Nevin Manimala

Hepatol Commun. 2022 Apr 19. doi: 10.1002/hep4.1957. Online ahead of print.

ABSTRACT

Patients with pre-existing liver diseases are considered to have an increased risk of morbidity and mortality from any type of infection, including viruses. The aim of this work was to explore the implications of metabolic dysfunction-associated fatty liver disease (MAFLD) and nonalcoholic fatty liver disease (NAFLD) definitions in coronavirus disease 2019 (COVID-19) and to study the interaction between advanced fibrosis (AF) and each of these diseases in the death and intubation of patients hospitalized with COVID-19. We performed a retrospective study with 359 patients hospitalized with confirmed COVID-19 infection in a tertiary referral hospital who were admitted between April and June 2020. A multivariate Cox model was performed regarding the interaction of AF with MAFLD and NAFLD in the mortality and intubation of patients with COVID-19. The death rate was statistically significantly higher in the MAFLD group compared to the control group (55% vs. 38.3%, p = 0.02). No significant difference was seen in the death rate between the NAFLD and control group. The MAFLD (44.09% vs. 20%, p = 0.001) and NAFLD (40.51% vs. 20%, p = 0.01) groups had statistically significantly higher intubation rates than the control group. A statistically significant interaction between NAFLD and AF was associated with an increase in mortality (p = 0.01), while a statistically significant interaction between MAFLD and AF was associated with an increased risk of mortality (p = 0.006) and intubation (p = 0.049). In the case of patients hospitalized with COVID-19, our results indicate that the death rate was higher in the MAFLD group but not the NAFLD group compared to that in the control group. The intubation rates were higher in the NAFLD and MAFLD groups compared to rates in the control group, suggesting that both could be associated with COVID-19 severity. In addition, we found interactions between AF with MAFLD and NAFLD.

PMID:35438253 | DOI:10.1002/hep4.1957

Ther Apher Dial. 2022 Apr 19. doi: 10.1111/1744-9987.13858. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of this study was to translate, linguistically validate and evaluate the psychometric properties of the Shortened Xerostomia Inventory (SXI) among Turkish patients undergoing hemodialysis.

METHODS: The study was conducted with 81 chronic hemodialysis patients in the hemodialysis units of two state hospitals between June and August 2020. Explanatory Factor Analysis (EFA) were implemented to test the construct validity. In addition, the test-retest method was performed to test the reliability and consistency of the scale over time.

RESULTS: A total of 81 patients participated in the study. The Cronbach’s alpha coefficient of SXI was 0.788. The mean values for the test was 12.84±6.78 and re-test scores was 11.03±6.88. ICC value calculated as 0.992 and accordingly a statistically significant relationship between the test and retest scores (p<0.001).

CONCLUSIONS: Our study showed that the SXI is a valid and reliable measurement tool for Turkish hemodialysis patients.

PMID:35438251 | DOI:10.1111/1744-9987.13858

Low Urin Tract Symptoms. 2022 Apr 19. doi: 10.1111/luts.12443. Online ahead of print.

ABSTRACT

OBJECTIVE: Urinary bladder ischemia has been implicated in the pathogenesis of lower urinary tract symptoms (LUTS). However, research regarding urinary molecular markers for diagnosis and prognosis of pelvic ischemia is still premature, hindering further implementation in clinical practice. The aim of this study is to systematically appraise biomarkers associated with bladder ischemia detected in urine.

METHODS: We performed a systematic review of PubMed/Medline, Embase, Web of Science, and the Cochrane Library in October 2021 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. A subsequent reference search of retrieved articles was also performed. The identified reports were reviewed according to Systematic Review Center for Laboratory Animal Experimentation’s risk-of-bias tool for animal studies.

RESULTS: Eight publications were selected for this analysis. The included reports used 8-hydroxy-2′-deoxyguanosine (8-OHdG) (in eight studies) as urinary marker of bladder ischemia. The pooled mean difference for urinary 8-OHdG levels between study and control groups was 13.73 ng/mg creatinine (95% CI, 9.79-17.67; P < .001; I² = 69%) for rat studies and 3.71 ng/mg creatinine (95% CI, 2.91-4.51; P < .001; I² = 94%) for rabbit studies. The result remained statistically significant favoring the control group independent of the type of intervention used to achieve bladder ischemia. Regarding secondary outcomes, mean voided volume and micturition interval were significantly lower in the ischemia group.

