Social Phenotyping for Cardiovascular Risk Stratification in Electronic Health Registries.

PURPOSE OF REVIEW: Evaluation of social influences on cardiovascular care requires a comprehensive analysis encompassing economic, societal, and environmental factors. The increased utilization of electronic health registries provides a foundation for social phenotyping, yet standardization in methodology remains lacking. This review aimed to elucidate the primary approaches to social phenotyping for cardiovascular risk stratification through electronic health registries. RECENT FINDINGS: Social phenotyping in the context of cardiovascular risk stratification within electronic health registries can be separated into four principal approaches: place-based metrics, questionnaires, ICD Z-coding, and natural language processing. These methodologies vary in their complexity, advantages and limitations, and intended outcomes. Place-based metrics often rely on geospatial data to infer socioeconomic influences, while questionnaires may directly gather individual-level behavioral and social factors. Z-coding, a relatively new approach, can capture data directly related to social determinant of health domains in the clinical context. Natural language processing has been increasingly utilized to extract social influences from unstructured clinical narratives-offering nuanced insights for risk prediction models. Each method plays an important role in our understanding and approach to using social determinants data for improving population cardiovascular health. These four principal approaches to social phenotyping contribute to a more structured approach to social determinant of health research via electronic health registries, with a focus on cardiovascular risk stratification. Social phenotyping related research should prioritize refining predictive models for cardiovascular diseases and advancing health equity by integrating applied implementation science into public health strategies.

Synthesis of a 3D Flower-Like BiOCl/Bi-MOF Heterostructure for High-Performance Removal of Rhodamine B and Tetracycline Hydrochloride.

Semiconductor materials based on bismuth metal have been extensively explored for their potential in photocatalytic applications owing to their distinctive crystal structure. Herein, we present the development of a hybrid photocatalyst, CAU-17/BiOCl, featuring a flower-like nanosheet morphology tailored for the photocatalytic degradation of organic contaminants such as rhodamine B (RhB) and tetracycline hydrochloride (TCH). The composite material is obtained by growing thin CAU-17 layers directly onto the host flower-like BiOCl nanosheets under solvothermal conditions. The optimized CAU-17/BiOCl composite possesses excellent photocatalytic performance, achieving a notable 96.0% removal rate for RhB and 78.4% for TCH after 60 and 90 min of LED light irradiation, respectively. This boosted activity is attributed to the heightened absorption of visible light caused by BiOCl and the provision of additional reaction sites due to the thin CAU-17 layers. Furthermore, the establishment of an S-scheme heterojunction mechanism enables efficient charge separation between CAU-17 and BiOCl, facilitating the separation of photoinduced electrons (e-) and holes (h+). Analysis of the degradation mechanism of RhB and TCH reveals the predominant role of superoxide radicals (•O2-), e-, and h+ in the photocatalytic degradation process. Moreover, the removal efficiency of TCH can reach approximately 64.5% after four cycles of recycling of CAU-17/BiOCl. Our work provides a facile, effective solution and a theoretically explained approach for the effective degradation of pollutants using heterojunction photocatalysts.

Pharmacological Management of Transthyretin Amyloid Cardiomyopathy: A scoping review.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is characterized by the accumulation of transthyretin (TTR) protein in the myocardium. The aim of this scoping review is to provide a descriptive summary of the clinical trials and observational studies that evaluated the clinical efficacy and safety of various agents used in ATTR-CM, with a goal of identifying the contemporary gaps in literature and to reveal future research opportunities. METHODS AND RESULTS: The search was performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search using several databases for observational and clinical trials investigating the treatment modalities for ATTR-CM was undertaken. We extracted data including study characteristics, primary endpoints, and adverse events from each study. A total of 19 studies were included in our scoping review. 8 were clinical trials and 11 were observational analyses. The drugs evaluated included tafamadis, acoramidis, revusiran, TUDCA and doxycycline, diflusinil, inotersan, eplontersen, and patisiran. Tafamidis has shown to be efficacious in the management of ATTR-CM, particularly when initiated at earlier stages. RNA interference and antisense oligonucleotide drugs have shown promising impacts on quality of life. Additionally, this review identified gaps in the literature, particularly among long-term outcomes, comparative effectiveness, and the translation of research into economic contexts. CONCLUSIONS: Multiple pharmacological options are potential disease-modifying therapies for ATTR-CM. However, many gaps exist in the understanding of these various drug therapies, warranting further research. The future directions for management of ATTR-CM are promising in regard to improving prognostic implications.

