A seasonal study on the microbiomes of Diploid vs. Triploid eastern oysters and their denitrification potential.

Oyster reefs are hotspots of denitrification mediated removal of dissolved nitrogen (N), however, information on their denitrifier microbiota is scarce. Furthermore, in oyster aquaculture, triploids are often preferred over diploids, yet again, microbiome differences between oyster ploidies are unknown. To address these knowledge gaps, farmed diploid and triploid oysters were collected over an annual growth cycle and analyzed using shotgun metagenomics and quantitative microbial elemental cycling (QMEC) techniques. Regardless of ploidy, Psychrobacter genus was abundant, with positive correlations found for genes of central metabolism, DNA metabolism, and carbohydrate metabolism. MAGs (metagenome-assembled genomes) yielded multiple Psychrobacter genomes harboring norB, narH, narI, and nirK denitrification genes, indicating their functional relevance within the eastern oysters. QMEC analysis indicated the predominance of carbon (C) and nitrogen (N) cycling genes, with no discernable patterns between ploidies. Among the N-cycling genes, the nosZII clade was overrepresented, suggesting its role in the eastern oyster's N removal processes.

Housing Characteristics and Hospital Admissions due to Falls on Stairs: A National Birth Cohort Study.

OBJECTIVE: To assess associations between housing characteristics and risk of hospital admissions related to falls on/from stairs in children, to help inform prevention measures. STUDY DESIGN: An existing dataset of birth records linked to hospital admissions up to age 5 for a cohort of 3,925,737 children born in England between 2008 and 2014, was linked to postcode-level housing data from Energy Performance Certificates. Association between housing construction age, tenure (eg, owner occupied), and built form and risk of stair-fall-related hospital admissions was estimated using Poisson regression. We stratified by age (<1 and 1-4 years), and adjusted for geographic region, Index of Multiple Deprivation, and maternal age. RESULTS: Incidence was higher in both age strata for children in neighborhoods with homes built before 1900 compared with homes built in 2003 or later (incidence rate ratio [IRR] 1.40, 95% confidence interval [CI] 1.10-1.77 [age <1 year], 1.20, 95% CI 1.05-1.36 [age 1-4 years]). For ages 1-4 years, incidence was higher for those in neighborhoods with housing built 1900-1929, compared with 2003 or later (IRR 1.26, 95% CI 1.13-1.41), or with predominantly social-rented homes compared with owner occupied (IRR 1.21, 95% CI 1.13-1.29). Neighborhoods with predominantly houses compared with flats had higher incidence (IRR 1.24, 95% CI 1.08-1.42 [<1 year] and IRR 1.16, 95% CI 1.08-1.25 [1-4 years]). CONCLUSION: Changes in building regulations may explain reduced fall incidence in newer homes compared with older homes. Fall prevention campaigns should consider targeting neighborhoods with older or social-rented housing. Future analyses would benefit from data linkage to individual homes, as opposed to local area level.

Identification of miRNAs and Their Target Genes Associated with Sunitinib Resistance in Clear Cell Renal Cell Carcinoma Patients.

Sunitinib has greatly improved the survival of clear cell renal cell carcinoma (ccRCC) patients in recent years. However, 20-30% of treated patients do not respond. To identify miRNAs and genes associated with a response, comparisons were made between biopsies from responder and non-responder ccRCC patients. Using integrated transcriptomic analyses, we identified 37 miRNAs and 60 respective target genes, which were significantly associated with the NF-kappa B, PI3K-Akt and MAPK pathways. We validated expression of the miRNAs (miR-223, miR-155, miR-200b, miR-130b) and target genes (FLT1, PRDM1 and SAV1) in 35 ccRCC patients. High levels of miR-223 and low levels of FLT1, SAV1 and PRDM1 were associated with worse overall survival (OS), and combined miR-223 + SAV1 levels distinguished responders from non-responders (AUC = 0.92). Using immunohistochemical staining of 170 ccRCC patients, VEGFR1 (FLT1) expression was associated with treatment response, histological grade and RECIST (Response Evaluation Criteria in Solid Tumors) score, whereas SAV1 and BLIMP1 (PRDM1) were associated with metachronous metastatic disease. Using in situ hybridisation (ISH) to detect miR-155 we observed higher tumoural cell expression in non-responders, and non-tumoural cell expression with increased histological grade. In summary, our preliminary analysis using integrated miRNA-target gene analyses identified several novel biomarkers in ccRCC patients that surely warrant further investigation.

