Nevin Manimala

J Math Biol. 2022 Sep 3;85(3):25. doi: 10.1007/s00285-022-01770-y.

ABSTRACT

Skin contraction is an important biophysical process that takes place during and after recovery of deep tissue injury. This process is mainly caused by fibroblasts (skin cells) and myofibroblasts (differentiated fibroblasts which exert larger pulling forces and produce larger amounts of collagen) that both exert pulling forces on the surrounding extracellular matrix (ECM). Modelling is done in multiple scales: agent-based modelling on the microscale and continuum-based modelling on the macroscale. In this manuscript we present some results from our study of the connection between these scales. For the one-dimensional case, we managed to rigorously establish the link between the two modelling approaches for both closed-form solutions and finite-element approximations. For the multi-dimensional case, we computationally evidence the connection between the agent-based and continuum-based modelling approaches.

PMID:36056978 | DOI:10.1007/s00285-022-01770-y

World J Microbiol Biotechnol. 2022 Sep 3;38(11):215. doi: 10.1007/s11274-022-03385-3.

ABSTRACT

Plant metabolism interacts strongly with the plant microbiome. Glucosinolates, secondary metabolites synthesized by Brassica plants, are hydrolyzed by myrosinase into bioactive compounds of great importance in human health and plant protection. Compared with myrosinase from plant sources, myrosinase enzymes of microbial origin have not been extensively investigated. Therefore, seven endophytic strains corresponding to Bacillus sp. were isolated from Eruca vesicaria ssp. sativa plants that could hydrolyse glucosinolates (sinigrin) in the culture medium and showed myrosinase activity (0.08-19.92 U mL^-1). The bglA myrosinase-related gene encoding the 6-phospho-β-glucosidase (GH 1) from Bacillus sp. NGB-B10, the most active myrosinase-producing bacterium, was successfully identified. Response surface methodology (RSM) was applied to statistically optimize culture conditions for myrosinase production from Bacillus sp. strain NGB-B10. The Plackett-Burman design indicated that nitrogen concentration, incubation period, and agitation speed were the significant parameters in myrosinase production. The application of the Box-Behnken design of RSM resulted in a 10.03-fold increase in enzyme activity as compared to the non-optimized culture conditions. The myrosinase was partially purified by 40% fractionation followed by SDS-PAGE analysis which yielded two subunits that had a molecular weight of 38.6 and 35.0 KDa. The purified enzyme was stable under a broad range of pH (5.5-10) and temperatures (10-65 °C). The hydrolysis products released by bacterial myrosinase from some glucosinolate extracts had higher and/or equivalent in vitro antagonistic activity against several phytopathogenic fungi compared to the nystatin (a broad-spectrum antifungal agent). This study provides original information about a new source of bacterial myrosinase and affords an optimized method to enhance myrosinase production.

PMID:36056962 | DOI:10.1007/s11274-022-03385-3

Brief Bioinform. 2022 Sep 2:bbac354. doi: 10.1093/bib/bbac354. Online ahead of print.

ABSTRACT

Identifying genomic regions influenced by natural selection provides fundamental insights into the genetic basis of local adaptation. However, it remains challenging to detect loci under complex spatially varying selection. We propose a deep learning-based framework, DeepGenomeScan, which can detect signatures of spatially varying selection. We demonstrate that DeepGenomeScan outperformed principal component analysis- and redundancy analysis-based genome scans in identifying loci underlying quantitative traits subject to complex spatial patterns of selection. Noticeably, DeepGenomeScan increases statistical power by up to 47.25% under nonlinear environmental selection patterns. We applied DeepGenomeScan to a European human genetic dataset and identified some well-known genes under selection and a substantial number of clinically important genes that were not identified by SPA, iHS, Fst and Bayenv when applied to the same dataset.

PMID:36056746 | DOI:10.1093/bib/bbac354

Brief Bioinform. 2022 Sep 2:bbac375. doi: 10.1093/bib/bbac375. Online ahead of print.

ABSTRACT

Copy number variation (CNV) is a class of key biomarkers in many complex traits and diseases. Detecting CNV from sequencing data is a substantial bioinformatics problem and a standard requirement in clinical practice. Although many proposed CNV detection approaches exist, the core statistical model at their foundation is weakened by two critical computational issues: (i) identifying the optimal setting on the sliding window and (ii) correcting for bias and noise. We designed a statistical process model to overcome these limitations by calculating regional read depths via an exponentially weighted moving average strategy. A one-run detection of CNVs of various lengths is then achieved by a dynamic sliding window, whose size is self-adopted according to the weighted averages. We also designed a novel bias/noise reduction model, accompanied by the moving average, which can handle complicated patterns and extend training data. This model, called PEcnv, accurately detects CNVs ranging from kb-scale to chromosome-arm level. The model performance was validated with simulation samples and real samples. Comparative analysis showed that PEcnv outperforms current popular approaches. Notably, PEcnv provided considerable advantages in detecting small CNVs (1 kb-1 Mb) in panel sequencing data. Thus, PEcnv fills the gap left by existing methods focusing on large CNVs. PEcnv may have broad applications in clinical testing where panel sequencing is the dominant strategy. Availability and implementation: Source code is freely available at https://github.com/Sherwin-xjtu/PEcnv.