Improving Micro-EDM Machining Efficiency for Titanium Alloy Fabrication with Advanced Coated Electrodes.

Enhancing the operational efficacy of electrical discharge machining (EDM) is crucial for achieving optimal results in various engineering materials. This study introduces an innovative solution-the use of coated electrodes-representing a significant advancement over current limitations. The choice of coating material is critical for micro-EDM performance, necessitating a thorough investigation of its impact. This research explores the application of different coating materials (AlCrN, TiN, and Carbon) on WC electrodes in micro-EDM processes specifically designed for Ti-6Al-4V. A comprehensive assessment was conducted, focusing on key quality indicators such as depth of cut (Z), tool wear rate (TWR), overcut (OVC), and post-machining surface quality. Through rigorous experimental methods, the study demonstrates substantial improvements in these quality parameters with coated electrodes. The results show significant enhancements, including increased Z, reduced TWR and OVC, and improved surface quality. This evidence underscores the effectiveness of coated electrodes in enhancing micro-EDM performance, marking a notable advancement in the precision and quality of Ti-6Al-4V machining processes. Among the evaluated coatings, AlCrN-coated electrodes exhibited the greatest increase in Z, the most significant reduction in TWR, and the best OVC performance compared to other coatings and the uncoated counterpart.

Navigating the liver landscape: upcoming pharmacotherapies for primary sclerosing cholangitis.

INTRODUCTION: Primary sclerosing cholangitis (PSC) is a bile duct disorder characterized by ductular reaction, hepatic inflammation, and liver fibrosis. The pathogenesis of PSC is still undefined, and treatment options for patients are limited. Previous clinical trials evaluated drug candidates targeting various cellular functions and pathways, such as bile acid signaling and absorption, gut bacteria and permeability, and lipid metabolisms. However, most of phase III clinical trials for PSC were disappointing, except vancomycin therapy, and there are still no established medications for PSC with efficacy and safety confirmed by phase IV clinical trials. AREAS COVERED: This review summarizes the currently ongoing or completed clinical studies for PSC, which are phase II or further, and discusses therapeutic targets and strategies, limitations, and future directions and possibilities of PSC treatments. A literature search was conducted in PubMed and ClinicalTrials.gov utilizing the combination of the searched term 'primary sclerosing cholangitis' with other keywords, such as 'clinical trials,' 'antibiotics,' or drug names. Clinical trials at phase II or further were included for consideration. EXPERT OPINION: Only vancomycin demonstrated promising therapeutic effects in the phase III clinical trial. Other drug candidates showed futility or inconsistent results, and the search for novel PSC treatments is still ongoing.

Radiological Features of Herpetic Encephalitis in Children.

BACKGROUND: Nonspecific clinical manifestations and unclear radiological features may delay treatment initiation in pediatric patients with Herpes simplex encephalitis (HSE). The aim of this study is to analyze the clinical and radiological features of the disease. METHODS: Clinical, laboratory, and magnetic resonance imaging (MRI) data were obtained retrospectively from a group of 37 hospitalized pediatric patients older than two months and with a polymerase chain reaction-confirmed HSE diagnosis. Clinical severity (i.e., mechanical ventilatory support) and outcome at discharge (i.e., pediatric modified Rankin Scale [ped-mRS]) were also assessed. RESULTS: Median age was 14 months (interquartile range: 10-36). All patients survived, 15 (41%) had complete recovery (i.e., ped-mRS = 0), and 10 (27%) had significant residual disability at discharge (i.e., ped-mRS ≥3). Brain MRI was obtained in 31 patients. T2-hyperintense lesions were usually bilateral (28, 90%) and multifocal (30, 97%). Hemorrhage and mass effect were observed in 13 (42%) and 15 (48%) patients, respectively. Parenchymal lesions involved the temporal lobes (94%), insula (90%), parietal lobes (84%), and frontal lobes (61%). Occipital lesions were rare. In multivariable binary logistic regression models the presence of altered consciousness was associated with mechanical ventilation (odds ratio [OR] = 8.2, Nagelkerke R2 = 0.22), whereas the involvement of the occipital lobes (OR = 7.8) and the administration of vasopressors (OR = 12.1) were independent predictors of poor outcome (Nagelkerke R2 = 0.41). CONCLUSIONS: Brain MRI is useful for diagnosis and outcome assessment in pediatric HSE. Radiological patterns with common frontotemporal involvement overlap adults, but multifocal and parietal lobe abnormalities are observed as well.