Simulating the Motion Underlying the Mechanism of Thioredoxin Reductase.

Thioredoxin reductase (TrxR) is an essential antioxidant in most cells; it reduces thioredoxin (Trx) and several more substrates, utilizing NADPH. However, the enzyme's internal active site is too small to accommodate the Trx substrate. Thus, TrxR evolved a disulfide shuttle that can carry reducing equivalents from the active site to the docking site of thioredoxin on the enzyme surface. Yet, in all available atomic structures of TrxR, access to the active site by the shuttle is sterically blocked. We find with computational dynamics that thermal motion at 37 °C allows the oxidized shuttle x to transiently access the active site. Once the shuttle is reduced, it becomes polar. Again, with molecular dynamics, we show that the polar shuttle will move outward toward the solution interface, whereas the oxidized, neutral shuttle will not. This work provides physical evidence for crucial steps in the enzyme mechanism that thus far were just conjectures. The total shuttle motion, from the active site toward the surface, is over 20 Å. TrxR may thus also be termed a molecular machine.

High-dimensional mapping of human CEACAM1 expression on immune cells and association with melanoma drug resistance.

BACKGROUND: Human carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an inhibitory cell surface protein that functions through homophilic and heterophilic ligand binding. Its expression on immune cells in human tumors is poorly understood. METHODS: An antibody that distinguishes human CEACAM1 from other highly related CEACAM family members was labeled with 159Tb and inserted into a panel of antibodies that included specificity for programmed cell death protein 1 (PD1) and PD-L1, which are targets of immunotherapy, to gain a data-driven immune cell atlas using cytometry by time-of-flight (CyTOF). A detailed inventory of CEACAM1, PD1, and PD-L1 expression on immune cells in metastatic lesions to lymph node or soft tissues and peripheral blood samples from patients with treatment-naive and -resistant melanoma as well as peripheral blood samples from healthy controls was performed. RESULTS: CEACAM1 is absent or at low levels on healthy circulating immune cells but is increased on immune cells in peripheral blood and tumors of melanoma patients. The majority of circulating PD1-positive NK cells, innate T cells, B cells, monocytic cells, dendritic cells, and CD4+ T cells in the peripheral circulation of treatment-resistant disease co-express CEACAM1 and are demonstrable as discrete populations. CEACAM1 is present on distinct types of cells that are unique to the tumor microenvironment and exhibit expression levels that are highest in treatment resistance; this includes tumor-infiltrating CD8+ T cells. CONCLUSIONS: To the best of our knowledge, this work represents the first comprehensive atlas of CEACAM1 expression on immune cells in a human tumor and reveals an important correlation with treatment-resistant disease. These studies suggest that agents targeting CEACAM1 may represent appropriate partners for PD1-related pathway therapies.

Some proteins, such as programmed cell death protein 1 (PD1), can stop the immune system from attacking cancer cells, allowing cancers to grow. Therapies targeting these proteins can be highly effective, but tumors can become resistant. It is important to identify factors involved in this resistance to develop improved cancer therapies. Human carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is a protein that inhibits an immune response and its levels have been associated with poor patient outcomes. We applied a method that allows for the detection of proteins on a single cell to uncover CEACAM1 patterns in melanoma. We found that increased CEACAM1 expression levels on multiple different immune cell types was associated with tumors that were resistant to therapy. These findings may help us to understand the role of CEACAM1 in cancer and to develop better cancer therapies.

Efficient enrichment of free target sequences in an integrated microfluidic device for point-of-care detection systems.

Nucleic acid biomarker detection has great importance in the diagnosis of disease, the monitoring of disease progression and the classification of patients according to treatment decision making. Nucleic acid biomarkers found in the blood of patients have generated a lot of interest due to the possibility of being detected non-invasively which makes them ideal for monitoring and screening tests and particularly amenable to point-of-care (POC) or self-testing. A major challenge to POC molecular diagnostics is the need to enrich the target to optimise detection. In this work, we describe a microfabricated device for the enrichment of short dsDNA target sequences, which is especially valuable for potential detection methods, as it improves the probability of effectively detecting the target in downstream analyses. The device integrated a heating element and a temperature sensor with a microfluidic chamber to carry out the denaturation of the dsDNA combined with blocking-probes to enrich the target. This procedure was validated by fluorescence resonance energy transfer (FRET) technique, labelling DNA with a fluorophore and a quencher. As proof of concept, a 23-mer long dsDNA sequence corresponding to the L858R mutation of the EGFR gene was used. The qualitative results obtained determined that the most optimal blocking rate was obtained with the incorporation of 11/12-mer blocking-probes at a total concentration of 6 µM. This device is a powerful DNA preparation tool, which is an indispensable initial step for subsequent detection of sequences via nucleic acid hybridisation methods.

