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Nevin Manimala Statistics

Meta-analysis of Bioaccumulation Data for Non-dissolvable Engineered Nanomaterials in Freshwater Aquatic Organisms

Environ Toxicol Chem. 2022 Feb 21. doi: 10.1002/etc.5312. Online ahead of print.

ABSTRACT

Understanding the bioaccumulation of engineered nanomaterials (ENMs) is essential for regulatory decisions on potential environmental risks. Research in the field of ENMs bioaccumulation has increased in recent years, but the compilation and statistical analysis of the available experimental data has not been updated. We therefore performed a meta-analysis of the existing literature on the bioaccumulation of eight types of non-dissolvable ENMs (TiO2 , Al2 O3 , Au, C60 , fullerenes, carbon nanotubes, FeOx , graphene, polystyrene) in non-mammalian freshwater aquatic organisms across three trophic levels including phytoplankton, zooplankton and fish. Three typical endpoints were used to assess the bioaccumulation potential: the bioconcentration factor (BCF), the bioaccumulation factor (BAF) and the biomagnification factor (BMF). Our results suggest that zooplankton has greater mean logarithmic BCF and BAF values than phytoplankton (3.31 vs. 1.42) and fish (2.04). ENMs are biomagnified in zooplankton with a mean BMF of 17.4 whereas trophic transfer from primary consumers (zooplankton) to secondary consumers (fish) is not observed (mean BMF of 0.13). No clear dependency was identified between the physico-chemical characteristics of ENMs (e.g. primary particle size, zeta potential, or shape) and bioaccumulation, except for coated vs. uncoated particles accumulated in phytoplankton. Carbonaceous ENMs were found to be more bioaccumulated than the other considered ENMs, except TiO2 . The meta-analysis of bioaccumulation data can i) deepen the understanding of bioconcentration, bioaccumulation and biomagnification of ENMs, ii) be used to support grouping strategies as a basis for a safer-by-design approach for ENMs, iii) be integrated into comprehensive hazard and risk assessments, iv) promote the standardization of testing guidelines, and v) enhance the future kinetic bioaccumulation modelling. This article is protected by copyright. All rights reserved. © 2022 SETAC.

PMID:35188281 | DOI:10.1002/etc.5312

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Nevin Manimala Statistics

Magnetic resonance imaging of the normal equine pituitary gland

Vet Radiol Ultrasound. 2022 Feb 21. doi: 10.1111/vru.13072. Online ahead of print.

ABSTRACT

Magnetic resonance imaging is increasingly available for evaluation of horses with suspected pituitary adenomas; however, published studies describing the MRI features of normal equine pituitary glands are currently lacking. This retrospective, descriptive, anatomic study describes the MRI appearance and size of presumed normal equine pituitary glands and assesses potential correlations between pituitary size, brain size, and patient weight. These findings serve as a reference for MRI evaluation of the equine pituitary gland. Inclusion criteria consisted of adult horses (2-15 years old), over 300 kg with no evidence of Pituitary pars intermedia dysfunction (PPID) and no pituitary abnormalities identified with MRI, yielding 27 horses. Histology was available on seven pituitary glands; all were considered normal by a board-certified anatomic pathologist. Imaging features of the glands were evaluated on T2-weighted and pre- and postcontrast T1-weighted images. Pituitary length, width, and height and brain height and width were measured by two authors on transverse and mid-sagittal plane postcontrast T1 weighted images. The mean ± SD pituitary gland width was 21.0 ± 2.4 mm, height: 10.4 ± 1.9 mm, and length: 24.5 ± 2.7 mm. There were no significant correlations using a Pearson’s correlation coefficient between pituitary and brain measurements, pituitary measurement, and body weight, or between brain measurements and body weight. A statistical difference was not identified using an unpaired t-test (p > 0.05) in pituitary and brain measurements between necropsied and non-necropsied horses. Relative to the cerebral white matter, all pituitary glands were isointense to slightly hyperintense on T1-weighted images and isointense on T2-weighted images, with the exception of a focal T1-weighted hyperintensity that was present in the caudal aspect of the pituitary gland in 88% of horses. All pituitary glands were homogenously contrast enhancing. Pituitary dimensions did not correlate with either brain size or body weight in horses.

PMID:35188303 | DOI:10.1111/vru.13072

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Nevin Manimala Statistics

Functional data analysis for longitudinal data with informative observation times

Biometrics. 2022 Feb 21. doi: 10.1111/biom.13646. Online ahead of print.