CONCLUSION: The lack of human randomized controlled trials is a major limitation. 8-OHdG is a urinary biomarker to be investigated in future studies for diagnosis and prognosis of LUTS in patients with vascular injury or bladder outlet obstruction.

PMID:35438247 | DOI:10.1111/luts.12443

J Periodontal Res. 2022 Apr 19. doi: 10.1111/jre.12993. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Titanium wear particles may participate in the etiology of peri-implantitis. However, the influence of titanium wear particles on biological behavior of human gingival fibroblasts (HGFs) in the presence of LPS is still not clear. The present study demonstrated the effects of titanium dioxide micro- and nanoparticles (TiO₂ MPs and NPs) on HGF cell viability, cytoskeletal organization, adhesion, migration, and proliferation in vitro, and LPS was used to mimic the in vivo condition.

METHODS: Primary HGFs were treated with TiO₂ MPs (primary particle size <5 μm, 0.1 mg/ml) and NPs (primary particle size <100 nm, 0.1 mg/ml) with or without 1 μg/ml LPS. The effects of TiO₂ MPs and NPs on HGFs cell viability was measured by CCK-8 assay. The proliferation of HGF was detected by Ki67 nuclear staining. The confocal laser scanning microscope (CLSM) was used to detect the internalization of TiO₂ MPs and NPs in HGFs as well as the arrangement of F-actin, vinculin, and vimentin organization. Wound healing assay and transwell assay were performed to measure the migration of HGFs induced by TiO₂ MPs and NPs. Cell adhesion was measured using fibronectin-coated plates. The relative mRNA and protein expression of adhesion relative protein such as focal adhesion kinase (FAK), fibronectin (FN), and type I collagen (COL1) were measured using quantitative RT-PCR and western blot analysis. One-way analysis of variance (ANOVA) and Student’s t-test were used to analyze the statistical significance, and p < .05 was considered statistically significant.

RESULTS: TiO₂ NPs significantly inhibited HGF cell viability, proliferation, and migration compared with TiO₂ MPs group and control group. Compared with control group (2.64 ± 0.09), the mean absorbance of the cells in 1 mg/ml TiO₂ MPs group and 0.25 mg/ml TiO₂ NPs group were significantly decreased to 1.93 ± 0.33 (p < .05) and 2.22 ± 0.18 (p < .01), respectively. The cytoskeleton disruption was found in TiO₂ NPs group. The mRNA and protein expression were significantly downregulated by TiO₂ NPs. Furthermore, both TiO₂ NPs and MPs induced more adverse effects on HGFs in the presence of LPS.

CONCLUSION: Our results indicate that TiO₂ NPs but not TiO₂ MPs significantly disrupt the cytoskeletal organization and inhibited cell adhesion, migration, and proliferation of HGFs. However, in the presence of LPS, TiO₂ MPs, and TiO₂ NPs enhance these negative effects in HGFs. Titanium wear particles are probably involved in the initiation and progression of peri-implant diseases.

PMID:35438207 | DOI:10.1111/jre.12993

Genet Epidemiol. 2022 Apr 19. doi: 10.1002/gepi.22451. Online ahead of print.

ABSTRACT

In this paper, we develop functional ordinal logistic regression (FOLR) models to perform gene-based analysis of ordinal traits. In the proposed FOLR models, genetic variant data are viewed as stochastic functions of physical positions and the genetic effects are treated as a function of physical positions. The FOLR models are built upon functional data analysis which can be revised to analyze the ordinal traits and high dimension genetic data. The proposed methods are capable of dealing with dense genotype data which is usually encountered in analyzing the next-generation sequencing data. The methods are flexible and can analyze three types of genetic data: (1) rare variants only, (2) common variants only, and (3) a combination of rare and common variants. Simulation studies show that the likelihood ratio test statistics of the FOLR models control type I errors well and have good power performance. The proposed methods achieve the goals of analyzing ordinal traits directly, reducing high dimensionality of dense genetic variants, being computationally manageable, facilitating model convergence, properly controlling type I errors, and maintaining high power levels. The FOLR models are applied to analyze Age-Related Eye Disease Study data, in which two genes are found to strongly associate with four ordinal traits.