Widespread correction of brain pathology in feline alpha-mannosidosis by dose escalation of intracisternal AAV vector injection.

Alpha-mannosidosis is caused by a genetic deficiency of lysosomal alpha-mannosidase, leading to the widespread presence of storage lesions in the brain and other tissues. Enzyme replacement therapy is available but is not approved for treating the CNS, since the enzyme does not penetrate the blood-brain barrier. However, intellectual disability is a major manifestation of the disease; thus, a complimentary treatment is needed. While enzyme replacement therapy into the brain is technically feasible, it requires ports and frequent administration over time that are difficult to manage medically. Infusion of adeno-associated viral vectors into the cerebrospinal fluid is an attractive route for broadly targeting brain cells. We demonstrate here the widespread post-symptomatic correction of the globally distributed storage lesions by infusion of a high dose of AAV1-feline alpha-mannosidase (fMANB) into the CSF via the cisterna magna in the gyrencephalic alpha-mannosidosis cat brain. Significant improvements in clinical parameters occurred, and widespread global correction was documented pre-mortem by non-invasive magnetic resonance imaging. Postmortem analysis demonstrated high levels of MANB activity and reversal of lysosomal storage lesions throughout the brain. Thus, CSF treatment by adeno-associated viral vector gene therapy appears to be a suitable complement to systemic enzyme replacement therapy to potentially treat the whole patient.

Disparities based on demographic features in the intensity and treatment of chronic pain in US patients with spinal cord injury.

OBJECTIVE: Informed by Minority Stress Theory, to investigate disparities in pain intensity, interference, and care in patients with spinal cord injuries (SCI) based on demographic features. DESIGN: Cross-sectional survey SETTING: Outpatient SCI clinics in two academic medical centers in the northwestern US. PARTICIPANTS: Sample of 242 SCI clinic patients who endorsed SCI-related pain, were 18-years-of-age or older, English-fluent, not diagnosed with bipolar or psychotic disorders, and able to make their own medical decisions. Participants were 74.8% male, an average of 48.5 years (range 18.1-89.8 years), 76.2% White, 31.9% privately insured, and 64.7% making less than $50,000 per year. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Exploratory analyses of screening data from a randomized controlled trial for pain treatment. Primary outcomes included pain intensity, pain interference, and the patient report of recommended pain treatments by a medical provider, tried by the patient, or that the patient would be willing to try. RESULTS: More treatments recommended was associated with younger age (ρ=-0.14, 95%CI: -0.01 to -0.27, p=.03) and private insurance ((ρ=-0.15, 95%CI: 0.02 to 0.27, p=.03), while more treatments tried was associated with private insurance alone (ρ=0.20, 95%CI: 0.07 to 0.32, p=.003). Number of treatments willing to be tried was associated with lower income (ρ=-0.15, 95%CI: -0.02 to -0.28, p=.03). SCI Patients of Color (POC) reported higher pain intensity (Cohen's D = 0.41, 95%CI:0.11-0.71) and greater odds of receiving psychotherapy for pain (OR: 7.12, 95%CI: 1.25-40.46) than their White peers. CONCLUSION(S): These exploratory findings indicate differences in SCI-related pain intensity based on identifying as POC, and differences in SCI-related pain treatment modalities based on identifying as POC, age, insurance type, and income. Further work exploring differences in SCI-related pain care based on patient social identities is warranted.

Atomic-scale origin of the enantiospecific decomposition of tartaric acid on chiral copper surfaces.

The origin of the enantiospecific decomposition of L- and D-tartaric acid on chiral Cu surfaces is elucidated on a structure-spread domed Cu(110) crystal by spatially resolved XPS and atomic-scale STM imaging. Extensive enantiospecific surface restructuring leads to the formation of surfaces vicinal to Cu(14,17,2) which are responsible for the enantiospecificity.

