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The compositions and volumes of basalt generated by partial melting of the Earth's mantle provide fundamental constraints on the thermo-chemical conditions of the upper mantle. However, using melting products to interpret uniquely these conditions is challenging given the complexity of the melting and melt aggregation processes. Forward models simulating melting of lithologically heterogeneous mantle sources can account for this complexity, but require assumptions about key model input parameters, and the quality of the model fits to the observations are rarely, if at all, considered. Alternatively, inverse melting models can provide estimates of the quality of model fits to the observations, but as of yet, do not account for the presence of lithologic heterogeneity in the mantle source. To overcome these limitations, we present an inverse method coupling a Markov chain Monte Carlo (MCMC) sampling method with the REEBOX PRO forward mantle melting model. We use this tool to constrain mantle potential temperature, melt volumes, and the trace element and isotopic compositions of mantle source lithologies beneath the Reykjanes Peninsula of Iceland. We consider a range of plausible pyroxenite compositions (KG1, G2, and MIX1G) that span much of the range of natural pyroxenite compositions, and constrain the mantle potential temperature between 1455 and 1480 °C and pyroxenite abundance between 6.5 and 8.5%. These results are independent of the choice of pyroxenite composition and indicate that elevated potential temperatures and modest pyroxenite abundances are robust features of the Reykjanes Peninsula mantle source. The permitted ranges of pyroxenite trace element compositions vary as a function of pyroxenite fertility and mineralogy, but differ from the compositions of subduction-modified recycled oceanic crust typically used in previous models, indicating a more complex petrogenetic origin for the pyroxenite source than previously considered. As all of the pyroxenites employed here yield equally good fits to the geochemical and geophysical observations along the Reykjanes Peninsula, forward models should not be used to constrain the major element character of pyroxenite present in mantle source regions based solely on the trace element/isotopic compositions (and volumes) of basalts. Given the range of lithologies included in REEBOX PRO and the flexibility of MCMC inversion, this method may be applied to constrain thermal and compositional source characteristics in a wide variety of basalt source regions.

Objective: The present study analysed the impact of using the 2006 WHO Child Growth Standards ('the WHO standards') compared with the 1977 National Center for Health Statistics (NCHS) international growth reference ('the NCHS reference') on the calculated prevalence of chronic malnutrition in children aged 6·0-59·9 months.Design: Anthropometric data were collected as part of a cross-sectional study exploring the association between household environments and nutritional status of children. Z-scores were computed for height-for-age (HAZ), weight-for-age (WAZ) and weight-for-height (WHZ) using each reference/standard. Results were compared using Bland-Altman plots, percentage agreement, kappa statistics, line graphs and proportion of children in Z-score categories.Setting: The study was conducted in thirteen rural villages within Honduras's department of Intibucá.Subjects: Children aged 6·0-59·9 months were the focus of the analysis, and households with children in this age range served as the sampling unit for the study.Results: The WHO standards yielded lower means for HAZ and higher means for WAZ and WHZ compared with the NCHS reference. The WHO standards and NCHS reference showed good agreement between Z-score categories, except for HAZ among males aged 24·0-35·9 months and WHZ among males aged >24·0 months. Using the WHO standards resulted in higher proportions of stunting (low HAZ) and overweight (high WHZ) and lower proportions of underweight (low WAZ). The degree of difference among these measures varied by age and gender.Conclusions: The choice of growth reference/standard employed in nutritional surveys may have important methodological and policy implications. While ostensibly comparable, data on nutritional indicators derived with different growth references/standards must be interpreted cautiously. [ABSTRACT FROM AUTHOR]

The purpose of this pilot study was to explore the approaches to depression care preferred by older home-care patients and examine characteristics associated with those preferences. Twenty-eight long-term home-care patients, ages 62 to 95, were interviewed. Patients ranked their depression care preferences and provided rationale for their responses. Results indicated prayer was preferred by the highest percentage of patients (50%). Comparing patients with and without depression experience, prayer was preferred by the latter group. The results highlight the importance of addressing patient preferences during care planning to improve participation in geriatric depression care management. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the completeness and accuracy of clinical information provided by referral sources to visiting nurses for patients admitted to receive home health care. METHODS: Clinical referral information for a representative sample of 243 older adults admitted to receive skilled home-health nursing was compared to medical record information from home-health charts and in-home research interviews to determine their concordance. Measures used included referral information, home-care chart documentation, in-home nurse review of medications, medication allergies, caregiver contact information, cognitive status, depression status, and follow-up plan. RESULTS: There were medication discrepancies between in-home nurse review and admission information in 215 cases (88.4%). Clinical information on medication allergies was lacking from referrers in 85 cases (34.9%). No information was provided by the referrers about cognitive status in 38 (73%) cases classified as cognitively impaired and in only 2 of 35 cases with major depression identified with the Structured Clinical Interview for Axis I Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID), was depression related information provided by referrers. CONCLUSIONS: The primary finding of this study is that during a transfer of an older adult to the home care service sector, essential clinical information is often missing, and there are significant discrepancies between medication regimens. These findings support the need for both educational initiatives and technology to address the complex care needs of older adults across settings to reduce the risk for medication errors and poor outcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective of the study was to assess whether herpes simplex virus antibody avidity is associated with risk of transmission of herpes simplex virus to the neonate. STUDY DESIGN: We developed a novel herpes simplex virus type 1 avidity test based on the commercially available Focus HerpeSelect-1 enzyme-linked immunosorbent assay kit using sera from nonpregnant subjects with genital herpes simplex virus-1 infection. We used this test, and the previously developed herpes simplex virus type 2 avidity test, to compare maternal herpes simplex virus-1 and herpes simplex virus-2 antibody avidity in women who transmitted herpes simplex virus to the neonate and women who had herpes simplex virus isolated from genital secretions at delivery but who did not transmit herpes simplex virus to their infants. RESULTS: Among nonpregnant subjects with genital herpes simplex virus-1 infection whose sera were used to develop the herpes simplex virus-1 avidity test, a significant relationship between herpes simplex virus-1 antibody avidity and time since herpes simplex virus-1 acquisition was observed (P < .001, mixed-effects model), with median avidity values increasing over time after primary infection. Among pregnant, herpes simplex virus-1, or herpes simplex virus-2 seropositive women, 4 of 8 women (50%) with avidity 40 or greater transmitted herpes simplex virus to the neonate, compared with only 12 of 97 (12%) of women with avidity greater than 40 (P = .02). CONCLUSIONS: Herpes simplex virus-1 antibody avidity increased over time after genital herpes simplex virus-1 acquisition, as has been previously observed for herpes simplex virus-2. Among women with herpes simplex virus antibody at delivery, low antibody avidity was associated with herpes simplex virus transmission to the neonate and may be a useful marker for recent seroconversion. [ABSTRACT FROM AUTHOR]

