Significant Association Research Articles

Progression of valve heart disease in a cohort of patients undergoing renal replacement therapy.

Cardiovascular disease is an important cause of death among patients with chronic kidney disease (CKD). Valve calcification is a predictor of cardiovascular mortality and coronary artery disease. To assess heart valve disease frequency, associated factors, and progression in CKD patients. We conducted a retrospective study on 291 CKD patients at Hospital das Clínicas de Pernambuco. Inclusion criteria were age ≥ 18 with CKD and valve disease, while those on conservative management or with missing data were excluded. Clinical and laboratory variables were compared, and patients were categorized by dialysis duration (<5 years; 5-10 years; >10 years). Statistical tests, including chi-square, Fisher's exact, ANOVA, and Kruskal-Wallis, were employed as needed. Simple and multivariate binary regression models were used to analyze valve disease associations with dialysis duration. Significance was defined as p < 0.05. Mitral valve disease was present in 82.5% (240) of patients, followed by aortic valve disease (65.6%; 86). Over time, 106 (36.4%) patients developed valve disease. No significant association was found between aortic, pulmonary, mitral, or tricuspid valve disease and dialysis duration. Secondary hyperparathyroidism was the sole statistically significant factor for mitral valve disease in the regression model (OR 2.59 [95% CI: 1.09-6.18]; p = 0.031). CKD patients on renal replacement therapy exhibit a high frequency of valve disease, particularly mitral and aortic valve disease. However, no link was established between dialysis duration and valve disease occurrence or progression.

Time-dependent sequential association rule-based survival analysis: A healthcare application

The analysis of event sequences with temporal dependencies holds substantial importance across various domains, including healthcare. This study introduces a novel approach that combines sequential rule mining and survival analysis to uncover significant associations and temporal patterns within event sequences. By integrating these techniques, we address the limitations linked to the loss of temporal information. The methodology extends traditional sequential rule mining by introducing time-dependent confidence functions, providing a comprehensive understanding of relationships between antecedent and consequent events. The incorporation of the Kaplan-Meier estimator of survival analysis enables the calculation of temporal distributions between events, resulting in time-dependent confidence functions. These confidence functions illuminate the probability of specific event occurrences considering temporal contexts. To present the application of the method, we demonstrated the usage within the healthcare domain. Analyzing the ICD-10 codes and the laboratory events, we successfully identified relevant sequential rules and their time-dependent confidence functions. This empirical validation underscores the potential of methodology to uncover clinically significant associations within intricate medical data.•The study presents a unique methodology that integrates sequential rule mining and survival analysis.•The methodology extends traditional sequential rule mining by introducing time-dependent confidence functions.•The application of the method is demonstrated within the healthcare domain.

Off-Label Reduced Dose Apixaban in Older Adults With Atrial Fibrillation and Associated Outcomes.

Apixaban is commonly used to prevent stroke in older adults with nonvalvular atrial fibrillation (AF). Although its package insert has specific dose reduction criteria, providers may dose reduce outside of these parameters based on clinical scenarios. The primary objective was to determine the incidence of apixaban off-label reduced dosing, while secondarily determining the safety and efficacy outcomes associated with such dosing. A retrospective analysis of patients aged 65 and older with orders for apixaban for AF was institutional review board (IRB)-approved and conducted across 3 academic medical centers. Patients receiving off-label reduced-dose apixaban (ie, "underdosed") were matched to a cohort of patients dosed according to the package insert at the standard dosing (5 mg twice daily) using stratified random sampling. Secondary outcomes included 1-year incidence of major bleeding, clinically relevant non-major bleeding (CRNMB), stroke or transient ischemic attack (TIA), and mortality. The Fisher exact tests were used to compare between-group differences. Of the 1172 patients meeting initial inclusion criteria, 201 (17%) were dosed off-label, with 175 (15%) "underdosed." The 147 "underdosed" patients with documented follow-up were matched with 139 patients receiving standard Food and Drug Administration (FDA)-labeled dosing. There were no significant differences in incidence of stroke (2.7% vs 2.2%), major bleeding (0% vs 0.7%), and CRNMB (2.7% vs 1.4%) in the off-label reduced dosing versus standard dosing groups. All-cause mortality was higher in the off-label reduced-dose group (16 [10.9%] vs 2 [1.4%], P < 0.05). Older adults with nonvalvular AF are commonly prescribed lower-than-recommended doses of apixaban. However, no significant association was found between empiric off-label reduced dosing and stroke or bleeding outcomes.