Advancing health equity in the aftermath of COVID-19: Confronting intensifying racial disparities.

The COVID-19 pandemic has exposed and exacerbated the persistent racial and ethnic health disparities in the United States. The pandemic has also had profound spillover effects on other aspects of health and wellbeing, such as mental health, chronic diseases, education, and income, for marginalized groups. In this article, we provide a thorough analysis of the pandemic's impact on racial and ethnic health disproportionalities, highlighting the multifaceted and interrelated factors that contribute to these inequities. We also argue for a renewed focus on health equity in healthcare policy and practice, emphasizing the need for systemic changes that address both the immediate and long-term consequences of these imbalances. We propose a framework for achieving health equity that involves creating equitable systems, care, and outcomes for all individuals, regardless of their race or ethnicity.

Axonal injury, sleep disturbances, and memory following traumatic brain injury.

OBJECTIVES: Traumatic brain injury (TBI) is associated with sleep deficits, but it is not clear why some report sleep disturbances and others do not. The objective of this study was to assess the associations between axonal injury, sleep, and memory in chronic and acute TBI. METHODS: Data were acquired from two independent datasets which included 156 older adult veterans (69.8 years) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with prior moderate-to-severe TBIs and 90 (69.2 years) controls and 374 (39.6 years) from Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) with a recent mild TBI (mTBI) and 87 controls (39.6 years), all who completed an MRI, memory assessment, and sleep questionnaire. RESULTS: Older adults with a prior TBI had a significant association between axonal injury and sleep disturbances [ß = 9.52, 95% CI (4.1, 14.9), p = 0.01]. Axonal injury predicted changes in memory over 1-year in TBI [ß = -8.72, 95% CI (-18, -2.7), p = 0.03]. We externally validated those findings in TRACK-TBI where axonal injury within 2 weeks after mTBI was significantly associated with higher sleep disturbances in the TBI group at 2 weeks[ß = -7.2, 95% CI (-14, -0.50), p = 0.04], 6 months [ß = -16, 95% CI (-24, -7.6), p ≤ 0.01], and 12 months post-injury [ß = -11, 95% CI (-19, -0.85), p = 0.03]. These associations were not significant in controls. INTERPRETATIONS: Axonal injury, specifically to the left anterior internal capsule is robustly associated with sleep disturbances in multiple TBI populations. Early assessment of axonal injury following mTBI could identify those at risk for persistent sleep disturbances following injury.

Electronic Vapor Products: Alarming Trends in United States Adolescents.

Background: The use of electronic vapor products (EVPs) increases the risks of nicotine addiction, drug-seeking behavior, mood disorders, and avoidable premature morbidities and mortality. We explored temporal trends in EVP use among US adolescents. Methods: We used data from the Youth Risk Behavior Survey for school grades 9 through 12 from 2015 (earliest available data) to 2021 (the most recently available data) from the US Centers for Disease Control and Prevention (n=57,006). Results: Daily use of EVPs increased from 2.0% in 2015 to 7.2% in 2019, a greater than 3.5-fold increase. Although the percentage decreased to 5.0% in 2021, it was still a >2.5-fold increase since 2015. In 2015, the percentage of EVP use was significantly higher in boys (2.8%) than girls (1.1%). By 2021, the percentage of EVP use was higher in girls (5.6%) than boys (4.5%), a 1.24-fold increase. In addition, the percentage of EVP use in 2021 was higher in White youth (6.5%) vs Black (3.1%), Asian (1.2%), and Hispanic/Latino (3.4%) youth compared to 2015, but White and Black adolescents had the highest increases of approximately 3.0-fold between 2015 and 2021. Adolescents in grade 12 had the highest percentages of EVP use at all periods. Conclusion: These data show alarming statistically significant and clinically important increases in EVP use in US adolescents in school grades 9 through 12. The magnitude of the increases may have been blunted by coronavirus disease 2019, a hypothesis that requires direct testing in analytic studies. These trends create clinical and public health challenges that require targeted interventions such as mass media campaigns and peer interventions to combat the influences of social norms that promote the adoption of risky health behaviors during adolescence.

Predictors of Physical Activity One Year After Moderate to Severe Traumatic Brain Injury.