ABSTRACT

In functional data analysis for longitudinal data, the observation process is typically assumed to be non-informative, which is often violated in real applications. Thus, methods that fail to account for the dependence between observation times and longitudinal outcomes may result in biased estimation. For longitudinal data with informative observation times, we find that under a general class of shared random effect models, a commonly used functional data method may lead to inconsistent model estimation while another functional data method results in consistent and even rate-optimal estimation. Indeed, we show that the mean function can be estimated appropriately via penalized splines and that the covariance function can be estimated appropriately via penalized tensor-product splines, both with specific choices of parameters. For the proposed method, theoretical results are provided, and simulation studies and a real data analysis are conducted to demonstrate its performance. This article is protected by copyright. All rights reserved.

PMID:35188270 | DOI:10.1111/biom.13646

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Nevin Manimala Statistics

Development of Kudzu (Pueraria Montana Var. lobata) Reference Materials for the Determination of Isoflavones and Toxic Elements

J AOAC Int. 2022 Feb 21:qsac023. doi: 10.1093/jaoacint/qsac023. Online ahead of print.

ABSTRACT

BACKGROUND: In collaboration with the Office of Dietary Supplements at the National Institutes of Health, the National Institute of Standards and Technology issued a suite of botanical matrix Reference Materials (RMs) and Standard Reference Material® (SRM) for determination of isoflavones and toxic elements in kudzu dietary supplement ingredients.

OBJECTIVE: RM 8650 Pueraria montana var. lobata (Kudzu) Rhizome, SRM 3268 Pueraria montana var. lobata (Kudzu) Extract, and RM 8652 Kudzu-Containing Solid Oral Dosage Form were issued with values assigned for isoflavones (puerarin, daidzin, and daidzein), toxic elements (arsenic, cadmium, and lead), and selenium.

METHODS: Isoflavone values were assigned using liquid chromatography with UV absorbance or mass spectrometry detection. Element values were assigned using inductively coupled plasma mass spectrometry and results from an interlaboratory comparison exercise.

RESULTS: Mass fractions for puerarin were (32.2 ± 3.2) mg/g, (128 ± 13) mg/g, and (68.2 ± 6.9) mg/g in RM 8650, SRM 3268, and RM 8652, respectively. Arsenic increases from (156 ± 14) ng/g to (849 ± 83) ng/g and cadmium decreases from (348 ± 14) ng/g to (82.1 ± 4.9) ng/g from rhizome to extract.

CONCLUSION: The kudzu RM/SRM suite complements previously issued soy-related SRMs with values assigned for isoflavones, which have been studied for their potential health benefits, and expands the analytical resource by providing values for puerarin, an isoflavone not found in soy.

HIGHLIGHTS: The three new kudzu materials are for use in the determination of isoflavones, toxic elements, and selenium. For the isoflavones, these new kudzu materials provide higher levels of daidzin and daidzein than existing soy-related SRMs, and they provide a value for an isoflavone not in existing SRMs (puerarin). Toxic elements in RM 8650 and SRM 3268 provide new botanical matrices for use by dietary supplement manufacturers for the verification of the safety of their raw materials.

PMID:35188206 | DOI:10.1093/jaoacint/qsac023

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Nevin Manimala Statistics

Pre-Existing Autoimmune Disease and Mortality in Patients Treated With Anti-PD-1 and Anti-PD-L1 Therapy

J Natl Cancer Inst. 2022 Feb 21:djac046. doi: 10.1093/jnci/djac046. Online ahead of print.

ABSTRACT

Although indications for immune checkpoint inhibitors (ICIs) have dramatically increased in the past decade, ICIs have been associated with autoinflammatory immune-related adverse events which can resemble autoimmune diseases (ADs). Little is known about the impact of baseline AD on mortality in cancer patients treated with ICIs. Here, we identified 17,497 patients with pre-existing autoimmune diagnoses prior to treatment with anti-PD-1 or anti-PD-L1 therapy and 17,497 matched controls through the TriNetX Diamond network of over 200 million patients across the US and Europe. Using a Cox proportional hazards model, we found that patients with history of AD were not at higher risk of mortality than non-AD controls (HR, 1.03; 95% CI, 1-1.07; p = 0.05). Additionally, history of Hashimoto’s disease (HR, 0.75; 95% CI, 0.62-0.90; p = 0.002) and vitiligo (HR,0.52; 95% CI, 0.34-0.81; p = 0.003) were statistically significantly associated with decreased mortality. This suggests that underlying AD need not be a contraindication to inclusion in clinical trials and administration of ICI for treatment of cancer.