Smartphone addiction and adolescent mental health: a cross-sectional study in West Sumatra province

In West Sumatra Province, Indonesia, approximately 13.01% of individuals aged 15 years or older are affected by mental and emotional disorders, ranking it as the third highest among the 34 provinces. Excessive smartphone use has emerged as a potential influencer of mental health, associated with social networking addiction, shyness, and low self-esteem. This study aimed to examine the relationship between smartphone addiction and mental health issues in adolescents using a cross-sectional design. The sample included 283 randomly selected students aged 15-17 years. Smartphone addiction was measured using the smartphone addiction scale-short version (SAS-SV), and mental health was assessed using the strength and difficulties questionnaire (SDQ). The study revealed a significant association (p&amp;lt;0.001) between smartphone addiction and mental health problems among adolescents, with 72.1% of respondents experiencing smartphone addiction and 26.9% classified as having abnormal mental health. These findings emphasize the need for increased awareness regarding the negative impact of excessive smartphone use on adolescent mental health. Schools should play a vital role in addressing this issue through the provision of guidance and counseling services. Future research should investigate causal relationships using longitudinal designs and consider diverse populations to enhance the generalizability of the results.

Association of Anxiety and Depressive Symptoms with Thyroid Hormone Concentrations in Patients with Primary Bone Tumors.

Timely identification and intervention of psychological disorders bear significant import in ameliorating the ensuing therapeutic trajectories in primary bone tumor patients. Moreover, perturbations in thyroxine and thyroid-stimulating hormone (TSH) levels have been linked to manifestations of depressive and anxiety-related symptoms. However, the precise interplay governing the nexus of anxiety, depression, and the levels of thyroxine and TSH within the context of primary bone tumor patients remains presently unexplored. The objective of this study is to investigate the potential correlation between the hypothalamus- pituitary-thyroxine (HPT) axis and the depressive as well as anxious states observed in patients afflicted with bone tumors. Patients with primary bone tumors were required to accept the assessments of anxiety and depressive symptoms as well as thyroid axis hormone concentrations. The depressive and anxiety symptoms were assessed using the Hamilton Depression Rating Scale (HAMD) and the Hamilton Anxiety Scale (HAMA) score. During each follow-up, peripheral venous blood samples were collected for subsequent analysis using radioimmunoassay methods to measure serum- free T3, free T4, and TSH levels, with the calculated free T3 to free T4 ratio indicating peripheral free T4 to free T3 conversion. Tests for trend were conducted to assess thyroid axis hormone concentrations, HAMA scores, and HAMD scores, while the correlation between HAMA or HAMD scores and thyroid axis hormone concentrations was examined through univariate regression analyses. The study included 30 primary bone tumor patients. Initial high HAMA and HAMD scores decreased over a year after surgery (P < 0.05), reflecting diminishing anxiety and depression. TSH levels reduced postoperatively, contrasting with increased free-T3 and free-T4 levels (p < 0.01). Multivariate analysis affirmed that positive correlations were noted between TSH and anxiety/depression scores, while free-T3 correlated negatively, adjusted for demographic factors (p < 0.05). No significant associations emerged between HAMA/HAMD scores and free-T4 or free-T3 to free-T4 ratio (p > 0.05). The early identification of the low T3 syndrome could prove instrumental in both intervening and preventing adverse emotional states associated with primary bone tumors.

Association between eNOS gene polymorphisms and the risk of unexplained recurrent spontaneous abortion in Yunnan province, China.

