Tag: nevin manimala

Bioinformatics. 2023 Aug 30:btad535. doi: 10.1093/bioinformatics/btad535. Online ahead of print.

ABSTRACT

MOTIVATION: Existing methods for simulating synthetic genotype and phenotype datasets have limited scalability, constraining their usability for large-scale analyses. Moreover, a systematic approach for evaluating synthetic data quality and a benchmark synthetic dataset for developing and evaluating methods for polygenic risk scores are lacking.

RESULTS: We present HAPNEST, a novel approach for efficiently generating diverse individual-level genotypic and phenotypic data. In comparison to alternative methods, HAPNEST shows faster computational speed and a lower degree of relatedness with reference panels, while generating datasets that preserve key statistical properties of real data. These desirable synthetic data properties enabled us to generate 6.8 million common variants and nine phenotypes with varying degrees of heritability and polygenicity across 1 million individuals. We demonstrate how HAPNEST can facilitate biobank-scale analyses through the comparison of seven methods to generate polygenic risk scoring across multiple ancestry groups and different genetic architectures.

AVAILABILITY AND IMPLEMENTATION: A synthetic dataset of 1,008,000 individuals and 9 traits for 6.8 million common variants is available at https://www.ebi.ac.uk/biostudies/studies/S-BSST936. The HAPNEST software for generating synthetic datasets is available as Docker/Singularity containers and open source Julia and C code at https://github.com/intervene-EU-H2020/synthetic_data.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:37647640 | DOI:10.1093/bioinformatics/btad535

Jpn J Clin Oncol. 2023 Aug 29:hyad113. doi: 10.1093/jjco/hyad113. Online ahead of print.

ABSTRACT

BACKGROUND: Wilms tumor is the most common cancer of the kidney that occurs during childhood, and histologically, it mimics renal embryogenesis. With the development and improvement of up-to-date treatment protocols, the survival rates of Wilms tumor have increased. However, metastases or local relapses are still observed in 15% of patients. The search for reliable biomarkers to identify at-risk patients is ongoing to predict the variability in treatment success. Currently, the evaluation of clinical, histopathological and genetic features are common diagnostic methods; however, epigenetic features can be examined with microRNA expression analyses and might allow us to comment on the behavior of the tumor and treatment response.

METHODS: In this study, we aimed to evaluate the relationship between microRNA-204 and microRNA-483-5p expression with clinicopathological data and the effect on Wilms tumor survival. For this purpose, the expression levels of RNU6B, microRNA-204 and microRNA-483-5p were evaluated in tumor and normal tissue by qreal time-polymerase chain reaction. We also investigated the relationship between microRNA expression levels with the clinicopathological and histological features of Wilms tumor.

RESULTS AND CONCLUSION: The results of our study indicate that the relative expression levels of microRNA-204 in Wilms tumor tissues were significantly lower than that in adjacent normal tissues. By contrast, tumor tissue had a higher microRNA-483-5p expression than the corresponding normal tissues. A statistically significant difference between microRNA-204 expression level with age and the presence of anaplasia was observed. The upregulation of microRNA-483-5p was found to have a significant correlation with patients after preoperative chemotherapy and complete tumor necrosis. Taken together, our data suggest that microRNA-204 could play a critical role as a tumor suppressor, whereas microRNA-483-5p acts as an oncogene in Wilms tumor progression. More importantly, microRNA-204 might be a novel predictive biomarker for anaplastic histology and could be useful for developing therapeutic interventions targeting this marker.

PMID:37647636 | DOI:10.1093/jjco/hyad113

Emerg Infect Dis. 2023 Aug 30;29(10). doi: 10.3201/eid2910.230286. Online ahead of print.

ABSTRACT

Little is known about co-occurring tuberculosis (TB) and COVID-19 in low TB incidence settings. We obtained a cross-section of 333 persons in the United States co-diagnosed with TB and COVID-19 within 180 days and compared them to 4,433 persons with TB only in 2020 and 18,898 persons with TB during 2017‒2019. Across both comparison groups, a higher proportion of persons with TB-COVID-19 were Hispanic, were long-term care facility residents, and had diabetes. When adjusted for age, underlying conditions, and TB severity, COVID-19 co-infection was not statistically associated with death compared with TB infection only in 2020 (adjusted prevalence ratio 1.0 [95% CI 0.8‒1.4]). Among TB-COVID-19 patients, death was associated with a shorter interval between TB and COVID-19 diagnoses, older age, and being immunocompromised (non-HIV). TB-COVID-19 deaths in the United States appear to be concentrated in subgroups sharing characteristics known to increase risk for death from either disease alone.

PMID:37647628 | DOI:10.3201/eid2910.230286

J Nerv Ment Dis. 2023 Aug 28. doi: 10.1097/NMD.0000000000001708. Online ahead of print.

