Nevin Manimala

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

J Korean Med Sci. 2022 Apr 18;37(15):e118. doi: 10.3346/jkms.2022.37.e118.

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has disrupted the lives of people around the world since 2020. This study aims to reveal perceived impact of the coronavirus pandemic on physical and mental health and eating behaviors among people with disabilities and without disabilities in South Korea, as compared to other countries.

METHODS: A secondary analysis of a prospective cross-sectional study which was conducted with a web-based global survey.

RESULTS: Among the 3,550 responses from 65 countries, 2,621 responses with nation information were set as full data, 189 for South Korea and 2,432 for other countries. In Korea, there was no significant difference in healthy lifestyle behaviors between people with and without disabilities before the COVID-19 pandemic. Perceived physical and mental health and changes in eating habits during the COVID-19 pandemic showed no significant difference between people with and without disabilities in Korea. There were significant differences in physical health and dietary habits, but no differences in its effect on mental health between people living in Korea and other countries in both people with and without disabilities groups. In other words, more than 60% of people in all groups (disability vs. non-disability, Korea vs. non-Korea) reported worse mental health than before the COVID-19 pandemic.

CONCLUSION: In Korea and other countries, mental health showed a tendency to deteriorate regardless of the presence or absence of disability during the COVID-19 pandemic. In terms of healthy eating habits, Koreans were relatively less affected than people from other countries.

PMID:35437966 | DOI:10.3346/jkms.2022.37.e118

Investig Clin Urol. 2022 Apr 12. doi: 10.4111/icu.20210281. Online ahead of print.

ABSTRACT

PURPOSE: The selection of open prostatectomy (OP) over transurethral laser surgery is controversial for large volume prostates. Thus, we aim to compare the efficacy and safety of transurethral laser versus OP, and provide the latest evidence of clinical practice for large-sized benign prostatic hyperplasia (BPH).

MATERIALS AND METHODS: This meta-analysis used Review Manager V5.3 software and the systematic literature search of Cochrane Library, Embase, PubMed, and Web of Science datasets was performed for citations published from 2000 to 2020 that compared transurethral laser with OP for the treatment of large BPH. Variables of interest assessing the two techniques included clinical characteristics, and the perioperation-, effectiveness-, and complication-related outcomes.

RESULTS: The meta-analysis included twelve studies containing 1,514 patients, with 792 laser and 722 OP. The transurethral laser group was associated with shorter hospital stay and catheterization duration, and less hemoglobin decreased in the perioperative variables. There was no significant difference in the international prostate symptom score, post-void residual urine volume, maximum flow rate, and quality of life score. Transurethral laser group had a significantly lower incidence of blood transfusion than OP group (odds ratio, 0.10; 95% confidence interval, 0.05 to 0.19; p<0.001; I²=8%), and no statistical differences were found with respect to the other complications.

CONCLUSIONS: Both OP and transurethral laser prostatectomy are effective and safe treatments for large prostate adenomas. With these advantages of less blood loss and transfusion, and shorter catheterization time and hospital stay, laser may be a better choice for large BPH.

PMID:35437960 | DOI:10.4111/icu.20210281

ESC Heart Fail. 2022 Apr 18. doi: 10.1002/ehf2.13937. Online ahead of print.

ABSTRACT

AIMS: Radiofrequency catheter ablation (RFCA) is now an established therapeutic option for patients with atrial fibrillation (AF), but the long-term recurrence rate of AF is still high. Sacubitril/valsartan (Sac/Val) is superior to valsartan in attenuating ventricular remodelling and improving clinical outcomes in heart failure patients, but whether this additional benefit exists in reversing atrial remodelling and reducing AF recurrence of RFCA-treated AF patients remains uncovered.