Recurrent spontaneous abortion affects approximately 1-2% of reproductive-age women, with roughly half of RSA cases classified as unexplained recurrent spontaneous abortion (URSA). Genetic polymorphisms in eNOS gene have been shown to have significant implications across various disease processes. Nevertheless, the potential impact of eNOS gene polymorphisms on the susceptibility to URSA in Yunnan population has yet to be explored or documented. This study aims to investigate the potential association between specific variations in the eNOS gene (VNTR 4b/a, -786T > C, and +894G > T) and the risk of URSA in Yunnan population. A total of 243 URSA patients and 241 healthy females are involved in this study. We conducted amplification of the eNOS gene fragment and performed sanger sequencing to detect the specific eNOS gene polymorphisms, including VNTR 4b/a, -786T > C, and +894G > T. Using a multivariate logistic regression model, we evaluate the potential association between eNOS gene polymorphisms (VNTR 4b/a, -786T > C, and +894G > T) and the risk of URSA. Furthermore, serum NO levels were measured in URSA patients. The presence of VNTR 4a, -786C, and +894T alleles was found to be associated with an increased risk of URSA. Additionally, our study revealed a significant association between the G-C-4b haplotype of the investigated eNOS gene polymorphisms and a predisposition to URSA. Notably, these eNOS polymorphisms were shown to reduce serum NO levels in URSA patients. This study provides evidence supporting the association between eNOS gene polymorphisms, VNTR 4b/a, -786T > C, and +894G > T, and the occurrence of URSA in Yunnan Province, China.

Olfactory Dysfunction in Healthcare Workers with COVID-19: Prevalence and Associated Factors.

The COVID-19 pandemic is a real global health crisis. Its clinical presentation has evolved over time with an increasing number of symptoms. Olfactory dysfunction (OD) has recently been recognized as a frequent symptom relevant to screening for COVID-19, especially in pauci-asymptomatic forms. However, the underlying mechanisms of OD are not yet fully understood. To determine the prevalence of OD in healthcare workers with SARS-CoV-2 and to identify its associated factors. This is a cross-sectional, analytical study, carried out during a period of six months and including all healthcare workers at Farhat Hached Academic Hospital (Tunisia) who were diagnosed with SARS-CoV-2 by PCR, RAT, or chest CT scan. A total of 474 healthcare workers were included, representing a participation rate of 85.4%. The mean age was 41.02±10.67 years with a sex ratio of 0.2. The distribution of this population by department noted that it was mainly maternity (13.9%). The most presented workstation was nursing (31.4%). OD represented 39.2% of the reasons for consultation. Hospitalization was indicated in 16 patients (3.4%). The average duration of hospitalization was 8.87 ± 7.8 days. The average time off work was 17.04 ± 11.6 days. OD persisted for more than 90 days in 35 patients (7.4%). After multiple binary logistic regression, OD was statistically associated with female gender (p =0.001; OR 95% CI: 2.46 [1.4-4.2]) and blue-collar occupational category (p =0.002; OR IC95%:3.1 [1.5-6.5]). A significant association was also noted between OD and professional seniority and absence from work duration (p =0.019; OR 95% CI: 0.97 [0.95-0.99] and p =0.03; OR 95% CI: 0.97 [0.95-0.99]) respectively. OD is common in COVID-19 patients. The identification of its associated factors may contribute to enhancing the understanding of its mechanism and drive therapeutic options.

Association Between Adequate Serum 25(OH)D Levels and Atherogenic Dyslipidemia in Young Adults.

