Association between Epstein-Barr virus infection and serum positivity rate of anti-nuclear antibodies in Chongqing, China: A cross-sectional observational study.

Epstein-Barr virus (EBV) infects over 95% of the global population and is strongly associated with various autoimmune diseases. Anti-nuclear antibodies (ANA) serve as valuable laboratory biomarkers for screening and supporting the diagnosis of various autoimmune diseases. The aim of this study was to assess the prevalence of EBV infection and its association with ANA. This retrospective study employed standard indirect immunofluorescence assay to determine ANA levels, EBV-specific immunofluorescence assay, or plasma EBV-DNA testing. Demographic data including gender and age were collected to observe variations in EBV infection status and ANA positivity rates among different populations. Incorporating 6492 hospitalized patients who underwent ANA antibody spectrum testing, it was observed that serum positivity rates gradually increased with age. The overall serum positivity rate of ANA in females (25.14%) was significantly higher than that in males (13.76%). Among hospitalized patients undergoing EBV-DNA testing, adults aged 21 to 40 years were least affected by EBV, with a positivity rate of 11.96%; however, as age increased, the positivity rate gradually increased. Among the 5225 patients undergoing EBV antibody spectrum testing, ANA-positive patients exhibited significantly higher serum positivity rates for Epstein-Barr nuclear antigen 1 immunoglobulin G, Epstein-Barr virus early antigen immunoglobulin G, Epstein-Barr virus early antigen immunoglobulin A, and Epstein-Barr virus viral capsid antigen immunoglobulin A antibodies compared to ANA-negative patients (P < .001; P < .001; P = .013; P < .001). The EBV-DNA positivity rate in ANA-positive patients was also significantly higher than in ANA-negative patients, yielding the same conclusion (P = .012). The positivity rates of ANA antibodies in patients with past EBV infection and reactivation were significantly higher than those in uninfected patients (P < .001; P = .006). The positivity rate of ANA antibodies in reactivated patients was significantly higher than that in primary infected patients and those with past infections (P < .001; P < .001). Among ANA-positive patients, the positivity rates of EBV antibody spectrum and EBV-DNA were higher compared to ANA-negative patients. The positivity rates of ANA in patients with past EBV infection and reactivation were higher than those in uninfected patients.

Inhomogeneous Diffusion-Induced Network for Multiview Semi-Supervised Classification.

The challenges posed by heterogeneous data in practical applications have made multiview semi-supervised classification a focus of attention for researchers. While several graph-based approaches have been suggested for this task, they tend to use homogeneous feature propagation, leading to even diffusion of node information to their neighbors. However, this diffusion strategy results in nodes acquiring information of equal proportion from dissimilar samples. In this article, we propose a solution to address these issues by introducing a graph diffusion-induced network for multiview semi-supervised classification. By formulating a discretized partial differential equation on a manifold, we derive a nonlinear and inhomogeneous diffusion equation to govern information propagation on the graph. Then, we investigate the impact of various nonlinear activation functions on random switching edge directions and their suppressive effects on information diffusion between different nodes. In addition, the cross-view consistency under the semi-supervised scenarios is defined and guaranteed for better information fusion. The comprehensive experimental results demonstrate the superiority of the proposed method compared with state-of-the-art approaches. The effectiveness of the proposed approach in handling diverse and heterogeneous data showcases its potential for advancing multiview semi-supervised classification techniques.

Unveiling the bidirectional role of MMP9: A key player in kidney injury.

Matrix metalloproteinases (MMPs) are a group of zinc-dependent proteolytic metalloenzymes that are involved in numerous pathological conditions, including nephropathy. MMP9, a member of the MMPs family, is categorized as a constituent of the gelatinase B subgroup, and its involvement in extracellular matrix (ECM) remodeling and renal fibrosis highlights its importance in the development and progression of renal diseases. The exact role of MMP9 in the development of kidney diseases is still controversial. This study investigated the dual role of MMP9 in kidney injury, discussing its implications in the pathogenesis of kidney diseases and investigating the design and mechanism of MMP9 inhibitors based on previous studies. This study provides an effective basis for the development of novel and selective MMP9 inhibitors for treating renal diseases.