Background. This study compares patient and informant reports of depressive disorders in a community sample of elderly medical homecare patients. The associations between specific patterns of agreement/disagreement and other patient and informant characteristics are examined.Method. A random sample of 355 elderly medical homecare patients and their informants were interviewed using the current mood section of the Structured Clinical Interview for DSM-IV (SCID).Results. Thirty-seven patients (10.4%) reported a depressive disorder (major or subsyndromal) that was also identified by their informant while 27 (7.6%) patients self-reported depression that the informant did not identify. There were 250 patients (70.4%) who were not depressed according to both patient and informant report and 41 patients (11.5%) were identified as depressed by informant report alone. Patients identified as depressed by informant report alone were similar to patients who self-reported depression on a number of the sociodemographic and clinical correlates of depression, but had significantly poorer performance on items assessing orientation and short-term recall. These patients also had poorer functioning in a number of domains (social, cognitive, and functional) when compared with patients who were not depressed according to both the patient and informant. Finally, patients with younger informants were more likely to be identified as depressed by their informant.Conclusions. Obtaining informant reports of depression may be a useful method for detecting clinically significant cases of late-life depression that would otherwise be missed when relying only on patient report. [ABSTRACT FROM AUTHOR]

Abstract Background Extent of atherosclerosis measured by amount of coronary artery calcium (CAC) in computed tomography (CT) has been traditionally assessed using thresholded scoring methods, such as the Agatston score (AS). These thresholded scores have value in clinical prediction, but important information might exist below the threshold, which would have important advantages for understanding genetic, environmental, and other risk factors in atherosclerosis. We developed a semi-automated threshold-free scoring method, the spatially weighted calcium score (SWCS) for CAC in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods Chest CT scans were obtained from 6814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The SWCS and the AS were calculated for each of the scans. Cox proportional hazards models and linear regression models were used to evaluate the associations of the scores with CHD events and CHD risk factors. CHD risk factors were summarized using a linear predictor. Results Among all participants and participants with AS > 0, the SWCS and AS both showed similar strongly significant associations with CHD events (hazard ratios, 1.23 and 1.19 per doubling of SWCS and AS; 95% CI, 1.16 to 1.30 and 1.14 to 1.26) and CHD risk factors (slopes, 0.178 and 0.164; 95% CI, 0.162 to 0.195 and 0.149 to 0.179). Even among participants with AS = 0, an increase in the SWCS was still significantly associated with established CHD risk factors (slope, 0.181; 95% CI, 0.138 to 0.224). The SWCS appeared to be predictive of CHD events even in participants with AS = 0, though those events were rare as expected. Conclusions The SWCS provides a valid, continuous measure of CAC suitable for quantifying the extent of atherosclerosis without a threshold, which will be useful for examining novel genetic and environmental risk factors for atherosclerosis.

Abstract Background The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes Human African Trypanosomiasis. Its cell cycle is complex and not fully understood at the molecular level. The T. brucei genome contains over 6000 protein coding genes with >50% having no predicted function. A small scale RNA interference (RNAi) screen was carried out in Trypanosoma brucei to evaluate the prospects for identifying novel cycle regulators. Results Procyclic form T. brucei were transfected with a genomic RNAi library and 204 clones isolated. However, only 76 RNAi clones were found to target a protein coding gene of potential interest. These clones were screened for defects in proliferation and cell cycle progression following RNAi induction. Sixteen clones exhibited proliferation defects upon RNAi induction, with eight clones displaying potential cell cycle defects. To confirm the phenotypes, new RNAi cell lines were generated and characterised for five genes targeted in these clones. While we confirmed that the targeted genes are essential for proliferation, we were unable to unambiguously classify them as cell cycle regulators. Conclusion Our study identified genes essential for proliferation, but did not, as hoped, identify novel cell cycle regulators. Screening of the RNAi library for essential genes was extremely labour-intensive, which was compounded by the suboptimal quality of the library. For such a screening method to be viable for a large scale or genome wide screen, a new, significantly improved RNAi library will be required, and automated phenotyping approaches will need to be incorporated.

Abstract Background In trials designed to estimate rates of perinatal mother to child transmission of HIV, HIV assays are scheduled at multiple points in time. Still, infection status for some infants at some time points may be unknown, particularly when interim analyses are conducted. Methods Logistic regression models are commonly used to estimate covariate-adjusted transmission rates, but their methods for handling missing data may be inadequate. Here we propose using coarsened multinomial regression models to estimate cumulative and conditional rates of HIV transmission. Through simulation, we compare the proposed models to standard logistic models in terms of bias, mean squared error, coverage probability, and power. We consider a range of treatment effect and visit process scenarios, while including imperfect sensitivity of the assay and contamination of the endpoint due to early breastfeeding transmission. We illustrate the approach through analysis of data from a clinical trial designed to prevent perinatal transmission. Results The proposed cumulative and conditional models performed well when compared to their logistic counterparts. Performance of the proposed cumulative model was particularly strong under scenarios where treatment was assumed to increase the risk of in utero transmission but decrease the risk of intrapartum and overall perinatal transmission and under scenarios designed to represent interim analyses. Power to estimate intrapartum and perinatal transmission was consistently higher for the proposed models. Conclusion Coarsened multinomial regression models are preferred to standard logistic models for estimation of perinatal mother to child transmission of HIV, particularly when assays are missing or occur off-schedule for some infants.