PMID:35438198 | DOI:10.1002/gepi.22451

QJM. 2022 Apr 19:hcac104. doi: 10.1093/qjmed/hcac104. Online ahead of print.

ABSTRACT

OBJECTIVE: The purposes of this survey were to show the current situation of oncology critical care medicine in China by questionnaire, to understand the resource distribution of oncology critical care medicine, and to analyze and evaluate the existing resources and reserve capacity of oncology critical care medicine in China.

METHODS: We conducted the survey mainly in the form of an online questionnaire. The Committee of Cancer Critical Care Medicine of the Chinese Anticancer Association (CACA) initiated the survey on November 1st, 2017, and 36 member hospitals nationwide participated in the survey. The questionnaire included ten items: investigator information, hospital information, general information of oncology critical care department, staffing of oncology critical care department, management in oncology critical care department, technical skills in oncology critical care department, patient source in oncology critical care department, equipment configuration in oncology critical care department, special skills in oncology critical care department and summary of the information.

RESULTS: The survey results included information from 28 member units, all of which were tertiary hospitals, distributed in 20 provinces and 4 direct-controlled municipalities. The results are as follows. (1) The total ratio of beds in the oncology critical care department to hospital beds was 1.06%, and the average number of beds in the oncology critical care department was 16.36. (2) The ratio of physicians in the oncology critical care department to beds was approximately 0.62:1, and the ratio of nurses to beds was approximately 1.98:1. (3) According to the census of the population and gross domestic product (GDP) of different regions conducted by the State Statistics Bureau in 2017, the ratio of beds in the oncology critical care department for tumor patients to population was 4.55 beds per 10 million people, and the ratio of beds in the oncology critical care department to GDP was 8.00 beds per RMB 100 billion, on average. (4) According to the requirements of the guidelines for the development and management of critical care medicine in China, the facilities in departments of oncology critical care medicine meet the requirements, and the technical skills of medical staff are competent.

CONCLUSION: The development of oncology critical care in China is becoming better, but there is still a certain gap compared with the intensive care unit (ICU) standards in China and the average level of the nationwide. The development of oncology critical care medicine is urgent.

PMID:35438153 | DOI:10.1093/qjmed/hcac104

Bioinformatics. 2022 Apr 19:btac279. doi: 10.1093/bioinformatics/btac279. Online ahead of print.

ABSTRACT

MOTIVATION: Tissue-level omics data such as transcriptomics and epigenomics are an average across diverse cell types. To extract cell-type-specific (CTS) signals, dozens of cellular deconvolution methods have been proposed to infer cell-type fractions from tissue-level data. However, these methods produce vastly different results under various real data settings. Simulation-based benchmarking studies showed no universally best deconvolution approaches. There have been attempts of ensemble methods, but they only aggregate multiple single-cell references or reference-free deconvolution methods.

RESULTS: To achieve a robust estimation of cellular fractions, we proposed EnsDeconv (Ensemble Deconvolution), which adopts CTS robust regression to synthesize the results from eleven single deconvolution methods, ten reference datasets, five marker gene selection procedures, five data normalizations, and two transformations. Unlike most benchmarking studies based on simulations, we compiled four large real datasets of 4,937 tissue samples in total with measured cellular fractions and bulk gene expression from different tissues. Comprehensive evaluations demonstrated that EnsDeconv yields more stable, robust, and accurate fractions than existing methods. We illustrated that EnsDeconv estimated cellular fractions enable various CTS downstream analyses such as differential fractions associated with clinical variables. We further extended EnsDeconv to analyze bulk DNA methylation data.

AVAILABILITY: EnsDeconv is freely available as an R-package from https://github.com/randel/EnsDeconv.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:35438146 | DOI:10.1093/bioinformatics/btac279

Bioinformatics. 2022 Apr 19:btac268. doi: 10.1093/bioinformatics/btac268. Online ahead of print.