Racial and Ethnic Differences in the Prevalence of Severe Aortic Stenosis by Echocardiography.

BACKGROUND: Understanding the burden of aortic stenosis (AS) across diverse racial and ethnic populations is important to ensure equitable resource allocation. This study explored whether severe AS rate varies by race and ethnicity. METHODS: The rates of severe AS, stratified by race and ethnicity, were calculated among 615,038 adults with a transthoracic echocardiogram. Logistic regression analysis was performed to identify factors associated with severe AS. RESULTS: Severe AS rates ranged from 0.08% in adults < 50 years old to 3.8% in those ≥ 90 years old. Compared to non-Hispanic White and Asian American [adjusted odds ratio (aOR) = 0.47, 95% confidence interval (CI): 0.42-0.53] and non-Hispanic Black (aOR = 0.44, 95% CI: 0.39-0.50) patients were less likely to have severe AS, whereas Hispanic patients (aOR = 0.91, 95% CI: 0.87-0.98) had near similar likelihood. Age was the strongest risk factor for severe AS (compared to age < 50 years, aOR = 21.8, 95% CI: 17.8-26.6 for age 80-89 years, and aOR = 43.8, 95% 35.5-54.0 for age ≥ 90 years). Additional factors associated with severe AS included male sex (aOR = 1.38, 95% CI: 1.30-1.46) and diabetes (aOR = 1.23, 95% CI: 1.15-1.31). CONCLUSIONS: Asian American and non-Hispanic Black adults had lower rates of severe AS compared to White and Hispanic patients. The rate of severe AS progressively increases with age in all racial and ethnic groups, with higher rates in men compared with women. With a demographic shift toward an aging and more diverse population, the burden of AS is anticipated to rise. Ensuring adequate allocation of resources to meet the evolving needs of a diverse population remains a shared health care imperative.

18F-FDG PET/CT for early prediction of pathological complete response in breast cancer neoadjuvant therapy: a retrospective analysis.

BACKGROUND: Neoadjuvant treatment has been developed as a systematic approach for patients with early breast cancer and has resulted in improved breast-conserving rate and survival. However, identifying treatment-sensitive patients at the early phase of therapy remains a problem, hampering disease management and raising the possibility of disease progression during treatment. METHODS: In this retrospective analysis, we collected 2-deoxy-2-[F-18] fluoro-d-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) images of primary tumor sites and axillary areas and reciprocal clinical pathological data from 121 patients who underwent neoadjuvant treatment and surgery in our center. The univariate and multivariate logistic regression analyses were performed to investigate features associated with pathological complete response (pCR). An 18F-FDG PET/CT-based prediction model was trained, and the performance was evaluated by receiver operating characteristic curves (ROC). RESULTS: The maximum standard uptake values (SUVmax) of 18F-FDG PET/CT were a powerful indicator of tumor status. The SUVmax values of axillary areas were closely related to metastatic lymph node counts (R = 0.62). Moreover, the early SUVmax reduction rates (between baseline and second cycle of neoadjuvant treatment) were statistically different between pCR and non-pCR patients. The early SUVmax reduction rates-based model showed great ability to predict pCR (AUC = 0.89), with all molecular subtypes (HR+HER2-, HR+HER2+, HR-HER2+, and HR-HER2-) considered. CONCLUSION: Our research proved that the SUVmax reduction rate of 18F-FDG PET/CT contributed to the early prediction of pCR, providing rationales for utilizing PET/CT in NAT in the future.

Active interface bulging in Bacillus subtilis swarms promotes self-assembly and biofilm formation.

