation. Ocular tissues from donors with seropositivity to HTLV, CMV, and/or EBV can be used for transplantation per current EBAA guidelines. Despite the potential for ocular infection by these viruses, there are no reported cases of viral transmission from ocular tissue transplantation, affirming the validity of the current EBAA guidelines.

Numerous observational studies are available to asymptomatic individuals at risk to carry or known carriers of pathogenic variations associated with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS-FTD) spectrum disorders. Little is known about such individuals' motivations for participation or the impact on their emotional well-being. Asymptomatic at-risk adults, with or without genetic status known, were recruited through social media advocacy groups and by National Society of Genetic Counselors ALS-FTD special interest group members. Interviews were conducted through secure videoconferencing. Two coders independently analyzed interview transcripts, followed by thematic content analysis. Twelve participants (9 status-aware and 3 status-unaware) were interviewed, representing experience with 11 observational studies. Some motivations for participation aligned with previous literature, including altruism, health focus, and intellectual interest. Motivations unique to this population stemmed from the hereditary nature of the disease, including fear of future disease onset and the desire to establish a relationship with a specialized clinical care team, reflecting individual, familial, and societal factors. Benefits of participation included meeting these motivational goals, social connection and support, psychological well-being, and practical benefits. Challenges to participation fell into research-related (e.g., struggles with the observational nature of research), disease-related (e.g., anxiety about disease risk), and logistical (e.g., travel and study procedures) categories. Compared with status-unaware participants, status-aware participants more frequently cited individual motivators for research participation and encountered more research-related challenges when their participation did not align with their anticipated personal health benefits. Interviewees found relationships with providers through research to be rewarding but noted confusion between research and clinical care as a significant challenge. Participation in observational research helps address unmet emotional and medical needs for asymptomatic individuals who are at risk of ALS-FTD spectrum disorders. However, some of these needs are beyond the scope of research, highlighting the need for new models of clinical care for at-risk individuals.

Food insecurity remains a critical challenge for many farming communities in Madagascar, underscoring the need for sustainable strategies to improve crop yields. Black soldier fly frass (BSFF) is an emerging organic fertilizer, and composting may enhance its agronomic effectiveness. This study evaluated the effects of composted BSFF (CBSFF), fresh BSFF (FBSFF), cattle manure (CM), and a no-fertilizer control on maize (Zea mays L.) germination, height growth, grain yield, and agronomic efficiency of nitrogen (AEN) in southeastern Madagascar’s acidic sandy clay soils. Fertilizers were applied at 43 kg N/ha, reflecting actual farmer practices in the region. This rate represents one-third of the recommendation by FOFIFA (Madagascar’s national agricultural research institute). Farmers in this region rarely apply the full recommended dose due to limited access, high input costs, and low return on investment, factors that contribute to persistent yield gaps even where recommended rates are followed. Maize treated with FBSFF had significantly lower germination rate than all other treatments. In contrast, there were no statistically significant differences in final plant height or grain yield among CBSFF and CM. However, CBSFF-treated plants were on average 6 and 13% taller than those receiving CM and FBSFF, respectively, and produced 38% more grain than CM. All fertilizer treatments yielded significantly more grain than the unfertilized control, which produced no harvestable maize. CBSFF also showed the highest agronomic efficiency of nitrogen (AEN: 46 kg grain/kg N), although this difference was not statistically significant. These results suggest that BSFF, particularly in composted form, can supply sufficient nitrogen to support maize growth. Overall trends point to composted BSFF as the most agronomically effective option. Timing of application should depend on the frass form: composted BSFF is better suited for pre-planting use, while fresh BSFF may be more appropriate after germination. Even at sub-recommended doses, BSFF has the potential to enhance maize productivity and contribute to local food security. Further research across diverse agroecological zones, including trials comparing BSFF with the full recommended fertilizer dose, and economic analyses incorporating frass cost, labor, and transport are recommended to identify optimal application strategies and support widespread adoption by smallholder farmers.

Lithology, alteration and Au mineralisation characteristics of the McPhillamys gold deposit in central NSW have proved difficult to interpret owing to structural overprinting. Previous models for the genesis of Au mineralisation include syngenetic (late Silurian Au-rich volcanic massive sulfide; VMS) or epigenetic (Carboniferous orogenic Au). We combine extensive new HyLogger spectral data (SWIR and TIR), petrographic analysis, geochronology and isotopic data to determine the alteration/mineralisation paragenesis, alteration zonation and effects of lithological control on mineralisation by using both downhole and broad-scale 3D mineralogical characterisation. The mineralisation at McPhillamys is stratabound within a coarse andesitic/dacitic volcaniclastic package. Alteration involved the development of an initial potassic core (microcline (ex-adularia)–quartz–pyrite) associated with the mineralised volcaniclastic package at the centre of the orebody and extending into the overlying non-mineralised andesitic volcanic/volcaniclastic package north and south of the mineralised zone. Propylitic-style alteration (albite–pyrite–chlorite–carbonate ± epidote) forms an outer shell to the mineralisation, except at the northern and southern extents of the mineralised trend. White mica, chlorite, feldspar and carbonate all display consistent and mappable compositional variation between mineralised and non-mineralised sequences. It is difficult to decipher the early history of the deposit and geochronology (U–Pb and Ar–Ar), presented in this study, is unable to distinguish if mineralisation and alteration developed just after deposition of the host sequences during the latest Silurian (ca 423 Ma) with extensive recrystallisation during both Tabberabberan (ca 390 Ma) and Kanimblan (ca 350 Ma) orogenic events, or if mineralisation developed solely during the Tabberabberan Orogeny (ca 390 Ma) with extensive recrystallisation during the Kanimblan Orogeny (ca 350 Ma). We suggest the mineralogy, broad spatial distribution (700 m long, 250 m width, and up to 700 m depth) and paragenesis of alteration and mineralisation at McPhillamys are consistent with a deformed late Silurian lithologically controlled low-sulfidation epithermal, or potentially a shallow water (subsea-floor) Au-rich VMS system.