Abstract Background Genetic variations in MBL2 that reduce circulating levels and alter functional properties of the mannose binding lectin (MBL) have been associated with many autoimmune and infectious diseases. We examined whether MBL2 variants influence the outcome of hepatitis C virus (HCV) infection. Methods Participants were enrolled in the Urban Health Study of San Francisco Bay area injection drug users (IDU) during 1998 through 2000. Study subjects who had a positive test for HCV antibody were eligible for the current study. Participants who were positive for HCV RNA were frequency matched to those who were negative for HCV RNA on the basis of ethnicity and duration of IDU. Genotyping was performed for 15 single nucleotide polymorphisms in MBL2. Statistical analyses of European American and African American participants were conducted separately. Results The analysis included 198 study subjects who were positive for HCV antibody, but negative for HCV RNA, and 654 IDUs who were positive for both antibody and virus. There was no significant association between any of the genetic variants that cause MBL deficiency and the presence of HCV RNA. Unexpectedly, the MBL2 -289X promoter genotype, which causes MBL deficiency, was over-represented among European Americans who were HCV RNA negative (OR = 1.65, 95% CI 1.05–2.58), although not among the African Americans. Conclusion This study found no association between genetic variants that cause MBL deficiency and the presence of HCV RNA. The observation that MBL2 -289X was associated with the absence of HCV RNA in European Americans requires validation.

Abstract Background From June to November 2005, 18 cases of community-acquired Legionnaires' disease (LD) were reported in Rapid City South Dakota. We conducted epidemiologic and environmental investigations to identify the source of the outbreak. Methods We conducted a case-control study that included the first 13 cases and 52 controls randomly selected from emergency department records and matched on underlying illness. We collected information about activities of case-patients and controls during the 14 days before symptom onset. Environmental samples (n = 291) were cultured for Legionella. Clinical and environmental isolates were compared using monoclonal antibody subtyping and sequence based typing (SBT). Results Case-patients were significantly more likely than controls to have passed through several city areas that contained or were adjacent to areas with cooling towers positive for Legionella. Six of 11 case-patients (matched odds ratio (mOR) 32.7, 95% CI 4.7-∞) reported eating in Restaurant A versus 0 controls. Legionella pneumophila serogroup 1 was isolated from four clinical specimens: 3 were Benidorm type strains and 1 was a Denver type strain. Legionella were identified from several environmental sites including 24 (56%) of 43 cooling towers tested, but only one site, a small decorative fountain in Restaurant A, contained Benidorm, the outbreak strain. Clinical and environmental Benidorm isolates had identical SBT patterns. Conclusion This is the first time that small fountain without obvious aerosol-generating capability has been implicated as the source of a LD outbreak. Removal of the fountain halted transmission.

Abstract Background We have demonstrated that moderate alcohol consumption (15 g/d, 30 g/d) for 8 weeks resulted in significantly increased levels of serum estrone sulfate and DHEAS in 51 postmenopausal women in a randomized, placebo-controlled trial. We now report on the relationships between serum estrone sulfate and dehydroepiandrosterone sulfate (DHEAS) levels after 4 weeks of moderate alcohol supplementation, and compare the results to the 8 weeks data to elucidate time-to-effect differences. Methods Postmenopausal women (n = 51) consumed 0 (placebo), 15 (1 drink), and 30 (2 drinks) g alcohol (ethanol)/ day for 8 weeks as part of a controlled diet in a randomized crossover design. Blood samples were drawn at baseline, at 4 weeks and at 8 weeks. Changes in estrone sulfate and DHEAS levels from placebo to 15 g and 30 g alcohol per day were estimated using linear mixed models. Results and Discussion At week 4, compared to the placebo, estrone sulfate increased an average 6.9% (P = 0.24) when the women consumed 15 g of alcohol per day, and 22.2% (P = 0.0006) when they consumed 30 g alcohol per day. DHEAS concentrations also increased significantly by an average of 8.0% (P < 0.0001) on 15 g of alcohol per day and 9.2% (P < 0.0001) when 30 g alcohol was consumed per day. Trend tests across doses for both estrone sulfate (P = 0.0006) and DHEAS (P < 0.0001) were significant. We found no significant differences between the absolute levels of serum estrone sulfate at week 4 versus week 8 (P = 0.32) across all doses. However, absolute DHEAS levels increased from week 4 to week 8 (P < 0.0001) at all three dose levels. Conclusions These data indicate that the hormonal effects due to moderate alcohol consumption are seen early, within 4 weeks of initiation of ingestion.

Objective: Metal and metalloid exposures (hereafter "metals") are associated with adverse health outcomes, including type 2 diabetes; however, previous studies were largely cross-sectional or underpowered. Furthermore, underserved racial and ethnic groups are underrepresented in environmental health research despite having higher rates of type 2 diabetes and a greater risk of metal exposures. Consequently, we evaluated continuous glycemic traits in relation to baseline urinary toxic metal, essential metal, and metal mixtures in a cohort of Mexican American adults., Research Design and Methods: A total of 510 participants were selected based upon self-reported diabetes status and followed over 3 years. Urinary metals were assessed at baseline. Linear mixed-effects models were used to estimate per-month changes in hemoglobin A1c, fasting plasma glucose, and postload glucose in relation to urinary metal levels. Multiple statistical approaches were used to assess the associations between glycemic traits and metal mixtures., Results: After adjustment, higher urinary levels of arsenic, selenium, copper, molybdenum, nickel, and tin were associated with faster increases in measures of glycemia. The toxic metal mixture composed of arsenic, lead, cadmium, nickel, and tin was associated with faster increases in postload glucose. Using postload glucose criteria, highest versus lowest arsenic was predicted to accelerate conversion of normoglycemia to prediabetes and diabetes by 23 and 65 months, respectively., Conclusions: In this underrepresented, high-risk Mexican American population, exposure to toxic metals and alterations in essential metal homeostasis were associated with faster increases in glycemia over time that may accelerate type 2 diabetes development., (© 2024 by the American Diabetes Association.)