Microbial communities such as biofilms are commonly found at interfaces. However, it is unclear how the physical environment of interfaces may contribute to the development and behavior of surface-associated microbial communities. Combining multimode imaging, single-cell tracking, and numerical simulations, here, we found that activity-induced interface bulging promotes colony biofilm formation in Bacillus subtilis swarms presumably via segregation and enrichment of sessile cells in the bulging area. Specifically, the diffusivity of passive particles is ~50% lower inside the bulging area than elsewhere, which enables a diffusion-trapping mechanism for self-assembly and may account for the enrichment of sessile cells. We also uncovered a quasilinear relation between cell speed and surface-packing density that underlies the process of active interface bulging. Guided by the speed-density relation, we demonstrated reversible formation of liquid bulges by manipulating the speed and local density of cells with light. Over the course of development, the active bulges turned into striped biofilm structures, which eventually give rise to a large-scale ridge pattern. Our findings reveal a unique physical mechanism of biofilm formation at air-solid interface, which is pertinent to engineering living materials and directed self-assembly in active fluids.

Gender and Age Differences in the Evaluation and Clinical Outcomes of Patients with Palpitations.

BACKGROUND: Palpitations represent a common clinic complaint. OBJECTIVE: To explore gender and age differences in the evaluation and outcomes of patients with palpitations in outpatient settings. DESIGN/PARTICIPANTS: This is a retrospective observational study of 58,543 patients with no known structural cardiac disease or arrythmias presenting to primary care and cardiology clinics in an integrated health system in California with palpitations between January 2017 and December 2021. The primary and secondary endpoints were hospitalization for arrhythmia and all-cause mortality at 1 year. Multivariable logistic regression models evaluated the association between gender, age, and outcomes. RESULTS: Men and women were equally as likely to be started on beta-blockers (adjusted OR 0.96, 95% CI 0.90-1.02) and evaluated with electrocardiograms (adjusted OR 0.95, 95% CI 0.90-1.01) and cardiac monitors (adjusted OR 1.04, 95% CI 0.99-1.08). Patients who completed Holter or event monitors had a lower rate of hospitalization for cardiovascular disease at 1 year than those without (2.3% vs. 2.7%, p = 0.001). At 1 year, women had a lower risk of all-cause mortality (adjusted OR 0.47, 95% CI 0.35-0.64) and hospitalization for atrial fibrillation (adjusted OR 0.47, 95% CI 0.30-0.72) and arrhythmias (adjusted OR 0.73, 95% CI 0.58-0.91) compared to men. Among older women and men (≥ 80 years), there was no significant difference in 1-year all-cause mortality (adjusted OR 0.57, 95% CI 0.29-1.12), hospitalization for atrial fibrillation (adjusted OR 0.58, 95% CI 0.17-1.97), or arrhythmias (adjusted OR 1.15, 95% CI 0.12-11.07). CONCLUSIONS: There were no gender differences in referrals for cardiac monitoring or prescriptions for beta-blockers. Women had a better prognosis with a lower risk of hospitalization for arrhythmias and death at 1 year compared to men. However, 1-year risks for mortality and hospitalization for arrythmias among older women were comparable to those of older men, underscoring the importance of considering age and gender in managing patients with palpitations.

Association of intrinsic capacity and medication non-adherence among older adults with non-communicable diseases in Taiwan.

OBJECTIVES: Medication non-adherence among older adults with non-communicable diseases (NCDs) remains prevalent worldwide, which causes hospitalization and mortality. Our study aimed to examine the association of medication non-adherence with level of overall intrinsic capacity (IC), pattern of IC, and specific IC component among older adults with NCDs. METHODS: A cross-sectional questionnaire-based survey of 1268 older adults aged 60 years and above was conducted in 2022 in southern Taiwan. Among them, 894 suffered from 1 more NCD were included in this study. The Integrated Care for Older People Screening Tool for Taiwanese and the Adherence to Refills and Medication Scale were used to assess IC and medication non-adherence, respectively. Latent class analysis (LCA) was used to identify patterns of IC impairment, and binary logistic regression was used to assess the association between medication non-adherence and IC. RESULTS: Older adults in the moderate (score: 1-2) or low (score≧3) overall IC groups were more likely to experience medication non-adherence (moderate: adjusted odds ratio (aOR) 1.57 [95% CI: 1.05-2.36]; low: 2.26 [1.40-3.67]). The "physical and nutritional impairments accompanied by depressive symptoms" group was associated with statistically higher odds of medication non-adherence (aOR 1.66 [1.01-2.73]). Older adults with cognitive impairment, hearing loss, or depressive symptoms showed greater likelihood of medication non-adherence (cognitive impairment: aOR 1.53 [1.03-2.27]; hearing loss: aOR 1.57 [1.03-2.37]; depressive symptoms: aOR 1.81 [1.17-2.80]). CONCLUSIONS: Intervention for improving medication non-adherence among older adults with NCDs should consider IC.

