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Nevin Manimala Statistics

Evidence-Based Health Informatics as the Foundation for the COVID-19 Response: A Joint Call for Action

Methods Inf Med. 2021 May 11. doi: 10.1055/s-0041-1726414. Online ahead of print.

ABSTRACT

BACKGROUND: As a major public health crisis, the novel coronavirus disease 2019 (COVID-19) pandemic demonstrates the urgent need for safe, effective, and evidence-based implementations of digital health. The urgency stems from the frequent tendency to focus attention on seemingly high promising digital health interventions despite being poorly validated in times of crisis.

AIM: In this paper, we describe a joint call for action to use and leverage evidence-based health informatics as the foundation for the COVID-19 response and public health interventions. Tangible examples are provided for how the working groups and special interest groups of the International Medical Informatics Association (IMIA) are helping to build an evidence-based response to this crisis.

METHODS: Leaders of working and special interest groups of the IMIA, a total of 26 groups, were contacted via e-mail to provide a summary of the scientific-based efforts taken to combat COVID-19 pandemic and participate in the discussion toward the creation of this manuscript. A total of 13 groups participated in this manuscript.

RESULTS: Various efforts were exerted by members of IMIA including (1) developing evidence-based guidelines for the design and deployment of digital health solutions during COVID-19; (2) surveying clinical informaticians internationally about key digital solutions deployed to combat COVID-19 and the challenges faced when implementing and using them; and (3) offering necessary resources for clinicians about the use of digital tools in clinical practice, education, and research during COVID-19.

DISCUSSION: Rigor and evidence need to be taken into consideration when designing, implementing, and using digital tools to combat COVID-19 to avoid delays and unforeseen negative consequences. It is paramount to employ a multidisciplinary approach for the development and implementation of digital health tools that have been rapidly deployed in response to the pandemic bearing in mind human factors, ethics, data privacy, and the diversity of context at the local, national, and international levels. The training and capacity building of front-line workers is crucial and must be linked to a clear strategy for evaluation of ongoing experiences.

PMID:33975375 | DOI:10.1055/s-0041-1726414

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Nevin Manimala Statistics

Diffusion Tensor Imaging Reveals Whole-Brain Microstructural Changes in the P301L Mouse Model of Tauopathy

Neurodegener Dis. 2021 May 11:1-12. doi: 10.1159/000515754. Online ahead of print.

ABSTRACT

INTRODUCTION: Increased expression of hyperphosphorylated tau and the formation of neurofibrillary tangles are associated with neuronal loss and white matter damage. Using high-resolution ex vivo diffusion tensor imaging (DTI), we investigated microstructural changes in the white and grey matter in the P301L mouse model of human tauopathy at 8.5 months of age. For unbiased computational analysis, we implemented a pipeline for voxel-based analysis (VBA) and atlas-based analysis (ABA) of DTI mouse brain data.

METHODS: Hemizygous and homozygous transgenic P301L mice and non-transgenic littermates were used. DTI data were acquired for generation of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) maps. VBA on the entire brain was performed using SPM8 and the SPM Mouse toolbox. Initially, all DTI maps were coregistered with the Allen mouse brain atlas to bring them to one common coordinate space. In VBA, coregistered DTI maps were normalized and smoothed in order to perform two-sample and unpaired t tests with false discovery rate correction to compare hemizygotes with non-transgenic littermates, homozygotes with non-transgenic littermates, and hemizygotes with homozygotes on each DTI parameter map. In ABA, the average values for selected regions of interests were computed with coregistered DTI maps and labels in Allen mouse brain atlas. Afterwards, a Kruskal-Wallis one-way ANOVA on ranks with a Tukey post hoc test was executed on the estimated average values.

RESULTS: With VBA, we found pronounced and brain-wide spread changes when comparing homozygous, P301L mice with non-transgenic littermates, which were not seen when comparing hemizygous P301L with non-transgenic animals. Statistical comparison of DTI metrics in selected brain regions by ABA corroborated findings from VBA. FA was found to be decreased in most brain regions, while MD, RD, and AD were increased in homozygotes compared to hemizygotes and non-transgenic littermates.

DISCUSSION/CONCLUSION: High-resolution ex vivo DTI demonstrated brain-wide microstructural and gene-dose-dependent changes in the P301L mouse model of human tauopathy. The DTI analysis pipeline may serve for the phenotyping of models of tauopathy and other brain diseases.

PMID:33975312 | DOI:10.1159/000515754

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Nevin Manimala Statistics

Hsa Circ 001839 Promoted Inflammation in Renal Ischemia-Reperfusion Injury Through NLRP3 by miR-432-3p

Nephron. 2021 May 11:1-13. doi: 10.1159/000515279. Online ahead of print.