This study aimed to investigate the association between vitamin D deficiency and novel biomarkers of atherogenic dyslipidemia among young adults. A total of 976 young adults were recruited between 2011 and 2019. Their serum 25(OH)D levels were measured, and lipid profile markers, including low-density lipoprotein cholesterol (LDL-C), low-density lipoprotein triglyceride (LDL-TG), and small-dense low-density lipoprotein cholesterol (sdLDL-C), were assessed as novel biomarkers of atherogenic dyslipidemia. Multivariable linear regression was used to analyze the association between vitamin D levels and lipid profile markers. Odds ratios were calculated to assess the risk of atherogenic dyslipidemia in individuals with serum 25(OH)D levels below 30 ng/mL compared to those with levels above 30 ng/mL. Structural equation modeling (SEM) was employed to explore potential mediation pathways. The study found a significant association between vitamin D levels and lower levels of LDL-C, LDL-TG, sdLDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and total cholesterol. Individuals with serum 25(OH)D levels below 30 ng/mL exhibited significantly higher odds ratios for developing atherogenic dyslipidemia in a dose-response pattern compared to those with vitamin D levels above 30 ng/mL. Notably, structural equation modeling (SEM) analysis revealed that vitamin D did not affect atherogenic lipid markers through the mediation of insulin resistance markers or high-sensitivity C-reactive protein. This study provides evidence of an association between vitamin D deficiency and atherogenic dyslipidemia in young adults. It further highlights that individuals with serum 25(OH)D levels below 30 ng/mL are at a significantly higher risk of developing atherogenic dyslipidemia in a dose-response manner compared to those with higher vitamin D levels. These findings underscore the potential role of vitamin D in dyslipidemia management and emphasize the importance of maintaining sufficient vitamin D levels for cardiovascular health in young adults.

Investigating tedium as a predictor of personality and techno-stress in school teachers during the Covid-19 pandemic

Being a demanding profession, teaching involves the intrinsic components of stress, tiredness along with sensations of inner uneasiness. This directed the current investigation which focused on exploring the predictive nature of tedium in reference to the constructs of personality and techno-stress levels experienced by school teachers during the Covid-19 pandemic. Through a cross-sectional correlation design a non-probability purposive sample of 200 (including n = 92 men and n = 108 women) school teachers from private sector, with an age range of 22-57 years (M = 35.2, SD = 8.54) were recruited. Following the APA-mandated guidelines, the participants provided sociodemographic information and their responses to study variables on the Big-Five Personality Scale, Teacher’s Techno-stress Levels Defining Scale, and Burnout Measure. Findings suggested that tedium had a significant positive correlation with both neuroticism, and techno-stress, while a significant negative association with extraversion, openness, conscientiousness, and agreeableness. Moreover, neuroticism and techno-stress were found to be the positive predictors of tedium, while conscientiousness and agreeableness negatively predicted tedium. Gender differences indicated that women teachers reported more tedium than their male counterparts. The results highlighted the need to seriously address the factors responsible for the decline in teachers’ efficiency and competence.

Vitamin E Intake and Prevalence Rates of Thyroid Dysfunction and Autoimmune Thyroiditis: A Cross-Sectional Analysis of NHANES Data.

Background: Thyroid disorders are associated with various dietary factors and nutritional elements. The aim of this study was to investigate the relationships between dietary vitamin E intake and the prevalence of thyroid dysfunction and thyroid antibody positivity using data from the National Health and Nutrition Examination Survey (NHANES) database. Methods: Data from the NHANES database collected between 2007 and 2012 were analyzed. A total of 7,773 nonpregnant adults without preexisting thyroid diseases and possessing complete thyroid and vitamin E data were included in the study. The participants were categorized into tertiles based on their dietary vitamin E intake: the lowest group (T1: ≤4.53 mg), the intermediate group (T2: 4.54-8.10 mg), and the highest group (T3: ≥8.11 mg). We used a complex multistage probability sampling design in conjunction with R software. We compared thyroid indices, the prevalence of overt and subclinical hyperthyroidism or hypothyroidism, and the occurrence of thyroid antibody positivity among the three groups based on vitamin E intake. Weighted multinomial logistic regression was used to assess the association between dietary vitamin E intake and thyroid disorders. Restricted cubic splines (RCSs) were used to explore potential nonlinear associations. Results: The prevalence rates of subclinical hypothyroidism (SCH) were 3.63%, 3.07%, and 1.85% in T1, T2, and T3, respectively, indicating a decreasing trend (P-trend = 0.013). In the general population, high vitamin E intake (T3) was significantly associated with a lower prevalence of SCH (OR = 0.28, CI = 0.15-0.54, p < 0.001). Subgroup analysis revealed a more pronounced protective effect in males, with both moderate (T2, OR = 0.45, CI = 0.23-0.87, p = 0.020) and high (T3, OR = 0.19, CI = 0.09-0.39, p < 0.001) dietary vitamin E intake being associated with a lower prevalence of SCH. In addition, moderate (T2, OR = 0.59, CI = 0.37-0.93, p = 0.024) and high (T3, OR = 0.52, CI = 0.36-0.75, p < 0.001) dietary vitamin E intake was associated with a lower prevalence of autoimmune thyroiditis (AIT) in males. However, no significant association was observed among females. Conclusion: The findings of this study suggest that a higher intake of vitamin E is associated with lower prevalence rates of SCH and autoimmune thyroiditis among males.

