Citations

Type 1 diabetes is characterized by the autoimmune destruction of pancreatic β cells, resulting in permanent loss of glucose homeostasis. Islet transplantation is a promising potential cure that remains hindered by immune rejection. We previously showed that ST8Sia6 expression on tumors reduced immune surveillance and hypothesized that this sialyltransferase could protect β cells from autoimmune destruction. Here, we demonstrate that ectopic expression of ST8Sia6 in β cells of female nonobese diabetic mice (NOD βST) decreased the spontaneous incidence of diabetes by 90% and preserved β cell mass. NOD βST mice had comparable insulitis at 8 weeks of age that did not progress over time compared with littermate controls. β Cell–autoreactive B and T cells were present in NOD βST mice, indicating a peripheral rather than central mechanism of immune tolerance. The islets of NOD βST mice displayed a dampened type 1 immune response and reduced IL-12p35 expression in dendritic cells compared with those of littermate controls. The peripheral protection persisted even after removal of ST8Sia6 expression at 20 weeks of age, indicating that transient expression was sufficient for establishment of tolerance. These results demonstrate that ST8Sia6 protects β cells from immune-mediated attack and rejection, highlighting its therapeutic potential for autoimmune disorders.

Abstract Introduction The prevalence of pre‐pregnancy obesity, including pre‐pregnancy class 3 obesity, has increased over time, with significant implications for maternal and neonatal well‐being. Regular physical activity may mitigate these risks. Available data suggest that most pregnant individuals do not meet the recommended physical activity guidelines of accumulating at least 150 min of moderate‐intensity exercise per week. Importantly, limited data are available regarding physical activity patterns in individuals with higher body mass index (BMI), particularly for those with class 3 obesity (BMI ≥ 40 kg/m 2 ). The aim of this study was to evaluate whether pregnant individuals are meeting physical activity guidelines. We assessed self‐reported physical activity across BMI categories including those with class 3 obesity, further subdivided into BMI of 40–49.9 and ≥ 50 kg/m 2 . Methods This is a retrospective cohort study of individuals at an academic hospital system who delivered between May 1, 2018 and May 1, 2023. To be included, individuals had to respond to the following two‐item physical activity questionnaire early in pregnancy: (1) “On average, how many days per week do you engage in moderate to strenuous exercise?” And (2) “On average, how many minutes do you engage in exercise at this level?” From these two questions, total minutes per week of activity were calculated. Individuals met physical activity guidelines if they engaged in ≥ 150 min of physical activity per week. Data were analyzed using Kruskal–Wallis and Chi‐square tests. Results A total of 6884 individuals were incl uded in the cohort. A total of 510 individuals met the criteria for class 3 obesity, with 61 having a pre‐pregnancy BMI ≥ 50 kg/m 2 . Among normal weight individuals (BMI 18.5–24.9 kg/m 2 ), 34% met physical activity guidelines. Overweight and obese individuals were significantly less physically active than those with normal BMI ( p < 0.05). Only 22% of those with BMI 40–49.9 kg/m 2 and 18% of those with BMI ≥ 50 kg/m 2 reported sufficient physical activity. Conclusion Our results are consistent with existing data, showing that pregnant individuals are not meeting physical activity goals. Pregnant individuals who are overweight or obese engage in significantly less physical activity compared to those with a BMI in the normal range, with the lowest levels of activity observed among individuals with class 3 obesity. More data are needed on physical activity among pregnant individuals with class 3 obesity, including evaluation of potential interventions to increase activity as well as barriers to participation. Increasing physical activity in this group may positively impact both maternal and neonatal health.

Blood iron levels are related to many health conditions, affecting hundreds of millions of individuals worldwide. To aid in the prevention and treatment of iron-related disorders, previous research has developed a low-cost, accurate, point-of-care method for measuring iron from a single finger-prick blood sample. This study builds upon that work by introducing an improved imaging method that accurately reads sensor images irrespective of variations in environmental illumination and camera quality. Smartphone cameras were used as analytical tools, demonstrating an average coefficient of variation of 5.13% across different phone models, and absorbance results were found to be improved by 8.80% compared to the method in a previous study. The proposed method successfully enhances iron detection accuracy under diverse lighting conditions, paving the way for smartphone-based sensing of other colorimetric reactions involving various analytes.