The analysis of vascular morphology and functionality enables the assessment of disease activity and therapeutic effects in various pathologies. Raster-scanning optoacoustic mesoscopy (RSOM) is an imaging modality that enables the visualization of superficial vascular networks in vivo. In murine models of colitis, deep vascular networks in the colon wall can be visualized by transrectal absorber guide raster-scanning optoacoustic mesoscopy (TAG-RSOM). In order to accelerate the implementation of this technology in translational studies of inflammatory bowel disease, an image-processing pipeline for TAG-RSOM data has been developed. Using optoacoustic data from a murine model of chemically-induced colitis, different image segmentation methods are compared for visualization and quantification of deep vascular patterns in terms of vascular network length and complexity, blood volume, and vessel diameter. The presented image-processing pipeline for TAG-RSOM enables label-free in vivo assessment of changes in the vascular network in murine colitis with broad applications for inflammatory bowel disease research., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Acute respiratory infections are a common reason for consultation with primary and emergency healthcare services. Identifying individuals with a bacterial infection is crucial to ensure appropriate treatment. However, it is also important to avoid overprescription of antibiotics, to prevent unnecessary side effects and antimicrobial resistance. We conducted a systematic review to summarise evidence on the diagnostic accuracy of symptoms, signs and point-of-care tests to diagnose bacterial respiratory tract infection in adults, and to diagnose two common respiratory viruses, influenza and respiratory syncytial virus., Methods: The primary approach was an overview of existing systematic reviews. We conducted literature searches (22 May 2023) to identify systematic reviews of the diagnostic accuracy of point-of-care tests. Where multiple reviews were identified, we selected the most recent and comprehensive review, with the greatest overlap in scope with our review question. Methodological quality was assessed using the Risk of Bias in Systematic Reviews tool. Summary estimates of diagnostic accuracy (sensitivity, specificity or area under the curve) were extracted. Where no systematic review was identified, we searched for primary studies. We extracted sufficient data to construct a 2 × 2 table of diagnostic accuracy, to calculate sensitivity and specificity. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies version 2 tool. Where possible, meta-analyses were conducted. We used GRADE to assess the certainty of the evidence from existing reviews and new analyses., Results: We identified 23 reviews which addressed our review question; 6 were selected as the most comprehensive and similar in scope to our review protocol. These systematic reviews considered the following tests for bacterial respiratory infection: individual symptoms and signs; combinations of symptoms and signs (in clinical prediction models); clinical prediction models incorporating C-reactive protein; and biological markers related to infection (including C-reactive protein, procalcitonin and others). We also identified systematic reviews that reported the accuracy of specific tests for influenza and respiratory syncytial virus. No reviews were found that assessed the diagnostic accuracy of white cell count for bacterial respiratory infection, or multiplex tests for influenza and respiratory syncytial virus. We therefore conducted searches for primary studies, and carried out meta-analyses for these index tests. Overall, we found that symptoms and signs have poor diagnostic accuracy for bacterial respiratory infection (sensitivity ranging from 9.6% to 89.1%; specificity ranging from 13.4% to 95%). Accuracy of biomarkers was slightly better, particularly when combinations of biomarkers were used (sensitivity 80-90%, specificity 82-93%). The sensitivity and specificity for influenza or respiratory syncytial virus varied considerably across the different types of tests. Tests involving nucleic acid amplification techniques (either single pathogen or multiplex tests) had the highest diagnostic accuracy for influenza (sensitivity 91-99.8%, specificity 96.8-99.4%)., Limitations: Most of the evidence was considered low or very low certainty when assessed with GRADE, due to imprecision in effect estimates, the potential for bias and the inclusion of participants outside the scope of this review (children, or people in hospital)., Future Work: Currently evidence is insufficient to support routine use of point-of-care tests in primary and emergency care. Further work must establish whether the introduction of point-of-care tests adds value, or simply increases healthcare costs., Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR159948.

Objective: The formation of functional vasculature in solid tumours enables delivery of oxygen and nutrients, and is vital for effective treatment with chemotherapeutic agents. Longitudinal characterisation of vascular networks can be enabled using mesoscopic photoacoustic imaging, but requires accurate image co-registration to precisely assess local changes across disease development or in response to therapy. Co-registration in photoacoustic imaging is challenging due to the complex nature of the generated signal, including the sparsity of data, artefacts related to the illumination/detection geometry, scan-to-scan technical variability, and biological variability, such as transient changes in perfusion. To better inform the choice of co-registration algorithms, we compared five open-source methods, in physiological and pathological tissues, with the aim of aligning evolving vascular networks in tumours imaged over growth at different time-points. Approach: Co-registration techniques were applied to 3D vascular images acquired with photoacoustic mesoscopy from murine ears and breast cancer patient-derived xenografts, at a fixed time-point and longitudinally. Images were pre-processed and segmented using an unsupervised generative adversarial network. To compare co-registration quality in different settings, pairs of fixed and moving intensity images and/or segmentations were fed into five methods split into the following categories: affine intensity-based using 1)mutual information (MI) or 2)normalised cross-correlation (NCC) as optimisation metrics, affine shape-based using 3)NCC applied to distance-transformed segmentations or 4)iterative closest point algorithm, and deformable weakly supervised deep learning-based using 5)LocalNet co-registration. Percent-changes in Dice coefficients, surface distances, MI, structural similarity index measure and target registration errors were evaluated. Main results: Co-registration using MI or NCC provided similar alignment performance, better than shape-based methods. LocalNet provided accurate co-registration of substructures by optimising subfield deformation throughout the volumes, outperforming other methods, especially in the longitudinal breast cancer xenograft dataset by minimising target registration errors. Significance: We showed the feasibility of co-registering repeatedly or longitudinally imaged vascular networks in photoacoustic mesoscopy, taking a step towards longitudinal quantitative characterisation of these complex structures. These tools open new outlooks for monitoring tumour angiogenesis at the meso-scale and for quantifying treatment-induced co-localised alterations in the vasculature., (Creative Commons Attribution license.)