Genetic Insights into the Association and Causality Between Blood Metabolites and Alzheimer's Disease.

Alzheimer's disease (AD) is an increasing public health concern with the aging of the global population. Understanding the genetic correlation and potential causal relationships between blood metabolites and AD may provide important insights into the metabolic dysregulation underlying this neurodegenerative disorder. The aim of this study was to investigate the causal relationship between blood metabolites and AD using Mendelian randomization (MR) analysis. Association data were obtained from three large-scale genome-wide association studies of 486 blood metabolites (N = 7,824), AD (71,880 cases and 383,378 controls), early-onset AD (N = 303,760), and late-onset AD (N = 307,112). Causal associations between blood metabolites and AD were assessed using inverse variance weighting (IVW), MR-Egger, and weighted median methods. Bidirectional two-sample MR analysis was used to identify causal blood metabolites. MR-PRESSO, MR-Egger, and Cochran-Q were used to quantify instrumental variable heterogeneity and horizontal pleiotropy. Using MR and sensitivity analysis, we identified 40 blood metabolites with potential causal associations with AD. After applying false discovery rate (FDR) correction, two metabolites, gamma-glutamylphenylalanine (OR = 1.15, 95% CI: 1.06-1.24, p = 3.88×10-4, q = 0.09) and X-11317 (OR = 1.16, 95% CI: 1.08-1.26, p = 1.14×10-4, q = 0.05), retained significant associations with AD. Reverse MR analysis indicated no significant causal effect of AD on blood metabolites. No significant instrumental variable heterogeneity or horizontal pleiotropy was found. This two-sample MR study provides compelling evidence for a potential causal relationship between blood metabolic dysregulation and susceptibility to AD. Further investigation of the biological relevance of the identified metabolites to AD and additional supporting evidence is warranted.

145 Encoding Brain Dynamics: Neuropsychological Test Scores as Predictors of iEEG Spectral Features in Epilepsy

INTRODUCTION: Intracranial EEG is a valuable tool for investigating the neural mechanisms underlying medically refractory epilepsy (MRE). Despite the advances made in understanding the condition, there is a lack of research exploring the relationship between iEEG data and neuropsychological test performance in MRE patients. METHODS: We performed a retrospective analysis of resting-state iEEG data from 70 MRE patients, extracting spectral features from 4.4 million 10-second time windows across 5201 electrodes. Using MATLAB and FieldTrip toolbox, we processed the data and used two brain atlases for probabilistic electrode assignment. Neuropsychological test scores were corrected for demographic factors. Relationships between preoperative neuropsychological test scores and spectral features were explored using nested hierarchical generalized linear mixed effects (GLME) models, focusing on the hippocampus. RESULTS: We found significant associations between neuropsychological tests and hippocampal power spectral densities (PSDs). Rey Auditory verbal learning test (RAVLT) recognition correct and short-term retention percentages were significantly associated with relative power (RP) in the beta-range (p &lt; 0.05, FDR-corrected). The Boston naming test and Trail Making Test (TMT)-A finishing time showed significant associations with high-beta/low-gamma PSD (p &lt; 0.05, FDR-corrected). TMT-B errors are positively correlated with delta/theta RP (p &lt; 0.05, FDR-corrected). CONCLUSIONS: Our study provides novel insights into the relationship between iEEG spectral features and neuropsychological test performance in MRE patients. The findings suggest that the heterogeneity in spectral features may explain relevant cognitive performance, highlighting the biological basis and circuits of neuropsychological testing.

Epizootiology and Pathology of Sarcoptic Mange in Two Species of Fox (Lycalopex spp.) in Human-Dominated Landscapes of Central Chile.