PMID:36056740 | DOI:10.1093/bib/bbac375

J Am Heart Assoc. 2022 Sep 3:e026603. doi: 10.1161/JAHA.122.026603. Online ahead of print.

ABSTRACT

Background Waveform parameters provide approximate data about aortic wave reflection. However, their association with cardiovascular events remains controversial and their role in cardiovascular prediction is unknown. Methods and Results We analyzed participants aged between 40 and 69 from the population-based CARTaGENE cohort. Baseline pulse wave analysis (central pulse pressure, augmentation index) and wave separation analysis (forward pressure, backward pressure, reflection magnitude) parameters were derived from radial artery tonometry. Associations between each parameter and major adverse atherosclerotic events (MACE; cardiovascular death, stroke, myocardial infarction) were obtained using adjusted Cox models. The incremental predictive value of each parameter compared with the 10-year atherosclerotic cardiovascular disease score alone was assessed using hazard ratios, c-index differences, continuous net reclassification indexes, and integrated discrimination indexes. From 17 561 eligible patients, 2315 patients had a MACE during a median follow-up of 10.1 years. Central pulse pressure, forward pressure, and backward pressure, but not augmentation index and reflection magnitude, were significantly associated with MACE after full adjustment. All parameters except forward pressure statistically improved MACE prediction compared with the atherosclerotic cardiovascular disease score alone. The greatest prediction improvement was seen with augmentation index and reflection magnitude but remained small in magnitude. These 2 parameters enhanced predictive performance more strongly in patients with low baseline atherosclerotic cardiovascular disease scores. Up to 5.7% of individuals were reclassified into a different risk stratum by adding waveform parameters to atherosclerotic cardiovascular disease scores. Conclusions Some waveform parameters are independently associated with MACEs in a population-based cohort. Augmentation index and reflection magnitude slightly improve risk prediction, especially in patients at low cardiovascular risk.

PMID:36056725 | DOI:10.1161/JAHA.122.026603

J Am Heart Assoc. 2022 Sep 3:e025229. doi: 10.1161/JAHA.121.025229. Online ahead of print.

ABSTRACT

Background Acute kidney injury (AKI) is a major risk factor for chronic kidney disease and increased mortality. Until now, no compelling preventive or therapeutic strategies have been identified. Dietary interventions have been proven highly effective in organ protection from ischemia reperfusion injury in mice and restricting dietary intake of sulfur-containing amino acids (SAA) seems to be instrumental in this regard. The UNICORN trial aimed to evaluate the protective impact of restricting SAA intake before cardiac surgery on incidence of AKI. Methods and Results In this single-center, randomized, controlled, double-blind trial, 115 patients were assigned to a SAA-reduced formula diet (LowS group) or a regular formula diet (control group) in a 1:1 ratio for 7 days before scheduled cardiac surgery. The primary end point was incidence of AKI within 72 hours after surgery, secondary end points included increase of serum creatinine at 24, 48, and 72 hours as well as safety parameters. Quantitative variables were analyzed with nonparametric methods, while categorical variables were evaluated by means of Chi-square or Fisher test. SAA intake in the group with SAA reduced formula diet was successfully reduced by 77% (group with SAA reduced formula diet, 7.37[6.40-7.80] mg/kg per day versus control group, 32.33 [28.92-33.60] mg/kg per day, P<0.001) leading to significantly lower serum levels of methionine. No beneficial effects of SAA restriction on the rate of AKI after surgery could be observed (group with SAA reduced formula diet, 23% versus control group, 16%; P=0.38). Likewise, no differences were recorded with respect to secondary end points (AKI during hospitalization, creatinine at 24, 48, 72 hours after surgery) as well as in subgroup analysis focusing on age, sex, body mass index and diabetes. Conclusions SAA restriction was feasible in the clinical setting but was not associated with protective properties in AKI upon cardiac surgery. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03715868.

PMID:36056721 | DOI:10.1161/JAHA.121.025229

Soft Matter. 2022 Sep 3. doi: 10.1039/d2sm00707j. Online ahead of print.

ABSTRACT

We observe novel positional control of a colloidal particle in microchannel flow of a nematic liquid crystal. Lattice Boltzmann simulations show multiple equilibrium particle positions, the existence and position of which are tunable using the driving pressure, in direct contrast to the classical Segré-Silberberg effect in isotropic liquids. In addition, particle migration in nematic flow occurs an order of magnitude faster. These new equilibria are determined through a balance of elastic forces, hydrodynamic lift and drag as well as order-flow interactions through the defect structure around the particle.

PMID:36056713 | DOI:10.1039/d2sm00707j

Int J Lab Hematol. 2022 Sep 3. doi: 10.1111/ijlh.13957. Online ahead of print.

ABSTRACT

INTRODUCTION: Established parameters for the investigation of suspected iron deficiency have recognized limitations that affect their sensitivity and specificity. Reticulocyte haemoglobin content (RHC) is an early biomarker of iron deficiency or restriction, which also demonstrates response to iron therapy. RHC parameters are offered on all major automated haematology analysers. There is no external quality assessment (EQA) for RHC in the UK, restricting its wider clinical application. The UK National External Quality Assessment Scheme (UKNEQAS) for Haematology has completed a pilot study on the use of stabilized blood for RHC EQA.