ABSTRACT

Social support provides protective effects for those with serious mental illness (SMI), but these effects may be attenuated by factors that hinder positive perceptions of support. Improved understanding of social support and its determinants may hold relevance for clinical interventions and provide avenues to promote recovery and improve functioning. The present study is a cross-sectional, correlational analysis investigating the relationships among social cognition (Mayer-Salovey-Caruso Emotional Intelligence Test-Managing Emotions subscale), social anxiety (Liebowitz Social Anxiety Scale), negative symptoms (Scale for the Assessment of Negative Symptoms), and perceived social support (Interpersonal Support Evaluation List) among individuals with SMI. Data were analyzed for 59 participants from a psychosocial rehabilitation treatment study at a public, urban academic-affiliated medical center in the Midwest. Bivariate Pearson correlations revealed statistically significant associations among perceived social support and social cognition (total perceived social support, p < 0.05; appraisal support, p < 0.01), negative symptoms (appraisal support, p < 0.05), and social anxiety (self-esteem support, p < 0.05). Further, multiple linear regression revealed social cognition remained a significant predictor of perceived social support (p < 0.05) when controlling for social anxiety and negative symptoms. Overall findings suggest a correlative relationship between social cognition and perceived social support. Conclusions, limitations, and future directions are discussed.

PMID:37647619 | DOI:10.1097/NMD.0000000000001708

Phlebology. 2023 Aug 30:2683555231199004. doi: 10.1177/02683555231199004. Online ahead of print.

ABSTRACT

OBJECTIVES: to evaluate direct oral anticoagulants (DOACs) in patients with hereditary thrombophilia and deep venous thrombosis (DVT).

METHODS: This is a retrospective observational study.

RESULTS: In total, 45 patients were treated between 01/2012 and 12/2022 (mean follow-up: 1.5 +/- 0.3 years). The most frequent thrombophilias were heterozygous V Leiden (20%), heterozygous MTHFR C677T (37.8%), heterozygous MTHFR A1298C (24.4%), and hyperhomocysteinemia (26.7%). The patients received rivaroxaban (n = 19), apixaban (n = 15), and dabigatran (n = 11). Three cases presented symptoms’ recurrence without evidence of thrombosis’ recurrence (two under rivaroxaban and one under apixaban; p > .05). These patients improved under parenteral anticoagulation and were further treated with dabigatran. No other event or major bleeding occurred during the follow-up. The presence of more than two factors was associated with acute recurrence of symptoms (OR = 25.9; 95% CI [1.454-461.262]; p = .026).

CONCLUSIONS: DOACs seem to be safe and efficient for patients with hereditary thrombophilia and DVT. The presence of more than two thrombophilia factors is associated with a higher risk for symptom recurrence. Although statistically non-significant, symptoms’ recurrence was also observed more frequently among patients under anti-Xa inhibitors than antithrombin inhibitors. This should be verified in larger comparative studies.

PMID:37647589 | DOI:10.1177/02683555231199004

Iran J Immunol. 2023 Aug 30;20(3). doi: 10.22034/iji.2023.99188.2622. Online ahead of print.

ABSTRACT

BACKGROUND: Buerger’s disease, also known as Thromboangiitis Obliterans (TAO), is a progressive, inflammatory vascular disease with unknown etiology.

OBJECTIVE: To address the degree of T cell immunosenescence in this inflammatory disease, the frequency of senescent T cells expressing CD57 and/or CD153 (CD30L) in patients with TAO.

METHODS: In this study, nine male cigarette smoker patients with TAO, nine male healthy cigarette smokers, and nine male healthy non-smoker blood donors were enrolled. PBMCs were extracted from the blood of all participants and stored in liquid nitrogen before use. The percentages of senescent T cells were detected by flow cytometry. The results were analyzed using non-parametric statistical tests.

RESULTS: The frequencies of senescent CD3+CD4+CD57+CD153+ and CD3+CD4+CD57-CD153+ T cells significantly increased in patients compared with the non-smoker controls (p=0.01 and p=0.04, respectively). The frequency of senescent CD3+CD4-CD57-CD153+ T cells was higher in patients compared with the smoker controls (p=0.02). In patients with TAO, CD57+CD153- cells were more frequent in CD3hiCD4- and CD3hiCD4+ T cells compared with the CD3loCD4- and CD3loCD4+ T cells (p=0.008 and p=0.0002, respectively). Conversely, the frequency of CD57-CD153+ T cells was significantly higher in CD3loCD4- T cells compared with the CD3hiCD4- T cells (p=0.004). The percentage of CD3+CD4+CD57+CD153- T cells correlated negatively with smoking level in smoker controls (p=0.02, Spearman r=-0.80).

CONCLUSION: Elevated frequencies of senescent CD4+CD57+CD153+ and CD4+CD57-CD153+ T cells in patients compared with non-smoker and smoker controls suggest the contribution of immunosenescence in TAO.

PMID:37647581 | DOI:10.22034/iji.2023.99188.2622

Diabetes. 2023 Aug 30:db230365. doi: 10.2337/db23-0365. Online ahead of print.