ABSTRACT

BACKGROUND: In recent years, increasing discovery of the extremely important regulatory effects of circular RNAs on biological development, angiogenesis, tumor genesis, and development, as well as stem cell proliferation and differentiation has provided new opportunities for investigating regulation mechanism in angiogenesis.

OBJECTIVES: This study explored the expression of circ 001839 in renal ischemia-reperfusion injury (RI-RI) rats and whether its upstream microRNA-432-3p (miR-432-3p) affects inflammation in both RI-RI rats and NRK52E cells.

METHODS: Rat model of RI-RI was made, and circ 001839 was identified by the gene-chip analysis in RI-RI rats. Expression of circ 001839 and miR-432-3p was measured by reverse transcription-quantitative polymerase chain reaction, protein expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)-γ, IL-6, and IL-18 in rat serum and cell supernatant was determined by ELISA, and the expression of NOD-like receptor 3 (NLRP3) and other gap-associated proteins in NRK52E cells was evaluated by Western blot analysis. Next, to verify the regulatory relationship between circ 001839 and miR-432-3p, 2 luciferase reporters were constructed.

RESULTS: Circ 001839 expression of RI-RI rats and NRK52E cells was significantly upregulated, compared with the control group. Circ 001839 overexpression significantly increased inflammation through promoting TNF-α, IFN-γ, and IL-6 expression levels in NRK52E cells. Overexpression of miR-432-3p significantly promoted inflammation in NRK52E cells via induction of NLRP3. Moreover, miR-432-3p decreased the effects of circ 001839-induced inflammation in NRK52E cells.

CONCLUSIONS: These findings suggested that circ 001839 promoted inflammation in RI-RI through NLRP3 by miR-432-3p.

PMID:33975327 | DOI:10.1159/000515279

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Nevin Manimala Statistics

WDNE: an integrative graphical model for inferring differential networks from multi-platform gene expression data with missing values

Brief Bioinform. 2021 May 11:bbab086. doi: 10.1093/bib/bbab086. Online ahead of print.

ABSTRACT

The mechanisms controlling biological process, such as the development of disease or cell differentiation, can be investigated by examining changes in the networks of gene dependencies between states in the process. High-throughput experimental methods, like microarray and RNA sequencing, have been widely used to gather gene expression data, which paves the way to infer gene dependencies based on computational methods. However, most differential network analysis methods are designed to deal with fully observed data, but missing values, such as the dropout events in single-cell RNA-sequencing data, are frequent. New methods are needed to take account of these missing values. Moreover, since the changes of gene dependencies may be driven by certain perturbed genes, considering the changes in gene expression levels may promote the identification of gene network rewiring. In this study, a novel weighted differential network estimation (WDNE) model is proposed to handle multi-platform gene expression data with missing values and take account of changes in gene expression levels. Simulation studies demonstrate that WDNE outperforms state-of-the-art differential network estimation methods. When applied WDNE to infer differential gene networks associated with drug resistance in ovarian tumors, cell differentiation and breast tumor heterogeneity, the hub genes in the estimated differential gene networks can provide important insights into the underlying mechanisms. Furthermore, a Matlab toolbox, differential network analysis toolbox, was developed to implement the WDNE model and visualize the estimated differential networks.

PMID:33975339 | DOI:10.1093/bib/bbab086

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Nevin Manimala Statistics

Glioblastoma in adolescents and young adults: An age-based comparative study from Jordan over a 17-year period

Cancer Epidemiol. 2021 May 8;73:101948. doi: 10.1016/j.canep.2021.101948. Online ahead of print.

ABSTRACT

BACKGROUND: Glioblastoma (GBM) is the most common primary brain tumor. Epidemiologic studies on GBM are rarely reported in the special age group of adolescents and young adults (AYA) in comparison to other age groups. We aim to present data on GBM in Jordan, with a focus on the AYA age, including the incidence, gender, location and outcome, as well as long term survival (LTS).

METHODS: Data on GBM was requested from the Jordan Cancer Registry (JCR), and statistical analysis was performed. All data were retrospective and anonymized.

RESULTS: Eight hundred GBM cases were analyzed from 2000 to 2016 including 505 males (63.1 %). Males outnumbered females across are studied years (p-value <0.001). There were 49 pediatrics (0-14 years, 6.1 %), 125 AYA (15-39 years, 15.6 %), 358 adults (40-59 years, 44.8 %) and 268 elderly (60+ years, 33.5 %) cases. Supratentorial location predominated across all age groups (p-value <0.001). The preponderance of males and supratentorial tumors remained across the AYA age group in comparison to others. The median overall survival (OS) was 23.61 months. AYA age group had a better outcome in comparison to the adults/elderly age group (p-value< 0.001). LTS appear to be more common in the AYA age group (p-value 0.021).