Activation of aryl hydrocarbon receptor (AhR) alleviates depressive-like behaviors in LPS-induced mice.

The role of the aryl hydrocarbon receptor (AhR) in regulating oxidative stress and immune responses has been increasingly recognized. However, its involvement in depression and the underlying mechanisms remain poorly understood. This study aimed to investigate the effect of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous AhR ligand, on a lipopolysaccharide (LPS)-induced depression model and the underlying mechanism. After being treated with FICZ (50 mg/kg), male C57BL/6J mice received intraperitoneal injection of LPS and underwent behavioral tests 24 h later. The levels of inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, were measured in the hippocampus and serum using enzyme-linked immunosorbent assay (ELISA). The expression levels of CYP1A1, AhR and NLRP3 were analyzed using qPCR and Western blot. The results showed that, compared with control group, LPS alone significantly down-regulated the expression levels of CYP1A1 mRNA and AhR protein in the hippocampus of mice, reduced glucose preference, prolonged immobility time in forced swimming test, increased IL-6 and IL-1ß levels in the hippocampus, increased serum IL-1ß level, and up-regulated NLRP3 mRNA and protein expression levels in mouse hippocampus, while FICZ significantly reversed the aforementioned effects of LPS. These findings suggest that AhR activation attenuates the inflammatory response associated with depression and modulates the expression of NLRP3. The present study provides novel insights into the role of AhR in the development of depression, and presents AhR as a potential therapeutic target for the treatment of depression.

Mesenchymal stem cells and their derived exosomes for the treatment of COVID-19.

Coronavirus disease 2019 (COVID-19) is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection typically presents with fever and respiratory symptoms, which can progress to severe respiratory distress syndrome and multiple organ failure. In severe cases, these complications may even lead to death. One of the causes of COVID-19 deaths is the cytokine storm caused by an overactive immune response. Therefore, suppressing the overactive immune response may be an effective strategy for treating COVID-19. Mesenchymal stem cells (MSCs) and their derived exosomes (MSCs-Exo) have potent homing abilities, immunomodulatory functions, regenerative repair, and antifibrotic effects, promising an effective tool in treating COVID-19. In this paper, we review the main mechanisms and potential roles of MSCs and MSCs-Exo in treating COVID-19. We also summarize relevant recent clinical trials, including the source of cells, the dosage and the efficacy, and the clinical value and problems in this field, providing more theoretical references for the clinical use of MSCs and MSCs-Exo in the treatment of COVID-19.

Assessing intrinsic capacity in Taiwan: Initial psychometric properties of the Integrated Care for Older People Screening Tool for Taiwanese (ICOPES-TW).

BACKGROUND: The World Health Organization (WHO) proposed the concept of intrinsic capacity (comprising composite physical and mental capacity) which aligns with their concepts of healthy aging and functional ability. Consequently, the WHO promotes the Integrated Care for Older People (ICOPE) framework as guidance for geriatric care. Consequently, each government should have a screening tool corresponding to ICOPE framework to promote geriatric care. The present study examined the initial psychometric properties of the Taiwan version of ICOPE (i.e., ICOPES-TW). METHODS: Older people (n = 1235; mean age = 72.63 years; 634 females [51.3%]) were approached by well-trained interviewers for participation. A number of measures were administered including the ICOPES-TW, WHOQOL-AGE (assessing quality of life [QoL]), Clinical Frailty Scale (assessing frailty), Barthel Index (assessing basic activity of daily living [BADL]), and Lawton Instrumental Activities of Daily Living Scale (assessing instrumental activity of daily living [IADL]). RESULTS: The ICOPES-TW had a two-factor structure (body functionality [eigenvalue = 1.932] and life adaptation [eigenvalue = 1.170]) as indicated by the results of exploratory factor analysis. Internal consistency of the ICOPES-TW was low (Cronbach's α = 0.55 [entire ICOPES-TW], 0.45 (body functionality factor), and 0.52 (life adaptation factor). ICOPES-TW scores were significantly (i) positively correlated with age (r = 0.321), IADL (r = 0.313), and frailty (r = 0.601), and (ii) negatively correlated with QoL (r=-0.447), and BADL (r=-0.447), with all p-values < 0.001. CONCLUSION: The ICOPES-TW could be a useful screening tool for healthcare providers to quickly evaluate intrinsic capacity for Taiwanese older people given that it has moderate to strong associations with age, BADL, IADL, QoL, and frailty.