A Longitudinal Analysis of Mortality Related to Chronic Viral Hepatitis and Hepatocellular Carcinoma in the United States.

(1) Background: Hepatocellular carcinoma (HCC) contributes to the significant burden of cancer mortality in the United States (US). Despite highly efficacious antivirals, chronic viral hepatitis (CVH) remains an important cause of HCC. With advancements in therapeutic modalities, along with the aging of the population, we aimed to assess the contribution of CVH in HCC-related mortality in the US between 1999-2020. (2) Methods: We queried all deaths related to CVH and HCC in the multiple-causes-of-death files from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) database between 1999-2020. Using the direct method of standardization, we adjusted all mortality information for age and compared the age-adjusted mortality rates (AAMRs) across demographic populations and by percentile rankings of social vulnerability. Temporal shifts in mortality were quantified using log-linear regression models. (3) Results: A total of 35,030 deaths were identified between 1999-2020. The overall crude mortality increased from 0.27 in 1999 to 8.32 in 2016, followed by a slight reduction to 7.04 in 2020. The cumulative AAMR during the study period was 4.43 (95% CI, 4.39-4.48). Males (AAMR 7.70) had higher mortality rates compared to females (AAMR 1.44). Mortality was higher among Hispanic populations (AAMR 6.72) compared to non-Hispanic populations (AAMR 4.18). Higher mortality was observed in US counties categorized as the most socially vulnerable (AAMR 5.20) compared to counties that are the least socially vulnerable (AAMR 2.53), with social vulnerability accounting for 2.67 excess deaths per 1,000,000 person-years. (4) Conclusions: Our epidemiological analysis revealed an overall increase in CVH-related HCC mortality between 1999-2008, followed by a stagnation period until 2020. CVH-related HCC mortality disproportionately affected males, Hispanic populations, and Black/African American populations, Western US regions, and socially vulnerable counties. These insights can help aid in the development of strategies to target vulnerable patients, focus on preventive efforts, and allocate resources to decrease HCC-related mortality.

Deconvolution analysis identified altered hepatic cell landscape in primary sclerosing cholangitis and primary biliary cholangitis.

Introduction: Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are characterized by ductular reaction, hepatic inflammation, and liver fibrosis. Hepatic cells are heterogeneous, and functional roles of different hepatic cell phenotypes are still not defined in the pathophysiology of cholangiopathies. Cell deconvolution analysis estimates cell fractions of different cell phenotypes in bulk transcriptome data, and CIBERSORTx is a powerful deconvolution method to estimate cell composition in microarray data. CIBERSORTx performs estimation based on the reference file, which is referred to as signature matrix, and allows users to create custom signature matrix to identify specific phenotypes. In the current study, we created two custom signature matrices using two single cell RNA sequencing data of hepatic cells and performed deconvolution for bulk microarray data of liver tissues including PSC and PBC patients. Methods: Custom signature matrix files were created using single-cell RNA sequencing data downloaded from GSE185477 and GSE115469. Custom signature matrices were validated for their deconvolution performance using validation data sets. Cell composition of each hepatic cell phenotype in the liver, which was identified in custom signature matrices, was calculated by CIBERSORTx and bulk RNA sequencing data of GSE159676. Deconvolution results were validated by analyzing marker expression for the cell phenotype in GSE159676 data. Results: CIBERSORTx and custom signature matrices showed comprehensive performance in estimation of population of various hepatic cell phenotypes. We identified increased population of large cholangiocytes in PSC and PBC livers, which is in agreement with previous studies referred to as ductular reaction, supporting the effectiveness and reliability of deconvolution analysis in this study. Interestingly, we identified decreased population of small cholangiocytes, periportal hepatocytes, and interzonal hepatocytes in PSC and PBC liver tissues compared to healthy livers. Discussion: Although further studies are required to elucidate the roles of these hepatic cell phenotypes in cholestatic liver injury, our approach provides important implications that cell functions may differ depending on phenotypes, even in the same cell type during liver injury. Deconvolution analysis using CIBERSORTx could provide a novel approach for studies of specific hepatic cell phenotypes in liver diseases.