Mesoscopic photoacoustic imaging (PAI) enables label-free visualization of vascular networks in tissues with high contrast and resolution. Segmenting these networks from 3D PAI data and interpreting their physiological and pathological significance is crucial yet challenging due to the time-consuming and error-prone nature of current methods. Deep learning offers a potential solution; however, supervised analysis frameworks typically require human-annotated ground-truth labels. To address this, an unsupervised image-to-image translation deep learning model is introduced, the Vessel Segmentation Generative Adversarial Network (VAN-GAN). VAN-GAN integrates synthetic blood vessel networks that closely resemble real-life anatomy into its training process and learns to replicate the underlying physics of the PAI system in order to learn how to segment vasculature from 3D photoacoustic images. Applied to a diverse range of in silico, in vitro, and in vivo data, including patient-derived breast cancer xenograft models and 3D clinical angiograms, VAN-GAN demonstrates its capability to facilitate accurate and unbiased segmentation of 3D vascular networks. By leveraging synthetic data, VAN-GAN reduces the reliance on manual labeling, thus lowering the barrier to entry for high-quality blood vessel segmentation (F1 score: VAN-GAN vs. U-Net = 0.84 vs. 0.87) and enhancing preclinical and clinical research into vascular structure and function., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Arsenic, cadmium, and lead are toxic elements that widely contaminate our environment. These toxicants are associated with acute and chronic health problems, and evidence suggests that minority communities, including Hispanic/Latino Americans, are disproportionately exposed. Few studies have assessed culturally specific predictors of exposure to understand the potential drivers of racial/ethnic exposure disparities., Objective: We sought to evaluate acculturation measures as predictors of metal/metalloid (hereafter "metal") concentrations among Mexican American adults to illuminate potential exposure sources that may be targeted for interventions., Methods: As part of a longitudinal cohort, 510 adults, aged 35 to 69 years, underwent baseline interview, physical examination, and urine sample collection. Self-reported acculturation was assessed across various domains using the Short Acculturation Scale for Hispanics (SASH). Multivariable linear regression was used to assess associations between acculturation and urinary concentrations of arsenic, cadmium, and lead. Ordinal logistic regression was utilized to assess associations between acculturation and a metal mixture score. Lastly, best subset selection was used to build a prediction model for each toxic metal with a combination of the acculturation predictors., Results: After adjustment, immigration factors were positively associated with arsenic and lead concentrations. For lead alone, English language and American media and food preferences were associated with lower levels. Immigration and parental heritage from Mexico were positively associated with the metal mixture, while preferences for English language, media, and food were negatively associated., Conclusion: Acculturation-related predictors of exposure provide information about potential sources of toxic metals, including international travel, foods, and consumer products. The findings in this research study provide information to empower future efforts to identify and address specific acculturation-associated toxicant exposures in order to promote health equity through clinical guidance, patient education, and public policy., (© 2024. W. Montague Cobb-NMA Health Institute.)

Introduction: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, but few studies have evaluated mortality risks among individuals with IBS. We explored the association between IBS and all-cause and cause-specific mortality in the UK Biobank., Methods: We included 502,369 participants from the UK Biobank with mortality data through 2022. IBS was defined using baseline self-report and linkage to primary care or hospital admission data. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality using multivariable Cox proportional hazards regression models within partitioned follow-up time categories (0-5, >5-10, and >10 years)., Results: A total of 25,697 participants (5.1%) had a history of IBS at baseline. After a median follow-up of 13.7 years, a total of 44,499 deaths occurred. Having an IBS diagnosis was strongly associated with lower risks of all-cause (HR = 0.70, 95% CI = 0.62-0.78) and all-cancer (HR = 0.69, 95% CI = 0.60-0.79) mortality in the first 5 years of follow-up. These associations were attenuated over follow-up, but even after 10 years of follow-up, associations remained inverse (all-cause: HR = 0.89, 95% CI = 0.84-0.96; all-cancer: HR = 0.87, 95% CI = 0.78-0.97) after full adjustment. Individuals with IBS had decreased risk of mortality from breast, prostate, and colorectal cancers in some of the follow-up time categories., Discussion: We found that earlier during follow-up, having diagnosed IBS was associated with lower mortality risk, and the association attenuated over time. Additional studies to understand whether specific factors, such as lifestyle and healthcare access, explain the inverse association between IBS and mortality are needed., (Copyright © 2024 by The American College of Gastroenterology.)

There is an urgent need to improve conventional cancer-treatments by preventing detrimental side effects, cancer recurrence and metastases. Recent studies have shown that presence of senescent cells in tissues treated with chemo- or radiotherapy can be used to predict the effectiveness of cancer treatment. However, although the accumulation of senescent cells is one of the hallmarks of cancer, surprisingly little progress has been made in development of strategies for their detection in vivo. To address a lack of detection tools, we developed a biocompatible, injectable organic nanoprobe (NanoJagg), which is selectively taken up by senescent cells and accumulates in the lysosomes. The NanoJagg probe is obtained by self-assembly of indocyanine green (ICG) dimers using a scalable manufacturing process and characterized by a unique spectral signature suitable for both photoacoustic tomography (PAT) and fluorescence imaging. In vitro, ex vivo and in vivo studies all indicate that NanoJaggs are a clinically translatable probe for detection of senescence and their PAT signal makes them suitable for longitudinal monitoring of the senescence burden in solid tumors after chemotherapy or radiotherapy., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Introduction: This study aimed to investigate the dynamics of programmed death-ligand 1 (PD-L1) expression, spatial heterogeneity, and binding affinity of FDA-approved anti-PD-L1 antibodies (avelumab and atezolizumab) in gastric cancer. Additionally, we determined how PD-L1 glycosylation impacts antibody accumulation in gastric cancer cells., Methods: Dynamic PD-L1 expression was examined in NCIN87 gastric cancer cells. Comparative binding studies of avelumab and atezolizumab were conducted in gastric cancer models, both in vitro and in vivo . Antibody uptake in tumors was visualized through positron emission tomography (PET) imaging. PD-L1 glycosylation status was determined via Western blot analyses before and after PNGase F treatment., Results: Consistent findings revealed time-dependent PD-L1 induction in NCIN87 gastric cancer cells and spatial heterogeneity in tumors, as shown by PET imaging and immunofluorescence. Avelumab displayed superior binding affinity to NCIN87 cells compared to atezolizumab, confirmed by in vivo PET imaging and ex vivo biodistribution analyses. Notably, PD-L1 glycosylation at approximately 50 kDa was observed, with PNGase F treatment inducing a shift to 35 kDa in molecular weight. Tissue samples from patient-derived xenografts (PDXs) validated the presence of both glycosylated and deglycosylated PD-L1 (degPD-L1) forms in gastric cancer. Immunofluorescence microscopy and binding assays demonstrated enhanced avelumab binding post-deglycosylation., Discussion: This study provides an understanding of dynamic and spatially heterogeneous PD-L1 expression in gastric cancer. Anti-PD-L1 immunoPET was able to visualize gastric tumors, and PD-L1 glycosylation has significant implications for antibody recognition. These insights contribute to demonstrating the complexities of PD-L1 in gastric cancer, holding relevance for refining PD-L1 imaging-based approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ibrahim, Simó, Brown, Shmuel, Panikar, Benton, DeWeerd, Dehdashti, Park and Pereira.)