Sarcoptic mange caused by Sarcoptes scabiei can have catastrophic consequences for wildlife. We inspected 122 Andean foxes (Lycalopex culpaeus), collected by active (n=66) or passive (n=56) surveillance, and 28 South American gray foxes (Lycalopex griseus; all from passive surveillance) for mange in Chile (2015-19). In Andean foxes, gross lesions of mange were diagnosed in 24% of passively and 9% of actively collected foxes, although observed prevalences might be underestimated. Seroprevalence was 37 and 18%, respectively, indicating that some individuals recovered from infection or were developing the disease. No differences were found between age and sex groups. Comparing data from passive surveillance, occurrence of gross lesions was lower in gray foxes (5%). Body condition was significantly better in Andean foxes without lesions than in diseased foxes, which had significantly lower albumin concentrations than healthy individuals. Among the 12 foxes with gross lesions, four, six and two individuals were categorized as having type I, type II, and type III lesions, respectively, based on clinical severity. Histologic severity correlated with gross lesions and included irregular epidermal hyperplasia with hyperkeratosis, which was marked in type II and III infections. Conventional PCR targeting of the cox1 gene fragment revealed four nucleotide sequence types, showing 99-100% identity among them and between 99% and 100% identity with previously published sequences of S. scabiei. A significant association between the occurrence of mange in foxes and distance to the nearest house was found. We speculate that diseased foxes tended to approach human settlements, perhaps in search of food. Visual inspection of 211 rural dogs from the study area did not reveal gross mange lesions in any animal. Sarcoptic mange is enzootic in the Andean fox in the study area and should be considered in the management of the species.

The role of specific emotion dysregulation facets in the association between child violence exposure and psychopathology.

African Americans living in low-income urban environments are disproportionately exposed to violence compared to other racial groups. Child exposure to community violence is linked to adverse psychological outcomes, including externalizing and internalizing behaviors. Emotion dysregulation may be one psychological process through which externalizing and internalizing behaviors develop in the context of childhood violence exposure. However, limited research exists on how different aspects of emotion dysregulation are affected by community violence exposure in children. The present study examined whether violence exposure was indirectly associated with externalizing and internalizing behaviors via facets of emotion dysregulation in a sample of 94 African American mother-child dyads. Mothers and children completed measures to assess child community violence exposure, externalizing and internalizing behaviors, and emotion dysregulation (anger, sadness, and worry dysregulation). Results indicated that maternal report of child community violence exposure was indirectly associated with externalizing behaviors via anger dysregulation and internalizing behaviors via worry dysregulation. Child report of community violence exposure was also indirectly associated with externalizing behavior via anger dysregulation; however, there were no significant associations with internalizing behavior. These findings suggest that certain components of emotion dysregulation serve as an indirect pathway of influence for community violence exposure on child behavior, and the pathways differ between externalizing and internalizing behavior outcomes. Emotion dysregulation may serve as an important potential treatment target in reducing long-term risks associated with violence exposure in urban communities of color. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Association of Antipsychotic Drugs with Venous Thromboembolism: Data Mining of Food and Drug Administration Adverse Event Reporting System and Mendelian Randomization Analysis.

Past observational studies have reported on the association between antipsychotic drugs and venous thromboembolism (VTE); however, the conclusions remain controversial, and its mechanisms are yet to be fully understood. Thus, in this study, we aim to determine the associations of antipsychotic drugs with VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), and their potential mechanisms. We first mined the adverse event signals of VTE, DVT, and PE caused by antipsychotic drugs in Food and Drug Administration Adverse Event Reporting System (FAERS). Next, we used two-sample Mendelian randomization (MR) method to investigate the association of antipsychotic drug target gene expression with VTE, DVT, and PE, using single-nucleotide polymorphisms as genetic instruments. We not only used the expression of all antipsychotic drug target genes as exposure to perform MR analyses but also analyzed the effect of single target gene expression on the outcomes. In the FAERS, 1694 cases of VTE events were reported by 16 drugs. However, using the MR approach, no significant association was determined between the expression of all antipsychotic target genes and VTE, DVT, or PE, either in blood or brain tissue. Although the analysis of single gene expression data showed that the expression of nine genes was associated with VTE events, these targets lacked significant pharmacological action. Adverse event mining results have supported the claim that antipsychotic drugs can increase the risk of VTE. However, we failed to find any genetic evidence for this causal association and potential mechanisms. Thus, vigilance is still needed for antipsychotic drug-related VTE despite the limited supporting evidence.