Early detection of retinal diseases is vital for preventing irreversible vision loss. Unlike traditional machine learning (ML) approaches, this study introduces OCT-Trans, an innovative transformer-based backbone that significantly enhances the performance of ML classifiers in analyzing Optical Coherence Tomography (OCT) images. OCT-Trans demonstrates superior capability in distinguishing between normal retinas, Diabetic Retinopathy (DR), and Age-related Macular Degeneration (AMD). Our approach integrates multimodal features from OCT images acquired using two distinct imaging devices, thereby enhancing both generalizability and reproducibility. First, using an atlas-based method, we automatically segment OCT images into eleven retinal layers, extracting clinically relevant features that mimic ophthalmologists' diagnostics to get a final diagnosis. By examining each layer, our approach identifies critical indicators of DR and AMD such as the percentage of subretinal and sub-RPE fluid accumulation, abnormal tissue presence, and missing OCT layers. Additionally, we enrich our feature set by analyzing morphological and texture characteristics like estimating layer curvature, thickness, and reflectivity. All extracted features are integrated and fed into OCT-Trans, which utilizes a transformer architecture tailored for complex multimodal data. This innovative framework generates contextual embeddings that are subsequently classified using a multilayer perceptron. In a comprehensive evaluation involving 541 patients, OCT-Trans achieved remarkable results, with an accuracy of 96.68%, a Cohen's Kappa of 94.07%, and an F1 Score of 96.12%, significantly outperforming current state-of-the-art methods. Statistical analysis using Wilcoxon signed-rank tests confirmed significant enhancements <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$(p &lt; 0.05)$</tex> over baseline architectures, including CaiT-T <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$(p=0.001)$</tex>, ViT-B <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$(p=0.001)$</tex>, and ConvNeXt-T <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$(p=0.041)$</tex>.

Abstract Introduction Inhalation injury is present in 10-20% of all burn admissions. Clinical diagnosis, triage, and prognostication remains difficult and with poor accuracy given the heterogeneity of injury patterns. In the setting of a mass casualty incident, the ability to accurately diagnosis inhalation injury is critical to triage and resource allocation for patients with inhalation injury. As such we sought to test the feasibility of using handheld ultrasound to detect smoke inhalation lung injury (SILI) in patients with smoke inhalation. Methods An observational survey study was conducted. Patients with a history of smoke inhalation were recruited from 6 ABA verified burn centers. The patients underwent serial lung ultrasound scanning, based on a 14-zone scan protocol, using a handheld, tablet-based, commercially available ultrasound device with a curvilinear (C5-2) transducer. Ultrasound videos were centrally stored, and blinded image analysis was performed by 2-3 reviewers from a panel of 11 physicians with expertise in lung ultrasound. Final clinical determination of clinical SILI negative, simple, or complex patient categorization was performed in a blinded fashion with chart review completed by three of the study PIs. Results 130 subjects were enrolled. 84 subjects whose first LUS scan was performed within 48 hours of smoke inhalation were included for this analysis. 65/84 were clinically identified as positive for SILI with the remaining 19/84 subjects negative for SILI. 91% of subjects with smoke inhalation had at least one abnormal lung feature. Of the 84 subjects, the mean score of pleural line abnormalities was greater in SILI+ vs. SILI- subjects (p = 0.02). When subjects with &amp;gt; 10% TBSA were excluded, the significance of pleural line abnormalities between SILI+ vs. SILI- subjects improved from p = 0.02 to p = 0.002. Within the SILI+ subjects, Mean Pleural abnormalities between clinically simple or complex SILI determinations were 0.77 and 0.56 respectively (P = 0.04). Between groups patients’ sex, age, body mass index, smoking history and admission carboxyhemoglobin were not statistically significant. Conclusions The detection of SILI induced lung injury with bedside ultrasound is feasible. It can detect abnormal lung features, and the presence of lung features correlates with the clinical diagnosis of SILI. Applicability of Research to Practice Results from this survey study demonstrates robust Lung Ultrasound Changes present in almost all patients with SILI. These findings also demonstrate the ease of use and potential for use for triage of smoke inhalation patients in mass casualty events, forest fires, or fires in municipalities. Future prospective studies are needed to define if early LUS detection of SILI can improve triage of patients. Funding for the Study DoD - 75A50120C000097