Rural-urban stroke mortality gaps in the United States.

INTRODUCTION: Disparities in stroke outcomes, influenced by the use of systemic thrombolysis, endovascular therapies, and rehabilitation services, have been identified. Our study assesses these disparities in mortality after stroke between rural and urban areas across the United States (US). METHODS: We analyzed the CDC data on deaths attributed to cerebrovascular disease from 1999 to 2020. Data was categorized into rural and urban regions for comparative purposes. Age-adjusted mortality rates (AAMR) were computed using the direct method, allowing us to examine the ratios of rural to urban deaths for the cumulative population and among demographic subpopulations. Linear regression models were used to assess temporal changes in mortality ratios over the study period, yielding beta-coefficients (ß). RESULTS: There was a total of 628,309 stroke deaths in rural regions and 2,556,293 stroke deaths within urban regions. There were 1.13 rural deaths for each one urban death per 100,000 population in 1999 and 1.07 in 2020 (ß = -0.001, ptrend = 0.41). The rural-urban mortality ratio in Hispanic populations decreased from 1.32 rural deaths for each urban death per 100,000 population in 1999 to 0.85 in 2020 (ß = -0.011, ptrend < 0.001). For non-Hispanic populations, mortality remained stagnant with 1.12 rural deaths for each urban death per 100,000 population in 1999 and 1.07 in 2020 (ß = -0.001, ptrend = 0.543). Regionally, the Southern US exhibited the highest disparity with a urban-rural mortality ratio of 1.19, followed by the Northeast (1.13), Midwest (1.04), and West (1.01). CONCLUSIONS: Our findings depict marked disparities in stroke mortality between rural and urban regions, emphasizing the importance of targeted interventions to mitigate stroke-related disparities.

United States-Mexico Border Disparities in Alcoholic Liver Disease Mortality: A Cross-Sectional Analysis 1999-2020.

BACKGROUND: US-Mexico (US-MX) border regions are impacted by socioeconomic disadvantages. Alcohol use disorder remains widely prevalent in US-MX border regions, which may increase the risk of alcoholic liver disease (ALD). GOALS: We aimed to characterize ALD mortality trends in border regions compared to non-border regions from 1999 to 2020 in the United States (US). METHODS: We performed a cross-sectional analysis using the CDC repository. We queried death certificates to find ALD-related deaths from 1999 to 2020, which included demographic information such as gender, race/ethnicity, and area of residence. We estimated age-adjusted mortality rates (AAMR) per 100,000 population and compared the AAMRs across border and non-border regions. We also explored yearly mortality shifts using log-linear regression models and calculated the average annual percentage change (AAPC) using the Monte Carlo permutation test. RESULTS: In all, 11,779 ALD-related deaths were identified in border regions (AAMR 7.29) compared with 361,523 in non-border regions (AAMR 5.03). Border male (AAMR 11.21) and female (AAMR 3.77) populations were higher compared with non-border male (AAMR 7.42) and female (2.85) populations, respectively. Border non-Hispanic populations (AAMR 7.53) had higher mortality compared with non-border non-Hispanic populations (4.79), while both populations experienced increasing mortality shifts (AAPC +1.7, P<0.001 and +3.1, P<0.001, respectively). Border metropolitan (AAMR 7.35) and non-metropolitan (AAMR 6.76) regions had higher mortality rates compared with non-border metropolitan (AAMR 4.96) and non-metropolitan (AAMR 5.44) regions. CONCLUSIONS: Mortality related to ALD was higher in border regions compared with non-border regions. Border regions face significant health disparities when comparing ALD-related mortality.

Construction of BiOCl/bismuth-based halide perovskite heterojunctions derived from the metal-organic framework CAU-17 for effective photocatalytic degradation.