Clinical outcomes in combination versus mono antibiotic therapy in ICU admitted patients with a suspected infection - A substudy of the DIANA study

PurposeIn a retrospective cohort study of intensive care unit (ICU) admitted adult patients with suspected or confirmed infection, associations between combination versus mono empirical antibiotic therapy and clinical cure at day 7 as well as mortality at day 7 and 28, were investigated. Materials and methodsPatients from the DIANA study were grouped and analysed by combination versus mono antibiotic therapy. Clinical cure was defined as survival and resolution of all signs and symptoms related to the infection. Odds ratios (ORs) were calculated by logistic regression analyses. ResultsOf the 1398 included patients, 568 patients (41%) received combination therapy. In total, 641(46%) patients achieved clinical cure and 135 (10%) patients had died as of day 7. There were no significant associations between combination and mono therapy relating to clinical cure and mortality. ConclusionsThis study found no differences in clinical cure and mortality between empirical combination versus mono therapy in a large cohort of ICU patients with a suspected infection.

Genetic diversity, population structure and marker-trait associations in Indian kale (Brassica oleracea L. gp. acephala) using cross-species microsatellite markers

Kale is known for its exceptional nourishing and functional benefits to human body. However, it is an understudied species from genomic as well as agronomic aspects. It is important to characterize niche kale germplasms around the world to systematically conserve and utilize its genetic variability, especially for commercial traits in the interest of growers, consumers and industry. With this view, genomic and phenotypic characterizations of 62 Kashmiri kale accessions including popular landraces were done to estimate and partition genetic diversity, understand trait relationships, develop population structure and divulge marker-trait associations of economic significance. Sixty-six cross species microsatellite (SSR) markers within Brassica genus amplified 269 alleles in the germplasm. Their polymorphic information content (PIC) ranged from 0.00078 to 0.953 with an average of 0.407. The population structure analysis and neighbour joining tree clustering categorized the germplasm into three sub-populations. AMOVA revealed more within-population variance (67.73 %) than among-populations (32.27 %) variance. The principal component analysis (PCA) involving 24 agronomical traits revealed seven PCs (PC1 to PC7) having Eigen values more than 1, which explained a cumulative variation of 69.21 %. Association mapping with respect to these 24 agronomical traits using mixed linear model and general linear model revealed six overlapping significant marker-trait relationships with five being significant at probability value of 0.001/0.0001. The highly significant associations of two SSRs with economically important traits (siliqua length and seed weight) significantly correlated/related with leaf yield and seed yield were revealed for their possible utilization in marker assisted breeding for higher leaf and seed yields.

Association of Baseline Tumor-Specific Neoantigens and CD8+ T-Cell Infiltration With Immune-Related Adverse Events Secondary to Immune Checkpoint Inhibitors.