Prognostic Value of Stress Myocardial Perfusion Imaging Across the Spectrum of Cardiovascular Risk.

BACKGROUND: Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is widely used to identify ischemia. There is limited research to evaluate if there is a risk threshold below which SPECT-MPI may not add significant prognostic value. METHODS: Between January 1, 2012, and December 31, 2018, individuals who underwent SPECT-MPI were stratified into 4 risk groups. The primary outcome was acute myocardial infarction (MI) or death. Multivariable Cox proportional hazards regression analysis was used to calculated hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Among 48,845 patients (52.3% male, median age 67 years), 8.5% were low risk, 4.8% borderline risk, 18.1% intermediate risk, and 68.6% high risk based on the American College of Cardiology pooled cohort equation. Ischemia was more commonly detected in the high-risk cohort (19.4% in high-risk vs 6.5% in low-risk). SPECT-MPI testing was associated with a significantly increased use of preventive medications such as statin therapy, regardless of stress test results. At a median follow-up of 4.2 years, there was no significant association between ischemia and death or MI in the low-risk cohort (adjusted HR, 1.91; 95% CI, 0.94-3.92) or the borderline-risk cohort (adjusted HR, 1.58; 95% CI, 0.79-3.15). Ischemia was associated with a higher risk of death or MI in the intermediate-risk (adjusted HR, 1.57; 95% CI, 1.24-1.99) and high-risk groups (adjusted HR, 1.54; 95% CI, 1.44-1.64). CONCLUSIONS: SPECT-MPI was less useful for risk stratification among low-risk patients because of their low event rates regardless of test results.

A simple scoring algorithm based on intrinsic capacity for functional ability in community-dwelling older adults in Taiwan.

BACKGROUND: Intrinsic capacity (IC) is a comprehensive indicator of the overall well-being of older adults, and assessing of IC can help identify early stage of disability and tailor intervention to individual needs. However, there is a lack of effective and simple IC assessment tools. This study aimed to establish predictive scoring algorithms of IC to identify older adults at high risk of impaired functional ability. METHODS: We conducted a cross-sectional study in Southern Taiwan, measuring IC using 7 subitems: cognition, locomotion, vitality, vision, hearing, psychological well-being, and medication usage were measured. Functional ability outcomes included frailty, basic activities of daily living, and instrumental activities of daily living (IADL). The capability of 7 domains of IC in predicting functional ability was assessed by multivariable logistic regression. The prediction of capability of scoring algorithms was indicated by receiver operating characteristic (AUC) curves and measures of sensitivity and specificity. RESULTS: A total of 1,152 older adults were recruited and analyzed. Locomotion emerged as a significant predictor of IADL disability and worsening frailty. The IC-based weighted scoring algorism for predicting IADL demonstrated satisfactory capability (AUC: 0.80), as did the algorithm for predicting worsening frailty (AUC: 0.90). The optimal cutoff points for predicting IADL disability and frailty worse were estimated respectively at 13 and 16, with sensitivity/specificity values of 0.74/0.75 for the IADL prediction algorithm and 0.92/0.77 for the frailty prediction algorithm. CONCLUSION: Our 7-domain IC screening tool proves to be sensitive and practical for early identification of functional disability and frailty among community-dwelling older adults in Taiwan.

