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Nevin Manimala Statistics

Two people, one graph: the effect of rotated viewpoints on accessibility of data visualizations

Cogn Res Princ Implic. 2021 Apr 13;6(1):31. doi: 10.1186/s41235-021-00297-y.

ABSTRACT

In co-located, multi-user settings such as multi-touch tables, user interfaces need to be accessible from multiple viewpoints. In this project, we investigated how this goal can be achieved for depictions of data in bar graphs. We designed a laboratory task in which participants answered simple questions based on information depicted in bar graphs presented from differently rotated points of view. As the dependent variable, we measured differences in response onsets relative to the standard viewpoint (i.e., upright graphs). In Experiment 1, we manipulated graph and label orientation independently of each other. We observed that rotations of the labels rather than rotations of the graph itself pose a challenge for accessing depicted information from rotated viewpoints. In Experiment 2, we studied whether replacing word labels with pictographs could overcome the detrimental effects of rotated labels. Rotated pictographs were less detrimental than rotated word labels, but performance was still worse than in the unrotated baseline condition. In Experiment 3, we studied whether color coding could overcome the detrimental effects of rotated labels. Indeed, for multicolored labels, the detrimental effect of label rotation was in the negligible range. We discuss the implications of our findings for the underlying psychological theory as well as for the design of depicted statistical information in multi-user settings.

PMID:33847833 | DOI:10.1186/s41235-021-00297-y

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Nevin Manimala Statistics

Squaring Things Up With R2: What it is, What it Can (and cannot) Tell You

J Anal Toxicol. 2021 Apr 13:bkab036. doi: 10.1093/jat/bkab036. Online ahead of print.

ABSTRACT

The coefficient of correlation (r) and the coefficient of determination (R2 or r2) have long been used in analytical chemistry, bioanalysis and forensic toxicology as figures demonstrating linearity of the calibration data in method validation. We clarify here what these two figures are and why they should not be used for this purpose in the context of model fitting for prediction. R2 evaluates whether the data are better explained by the regression model used than by no model at all (i.e., a flat line of slope = 0 and intercept $bar y$), and to what degree. Hopefully, in the context of calibration curves, the fact that a linear regression better explains the data than no model at all should not be a point of contention. Upon closer examination, a series of restrictions appear in the interpretation of these coefficients. They cannot indicate whether the dataset at hand is linear or not, because they assume that the regression model used is an adequate model for the data. For the same reason, they cannot disprove the existence of another functional relationship in the data. By definition, they are influenced by the variability of the data. The slope of the calibration curve will also change their value. Finally, when heteroscedastic data are analyzed, the coefficients will be influenced by calibration levels spacing within the dynamic range, unless a weighted version of the equations is used. With these considerations in mind, we suggest to stop using r and R2 as figures of merit to demonstrate linearity of calibration curves in method validations. Of course, this does not preclude their use in other contexts. Alternative paths for evaluation of linearity and calibration model validity are summarily presented.

PMID:33847757 | DOI:10.1093/jat/bkab036

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Nevin Manimala Statistics

The effect of pessary treatment on puborectalis muscle function

Int Urogynecol J. 2021 Apr 13. doi: 10.1007/s00192-021-04766-2. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: The objective was to assess if puborectalis muscle (PRM) function changes in women with pelvic organ prolapse (POP) undergoing pessary treatment.

METHODS: This was a prospective cohort study of women with symptomatic POP choosing pessary treatment. An interview, clinical examination and 3D/4D transperineal ultrasound were performed at baseline and at 3-month follow-up. POP was assessed using the Pelvic Organ Prolapse Quantification system (POPQ). Parameters compared between baseline and follow-up were: hiatal area at rest (HArest), maximal contraction (HActx), and maximal Valsalva maneuver (HAVal), displacement in contraction (DISPL-ctx, i.e., relative difference between HArest and HActx), and displacement in Valsalva (DISPL-Val, i.e., relative difference between and HAVal and HArest). Parameters were compared in women with and those without complete avulsion.