Background: Acute heart failure (AHF) is a common emergency department (ED) presentation that may have poor outcomes but often does not require hospital admission. There is little evidence to guide dispositional decisions., Objectives: The authors sought to create a risk score for predicting short-term serious outcomes (SSO) in patients with AHF., Methods: We pooled data from 3 prospective cohorts: 2 published studies and 1 new cohort. The 3 cohorts prospectively enrolled patients who required treatment for AHF at 10 tertiary care hospital EDs. The primary outcome was SSO, defined as death <30 days, intubation or noninvasive ventilation (NIV), myocardial infarction, or relapse to ED <14 days. The logistic regression model evaluated 13 predictors, used an AIC-based step-down procedure, and bootstrapped internal validation., Results: Of the 2,246 patients in the 3 cohorts (N = 559; 1,100; 587), the mean age was 77.4 years, 54.5% were male, 3.1% received intravenous nitroglycerin, 5.2% received ED NIV, and 48.6% were admitted to the hospital. There were 281 (12.5%) SSOs including 70 deaths (3.1%) with many in discharged patients. The final HEARTRISK6 Scale included 6 variables: valvular heart disease, tachycardia, need for NIV, creatinine, troponin, and failed reassessment (walk test). Choosing HEARTRISK6 total-point admission thresholds of ≥1 or ≥2 would yield, respectively, sensitivities of 88.3% (95% CI: 83.9%-91.8%) and 71.5% (95% CI: 65.9%-76.7%) and specificities of 24.7% (95% CI: 22.8%-26.7%) and 50.1% (95% CI: 47.9%-52.4%) for SSO., Conclusions: Using 3 large prospectively collected datasets, we created a concise and sensitive risk scale for patients with AHF in the ED. Implementation of the HEARTRISK6 scale could lead to safer and more efficient disposition decisions., Competing Interests: This study was funded by a 10.13039/501100000024Canadian Institutes of Health Research (CIHR) Foundation grant held by IGS. The funding agency had no role in the study design, collection, analysis, or manuscript preparation. The study was sponsored by the 10.13039/100009519Ottawa Hospital Research Institute. Dr Perry is supported by a mid-career salary award from the Heart and Stroke Foundation of Ontario. Dr Rowe’s research is supported by a Scientific Director’s Grant (SOP 168483) from the CIHR (Ottawa, Ontario). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Purpose: The purpose of the study was to explore the feasibility of using commonly available technology, such as text messaging, for diabetes prevention in rural Mexican American communities during COVID-19., Methods: Participants were selected from a diabetes prevention study funded by the National Institutes of Health that, prior to COVID-19, involved in-person group intervention sessions. Participants were predominantly female adults born in Mexico and Spanish-speaking. A subsample (n = 140) was divided into 3 cohorts: (1) 50 who completed the initial in-person intervention prior to the COVID-19 research pause, (2) 60 who needed additional support sessions to complete the intervention and thus received 10 text messages with links to relevant online diabetes prevention videos (TM+), and (3) 30 who received enhanced usual care involving health guidance offered during data collection (control). Repeated measures analysis of covariance was used to evaluate cohort differences at 24 months post baseline., Results: No significant cohort differences were found for depression, eating self-efficacy, alcohol intake, fat avoidance, or sedentary behaviors. Differences in A1C showed both in-person and TM+ cohorts having lower mean A1C levels (5.5%) than the control cohort (5.7%). The TM+ cohort had lower body mass index than other cohorts and a lower diabetes conversion rate (22.2%) compared to the control cohort (28%). Participants indicated preferences for in-person/TM+ combination interventions. The strongest positive feedback was for the TM+ intervention cooking demonstration videos., Conclusions: Augmented text messaging combined with in-person sessions had similar outcomes to the all in-person strategy and thus has the potential for expanding the reach of diabetes prevention to many Mexican American communities., Competing Interests: Conflicts of InterestThe authors declare that there are no conflicts of interest.