Secondary Amine Catalysis in Enzyme Design: Broadening Protein Template Diversity through Genetic Code Expansion.

Secondary amines, due to their reactivity, can transform protein templates into catalytically active entities, accelerating the development of artificial enzymes. However, existing methods, predominantly reliant on modified ligands or N-terminal prolines, impose significant limitations on template selection. In this study, genetic code expansion was used to break this boundary, enabling secondary amines to be incorporated into alternative proteins and positions of choice. Pyrrolysine analogues carrying different secondary amines could be incorporated into superfolder green fluorescent protein (sfGFP), multidrug-binding LmrR and nucleotide-binding dihydrofolate reductase (DHFR). Notably, the analogue containing a D-proline moiety demonstrated both proteolytic stability and catalytic activity, conferring LmrR and DHFR with the desired transfer hydrogenation activity. While the LmrR variants were confined to the biomimetic 1-benzyl-1,4-dihydronicotinamide (BNAH) as the hydride source, the optimal DHFR variant favorably used the pro-R hydride from NADPH for stereoselective reactions (e.r. up to 92 : 8), highlighting that a switch of protein template could broaden the nucleophile option for catalysis. Owing to the cofactor compatibility, the DHFR-based secondary amine catalysis could be integrated into an enzymatic recycling scheme. This established method shows substantial potential in enzyme design, applicable from studies on enzyme evolution to the development of new biocatalysts.

Self-enhanced mobility enables vortex pattern formation in living matter.

Ranging from subcellular organelle biogenesis to embryo development, the formation of self-organized structures is a hallmark of living systems. Whereas the emergence of ordered spatial patterns in biology is often driven by intricate chemical signalling that coordinates cellular behaviour and differentiation1-4, purely physical interactions can drive the formation of regular biological patterns such as crystalline vortex arrays in suspensions of spermatozoa5 and bacteria6. Here we discovered a new route to self-organized pattern formation driven by physical interactions, which creates large-scale regular spatial structures with multiscale ordering. Specifically we found that dense bacterial living matter spontaneously developed a lattice of mesoscale, fast-spinning vortices; these vortices each consisted of around 104-105 motile bacterial cells and were arranged in space at greater than centimetre scale and with apparent hexagonal order, whereas individual cells in the vortices moved in coordinated directions with strong polar and vortical order. Single-cell tracking and numerical simulations suggest that the phenomenon is enabled by self-enhanced mobility in the system-that is, the speed of individual cells increasing with cell-generated collective stresses at a given cell density. Stress-induced mobility enhancement and fluidization is prevalent in dense living matter at various scales of length7-9. Our findings demonstrate that self-enhanced mobility offers a simple physical mechanism for pattern formation in living systems and, more generally, in other active matter systems10 near the boundary of fluid- and solid-like behaviours11-17.

Sequencing of cerebrospinal fluid cell-free DNA facilitated early differential diagnosis of intramedullary spinal cord tumors.

Pre-surgery differential diagnosis is valuable for personalized treatment planning in intramedullary spinal cord tumors. This study assessed the performance of sequencing cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) for differential diagnosis of these tumors. Prospectively enrolling 45 patients with intramedullary spinal cord lesions, including diffuse midline glioma (DMG), H3K27-altered (14/45), glioblastoma (1/45), H3-wildtype-astrocytoma (10/45), ependymoma (11/45), and other lesions (9/45), CSF samples were collected via lumbar puncture (41/45), intraoperative extraction (3/45), and Ommaya reservoir (1/45). Then, these samples underwent targeted sequencing along with paired tissue DNA. DMG, H3K27-altered patients exhibited a higher ctDNA positivity (85.7%, 12/14) compared to patients with H3-wildtype-astrocytoma (0/8, P = 0.0003), ependymoma (2/10, P = 0.003), and glioneuronal tumor (0/3, P = 0.009). The histological-grade-IV (P = 0.0027), Ki-67 index ≥10% (P = 0.014), and tumor reaching spinal cord surface (P = 0.012) are also associated with higher ctDNA positivity. Interestingly, for patients with TERT promoter mutant tumors, TERT mutation was detectable in the CSF cfDNA of one DMG case, but not other five cases with histological-grade-II tumors. Shared copy number variants were exclusively observed in DMG, H3K27-altered, and showed a strong correlation (Correlation = 0.95) between CSF and tissue. Finally, H3K27M mutations in CSF exhibited high diagnostic efficiency for DMG, H3K27-altered (Sensitivity = 85.7%, Specificity = 100.0%, AUC = 0.929). Notably, H3K27M was detectable in CSF from patients with recurrent tumors, making it easily applicable for postoperative monitoring. In conclusion, the molecular profile from ctDNA released into CSF of malignant tumors was more frequently detected compared to relatively benign ones. Sequencing of ctDNA in CSF exhibited high efficiency for the differential diagnosis of DMG, H3K27-altered.