RESULTS: A total of 162 women were assessed and 34 were included. Mean age was 64 years (SD 11.4), and mean BMI 24 kg/m2 (SD 3.1). Thirty-one women had a cystocele, 8 a uterine prolapse, and 12 had a posterior compartment prolapse. Twenty-one women (61.8%) had a POP stage II, and 13 (38.2%) a POP stage III. Ring pessaries were most frequently used (97%). In the entire group a statistically significant increase in DISPL-ctx was observed (mean difference 2.1%, p = 0.017). In the no avulsion group HArest and DISPL-ctx increased significantly (mean difference 4.1%, p = 0.016 and 2.7%, p = 0.016 respectively) and the increase in DISPL-ctx was higher than in the avulsion group (mean difference 2.7% vs 0.2%, p = 0.056).

CONCLUSION: Our results show that PRM function changes in women with POP undergoing pessary treatment and suggest that such change occurs mainly in the absence of complete avulsion.

PMID:33847771 | DOI:10.1007/s00192-021-04766-2

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Nevin Manimala Statistics

The ratio and difference of urine protein-to-creatinine ratio and albumin-to-creatinine ratio facilitate risk prediction of all-cause mortality

Sci Rep. 2021 Apr 12;11(1):7851. doi: 10.1038/s41598-021-86541-3.

ABSTRACT

The role of the difference and ratio of albuminuria (urine albumin-to-creatinine ratio, uACR) and proteinuria (urine protein-to-creatinine ratio, uPCR) has not been systematically evaluated with all-cause mortality. We retrospectively analyzed 2904 patients with concurrently measured uACR and uPCR from the same urine specimen in a tertiary hospital in Taiwan. The urinary albumin-to-protein ratio (uAPR) was derived by dividing uACR by uPCR, whereas urinary non-albumin protein (uNAP) was calculated by subtracting uACR from uPCR. Conventional severity categories of uACR and uPCR were also used to establish a concordance matrix and develop a corresponding risk matrix. The median age at enrollment was 58.6 years (interquartile range 45.4-70.8). During the 12,391 person-years of follow-up, 657 deaths occurred. For each doubling increase in uPCR, uACR, and uNAP, the adjusted hazard ratios (aHRs) of all-cause mortality were 1.29 (95% confidence interval [CI] 1.24-1.35), 1.12 (1.09-1.16), and 1.41 (1.34-1.49), respectively. For each 10% increase in uAPR, it was 1.02 (95% CI 0.98-1.06). The linear dose-response association with all-cause mortality was only observed with uPCR and uNAP. The 3 × 3 risk matrices revealed that patients with severe proteinuria and normal albuminuria had the highest risk of all-cause mortality (aHR 5.25, 95% CI 1.88, 14.63). uNAP significantly improved the discriminative performance compared to that of uPCR (c statistics: 0.834 vs. 0.828, p-value = 0.032). Our study findings advocate for simultaneous measurements of uPCR and uACR in daily practice to derive uAPR and uNAP, which can provide a better mortality prognostic assessment.

PMID:33846379 | DOI:10.1038/s41598-021-86541-3

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Nevin Manimala Statistics

The impact of baseline glomerular filtration rate on subsequent changes of glomerular filtration rate in patients with chronic kidney disease

Sci Rep. 2021 Apr 12;11(1):7894. doi: 10.1038/s41598-021-86955-z.

ABSTRACT

Higher baseline glomerular filtration rate (GFR) may yield subsequent steeper GFR decline, especially in patients with diabetes mellitus (DM). However, this correlation in patients with chronic kidney disease (CKD) and the presence or absence of DM remains controversial. We conducted a longitudinal cohort study in a single medical center between 2011 and 2018. Participants with CKD stage 1 to 3A were enrolled and divided into DM groups and non-DM groups, and then followed up at least every 6 months. We used a linear mixed regression model with centering time variable to overcome the problem of mathematical coupling in the analysis of the relation between baseline GFR and the changes, and compared the results from correct and incorrect specifications of the mixed models. A total number of 1002 patients with 285 diabetic and 717 non-diabetic persons was identified. The linear mixed regression model revealed a significantly negative correlation between baseline GFR and subsequent GFR change rate in both diabetic group and non-diabetic group (r = – 0.44 [95% confidence interval [CI], – 0.69 to – 0.09]), but no statistical significance in non-diabetic group after within-subject mean centering of time variable (r = – 0.09 [95% CI, – 0.41 to 0.25]). Our study showed that higher baseline GFR was associated with a subsequent steeper GFR decline in the DM group but not in the non-DM group among patients with early-stage CKD. Exact model specifications should be described in detail to prevent from a spurious conclusion.