OBJECTIVE: To identify predictors of moderate to vigorous physical activity (MVPA) at 12-months post-moderate-severe traumatic brain injury (TBI). Setting: Four inpatient rehabilitation centers. PARTICIPANTS: Individuals enrolled in the TBI Model Systems with moderate to severe TBI, admitted to inpatient rehabilitation, and able to ambulate without physical assistance from another person. DESIGN: Prospective longitudinal cohort study. MVPA was measured by having participants wear an ActiGraph GT3X on their wrist for 7 consecutive days. MAIN ANALYSES: We used multivariate regression to predict minutes per week of MVPA at 12 months after TBI. Three classes of predictors were entered hierarchically-demographic and clinical variables (age, sex, body mass index, education, TBI severity, neighborhood walkability score, and self-reported preinjury physical activity [PA] level), baseline TBI-related comorbid conditions (eg, measures of sleep, pain, mood, fatigue, and cognition), and intention to exercise and exercise self-efficacy assessed approximately 1 week after discharge from inpatient rehabilitation. RESULTS: 180 participants (ages 17.7-90.3 years) were enrolled, and 102 provided at least 5 days of valid accelerometer data at 12 months. At 12 months, participants recorded an average of 703 (587) minutes per week of MVPA. In univariate and multivariate analyses, age was the only significant predictor of 12-month MVPA (r = -0.52). A sharp decline in MVPA was observed in the tertile of participants who were over the age of 61. CONCLUSIONS: Older adults with TBI are at elevated risk of being physically inactive. Assuming PA may enhance health after TBI, older adults are a logical target for prevention or early intervention studies. Studies with longer outcomes are needed to understand the trajectory of PA levels after TBI.

Decoding Early Psychoses: Unraveling Stable Microstructural Features Associated with Psychopathology Across Independent Cohorts.

BACKGROUND: Early Psychosis patients (EP, within 3 years after psychosis onset) show significant variability, making outcome predictions challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, limiting the development of early interventions. METHODS: A data-driven approach, Partial Least Squares (PLS) correlation, was used across two independent datasets to examine multivariate relationships between white matter (WM) properties and symptomatology, to identify stable and generalizable signatures in EP. The primary cohort included EP patients from the Human Connectome Project-Early Psychosis (n=124). The replication cohort included EP patients from the Feinstein Institute for Medical Research (n=78). Both samples included individuals with schizophrenia, schizoaffective disorder, and psychotic mood disorders. RESULTS: In both cohorts, a significant latent component (LC) corresponded to a symptom profile combining negative symptoms, primarily diminished expression, with specific somatic symptoms. Both LCs captured comprehensive features of WM disruption, primarily a combination of subcortical and frontal association fibers. Strikingly, the PLS model trained on the primary cohort accurately predicted microstructural features and symptoms in the replication cohort. Findings were not driven by diagnosis, medication, or substance use. CONCLUSIONS: This data-driven transdiagnostic approach revealed a stable and replicable neurobiological signature of microstructural WM alterations in EP, across diagnoses and datasets, showing a strong covariance of these alterations with a unique profile of negative and somatic symptoms. This finding suggests the clinical utility of applying data-driven approaches to reveal symptom domains that share neurobiological underpinnings.

Electroconvulsive Therapy Changes Immunological Markers in Patients With Major Depressive Disorder: A Scoping Review.

ABSTRACT: Major depressive disorder (MDD) is a highly prevalent and disabling condition. As such, understanding the causes of and treatment options for MDD is critical. Electroconvulsive therapy (ECT) remains the gold standard depression treatment, but the molecular mechanisms that underlie its effects are still largely unknown. One such explanation hinges on the immuno-inflammatory correlates of ECT treatment, given mounting evidence supporting the inflammatory hypothesis of depression. This review aims to provide an overview of the suggested immunomodulatory effects of ECT and the predictive value of immune biomarkers in relation to treatment outcomes and side effects. We conducted a preregistered, systematic literature search utilizing MEDLINE (PubMed), Embase (Elsevier), and PsycINFO (EBSCO) databases. We employed keywords related to MDD, ECT, gut microbiome, and the immune system. We only included human subjects research published between 1985 and January 13, 2021. Twenty-six unique studies were included in our analyses. Findings indicate a proinflammatory profile associated with MDD, with immune biomarkers exhibiting acute and chronic changes following ECT. Consistently, lower baseline interleukin 6 levels and higher C-reactive protein levels are correlated with a greater reduction in depressive symptoms following ECT. Furthermore, included studies emphasize the predictive value of peripheral immune changes, specifically interleukin 6 and tumor necrosis factor α, on cognitive outcomes following ECT. Given these results, further exploration of the potential roles of immunomodulatory effects on ECT treatment outcomes, as well as adverse cognitive side effects, is indicated.