METHODS: Blood was obtained from two JAK2 V617F mutation-positive, polycythaemia vera patients undergoing regular venesection, and from a healthy volunteer donor. Aliquots of each donation were distributed to users of Abbott, Horiba, Siemens and Sysmex automated analysers for RHC analysis on days 1, 3, 5 and 7.

RESULTS: Results were received from 20 laboratories using four different platforms. The daily mean and standard deviation (SD) were calculated for each aliquot, by day of analysis and platform. With RHC there was no significant within-platform difference (p > 0.5) between testing days, although there were statistically significant differences (p < 0.001) between different platforms. The greatest difference was seen between Abbott MCHr and Horiba RhCc (-6.14 ± 1.25 pg). Despite inter-platform differences, it was possible to define iron deficient, borderline, and normal cut-offs to classify 95% of results correctly.

CONCLUSIONS: The results demonstrate that it is possible to provide RHC EQA material using UKNEQAS standard procedures. The results are clinically relevant but indicate a requirement for inter-user comparison.

PMID:36056688 | DOI:10.1111/ijlh.13957

J Magn Reson Imaging. 2022 Sep 3. doi: 10.1002/jmri.28407. Online ahead of print.

ABSTRACT

BACKGROUND: Dynamic diffusion magnetic resonance imaging (ddMRI) metrics can assess transient microstructural alterations in tissue diffusivity but requires additional scan time hindering its clinical application.

PURPOSE: To determine whether a diffusion gradient table can simultaneously acquire data to estimate dynamic and diffusion tensor imaging (DTI) metrics.

STUDY TYPE: Prospective.

SUBJECTS: Seven healthy subjects, 39 epilepsy patients (15 female, 31 male, age ± 15).

FIELD STRENGTH/SEQUENCE: Two-dimensional diffusion MRI (b = 1000 s/mm² ) at a field strength of 3 T. Sessions in healthy subjects-standard ddMRI (30 directions), standard DTI (15 and 30 directions), and nested cubes scans (15 and 30 directions). Sessions in epilepsy patients-two 30 direction (standard ddMRI, 10 nested cubes) or two 15 direction scans (standard DTI, 5 nested cubes).

ASSESSMENT: Fifteen direction DTI was repeated twice for within-session test-retest measurements in healthy subjects. Bland-Altman analysis computed bias and limits of agreement for DTI metrics using test-retest scans and standard 15 direction vs. 5 nested cubes scans. Intraclass correlation (ICC) analysis compared tensor metrics between 15 direction DTI scans (standard vs. 5 nested cubes) and the coefficients of variation (CoV) of trace and apparent diffusion coefficient (ADC) between 30 direction ddMRI scans (standard vs. 10 nested cubes).

STATISTICAL TESTS: Bland-Altman and ICC analysis using a P-value of 0.05 for statistical significance.

RESULTS: Correlations of mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were strong and significant in gray (ICC > 0.95) and white matter (ICC > 0.95) between standard vs. nested cubes DTI acquisitions. Correlation of white matter fractional anisotropy was also strong (ICC > 0.95) and significant. ICCs of the CoV of dynamic ADC measured using repeated cubes and nested cubes acquisitions were modest (ICC >0.60), but significant in gray matter.

CONCLUSION: A nested cubes diffusion gradient table produces tensor-based and dynamic diffusion measurements in a single acquisition.

LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

PMID:36056625 | DOI:10.1002/jmri.28407

J Clin Endocrinol Metab. 2022 Sep 3:dgac500. doi: 10.1210/clinem/dgac500. Online ahead of print.

ABSTRACT

OBJECTIVE: To better delineate fracture risk in patients with Multiple Endocrine Neoplasia Type 2B (MEN2B).

STUDY DESIGN: Case series with chart review.

SETTING: National Institutes of Health, Pediatric Oncology Branch.

SUBJECTS AND METHODS: Forty-eight patients with MEN2B were identified. Age range 5-36 years, median of 19; 24/48 (50%) patients were female. Medical records, demographic information, available imaging, and laboratory results were reviewed. History up to the age of 19 was included in the statistical analyses.

RESULTS: Of 48 patients with MEN2B, 20 patients experienced at least one fracture. The majority (n = 18) experienced their first fracture at or before the age of 19. The observed frequency of fracture occurrence throughout childhood (0-19 years) was 38%, with very little difference between males and females. This frequency is higher than the 9.47 to 36.1 fractures per 1000 persons per year that has been reported in healthy pediatric cohorts in the United States. Less common sites of fracture including vertebral compression fracture and pelvic fractures were observed in patients with MEN2B.

CONCLUSION: In this group of patients with MEN2B, there was an increased overall risk of fracture compared to general pediatric cohorts in the United States. Less common sites of fracture were also observed. This suggests a possible impact of an activating RET mutation on bone physiology and warrants further investigation.

PMID:36056624 | DOI:10.1210/clinem/dgac500