The designed synthesis of an S-scheme heterojunction has possessed a great potential for improving photocatalytic wastewater treatment by demonstrating increased the photoredox capacity and improved the charge separation efficiency. Here, we introduce the fabrication of a heterojunction-based photocatalyst comprising bismuth oxychloride (BiOCl) and bismuth-based halide perovskite (BHP) nanosheets, derived from metal-organic frameworks (MOFs). Our composite photocatalyst is synthesized through a one-pot solvothermal strategy, where a halogenation process is applied to a bismuth-based metal-organic framework (CAU-17) as the precursor for bismuth sourcing. As a result, the rod-like structure of CAU-17 transforms into well-defined plate and nanosheet architectures after 4 and 8 h of solvothermal treatment, respectively. The modulation of the solvothermal reaction time facilitates the establishment of an S-scheme heterojunction, resulting in an increase in the photocatalytic degradation efficiency of rhodamine B (RhB) and sulfamethoxazole (SMX). The optimized BiOCl/BHP composite exhibits superior RhB and SMX degradation rates, achieving 99.8% degradation of RhB in 60 min and 75.1% degradation of SMX in 300 min. Also, the optimized BiOCl/BHP composite (CAU-17-st-8h sample) exhibited the highest rate constant (k = 3.48 × 10-3 min-1), nearly 6 times higher than that of the bare BHP in the photocatalytic degradation process of SMX. The enhanced photocatalytic efficiency can be endorsed to various factors: (i) the in-situ formation of two-components BiOCl/BHP photocatalyst, derived from CAU-17, effectively suppresses the aggregation of pristine BHP and BiOCl particles; (ii) the S-scheme heterostructure establishes a closely-knit interfacial connection, thereby facilitating efficient pathways for charge separation/transfer; and (iii) the BiOCl/BHP heterostructure enhances its capacity to absorb visible light. Our investigation establishes an effective strategy for constructing heterostructured photocatalysts, offering significant potential for application in photocatalytic wastewater treatment.

Influence of social vulnerability index on Medicare beneficiaries' expenditures upon discharge.

Medicare beneficiaries' healthcare spending varies across geographical regions, influenced by availability of medical resources and institutional efficiency. We aimed to evaluate whether social vulnerability influences healthcare costs among Medicare beneficiaries. Multivariable regression analyses were conducted to determine whether the social vulnerability index (SVI), released by the Centers for Disease Control and Prevention (CDC), was associated with average submitted covered charges, total payment amounts, or total covered days upon hospital discharge among Medicare beneficiaries. We used information from discharged Medicare beneficiaries from hospitals participating in the Inpatient Prospective Payment System. Covariate adjustment included demographic information consisting of age groups, race/ethnicity, and Hierarchical Condition Category risk score. The regressions were performed with weights proportioned to the number of discharges. Average submitted covered charges significantly correlated with SVI (ß = 0.50, p < 0.001) in the unadjusted model and remained significant in the covariates-adjusted model (ß = 0.25, p = 0.039). The SVI was not significantly associated with the total payment amounts (ß = -0.07, p = 0.238) or the total covered days (ß = 0.00, p = 0.953) in the adjusted model. Regional variations in Medicare beneficiaries' healthcare spending exist and are influenced by levels of social vulnerability. Further research is warranted to fully comprehend the impact of social determinants on healthcare costs.

Loss-of-function mutation in PRMT9 causes abnormal synapse development by dysregulation of RNA alternative splicing.

Protein arginine methyltransferase 9 (PRMT9) is a recently identified member of the PRMT family, yet its biological function remains largely unknown. Here, by characterizing an intellectual disability associated PRMT9 mutation (G189R) and establishing a Prmt9 conditional knockout (cKO) mouse model, we uncover an important function of PRMT9 in neuronal development. The G189R mutation abolishes PRMT9 methyltransferase activity and reduces its protein stability. Knockout of Prmt9 in hippocampal neurons causes alternative splicing of ~1900 genes, which likely accounts for the aberrant synapse development and impaired learning and memory in the Prmt9 cKO mice. Mechanistically, we discover a methylation-sensitive protein-RNA interaction between the arginine 508 (R508) of the splicing factor 3B subunit 2 (SF3B2), the site that is exclusively methylated by PRMT9, and the pre-mRNA anchoring site, a cis-regulatory element that is critical for RNA splicing. Additionally, using human and mouse cell lines, as well as an SF3B2 arginine methylation-deficient mouse model, we provide strong evidence that SF3B2 is the primary methylation substrate of PRMT9, thus highlighting the conserved function of the PRMT9/SF3B2 axis in regulating pre-mRNA splicing.

Ischemic heart disease mortality in individuals with inflammatory bowel disease: A nationwide analysis of disparities in the United States.