Recent evidence has shown that higher tumor mutational burden strongly correlates with an increased risk of immune-related adverse events (irAEs). By using an integrated multiomics approach, we further studied the association between relevant tumor immune microenvironment (TIME) features and irAEs. Leveraging the US Food and Drug Administration Adverse Event Reporting System, we extracted cases of suspected irAEs to calculate the reporting odds ratios (RORs) of irAEs for cancers treated with immune checkpoint inhibitors (ICIs). TIME features for 32 cancer types were calculated on the basis of the cancer genomic atlas cohorts and indirectly correlated with each cancer's ROR for irAEs. A separate ICI-treated cohort of non-small-cell lung cancer (NSCLC) was used to evaluate the correlation between tissue-based immune markers (CD8+, PD-1/L1+, FOXP3+, tumor-infiltrating lymphocytes [TILs]) and irAE occurrence. The analysis of 32 cancers and 33 TIME features demonstrated a significant association between irAE RORs and the median number of base insertions and deletions (INDEL), neoantigens (r = 0.72), single-nucleotide variant neoantigens (r = 0.67), and CD8+ T-cell fraction (r = 0.51). A bivariate model using the median number of INDEL neoantigens and CD8 T-cell fraction had the highest accuracy in predicting RORs (adjusted r2 = 0.52, P = .002). Immunoprofile assessment of 156 patients with NSCLC revealed a strong trend for higher baseline median CD8+ T cells within patients' tumors who experienced any grade irAEs. Using machine learning, an expanded ICI-treated NSCLC cohort (n = 378) further showed a treatment duration-independent association of an increased proportion of high TIL (>median) in patients with irAEs (59.7% v 44%, P = .005). This was confirmed by using the Fine-Gray competing risk approach, demonstrating higher baseline TIL density (>median) associated with a higher cumulative incidence of irAEs (P = .028). Our findings highlight a potential role for TIME features, specifically INDEL neoantigens and baseline-immune infiltration, in enabling optimal irAE risk stratification of patients.

Brief Report: Relationship Between Adiposity and Biomarkers of Aging and Frailty Among Adults Aging With HIV.

This study examined the relationships among adiposity, handgrip, physical function, inflammation (ie, senescence-associated secretory phenotype chemokines as biomarkers of aging and frailty), and sex hormones in aging people with HIV. This cross-sectional exploratory study included 150 people with HIV aged ≥40 years (67.3% of participants were male). Our measures included (1) body mass index and waist circumference as measures of adiposity; (2) handgrip as a measure of muscle strength; (3) short physical performance battery as a measure of physical function; (4) interleukin-6, tumor necrosis factor alpha receptor II, high sensitivity C-reactive protein, C-X-C motif chemokine 10, and C-X3-C motif chemokine ligand 1 also known as fractalkine as senescence-associated secretory phenotype chemokines; and (5) free testosterone, estradiol, sex hormone-binding globulin, and dehydroepiandrosterone as sex hormones. Quantile regression analyses were used to identify relationships among inflammatory markers and hormones with age, adiposity, handgrip, and physical function. Overall, 74% (n = 111) of participants were classified as overweight or obese and 53.3% (n = 80) presented with abdominal obesity. After controlling for age and sex, body mass index was positively associated with estradiol (β = 0.043, P < 0.01), and waist circumference was positively associated with high sensitivity C-reactive protein (β = 2.151, P < 0.01). After controlling for sex, age was positively associated with C-X-C motif chemokine 10 (β = 0.024, P = 0.03) and tumor necrosis factor alpha receptor II (β = 2.205, P = 0.01). After controlling for age and sex, short physical performance battery was negatively associated with dehydroepiandrosterone (β = -0.004, P = 0.01); no statistically significant associations were observed for handgrip. Adiposity levels and aging were associated with inflammation (ie, C-X-C motif chemokine 10, tumor necrosis factor alpha receptor II, and high sensitivity C-reactive protein) among people with HIV aged 40 years and older.

Associations Between Social–Emotional Teaching Practices and Reductions in Preschoolers' Challenging Behavior

It is widely assumed that (1) children with challenging behavior may lack the social–emotional skills to be successful in classroom settings and (2) instruction in social–emotional skills can help prevent the occurrence of young children's challenging behavior. However, no data are available to indicate whether specific social–emotional skills might be most effective in reducing existing challenging behavior. In this study, we used an archival database to examine possible relationships between types of social–emotional instruction and changes over a 4-month period in levels of social skills and challenging behavior. The database, from a randomized trial of an intervention for preschoolers' challenging behavior, included measures of types of social–emotional instruction and children's social skills and challenging behaviors. Correlational analyses revealed statistically significant relationships between two types of social–emotional teaching practices and reductions in preschoolers' challenging behavior for children in the intervention group, teaching children behavior expectations and teaching problem-solving. No other statistically significant associations were identified. The results are discussed in relation to possible implications for social–emotional instruction for preschool children already exhibiting challenging behavior and the value of further research focused on preventing challenging behavior in young children.