Association between dietary selenium intake and the prevalence of hypertension: results from the National Health and Nutrition Examination Survey 2003-2018.

Aim: The epidemiological evidence regarding the impact of dietary selenium intake on hypertension continues to be a subject of controversy. Our objective is to examine the correlation between dietary selenium intake and the prevalence of hypertension within a substantial and diverse population in the United States. Methods: We carried out a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) to assess the association between dietary selenium intake and hypertension prevalence. Weight logistic regression analysis and smooth curve fitting were utilized to explore potential linear relationships. Subgroup analysis was further employed to investigate potential differences in this relationship across populations and assess potential synergies. Results: The study included 32,928 individuals, and the average dietary selenium intake was 1.12 ± 0.53 µg. The prevalence rate of hypertension was 36.55% overall and decreased with the higher dietary selenium intake quartiles (quartiles 1, 40.25%; quartiles 2, 37.71%; quartiles 3, 36.04%, quartiles 4, 32.23%, p < 0.001). Each quartile increase in dietary selenium intake associated with 11% decreased the likelihood of prevalence of hypertension [OR = 0.89; 95% CI: 0.80-1.00; p = 0.0425]. Subgroup analyses revealed that there was no significant correlation between gender, age, body mass index, smoking status, alcohol consumption, and diabetes mellitus in relation to the association between dietary selenium intake and the prevalence of hypertension. Conclusion: The prevalence of hypertension in adults was found to be linearly and negatively correlated with dietary selenium intake. In order to improve the prevention and treatment of hypertension, greater emphasis should be placed on selenium consumption.

GlioPredictor: a deep learning model for identification of high-risk adult IDH-mutant glioma towards adjuvant treatment planning.

Identification of isocitrate dehydrogenase (IDH)-mutant glioma patients at high risk of early progression is critical for radiotherapy treatment planning. Currently tools to stratify risk of early progression are lacking. We sought to identify a combination of molecular markers that could be used to identify patients who may have a greater need for adjuvant radiation therapy machine learning technology. 507 WHO Grade 2 and 3 glioma cases from The Cancer Genome Atlas, and 1309 cases from AACR GENIE v13.0 datasets were studied for genetic disparities between IDH1-wildtype and IDH1-mutant cohorts, and between different age groups. Genetic features such as mutations and copy number variations (CNVs) correlated with IDH1 mutation status were selected as potential inputs to train artificial neural networks (ANNs) to predict IDH1 mutation status. Grade 2 and 3 glioma cases from the Memorial Sloan Kettering dataset (n = 404) and Grade 3 glioma cases with subtotal resection (STR) from Northwestern University (NU) (n = 21) were used to further evaluate the best performing ANN model as independent datasets. IDH1 mutation is associated with decreased CNVs of EGFR (21% vs. 3%), CDKN2A (20% vs. 6%), PTEN (14% vs. 1.7%), and increased percentage of mutations for TP53 (15% vs. 63%), and ATRX (10% vs. 54%), which were all statistically significant (p < 0.001). Age > 40 was unable to identify high-risk IDH1-mutant with early progression. A glioma early progression risk prediction (GlioPredictor) score generated from the best performing ANN model (6/6/6/6/2/1) with 6 inputs, including CNVs of EGFR, PTEN and CDKN2A, mutation status of TP53 and ATRX, patient's age can predict IDH1 mutation status with over 90% accuracy. The GlioPredictor score identified a subgroup of high-risk IDH1-mutant in TCGA and NU datasets with early disease progression (p = 0.0019, 0.0238, respectively). The GlioPredictor that integrates age at diagnosis, CNVs of EGFR, CDKN2A, PTEN and mutation status of TP53, and ATRX can identify a small cohort of IDH-mutant with high risk of early progression. The current version of GlioPredictor mainly incorporated clinically often tested genetic biomarkers. Considering complexity of clinical and genetic features that correlate with glioma progression, future derivatives of GlioPredictor incorporating more inputs can be a potential supplement for adjuvant radiotherapy patient selection of IDH-mutant glioma patients.