C-reactive protein (CRP) is a commonly used marker of low-grade inflammation as well as a marker of acute infection. CRP levels are elevated in those with diabetes and increased CRP concentrations are a risk factor for developing type 2 diabetes. Gut microbiome effects on metabolism and immune responses can impact chronic inflammation, including affecting CRP levels, that in turn can lead to the development and maintenance of dysglycemia. Using a high-sensitivity C-reactive protein (hsCRP) assay capable of detecting subtle changes in C-reactive protein, we show that higher hsCRP levels specifically correlate with worsening glycemia, reduced microbial richness and evenness, and with a reduction in the Firmicutes/Bacteroidota ratio. These data demonstrate a pivotal role for CRP not only in the context of worsening glycemia and changes to the gut microbiota, but also highlight CRP as a potential target for mitigating type 2 diabetes progression or as a therapeutic target that could be manipulated through the microbiome. Understanding these processes will provide insights into the etiology of type 2 diabetes in addition to opening doors leading to possible novel diagnostic strategies and therapeutics., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Inflammatory bowel disease (IBD) has a rising global prevalence. However, the understanding of its impact on mortality remains inconsistent so we explored the association between IBD and all-cause and cause-specific mortality., Methods: This study included 502,369 participants from the UK Biobank, a large, population-based, prospective cohort study with mortality data through 2022. IBD was defined by baseline self-report or from primary care or hospital admission data. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality in multivariable Cox proportional hazards regression models., Results: A total of 5799 (1.2%) participants had a history of IBD at baseline. After a median follow-up of 13.7 years, 44,499 deaths occurred. Having IBD was associated with an increased risk of death from all causes (HR = 1.16, 95% CI = 1.07-1.24) and cancer (HR = 1.16, 95% CI = 1.05-1.30), particularly colorectal cancer (CRC) (HR = 1.56, 95% CI = 1.17-2.09). We observed elevated breast cancer mortality rates for individuals with Crohn's disease, and increased CRC mortality rates for individuals with ulcerative colitis. In stratified analyses of IBD and all-cause mortality, mortality risk differed by individuals' duration of IBD, age at IBD diagnosis, body mass index (BMI) (P Heterogeneity = 0.03) and smoking status (P Heterogeneity = 0.01). Positive associations between IBD and all-cause mortality were detected in individuals diagnosed with IBD for 10 years or longer, those diagnosed before the age of 50, all BMI subgroups except obese individuals, and in never or current, but not former smokers., Conclusions: We found that having IBD was associated with increased risks of mortality from all causes, all cancers, and CRC. This underscores the importance of enhanced patient management strategies and targeted prevention efforts in individuals with IBD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Tracking infectious diseases at the community level is challenging due to asymptomatic infections and the logistical complexities of mass surveillance. Wastewater surveillance has emerged as a valuable tool for monitoring infectious disease agents including SARS-CoV-2 and Mpox virus. However, detecting the Mpox virus in wastewater is particularly challenging due to its relatively low prevalence in the community. In this study, we aim to characterize three molecular assays for detecting and tracking the Mpox virus in wastewater from El Paso, Texas, during February and March 2023., Methods: In this study, a combined approach utilizing three real-time PCR assays targeting the C22L, F3L, and F8L genes and sequencing was employed to detect and track the Mpox virus in wastewater samples. The samples were collected from four sewersheds in the City of El Paso, Texas, during February and March 2023. Wastewater data was compared with reported clinical case data in the city., Findings: Mpox virus DNA was detected in wastewater from all the four sewersheds, whereas only one Mpox case was reported during the sampling period. Positive signals were still observed in multiple sewersheds after the Mpox case was identified. Higher viral concentrations were found in the pellet than in the supernatant of wastewater. Notably, an increasing trend in viral concentration was observed approximately 1-2 weeks before the reporting of the Mpox case. Further sequencing and epidemiological analysis provided supporting evidence for unreported Mpox infections in the city., Interpretation: Our analysis suggests that the Mpox cases in the community is underestimated. The findings emphasize the value of wastewater surveillance as a public health tool for monitoring infectious diseases even in low-prevalence areas, and the need for heightened vigilance to mitigate the spread of Mpox disease for safeguarding global health., Funding: Center of Infectious Diseases at UTHealth, the University of Texas System, and the Texas Epidemic Public Health Institute. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of these funding organizations., Competing Interests: The authors declare no competing interest., (© 2023 The Author(s).)

Recent studies have emphasized the importance of single-cell spatial biology, yet available assays for spatial transcriptomics have limited gene recovery or low spatial resolution. Here we introduce CytoSPACE, an optimization method for mapping individual cells from a single-cell RNA sequencing atlas to spatial expression profiles. Across diverse platforms and tissue types, we show that CytoSPACE outperforms previous methods with respect to noise tolerance and accuracy, enabling tissue cartography at single-cell resolution., (© 2023. The Author(s).)

The human epidermal growth factor receptor 2 (HER2)-targeting trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) are antibody-drug conjugates (ADC) clinically used to treat HER2-positive breast cancer, with the latter receiving clinical approval in 2021 for HER2-positive gastric cancer. Lovastatin, a cholesterol-lowering drug, temporally elevates cell-surface HER2 in ways that enhance HER2-ADC binding and internalization. Methods: In an NCIN87 gastric xenograft model and a gastric patient-derived xenograft model, we used the 89 Zr-labeled or 64 Cu-labeled anti-HER2 antibody trastuzumab to investigate the dosing regimen of ADC therapy with and without coadministration of lovastatin. We compared the ADC efficacy of a multiple-dose ADC regime, which replicates the clinical dose regimen standard, with a single-dose regime. Results: T-DM1/lovastatin treatment inhibited tumor growth, regardless of multiple- or single-dose T-DM1 administration. Coadministration of lovastatin with T-DM1 or T-DXd as a single dose enhanced tumor growth inhibition, which was accompanied by a decrease in signal on HER2-targeted immuno-PET and a decrease in HER2-mediated signaling at the cellular level. DNA damage signaling was increased on ADC treatment in vitro. Conclusion: Our data from a gastric cancer xenograft show the utility of HER2-targeted immuno-PET to inform the tumor response to ADC therapies in combination with modulators of cell-surface target availability. Our studies also demonstrate that statins enhance ADC efficacy in both a cell-line and a patient-derived xenograft model in ways that enable a single-dose administration of the ADC., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: To investigate the association between body mass index (BMI) spectrum and complicated appendicitis and postoperative complications in pediatric patients., Background: Despite the impact of being overweight and obese on complicated appendicitis and postoperative complications, the implications of being underweight are unknown., Methods: A retrospective review of pediatric patients was conducted using NSQIP (2016-2020) data. Patient's BMI percentiles were categorized into underweight, normal weight, overweight, and obese. The 30-day postoperative complications were grouped into minor, major, and any. Univariate and multivariable logistic regression models were performed., Results: Among 23,153 patients, the odds of complicated appendicitis were 66% higher in underweight patients [odds ratio (OR)=1.66; 95% CI: 1.06-2.59] and 28% lower in overweight patients (OR=0.72; 95% CI: 0.54-0.95) than normal-weight patients. A statistically significant interaction between overweight and preoperative white blood cells (WBCs) increased the odds of complicated appendicitis (OR=1.02; 95% CI: 1.00-1.03). Compared to normal-weight patients, obese patients had 52% higher odds of minor (OR=1.52; 95% CI: 1.18-1.96) and underweight patients had 3 times the odds of major (OR=2.77; 95% CI: 1.22-6.27) and any (OR=2.82; 95% CI: 1.31-6.10) complications. A statistically significant interaction between underweight and preoperative WBC lowered the odds of major (OR=0.94; 95% CI: 0.89-0.99) and any complications (OR=0.94; 95% CI: 0.89-0.98)., Conclusions: Underweight, overweight, and interaction between overweight and preoperative WBC were associated with complicated appendicitis. Obesity, underweight, and interaction between underweight and preoperative WBC were associated with minor, major, and any complications. Thus, personalized clinical pathways and parental education targeting at-risk patients can minimize postoperative complications., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: People living with dementia or other cognitive decline and their caregivers (PLWD) increasingly rely on the web to find information about their condition and available resources and services. The recent advancements in large language models (LLMs), such as ChatGPT, provide a new alternative to the more traditional web search engines, such as Google., Objective: This study compared the quality of the results of ChatGPT and Google for a collection of PLWD-related queries., Methods: A set of 30 informational and 30 service delivery (transactional) PLWD-related queries were selected and submitted to both Google and ChatGPT. Three domain experts assessed the results for their currency of information, reliability of the source, objectivity, relevance to the query, and similarity of their response. The readability of the results was also analyzed. Interrater reliability coefficients were calculated for all outcomes., Results: Google had superior currency and higher reliability. ChatGPT results were evaluated as more objective. ChatGPT had a significantly higher response relevance, while Google often drew upon sources that were referral services for dementia care or service providers themselves. The readability was low for both platforms, especially for ChatGPT (mean grade level 12.17, SD 1.94) compared to Google (mean grade level 9.86, SD 3.47). The similarity between the content of ChatGPT and Google responses was rated as high for 13 (21.7%) responses, medium for 16 (26.7%) responses, and low for 31 (51.6%) responses., Conclusions: Both Google and ChatGPT have strengths and weaknesses. ChatGPT rarely includes the source of a result. Google more often provides a date for and a known reliable source of the response compared to ChatGPT, whereas ChatGPT supplies more relevant responses to queries. The results of ChatGPT may be out of date and often do not specify a validity time stamp. Google sometimes returns results based on commercial entities. The readability scores for both indicate that responses are often not appropriate for persons with low health literacy skills. In the future, the addition of both the source and the date of health-related information and availability in other languages may increase the value of these platforms for both nonmedical and medical professionals., (©Vagelis Hristidis, Nicole Ruggiano, Ellen L Brown, Sai Rithesh Reddy Ganta, Selena Stewart. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 25.07.2023.)