Accuracy of Phantomless Calibration of Routine Computed Tomography Scans for Opportunistic Osteoporosis Screening in the Spine Clinic.

STUDY DESIGN: Diagnostic accuracy study. OBJECTIVE: To establish a simple method of phantomless bone mineral density (BMD) measurement by using preoperative lumbar Computed Tomography (CT) scans, and compare the accuracy of reference tissue combinations to diagnose low BMD against uncalibrated Hounsfield units (HUs). SUMMARY OF BACKGROUND DATA: HUs are used as a measure of BMD; however, associations between HU and T-scores vary widely. Quantitative CT (qCT) scans are more accurate, but they require density calibration with an object of known density (phantom), which limits feasibility. As an emerging technique, phantomless (internal) calibration of routine CT scans may provide a good opportunity for screening. METHODS: Patients who were scheduled to undergo lumbar surgery, with a preoperative CT scan, and a dual-energy x-ray absorptiometry (DXA) scan within six months were included. Four tissues were selected for calibration: subcutaneous adipose (A), erector spinae (ES), psoas (P) and aortic blood (AB). The HUs of these tissues were used in linear regression against ground-truth values. Calibrations were performed by using two different internal tissues at a time to maintain simplicity and in-office applicability.Volumetric bone mineral densities (vBMD) derived from internally calibrated CT scans were analyzed for new threshold values for low bone density. Areas under the curve (AUC) were calculated with 95% confidence intervals (CI). RESULTS: 45 patients were included (M/F=10/35, mean age:63.3). Calibrated vBMDs had stronger correlations with DXA T-scores when compared with HUs, with L2 exhibiting the highest coefficients. Calibration by using A and ES with the threshold of 162 mg/cm3 had a sensitivity of 90% in detecting low BMD (AUC=0.671). CONCLUSIONS: This novel method allows simple, in-office calibration of routine preoperative CT scans without the use of a phantom. Calibration using adipose and erector spinae with a threshold of 162 mg/cm3 is proposed for low bone density screening with high sensitivity (90%). LEVEL OF EVIDENCE: Level III.

Synthetic Roadmap to a Large Library of Colloidal High-Entropy Rare Earth Oxyhalide Nanoparticles Containing up to Thirteen Metals.

Nanoparticles of high-entropy materials that incorporate five or more elements randomized on a crystalline lattice often exhibit synergistic properties that can be influenced by both the identity and number of elements combined. These considerations are especially important for structurally and compositionally complex materials such as multimetal multianion compounds, where cation and anion mixing can influence properties in competitive and contradictory ways. Here, we demonstrate the synthesis of a large library of colloidal high-entropy rare earth oxyhalide (REOX) nanoparticles. We begin with the synthesis of (LaCePrNdSmEuGdDyHoErYbScY)OCl, which homogeneously incorporates 13 distinct rare earth elements. Through time point studies, we find that (LaNdSmGdDy)OCl, a 5-metal analogue, forms through in situ generation of compositionally segregated core@shell@shell intermediates that convert to homogeneously mixed products through apparent core-shell interdiffusion. Assuming that all possible combinations of 5 through 13 rare earth metals are synthetically accessible, we propose the existence of a 7099-member REOCl nanoparticle library, of which we synthesize and characterize 40 distinct members. We experimentally validate the incorporation of a large number of rare earth elements using energy dispersive X-ray spectra, despite closely spaced and overlapping X-ray energy lines, using several fingerprint matching strategies to uniquely correlate experimental and simulated spectra. We confirm homogeneous mixing by analyzing elemental distributions in high-entropy nanoparticles versus physical mixtures of their constituent compounds. Finally, we characterize the band gaps of the 5- and 13-metal REOCl nanoparticles and find a significantly narrowed band gap, relative to the constituent REOCl phases, in (LaCePrNdSmEuGdDyHoErYbScY)OCl but not in (LaNdSmGdDy)OCl.