PMID:33846427 | DOI:10.1038/s41598-021-86955-z

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Nevin Manimala Statistics

Key biomarkers within the colorectal cancer related inflammatory microenvironment

Sci Rep. 2021 Apr 12;11(1):7940. doi: 10.1038/s41598-021-86941-5.

ABSTRACT

Therapeutic approaches focused on the inflammatory microenvironment are currently gaining more support, as biomolecules involved in the inflammatory colorectal cancer (CRC) tumor microenvironment are being explored. We analyzed tumor and paired normal tissue samples from CRC patients (n = 22) whom underwent tumor resection surgery. We assessed 39 inflammation-involved biomolecules (multiplex magnetic bead-based immunoassay), CEA and CA19-9 (ELISA assay) and the tissue expression levels of occludin and also pErk, STAT1 and STAT3 transcriptional factors (western blot). Tumor staging has been established by histopathological evaluation of HE stained tumor tissue sections. We report 32 biomarkers displaying statistically significant differences in tumor vs. control. Additionally, positive statistical biomarker correlations were found between MMP2-IL8 and BAFF-IL8 (Pearson correlation coefficients > 0.751), while APRIL-MMP2, APRIL-BAFF and APRIL-IL8 were negatively correlated (correlation coefficients < – 0.650). While APRIL, BAFF, IL8 and MMP2 did not modulate with tumor stage, they were inversely related to the immune infiltrate level and CD163 tissue expression. We conclude that the significantly decreased APRIL and increased BAFF, IL8 and MMP2 expression were tumor-specific and deserve consideration in the development of new treatments. Also, the positive correlation between Chitinase 3-like 1 and IL8 (0.57) or MMP2 (0.50) suggest a role in tumor growth and metastasis pathways.

PMID:33846436 | DOI:10.1038/s41598-021-86941-5

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Nevin Manimala Statistics

Complement C3 identified as a unique risk factor for disease severity among young COVID-19 patients in Wuhan, China

Sci Rep. 2021 Apr 12;11(1):7857. doi: 10.1038/s41598-021-82810-3.

ABSTRACT

Given that a substantial proportion of the subgroup of COVID-19 patients that face a severe disease course are younger than 60 years, it is critical to understand the disease-specific characteristics of young COVID-19 patients. Risk factors for a severe disease course for young COVID-19 patients and possible non-linear influences remain unknown. Data were analyzed from COVID-19 patients with clinical outcome in a single hospital in Wuhan, China, collected retrospectively from Jan 24th to Mar 27th. Clinical, demographic, treatment and laboratory data were collected from patients’ medical records. Uni- and multivariable analysis using logistic regression and random forest, with the latter allowing the study of non-linear influences, were performed to investigate the clinical characteristics of a severe disease course. A total of 762 young patients (median age 47 years, interquartile range [IQR] 38-55, range 18-60; 55.9% female) were included, as well as 714 elderly patients as a comparison group. Among the young patients, 362 (47.5%) had a severe/critical disease course and the mean age was statistically significantly higher in the severe subgroup than in the mild subgroup (59.3 vs. 56.0, Student’s t-test: p < 0.001). The uni- and multivariable analysis suggested that several covariates such as elevated levels of serum amyloid A (SAA), C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased lymphocyte counts influence disease severity independently of age. Elevated levels of complement C3 (odds ratio [OR] 15.6, 95% CI 2.41-122.3; p = 0.039) are particularly associated with the risk of developing severe COVID-19 specifically in young patients, whereas no such influence seems to exist for elderly patients. Additional analysis suggests that the influence of complement C3 in young patients is independent of age, gender, and comorbidities. Variable importance values and partial dependence plots obtained using random forests delivered additional insights, in particular indicating non-linear influences of risk factors on disease severity. This study identified increased levels of complement C3 as a unique risk factor for adverse outcomes specific to young COVID-19 patients.