ABSTRACT

Understanding differences in adipose gene expression between individuals with different levels of clinical traits may reveal the genes and mechanisms leading to cardiometabolic diseases. However, adipose is a heterogeneous tissue. To account for cell-type heterogeneity, we estimated cell-type proportions in 859 subcutaneous adipose tissue samples with bulk RNA-sequencing (RNA-seq) using a reference single nuclear RNA-seq dataset. Cell-type proportions were associated with cardiometabolic traits; for example, higher macrophage and adipocyte proportions were associated with higher and lower body mass index (BMI), respectively. We evaluated cell-type proportions and BMI as covariates in tests of association between >25,000 gene expression levels and 22 cardiometabolic traits. For >95% of genes, the optimal, or best fit, models included BMI as a covariate, and for 79% of associations, the optimal models also included cell type. After adjusting for the optimal covariates, we identified 2,664 significant associations (P ≤ 2e-6) for 1,252 genes and 14 traits. Among genes proposed to affect cardiometabolic traits based on colocalized genome-wide association study and adipose expression quantitative trait locus signals, 25 showed a corresponding association between trait and gene expression levels. Overall, these results suggest the importance of modeling cell-type proportion when identifying gene expression associations with cardiometabolic traits.

PMID:37647564 | DOI:10.2337/db23-0365

Nurse Educ. 2023 Aug 25. doi: 10.1097/NNE.0000000000001508. Online ahead of print.

ABSTRACT

BACKGROUND: Nursing faculty may have concerns about unfair advantages and inflated examination grades when students take an examination late.

PURPOSE: The purpose of the study was to compare make-up examination scores with on-time examination scores to determine whether scores were higher in students who took an examination late.

METHODS: A descriptive, comparative study using retrospective examination scores from a large nursing program was analyzed. Late examination scores were compared with the student’s individual on-time examination average and the class’s average of on-time examination scores.

RESULTS: A total of 156 examinations were taken late. There were no statistically significant differences between students’ late examination scores when compared with the student’s on-time examinations or the class average of the examination.

CONCLUSION: Students do not appear to gain an advantage when taking an examination late. Findings may assist faculty in developing policies for taking make-up examinations.

PMID:37647528 | DOI:10.1097/NNE.0000000000001508

Anal Chem. 2023 Aug 30. doi: 10.1021/acs.analchem.3c02679. Online ahead of print.

ABSTRACT

This study reports a simple modification to a commercial resin 3D printer that significantly reduces the amount of prepolymer material needed for the production of extraction sorbents. The modified printing platform is demonstrated in the printing of two imidazolium-based ionic liquid (IL) monomers. Two geometries resembling a blade-type polymeric ionic liquid (PIL) sorbent used in thin-film microextraction and a fiber-type sorbent used in solid-phase microextraction (SPME) were printed. The SPME PIL sorbents were used to extract 10 organic contaminants, including plasticizers, antimicrobial agents, UV filters, and pesticides, from water followed by high-performance liquid chromatographic (HPLC) analysis. To compare the extraction performance of the SPME sorbents, seven fibers printed with the same prepolymer composition from the same printing batch as well as different batches were evaluated. The results revealed highly reproducible extraction efficiencies for all tested sorbents with no statistical difference in their extraction performance. Method validation showed acceptable linearity (R² > 0.92) for all analytes with limits of detection and limits of quantification ranging from 0.13 to 45 μg L^-1 and 0.43 to 150 μg L^-1, respectively.

PMID:37647518 | DOI:10.1021/acs.analchem.3c02679

Plast Reconstr Surg. 2023 Aug 29. doi: 10.1097/PRS.0000000000011032. Online ahead of print.

ABSTRACT

INTRODUCTION: In advanced lymphedema, lymphovenous anastomosis (LVA) can be a solution based on utilizing the pressure gradient between the high pressure lymphatics and low pressure veins. If the vein pressure in high, the effect affect surgery will be less optimal. This study evaluated the effect of axillary vein perivascular scar release on LVA.

MATERIALS AND METHODS: This is a retrospective study of 40 upper limb stage 2 and 3 lymphedema patients divided into 2 groups with an average follow-up of 33 months (minimal of at least 12 months); scar-released group (n=25) and control group (n=15). All patients underwent LVA with or without lymph node transfer. Demographic data, outcome (volumetric change and bioimpedence analysis (BIA)), and major veins (axillary, basilic and cephalic) diameter changes were evaluated.

RESULTS: Both groups showed significant reduction in volume and BIA parameters after LVA. The scar-released groups (24/25 with lymph node transfer and 1 without) showed statistically higher reduction of BIA analysis compared to the control group at 1, 6 and 12 months after LVA. The changes in the major veins after axilla scar release showed significant changes in all 3 veins. There was a significant correlation between cephailic vein dimeter reduction and BIA measurement.

CONCLUSION: The release of perivascular scar in the axially vein may result in better outcome after LVA. This is based on the finding that scar release shows correlation between cephailic vein dimeter reduction and BIA measurement suggesting reduction of venous pressure in the peripheral vein increasing the pressure gradient between the lymphatic and venous system allowing better outflow after LVA.

PMID:37647513 | DOI:10.1097/PRS.0000000000011032