INTRODUCTION: Inflammatory bowel disease (IBD) is linked to immune-mediated pathogenesis and a pro-inflammatory state, leading to accelerated atherosclerosis. This earlier onset of clinical cardiovascular disease poses significant morbidity and mortality. We sought to identify IHD mortality trends in individuals with IBD in the United States (US). METHODS: Mortality due to ischemic heart diseases (IHD) as the underlying cause of death with the IBD as a contributor of death were queried from death certificates using the CDC database from 1999 to 2020. Yearly crude mortality rates (CMR) were estimated by dividing the death count by the respective population size, reported per 100,000 persons. Mortality rates were adjusted for age using the Direct method and compared by demographic subpopulations. Log-linear regression models were utilized to assess temporal variation (annual percentage change [APC]) in mortality. RESULTS: Age-adjusted mortality rates (AAMR) decreased from 0.11 in 1999 to 0.07 in 2020, primarily between 1999 and 2018 (APC -4.41, p < 0.001). AAMR was higher among male (AAMR 0.08) and White (AAMR 0.08) populations compared to female populations (AAMR 0.06) and Black (AAMR 0.04) populations, respectively. No significant differences were seen when comparing mortality between urban (AAMR 0.07) and rural (AAMR 0.08) regions. Southern US regions (AAMR 0.06) had the lowest mortality rates when compared to the other US census regions: Northeastern (AAMR 0.08), Midwestern (AAMR 0.08), and Western (AAMR 0.08). CONCLUSION: Disparities in IHD mortality exist among individuals with IBD in the US based on demographic factors, with an overall decline in mortality during the 22-year period. Further investigation is warranted to confirm these findings and evaluate for contributors to the observed disparities.

A bibliometric literature review of stock price forecasting: From statistical model to deep learning approach.

We introduce a comprehensive analysis of several approaches used in stock price forecasting, including statistical, machine learning, and deep learning models. The advantages and limitations of these models are discussed to provide an insight into stock price forecasting. Traditional statistical methods, such as the autoregressive integrated moving average and its variants, are recognized for their efficiency, but they also have some limitations in addressing non-linear problems and providing long-term forecasts. Machine learning approaches, including algorithms such as artificial neural networks and random forests, are praised for their ability to grasp non-linear information without depending on stochastic data or economic theory. Moreover, deep learning approaches, such as convolutional neural networks and recurrent neural networks, can deal with complex patterns in stock prices. Additionally, this study further investigates hybrid models, combining various approaches to explore their strengths and counterbalance individual weaknesses, thereby enhancing predictive accuracy. By presenting a detailed review of various studies and methods, this study illuminates the direction of stock price forecasting and highlights potential approaches for further studies refining the stock price forecasting models.

The effect of HIV and mpox co-infection on clinical outcomes: Systematic review and meta-analysis.

INTRODUCTION: Co-infection with HIV and mpox is a significant issue for public health because of the potential combined impact on clinical outcomes. However, the existing literature lacks a comprehensive synthesis of the available evidence. The purpose of this meta-analysis is to provide insight into the impact of HIV and mpox co-infection on clinical outcomes. METHODS: We systematically searched major electronic databases (PubMed, Embase, Cochrane Central, and Web of Science) for pertinent studies published up to June 2023. Included were studies that described the clinical outcomes of people who had both mpox and HIV. We performed the analysis using OpenMeta and STATA 17 software. RESULTS: With an overall number of participants of 35 207, 21 studies that met the inclusion criteria were considered. The greatest number of the studies (n = 10) were cohort designs, with three being cross-sectional and eight being case series studies. The meta-analysis found that people who had both HIV and mpox had a higher hospitalization rate than those who only had mpox (odds ratio [OR] 1.848; 95% confidence interval [CI] 0.918-3.719, p = 0.085, I2 = 60.19%, p = 0.020). Furthermore, co-infected patients had higher mortality rates than those who did not have HIV co-infection (OR 3.887; 95% CI 2.272-6.650, p < 0.001). Meta-regression analysis showed that CD4 levels can significantly predict the risk of hospitalization (p = 0.016) and death (p = 0.031). DISCUSSION: HIV causes immunosuppression, making it difficult for the body to mount an effective immune response against pathogens such as mpox. Individuals who are co-infected are at a higher risk of severe disease and death, according to our findings. Although hospitalization rates did not differ significantly between the two groups, it is critical to prioritize interventions and improve management strategies tailored specifically for people living with HIV. CONCLUSION: This meta-analysis provides substantial evidence that HIV and mpox co-infection has a negative impact on clinical outcomes. Co-infected individuals had higher hospitalization and significantly higher mortality rates. These findings highlight the significance of early diagnosis, prompt treatment initiation, and effective management strategies for people living with HIV and mpox.