PMID:35188215 | DOI:10.1093/jnci/djac046

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Nevin Manimala Statistics

Causes of America’s Lagging Life Expectancy: An International Comparative Perspective

J Gerontol B Psychol Sci Soc Sci. 2022 Feb 21:gbab129. doi: 10.1093/geronb/gbab129. Online ahead of print.

ABSTRACT

OBJECTIVES: This study assesses how American life expectancy compares to other high-income countries and identifies key age groups and causes of death responsible for the U.S. life expectancy shortfall.

METHODS: Data from the Human Mortality Database, World Health Organization Mortality Database, and vital statistics agencies for 18 high-income countries are used to examine trends in U.S. life expectancy gaps and how American age-specific death rates compare to other countries. Decomposition is used to estimate the contribution of 19 age groups and 16 causes to the U.S. life expectancy shortfall.

RESULTS: In 2018, life expectancy for American men and women was 5.18 and 5.82 years lower than the world leaders and 3.60 and 3.48 years lower than the average of the comparison countries. Americans aged 25-29 experience death rates nearly three times higher than their counterparts. Together, injuries (drug overdose, firearm-related deaths, motor vehicle accidents, homicide), circulatory diseases, and mental disorders/nervous system diseases (including Alzheimer’s disease) account for 86% and 67% of American men’s and women’s life expectancy shortfall.

DISCUSSION: American life expectancy has fallen far behind its peer countries. The U.S.’s worsening mortality at the prime adult ages and eroding old-age mortality advantage drive its deteriorating performance in international comparisons.

PMID:35188201 | DOI:10.1093/geronb/gbab129

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Nevin Manimala Statistics

Cardiac magnetic resonance in systemic sclerosis myocarditis: the value of T2 mapping to detect myocardial inflammation

Rheumatology (Oxford). 2022 Feb 21:keac098. doi: 10.1093/rheumatology/keac098. Online ahead of print.

ABSTRACT

OBJECTIVES: Myocarditis in systemic sclerosis (SSc) is associated with a poor prognosis. Cardiac Magnetic Resonance (CMR) is the non-invasive diagnostic modality of choice for SSc-myocarditis. Our study investigates the performance of the mapping techniques, included in the revised Lake Louise Criteria (LLC), for the identification of SSc-myocarditis.

METHODS: CMR data (right and left ventricular function and morphology, early and late gadolinium enhancement [LGE], T2 ratio, and T1 mapping, extra-cellular volume [ECV] and T2 mapping) of SSc patients diagnosed with myocarditis were reviewed. Myocarditis was defined by the presence of symptoms of SSc-heart involvement with increased high-sensitive troponin T(hs-TnT) and/or NT-proBNP and at least an abnormality at 24 h-ECG-Holter and/or echocardiography and/or CMR. A p-value < 0.05 was considered as statistically significant.

RESULTS: 19 patients (median age 54 [46-70] years; females 78.9%; diffuse SSc 52.6%; anti-Scl70 + 52.6%) were identified: 11(57.9%) had echocardiographic, and 8(42.8%) 24 h-ECG Holter abnormalities. All patients had at least one CMR abnormality: LGE in 18(94.7%), increased ECV in 10(52.6%), T2 mapping > 50ms in 15(78.9%). Median T1 and T2 mapping were 1085[1069-1110]ms and 53.1[52-54]ms, respectively. T1 mapping directly correlated with NT-proBNP(r = 0.620; p= 0.005), ESR(r = 0.601; p= 0.008), CRP(r = 0.685; p= 0.001) and skin score(r = 0.507; p= 0.027); ECV correlated with NT-proBNP serum levels(r = 0.702; p= 0.001). No correlations emerged between T2 mapping and other parameters. Ten patients satisfied the 2009 LLC, 17 the 2018 LLC. With the new criteria including T2-mapping, the sensitivity improved from 52.6% to 89.5%.

CONCLUSION: the CMR mapping techniques improve the sensitivity to detect myocardial inflammation in patients with SSc-heart involvement. The evaluation of T2 mapping increases diagnostic accuracy for the recognition of myocardial inflammation in SSc.