CONCLUSIONS: This is the first comparative epidemiologic study of GBM in Jordan, focusing on the AYA age group. The AYA age group appears to be associated with a better outcome compared to older age groups, with more LTS compared to others.

PMID:33975256 | DOI:10.1016/j.canep.2021.101948

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Impacts of group stunning on the behavioral and physiological parameters of pigs and sheep in a small abattoir

Meat Sci. 2021 May 5;179:108538. doi: 10.1016/j.meatsci.2021.108538. Online ahead of print.

ABSTRACT

This study investigated reactions of pigs (N = 148) and sheep (N = 77) to group stunning where animals were present for the slaughter of others. Mock stunning with an isolated animal was used as the control. In both species, there was little evidence to suggest a difference in blood glucose and cortisol with stun order (P ≥ 0.21). In pigs, lactate differed by stun order (P < 0.001). Control pigs had lower lactate than pigs stunned first (P = 0.009) likely due to longer rest time after pre-slaughter handling. Conversely, the control sheep had greater average lactate than other groups. However, due to limited sample size and large variation there was not enough evidence to conclude an effect of stun order on sheep lactate (P = 0.28). Overall, there was limited evidence of an impact of stun order on behavior. The last pigs stunned exhibited a greater likelihood of grunting compared with other stun orders (P ≤ 0.05).

PMID:33975260 | DOI:10.1016/j.meatsci.2021.108538

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Nevin Manimala Statistics

Optimising the cost of roadkill surveys based on an analysis of carcass persistence

J Environ Manage. 2021 May 8;291:112664. doi: 10.1016/j.jenvman.2021.112664. Online ahead of print.

ABSTRACT

Reliable estimates of wildlife mortality due to wildlife-vehicle collisions are key to understanding its impact on wildlife populations and developing strategies to prevent or reduce collisions. Standardised approaches for monitoring roadkill are needed to derive robust and unbiased estimates of mortality that are comparable across different study systems and ecological contexts. When designing surveys, there is a trade-off between survey frequency (and hence logistical effort and financial cost) and carcass detection. In this regard, carcass persistence (the period a carcass remains detectable before being removed by decomposition or scavengers) is important; the longer a carcass persists, the greater the likelihood it will be detected with lower survey effort by conducting more infrequent surveys. Using multi-taxon carcass data collected over a month of repeated driven surveys, combined with five covariates (species functional group, body weight, carcass position on road, carcass condition [either flattened or not after impact], and rainfall prior to each survey), we explored the drivers of carcass persistence with the overall aim of providing information to optimise the design of carcass surveys along linear infrastructure. Our methodological approach included a survival analysis to determine carcass persistence, linear regressions to test the effect of covariates, a subsampling analysis (using field data and a simulation exercise) to assess how the proportion of carcasses detected changes according to survey frequency, and an analysis to compare the costs of surveys based on study duration, transect length and survey frequency. Mean overall carcass persistence was 2.7 days and was significantly correlated with position on road and within-functional group body weight. There was no evidence for a significant effect of rainfall, while the effect of carcass condition was weakly non-significant. The proportion of carcasses detected decreased sharply when survey intervals were longer than three days. However, we showed that survey costs can be reduced by up to 80% by conducting non-daily surveys. Expanding on the call for a standardised methodology for roadkill surveys, we propose that carcass persistence be explicitly considered during survey design. By carefully considering the objectives of the survey and characteristics of the focal taxa, researchers can substantially reduce logistical costs. In addition, we developed an R Shiny web app that can be used by practitioners to compare survey costs across a variety of survey characteristics. This web app will allow practitioners to easily assess the trade-off between carcass detection and logistical effort.

PMID:33975269 | DOI:10.1016/j.jenvman.2021.112664

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Impact of short stature on quality of life: A systematic literature review

Growth Horm IGF Res. 2021 Apr 30;57-58:101392. doi: 10.1016/j.ghir.2021.101392. Online ahead of print.

ABSTRACT

OBJECTIVE: We sought to obtain a better understanding of the burden of short stature using a systematic literature review.

METHODS: Studies of the burden of short stature, of any cause in adults and children, were searched using Embase, MEDLINE and Cochrane databases in April 2020, capturing publications from 2008 onwards. Case series and populations with adult-onset growth hormone deficiency (GHD) were excluded.