ABSTRACT

MOTIVATION: High parameter histological techniques have allowed for the identification of a variety of distinct cell types within an image, providing a comprehensive overview of the tissue environment. This allows the complex cellular architecture and environment of diseased tissue to be explored. While spatial analysis techniques have revealed how cell-cell interactions are important within the disease pathology, there remains a gap in exploring changes in these interactions within the disease process. Specifically, there are currently few established methods for performing inference on cell type co-localisation changes across images, hindering an understanding of how cellular environments change with a disease pathology.

RESULTS: We have developed the spicyR R package to perform inference on changes in the spatial co-localisation of cell types across groups of images. Application to simulated data demonstrates a high sensitivity and specificity. We demonstrate the utility of spicyR by applying it to a type 1 diabetes imaging mass cytometry dataset, revealing changes in cellular associations that were relevant to the disease progression. Ultimately, spicyR allows changes in cellular environments to be explored under different pathologies or disease states.

AVAILABILITY AND IMPLEMENTATION: R package freely available at http://bioconductor.org/packages/release/bioc/html/spicyR.html and shiny app implementation at http://shiny.maths.usyd.edu.au/spicyR/.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:35438129 | DOI:10.1093/bioinformatics/btac268

Food Funct. 2022 Apr 19. doi: 10.1039/d1fo03921k. Online ahead of print.

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease and threatens human health worldwide. As shown in our previous study, co-supplementation with phytosterol ester (PSE) (3.3 g day^-1) and n-3 polyunsaturated fatty acids (PUFAs) (450 mg eicosapentaenoic acid (EPA) + 1500 mg docosahexaenoic acid (DHA) per day) was more effective at ameliorating hepatic steatosis than treatment with PSE or n-3 PUFAs alone. In the present study, we further investigated the changes in the serum metabolic profiles of subjects with NAFLD in response to n-3 PUFAs and PSE. Thirty-one differentially altered serum metabolites were annotated using the nontargeted ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF-MS^E) analysis technique. Multivariable statistical and clustering analyses showed that co-supplementation of n-3 PUFAs and PSE was more effective at improving metabolic disorders in patients with NAFLD than treatment with n-3 PUFAs or PSE alone. The regulated metabolic pathways included metabolism of retinol, linoleic acid, arachidonic acid, glycerophospholipid, sphingolipid, and steroid hormone biosynthesis. Overall, the co-supplementation of n-3 PUFAs and PSE significantly increased the serum levels of PUFA-containing phosphatidylcholine (PC), lysophosphatidylcholine (LysoPC), perillyl alcohol and retinyl ester in patients with NAFLD after 12 weeks of intervention, and the levels of PC (14:0/20:5, 15:0/20:5), LysoPC (20:5, 22:6) and retinyl ester correlated negatively with the degree of hepatic steatosis. The regulatory effect of co-supplementation of n-3 PUFAs and PSE on metabolomic profiles may explain their potential role in alleviating hepatic steatosis in patients with NAFLD.

PMID:35438091 | DOI:10.1039/d1fo03921k

Blood Press Monit. 2022 Apr 18. doi: 10.1097/MBP.0000000000000597. Online ahead of print.

ABSTRACT

OBJECTIVES: The frontal QRS-T (f-QRST) angle is a measure of depolarization and repolarization heterogeneity and may be a predictor of poor ventricular health. We aimed to investigate whether the f-QRST angle indicates myocardial damage and predicts newly diagnosed true hypertension (HT) in patients with white coat hypertension.

METHODS: We measured the f-QRST angle of 63 subjects with WHC and 105 patients with newly diagnosed HT. Laboratory tests and ABPM were followed up in all patients. The f-QRST angle was calculated on the surface ECGs.

RESULTS: Of the patients in the study, 38.9% were female and 61.1% were male. The mean age was calculated as 59 ± 11 years. A comparison between both groups with the f-QRST angles was seen to be statistically significantly higher in the true HT group. The results of the receiving operating characteristic curve showed that the AUC value of the f-QRST angle was 0.94 (95% confidence interval, 0.91-0.97), the cutoff value was 60.5°, the sensitivity was 89.5%, and the specificity was 81%.

CONCLUSION: In our study, the f-QRST angle was found to be lower in patients with WHC than in true hypertensive patients. We think that ECG, which is a simple test, can be used to distinguish between true HT and WHC.

PMID:35438080 | DOI:10.1097/MBP.0000000000000597