PMID:35188182 | DOI:10.1093/rheumatology/keac098

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Nevin Manimala Statistics

A Standardized Pipeline for Examining Human Cerebellar Grey Matter Morphometry using Structural Magnetic Resonance Imaging

J Vis Exp. 2022 Feb 4;(180). doi: 10.3791/63340.

ABSTRACT

Multiple lines of research provide compelling evidence for a role of the cerebellum in a wide array of cognitive and affective functions, going far beyond its historical association with motor control. Structural and functional neuroimaging studies have further refined understanding of the functional neuroanatomy of the cerebellum beyond its anatomical divisions, highlighting the need for the examination of individual cerebellar subunits in healthy variability and neurological diseases. This paper presents a standardized pipeline for examining cerebellum grey matter morphometry that combines high-resolution, state-of-the-art approaches for optimized and automated cerebellum parcellation (Automatic Cerebellum Anatomical Parcellation using U-Net Locally Constrained Optimization; ACAPULCO) and voxel-based registration of the cerebellum (Spatially Unbiased Infra-tentorial Template; SUIT) for volumetric quantification. The pipeline has broad applicability to a range of neurological diseases and is fully automated, with manual intervention only required for quality control of the outputs. The pipeline is freely available, with substantial accompanying documentation, and can be run on Mac, Windows, and Linux operating systems. The pipeline is applied in a cohort of individuals with Friedreich ataxia (FRDA), and representative results, as well as recommendations on group-level inferential statistical analyses, are provided. This pipeline could facilitate reliability and reproducibility across the field, ultimately providing a powerful methodological approach for characterizing and tracking cerebellar structural changes in neurological diseases.

PMID:35188124 | DOI:10.3791/63340

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Nevin Manimala Statistics

scanMiR: a biochemically-based toolkit for versatile and efficient microRNA target prediction

Bioinformatics. 2022 Feb 21:btac110. doi: 10.1093/bioinformatics/btac110. Online ahead of print.

ABSTRACT

MOTIVATION: microRNAs are important post-transcriptional regulators of gene expression, but the identification of functionally relevant targets is still challenging. Recent research has shown improved prediction of microRNA-mediated repression using a biochemical model combined with empirically-derived k-mer affinity predictions, however these findings are not easily applicable.

RESULTS: We translate this approach into a flexible and user-friendly bioconductor package, scanMiR, also available through a web interface. Using lightweight linear models, scanMiR efficiently scans for binding sites, estimates their affinity, and predicts aggregated transcript repression. Moreover, flexible 3′-supplementary alignment enables the prediction of unconventional interactions, such as bindings potentially leading to target-directed microRNA degradation or slicing. We showcase scanMiR through a systematic scan for such unconventional sites on neuronal transcripts, including lncRNAs and circRNAs. Finally, in addition to the main bioconductor package implementing these functions, we provide a user-friendly web application enabling the scanning of sequences, the visualization of predicted bindings, and the browsing of predicted target repression.

AVAILABILITY: scanMiR and companion packages are implemented in R, released under the GPL-3 and accessible on Bioconductor (https://bioconductor.org/packages/release/bioc/html/scanMiR.html) as well as through a shiny web server (https://ethz-ins.org/scanMiR/).

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:35188178 | DOI:10.1093/bioinformatics/btac110

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Nevin Manimala Statistics

Cellular organization in lab-evolved and extant multicellular species obeys a maximum entropy law

Elife. 2022 Feb 21;11:e72707. doi: 10.7554/eLife.72707.

ABSTRACT

The prevalence of multicellular organisms is due in part to their ability to form complex structures. How cells pack in these structures is a fundamental biophysical issue, underlying their functional properties. However, much remains unknown about how cell packing geometries arise, and how they are affected by random noise during growth – especially absent developmental programs. Here, we quantify the statistics of cellular neighborhoods of two different multicellular eukaryotes: lab-evolved ‘snowflake’ yeast and the green alga Volvox carteri. We find that despite large differences in cellular organization, the free space associated with individual cells in both organisms closely fits a modified gamma distribution, consistent with maximum entropy predictions originally developed for granular materials. This ‘entropic’ cellular packing ensures a degree of predictability despite noise, facilitating parent-offspring fidelity even in the absence of developmental regulation. Together with simulations of diverse growth morphologies, these results suggest that gamma-distributed cell neighborhood sizes are a general feature of multicellularity, arising from conserved statistics of cellular packing.

PMID:35188101 | DOI:10.7554/eLife.72707