Single-cell analysis of age-related changes in leukocytes of diabetic mouse hindpaws.

Complications associated with Type 1 and Type 2 diabetes, such as diabetic peripheral neuropathy and diabetic foot ulcers, are a growing health-care concern. In addition, this concern increases as diabetic patients age due to their increased susceptibility to complications. To address this growing problem, it is important to understand fluctuations in physiology which lead to pathological changes associated with the metabolic disturbances of diabetes. Our study explores dysregulation of immune cell populations in the hindpaws of healthy and diabetic mice at 12 and 21 weeks of age using single-cell RNA sequencing to provide insight into immune disruptions occurring in the distal limb during chronic diabetes. In 21-week-old Leprdb/db mice, increases were seen in mast cells/basophils, dermal γδ T cells, heterogeneous T cells, and Type 2 innate lymphoid cells. In addition, macrophages represented the largest cluster of immune cells and showed the greatest increase in genes associated with immune-specific pathways. Sub-clustering of macrophages revealed a bias toward angiogenic Lyve1+MHCIIlo macrophages in the hindpaws of 21-week-old diabetic mice, which corresponded to an increase in Lyve1+ macrophages in the hindpaws of 21-week-old diabetic mice on histology. Our results show that in Type 2 diabetes, the immunological function and phenotype of multiple immune cell types shift not only with metabolic disturbance, but also with duration of disease, which may explain the increased susceptibility to pathologies of the distal limb in patients with more chronic diabetes.

Impact of social vulnerability on comorbid COVID-19 and acute myocardial infarction mortality in the United States.

The trajectory of several cardiovascular diseases (CVD), including acute myocardial infarction (AMI), has been adversely impacted by COVID-19, resulting in a worse prognosis. The Social Vulnerability Index (SVI) has been found to affect certain CVD outcomes. In this cross-sectional analysis, we investigated the association between the SVI and comorbid COVID-19 and AMI mortality using the CDC databases. The SVI percentile rankings were divided into four quartiles, and age-adjusted mortality rates were compared between the lowest and highest SVI quartiles. Univariable Poisson regression was utilized to calculate risk ratios. A total of 5779 excess deaths and 1.17 excess deaths per 100,000 person-years (risk ratio 1.62) related to comorbid COVID-19 and AMI were attributable to higher social vulnerability. This pattern was consistent across the majority of US subpopulations. Our findings offer crucial epidemiological insights into the influence of the SVI and underscore the necessity for targeted therapeutic interventions.

The Impact of Chemotherapy on Cardiovascular Mortality across Breast Cancer Subtypes.

Breast cancer is associated with cardiovascular mortality as an adverse effect of chemotherapy. Considering the variances across breast cancer subtypes, this study aims to investigate the cardiovascular mortality patterns in each subtype. METHODS: This retrospective study used the SEER database of chemotherapy-receiving breast cancer patients (diagnosed in 2013-2020). The study population was categorized by cancer subtype, stage, patient age, and cause of death (COD). The percentage of cardiovascular CODs, odds ratio (ORs), 5-year cumulative crude probability of death, and standardized mortality ratios (SMRs) of each group were analyzed. RESULTS: Among 23,263 nonsurviving breast cancer patients, 5.8% died from cardiovascular disease, whereas the HER2+/HR+ and HER2+/HR- subtypes exhibited the highest ORs of cardiovascular death and percentages of cardiovascular CODs, at 8.21% and 6.55%, respectively. The cardiovascular SMR increased with advancing stages and decreasing patient age. The HER2+/HR- subtype had the highest cardiovascular SMR, at 0.83 (p < 0.05), followed by TNBC, at 0.78 (p < 0.05). The 5-year cumulative probability of cardiovascular CODs also showed the highest risk in the HER2+/HR- subtype (1.02 ± 0.11%) and the TNBC subtype (0.95 ± 0.07%). CONCLUSION: Breast cancer patients on chemotherapy face an elevated cardiovascular mortality risk, especially with aggressive subtypes (HER2-enriched, TNBC), advanced age, or HER2+/HR+ cancer receiving long-term treatment.