Background: Differences in arsenic metabolism capacity may influence risk for type 2 diabetes, but the mechanistic drivers are unclear. We evaluated the associations between arsenic metabolism with overall diabetes prevalence and with static and dynamic measures of insulin resistance among Mexican Americans living in Starr County, Texas., Methods: We utilized data from cross-sectional studies conducted in Starr County, Texas, from 2010-2014. A Mendelian randomization approach was utilized to evaluate the associations between arsenic metabolism and type 2 diabetes prevalence using the intronic variant in the arsenic methylating gene, rs9527, as the instrumental variable for arsenic metabolism. To further assess mechanisms for diabetes pathogenesis, proportions of the urinary arsenic metabolites were employed to assess the association between arsenic metabolism and insulin resistance among participants without diabetes. Urinary biomarkers of arsenic metabolites were modeled as individual proportions of the total. Arsenic metabolism was evaluated both with a static outcome of insulin resistance, homeostatic measure of assessment (HOMA-IR), and a dynamic measure of insulin sensitivity, Matsuda Index., Results: Among 475 Mexican American participants from Starr County, higher metabolism capacity for arsenic is associated with higher diabetes prevalence driven by worse insulin resistance. Presence of the minor T allele of rs9527 is independently associated with an increase in the proportion of monomethylated arsenic (MMA%) and is associated with an odds ratio of 0.50 (95% CI: 0.24, 0.90) for type 2 diabetes. This association was conserved after potential covariate adjustment. Furthermore, among participants without type 2 diabetes, the highest quartile of MMA% was associated with 22% (95% CI: -33.5%, -9.07%) lower HOMA-IR and 56% (95% CI: 28.3%, 91.3%) higher Matsuda Index for insulin sensitivity., Conclusions: Arsenic metabolism capacity, indicated by a lower proportion of monomethylated arsenic, is associated with increased diabetes prevalence driven by an insulin resistant phenotype among Mexican Americans living in Starr County, Texas.

This survey study aimed to assess the willingness of culturally diverse older adults to participate in COVID-19 research. The majority of the 276 participants were women (81%, n  = 223) and Black/African American (62%, n  = 172) or White Hispanic (20%, n  = 56). A key finding from the survey was less than 1 of 10 respondents would be likely to participate in COVID-19 related research if given the opportunity. There were no differences observed by gender, race or ethnicity. Implications of these findings are considered. These study findings indicate continued effort and better messaging strategies are required to increase awareness that COVID-19 related research needs to include culturally diverse older adults to ensure vaccines and treatments are efficacious in different populations., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background/aims: In pediatric populations, the epidemiology of facial trauma, their injury patterns, distribution, and outcomes are well known, However, little is known about the risk factors and impacts of minor and moderate facial injuries on in-hospital mortality among children in the United States of America (USA). The aim of this study was to determine the prevalence and risk factors for in-hospital mortality among pediatric patients following facial injuries in the USA., Material and Methods: A cross-sectional study was conducted with data from the National Trauma Data Bank's pediatric hospitalized patients (<18 years) with facial injuries (International Classification of Diseases, Ninth Revision codes 802.00 to 802.9 and Tenth Revision codes S02.2 to S02.92) between January 01, 2016-December 31, 2019. A multivariable logistic regression model was utilized to identify the risk factors for in-hospital mortality., Results: A total of 61,294 pediatric patients (mean age 11.9 years, 69.6% males) were included in the analysis. The estimated prevalence of in-hospital mortality following facial injuries was 2.4% (n = 1480). In terms of mortality, compared to those who sustained minor facial injuries, patients with (1) moderate injuries had 43% higher odds (OR = 1.43; 95% CI: 1.25-1.64, p < .0001), (2) serious injuries had seven times higher odds (OR = 7.81; 95% CI: 6.67-9.14, p < .0001), (3) severe injuries had 16 times higher odds (OR = 16.07; 95% CI: 12.62-20.46, p < .0001), and (4) critical/maximum injury virtually unsurvivable had 145 times higher odds (OR = 145.24; 95% CI: 113.82-185.33, p < .0001) of death after controlling for age, race, insurance status, comorbidities, and hospital complications., Conclusions: The severity of facial injury, age 5-17 years, uninsured status, and those with a mental/personality disorder were risk factors for in-hospital mortality among pediatric patients following facial injuries in this population-level analysis. A better understanding of these risk factors is needed for clinical management of pediatric patients to prevent in-hospital mortality following facial injuries., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)