Objectives: This study evaluates the efficacy of existing and new aerosol mitigation methods during nebulization (Neb) in combination with high-flow nasal cannula (HFNC) oxygen supplementation and non-invasive ventilation (NIV). Methods: We recorded fugitive aerosol particle concentrations over time and assessed the peak (P) and area (A) efficacy of active and passive mitigation methods, comparing them to a no-mitigation condition. Peak efficacy was measured by the reduction in maximum aerosol concentration, while area efficacy was quantified by the reduction of the area under the aerosol concentration–time curve. Results: For HFNC with Neb, we found that active mitigation using a mask with a biofilter and a fan (referred to as the aerosol barrier mask) significantly outperformed passive mitigation with a face mask. The peak and area efficacy for aerosol reduction were 99.0% and 96.4% for active mitigation and 35.9% and 7.6% for passive mitigation, respectively. For NIV with Neb, the active mitigation method, using a box with a biofilter and fan, also outperformed passive mitigation using only the box. The peak and area efficacy for aerosol reduction were 92.1% and 85.5% for active mitigation and 53.7.0% and 25.4% for passive mitigation, respectively. Conclusion: We concluded that active mitigation set up systems advantageous for effective reduction of airborne aerosols during aerosol generated procedures.

Abstract INTRODUCTION African American (AA) individuals are underrepresented in biomarker studies for Alzheimer's disease (AD). Biomarkers that reflect the heterogeneity of AD and achieve the greatest accuracy across populations are sorely needed. METHODS Untargeted proteome measurements were obtained using the SomaScan 7k platform to identify novel plasma biomarkers for AD in AA participants with clinical diagnoses of AD dementia ( n = 181) and cognitively unimpaired (CU, n = 142). Machine learning was used to identify a set of plasma proteins that yielded the best classification accuracy. RESULTS A set of 36 proteins achieved an area under the curve (AUC) of 0.94 to classify AD dementia versus CU, a 16% improvement over age, sex, and apolipoprotein E ( APOE) . This finding was replicated in multiple plasma and brain datasets (AUCs 0.73–0.97). Our findings underscore the importance of matrisome and cerebrovascular dysfunction in AD pathophysiology. DISCUSSION This study demonstrates the potential of biomarker discovery through untargeted plasma proteomics and machine learning. Highlights Conducted large‐scale plasma proteomics in Alzheimer's disease (AD) versus cognitively unimpaired controls. Machine learning biomarker discovery was replicated in an independent cohort. Novel set of proteins distinguishes AD versus controls with high accuracy (area under the curve [AUC] = 0.94). Achieved reproducibility across multiple replication cohorts (AUC = 0.73–0.97). Network analyses implicates matrisome biology and cerebrovascular dysfunction.

ABSTRACTObjectiveTo conduct an economic evaluation of a group mindfulness program compared to an education support program for breast cancer survivors (BCS).MethodsThe cost‐utility analysis (cost per quality‐adjusted life year [QALY]) was performed from a single‐center randomized controlled trial in the United States. Data from 181 BCS were included in the analysis (91 from the mindfulness‐based stress reduction for breast cancer, MBSR(BC) and 90 from the Breast Cancer Education Support, (BCES)). Analyses were conducted from two perspectives: societal and healthcare system. The EuroQol EQ‐5D‐5L was used to measure quality of life and the Client Service Receipt Inventory (CSRI) was used to measure health services utilization from baseline through 26 weeks. The impact of MBSR(BC) on health services utilization and costs was estimated with generalized linear models.ResultsIn the reference case analyses (societal perspective), the average total cost in the MBSR(BC) group was $5744 compared with $6140 in the BCES group. At the end of follow‐up, the MBSR(BC) group dominated BCES in terms of Incremental Cost Utility Ratio (ICUR), with MBSR(BC) providing an incremental cost of −$541 (95% CI: −$3400, $2318) and a 0.021 QALY (95% CI: −0.014, 0.055). Net monetary benefit (NMB) analysis showed that MBSR(BC) has a higher probability of achieving positive NMB across a range of possible societal willingness‐to‐pay for improving quality of life.ConclusionsOur findings suggest that MBSR(BC) is likely to be cost‐effective for breast cancer survivors over 6 months. Cost savings primarily resulted from reduced ER and hospital admissions and tests.