The impact of sleep disturbances on suicide risk among people living HIV: An eleven-year national cohort.

OBJECTIVES: The suicide rate among individuals who experience sleep disturbances is five times higher than in the general population. Up to 70 % of people living with HIV (PLHIV) experience sleep disturbances. This study's purpose was to determine whether this population has higher rates of suicide compared to those without sleep disorders. Possible risk factors were also explored. METHODS: A secondary analysis of nationwide data on all males and females over 15 years old with HIV living in Taiwan was conducted from January 1, 2005, to December 31, 2016. Sleep disturbances were identified through recorded diagnoses and medical treatments. Cox proportional hazard models and hazard ratios (HRs) and mediation analysis were employed to estimate the association between sleep disturbances and suicide risk during the follow-up period. RESULTS: Of the 5680 PLHIV, 72 suicide events were reported. The suicide incidence rate among PLHIV suffering from sleep disturbances was 769 per 100,000 person-years. Sleep disturbances were associated with a significantly increased risk of suicide (AHR = 1.75, 95 % CI 1.02-3.02, p = 0.0429). A premium-based monthly salary of <24,000 (NT $) was also associated with an increased hazard of suicide (AHR = 4.14, 95 % CI 1.60-10.75, p = 0.0035). The pathway effect analysis using potential outcomes showed that depression did not mediate the effect of sleep disturbance on suicide. CONCLUSIONS: Sleep disturbances were associated with higher suicide rates, even after adjusting for pre-existing depression. These findings suggest that paying attention to suicidal ideation among PLHIV suffering from sleep disturbances is necessary.

Cytogenetic Profile in Monoclonal Gammopathy of Undetermined Significance, Smoldering and Symptomatic Multiple Myeloma: A Study of 1087 Patients with Highly Purified Plasma Cells.

The aim of this study was to examine the cytogenetic profiles of plasma cell neoplasms (PCNs) at various disease stages, encompassing 1087 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), newly diagnosed multiple myeloma (NDMM), and refractory/relapsed multiple myeloma (RRMM). Fluorescence in situ hybridization (FISH) analyses were conducted on highly purified plasma cell samples, revealing that 96% of patients exhibited at least one cytogenetic abnormality. The genomic complexity escalated from MGUS to SMM and further to NDMM and RRMM, largely driven by 1q gain, del(17p), MYC-rearrangement (MYC-R), del(1p), and tetraploidy. Elevated frequencies of high-risk cytogenetics (59%), 1q gain (44%), and del(17p) (23%), as well as the presence of subclones (48%), were particularly notable in RRMM cases. IGH::CCND1 was observed in 26% of the cases, with no apparent variations across races, ages, or disease groups. Concurrent chromosomal analysis with FISH revealed that the incidence of abnormal karyotypes was strongly correlated with the extent of neoplastic plasma cell infiltration, genomic complexity, and the presence of specific abnormalities like del(17p) and MYC-R. Approximately 98% of the cases with abnormal karyotypes were complex, with most featuring five or more abnormalities. Chromosome 1 structural abnormalities were the most prevalent, found in 65% of cases. The frequent presence of subclones and composite karyotypes underscored the genomic heterogeneity and instability in this cohort.