RESULTS: Of 1684 publications identified, 41 studies (33 in children, 8 in adults) were included. All studies assessed human burden. Most study populations in children included short stature due to GHD, idiopathic short stature (ISS) and short stature after being born small for gestational age (SGA). In these populations, four studies showed that quality of life (QoL) in children with short stature was significantly worse than in children with normal stature. A significant association between QoL and short stature was observed in children with chronic kidney disease (CKD) (3 studies), achondroplasia (1 study) and transfusion-dependent β-thalassaemia (1 study), and in samples with mixed causes of short stature (3 studies). Three studies (one in GHD/ISS/SGA and two in CKD) found no significant association between short stature and QoL, and several studies did not report statistical significance. Approximately half of adult studies showed that QoL was reduced with short stature, and the other half showed no association. Two studies, one in adults with Prader-Willi syndrome and one in children with GHD, suggested a potential association between short stature and poorer cognitive outcomes. Three studies demonstrated an increased caregiver burden in parents of children with short stature.

CONCLUSIONS: Evidence suggests that, compared with those with normal stature, children and adults with short stature of any cause may experience poorer QoL. Further research could extend our understanding of the human burden in this field.

PMID:33975197 | DOI:10.1016/j.ghir.2021.101392

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Tomographic similarity scan with a computed modified absolute mandibular midsagittal plane for precise and objective localization of mandibular asymmetry

Comput Biol Med. 2021 May 4;134:104465. doi: 10.1016/j.compbiomed.2021.104465. Online ahead of print.

ABSTRACT

The application of 3D imaging is at its cusp in craniofacial diagnosis and treatment planning. However, most applications are limited to simple subjective superimposition-based analysis. As the diagnostic accuracy dictates the precision in operability, we propose a novel method that enables objective clinical decision making for patients with mandibular asymmetry. We analyzed cone-beam computed tomography (CBCT) scans of 34 patients who underwent surgical correction for mandibular asymmetry using a high-throughput computing algorithm. Radiomic segmentation of quantitative features of surface and volume followed by exploration resulted in identification of a computed modified absolute mandibular midsagittal plane (cmAMP). Tomographic similarity scan (ToSS) curves were generated via bilateral equidistant scanning in an antero-posterior direction with cmAMP as the reference. ToSS comprised of a comprehensive similarity index (SI) score curve and a segment-wise volume curve. The SI score was computed using the Sørensen-Dice similarity coefficient ranging from 0 to 1. The volumetric analysis was represented as the non-overlapping volume (NOV) and overlapping volume (OV) for each segment, with two segmentation lines, at the mental foramen anteriorly and the intraoral vertical ramus osteotomy region posteriorly. Statistical analysis showed strong negative correlation between the NOV and SI scores for the anterior, middle, and total mandible (P < 0.001). Additionally, a significant correlation was observed between the change in the SI scores for anterior (P = 0.044) and middle segments (P < 0.001) to the total mandible when comparing the data before and after the surgery. This work demonstrated the potential of incorporating ToSS curves in surgical simulation software to improve precision in the clinical decision-making process.

PMID:33975208 | DOI:10.1016/j.compbiomed.2021.104465

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Nevin Manimala Statistics

Spatial pattern analysis reveals multiple sources of organophosphorus flame retardants in coastal waters

J Hazard Mater. 2021 Apr 15;417:125882. doi: 10.1016/j.jhazmat.2021.125882. Online ahead of print.

ABSTRACT

Organophosphorus flame retardants (PFRs) are a group of emerging contaminants which have been detected in worldwide waters. However, source of various PFRs in the large-scale area like coastal water environment have not been clearly revealed. In this study, fifteen PFRs in coast of Guangdong-Hong Kong-Macao Greater Bay area (GBA), China were investigated, and a method of spatial pattern analysis was firstly used for pollution source identification. Seawater samples from different segments of GBA coast were analyzed and thirteen PFRs were quantified with total concentrations ranging from 32.7 to 1032.7 ng L-1. GBA coasts have been seriously polluted by PFRs. A hierarchical cluster analysis of the PFR concentrations in different GBA sites showed significant spatial distributions for different types of PFRs. A series of correlation analysis between PFRs distributions and spatial pattern of GBA socio-economic indicators were performed, and multiple sources including human settlement, wastewater, manufacture, construction industry, vehicles, and shipping transport were found to be correlated to PFRs pollutions in the coasts. This study indicates that spatial pattern analysis based on statistical analysis would be a promising method of analyzing environmental data and exploring pollution source in large-scale area.

PMID:33975162 | DOI:10.1016/j.jhazmat.2021.125882