PMID:33846344 | DOI:10.1038/s41598-021-82810-3

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Nevin Manimala Statistics

RA3 is a reference-guided approach for epigenetic characterization of single cells

Nat Commun. 2021 Apr 12;12(1):2177. doi: 10.1038/s41467-021-22495-4.

ABSTRACT

The recent advancements in single-cell technologies, including single-cell chromatin accessibility sequencing (scCAS), have enabled profiling the epigenetic landscapes for thousands of individual cells. However, the characteristics of scCAS data, including high dimensionality, high degree of sparsity and high technical variation, make the computational analysis challenging. Reference-guided approaches, which utilize the information in existing datasets, may facilitate the analysis of scCAS data. Here, we present RA3 (Reference-guided Approach for the Analysis of single-cell chromatin Accessibility data), which utilizes the information in massive existing bulk chromatin accessibility and annotated scCAS data. RA3 simultaneously models (1) the shared biological variation among scCAS data and the reference data, and (2) the unique biological variation in scCAS data that identifies distinct subpopulations. We show that RA3 achieves superior performance when used on several scCAS datasets, and on references constructed using various approaches. Altogether, these analyses demonstrate the wide applicability of RA3 in analyzing scCAS data.

PMID:33846355 | DOI:10.1038/s41467-021-22495-4

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Nevin Manimala Statistics

Cardiometabolic risks of SARS-CoV-2 hospitalization using Mendelian Randomization

Sci Rep. 2021 Apr 12;11(1):7848. doi: 10.1038/s41598-021-86757-3.

ABSTRACT

Many cardiometabolic conditions have demonstrated associative evidence with COVID-19 hospitalization risk. However, the observational designs of the studies in which these associations are observed preclude causal inferences of hospitalization risk. Mendelian Randomization (MR) is an alternative risk estimation method more robust to these limitations that allows for causal inferences. We applied four MR methods (MRMix, IMRP, IVW, MREgger) to publicly available GWAS summary statistics from European (COVID-19 GWAS n = 2956) and multi-ethnic populations (COVID-19 GWAS n = 10,908) to better understand extant causal associations between Type II Diabetes (GWAS n = 659,316), BMI (n = 681,275), diastolic and systolic blood pressure, and pulse pressure (n = 757,601 for each) and COVID-19 hospitalization risk across populations. Although no significant causal effect evidence was observed, our data suggested a trend of increasing hospitalization risk for Type II diabetes (IMRP OR, 95% CI 1.67, 0.96-2.92) and pulse pressure (OR, 95% CI 1.27, 0.97-1.66) in the multi-ethnic sample. Type II diabetes and Pulse pressure demonstrates a potential causal association with COVID-19 hospitalization risk, the proper treatment of which may work to reduce the risk of a severe COVID-19 illness requiring hospitalization. However, GWAS of COVID-19 with large sample size is warranted to confirm the causality.

PMID:33846372 | DOI:10.1038/s41598-021-86757-3

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Nevin Manimala Statistics

Genetic evidence for the association between COVID-19 epidemic severity and timing of non-pharmaceutical interventions

Nat Commun. 2021 Apr 12;12(1):2188. doi: 10.1038/s41467-021-22366-y.

ABSTRACT

Unprecedented public health interventions including travel restrictions and national lockdowns have been implemented to stem the COVID-19 epidemic, but the effectiveness of non-pharmaceutical interventions is still debated. We carried out a phylogenetic analysis of more than 29,000 publicly available whole genome SARS-CoV-2 sequences from 57 locations to estimate the time that the epidemic originated in different places. These estimates were examined in relation to the dates of the most stringent interventions in each location as well as to the number of cumulative COVID-19 deaths and phylodynamic estimates of epidemic size. Here we report that the time elapsed between epidemic origin and maximum intervention is associated with different measures of epidemic severity and explains 11% of the variance in reported deaths one month after the most stringent intervention. Locations where strong non-pharmaceutical interventions were implemented earlier experienced much less severe COVID-19 morbidity and mortality during the period of study.

PMID:33846321 | DOI:10.1038/s41467-021-22366-y