Abstract: Papillary eccrine adenoma/tubular apocrine adenoma (PEA/TAA) is a rare sweat gland neoplasm. Because PEA/TAA shares morphologic features with other sweat gland tumors, including digital papillary adenocarcinoma, histologic diagnosis may be challenging. We report a case of PEA/TAA presenting as a nodule on the left foot of a 43-year-old man. Histopathologic examination revealed a well-circumscribed dermal proliferation of variably sized glands composed of ductal cells with an outer layer of myoepithelial cells. By immunohistochemistry, the ductal tumor cells showed strong, diffuse expression of BRAF V600E, and the myoepithelial cells were positive for p63. This case illustrates the utility of immunohistochemistry in the diagnosis of this rare neoplasm. Particularly when PEA/TAA is located on an acral site, distinction from digital papillary adenocarcinoma is critical, because these tumors show significant differences in clinical behavior.

Objective Mechanical thrombectomy (MT) is well-established for the treatment of acute ischemic stroke (AIS) from large vessel occlusion (LVO), with growing data supporting the expansion to distal and medium vessel occlusions (DMVO). Despite successful recanalization in DMVO, certain patients still experience poor long-term clinical outcomes, prompting our study to comprehensively explore pre-MT factors influencing outcome despite excellent recanalization (final modified Thrombolysis in Cerebral Infarction [mTICI] score ≥2c). Methods We retrospectively examined data from patients who consecutively underwent MT for a primary middle cerebral artery (MCA) DMVO across 37 centers in North America, Asia, and Europe. We identified baseline clinical and imaging factors associated with poor clinical outcome (defined as a modified Rankin Scale [mRS] score of 3–6) at 3 months, despite excellent recanalization using a multivariable model. Results Between September 2017 and July 2021, 623 patients achieved mTICI > 2b and they were included in our study. Among them, 198 (32%) experienced a poor clinical outcome (mRS 3–6). Predictors of poor clinical outcome included higher age (OR 1.05 [1.03–1.07], p < 0.001), higher NIHSS at admission (OR 1.12 [1.08–1.15], p < 0.001), higher baseline mRS (OR 1.77 [0.96–3.26], p = 0.067), and diabetes (OR 1.59 [1.01–2.48], p = 0.044). Higher ASPECTS was associated with a decreased risk of poor clinical outcome (OR 0.82 [0.71–0.94], p = 0.006). Conclusion Older age, diabetes, higher baseline mRS, and NIHSS were associated with poor clinical outcome in MCA DMVO despite excellent recanalization. Conversely, a higher ASPECTS decreased the probability of such an outcome.

Introduction: Amyloidosis complicated by heart failure (HF) poses significant mortality. We sought to identify trends in comorbid amyloidosis and HF mortality in the recent 22- year period. Methods: Mortality due to amyloid and HF as contributors of death were queried from death certificates using the CDC database from 1999 to 2020. Mortality rates and their 95% confidence intervals were adjusted for age (AAMR) through the Direct method and compared by demographic subpopulations. The Monte-Carlo permutation test was used to estimate the annual percentage change (APC). Log-linear regression models were utilized to assess temporal variation in mortality. Results: Age-adjusted mortality rates (AAMR) increased from 0.09 [0.08-0.10] in 1999 to 0.27 [0.25-0.29] in 2020. Mortality increased from 1999 to 2013 (APC +1.4, p=0.048) with an accelerating inflection point in 2013 to 2020 (APC +13.3, p<0.001). AAMR was higher among male populations (AAMR 0.20 [0.20-0.21]) compared to female populations (AAMR 0.07 [0.07- 0.07]). A significant inflection point in uprising mortality rates was observed for both male and female populations in 2013 (p<0.001). Mortality was highest among Black populations (AAMR 0.33), followed by White (AAMR 0.10), Asian/Pacific Islander (AAMR 0.06), and American Indian/Alaska Native populations (AAMR 0.04). Among Black populations, mortality remained consistent from 1999 to 2012 (APC +1.1, p=0.184), followed by an increase from 2012 to 2020 (APC +14.0, p<0.001). Among White populations, mortality remained stagnant from 1999 to 2013 (APC +0.7, p=0.302), followed by an increase starting in 2013 to 2020 (APC +13.5, p<0.001). Discussion: Our findings of a marked rise in HF-related mortality in patients with amyloidosis since 2013 highlighted the profound impact of enhanced diagnostic awareness, novel imaging techniques, and emerging therapeutics. Our analysis also showed mortality disparities between sexes, and geographic locations, races, and ethnicity that warrant targeted public health interventions. Conclusions: Amyloid and HF mortality increased in the recent 22-year period, primarily starting in 2013, emphasizing the urgent need for targeted intervention to address these disparities.