METHODS AND RESULTS: Patients that had undergone RFCA were enrolled and randomly assigned 1:1 to valsartan (160 mg/day) or Sac/Val (200 mg/day) treatment group, in addition to other standard treatment of AF. Patients were followed up for 24 weeks. Echocardiography and ambulatory Holter monitoring for 24 h was performed at 24 weeks after RFCA. The primary end point was the change of atrial diameter from baseline to 24 weeks after RFCA. Second end points included the recurrence rate of AF, all-cause hospitalization and all-cause death. A total of 64 AF patients were enrolled, 32 of which received Sac/Val and 32 received valsartan treatment. There was no difference in the age (64.8 ± 9.8 vs. 63.7 ± 9.0, P = 0.634), gender (per cent of male: 59.4% vs. 50.0%, P = 0.616), heart rate (84.7 ± 4.1 b.p.m. vs. 80.9 ± 2.6 b.p.m., P = 0.428), systolic (127.5 ± 15.4 mmHg vs. 130.0 ± 17.8 mmHg, P = 0.549) or diastolic (81.7 ± 9.8 mmHg vs. 79.9 ± 12.6, P = 0.537) blood pressure upon admission between valsartan and Sac/Val treatment groups. The percentage of persistent AF was also comparable (43.8% vs. 53.1%, P = 0.617) in both treatment groups. Patients receiving Sac/Val treatment displayed significant decrease in the left atrial diameter (4.3 ± 0.5 cm to 3.8 ± 0.5 cm, P < 0.001), volume index (48.0 ± 6.4 mL/m² to 41.7 ± 7.0 mL/m² , P < 0.001), and right atrial diameter (4.4 ± 0.8 cm to 3.9 ± 0.7 cm, P = 0.017) from baseline to 24 weeks after RFCA. This effect was not observed in valsartan treatment group. There was a numerical decrease in AF recurrence rate in the Sac/Val group compared with valsartan group (9.4% vs. 15.6%), although this difference did not reach a statistical significance (P = 0.708). No difference in all-cause hospitalization rate (6.3% in each group) or all-cause death rate (0% in each group) was observed.

CONCLUSIONS: Our data indicate that Sac/Val is superior to valsartan in attenuating atrial structural remodelling in catheter ablation-treated AF patients.

PMID:35437929 | DOI:10.1002/ehf2.13937

Thorac Cancer. 2022 Apr 18. doi: 10.1111/1759-7714.14429. Online ahead of print.

ABSTRACT

BACKGROUND: MET dysregulation has been implicated in the development of primary and secondary resistance to EGFR tyrosine kinase inhibitor (TKI) therapy. However, the clinicopathological characteristics and outcomes of patients harboring EGFR-sensitive mutations and de novo MET amplifications still need to be explored.

METHODS: A total of 54 patients from our hospital with non-small cell lung cancer harboring EGFR-sensitive mutations and/or de novo MET amplifications were included in this study. Survival rates were estimated by the Kaplan-Meier method with log-rank statistics. Lung cancer organoids (LCOs) were generated from patient-derived malignant pleural effusion to perform drug sensitivity assays.

RESULTS: Fifty-four patients with the appropriate clinicopathological characteristics were enrolled. MET FISH was performed in 40 patients who were stratified accordingly into two groups: EGFR+/METamp- (n = 22) and EGFR+/METamp + (n = 18). Survival rates for EGFR+/METamp- and EGFR+/METamp + patients respectively, were as follows: the median progression-free survival (PFS) was 12.1 and 1.9 months (p<0.001); the median post-progression overall survival (pOS) was 25.6 and 11.6 months (p = 0.023); the median overall survival (OS) was 33.2 and 12.7 months (p = 0.013). Drug testing conducted in LCOs derived from malignant pleural effusion from EGFR+/METamp + patients showed that dual targeted therapy was more effective than TKI monotherapy.

CONCLUSION: EGFR+/METamp + patients treated with first-line TKI monotherapy had poor clinical outcomes. Dual targeted therapy showed potent anticancer activity in the LCO drug testing assay, suggesting that it is a promising first-line treatment for EGFR+/METamp + patients. Randomized controlled trials are needed to further validate these results.

PMID:35437920 | DOI:10.1111/1759-7714.14429

Vet Surg. 2022 Apr 18. doi: 10.1111/vsu.13810. Online ahead of print.

ABSTRACT

OBJECTIVE: To provide a systematic assessment of the efficacy of preoperative skin asepsis using chlorhexidine versus povidone-iodine based protocols for surgical site infection (SSI) prevention in veterinary surgery.

STUDY DESIGN: Systematic meta-analytical review according to PRISMA-P guidelines.

SAMPLE POPULATION: Studies comparing preoperative skin asepsis protocols using chlorhexidine versus povidone-iodine in veterinary surgery identified by systematic search between 1990 and 2020.

METHODS: A search using MEDLINE/Pubmed, Web of Science and CAB Abstracts was performed, followed by secondary searches of Google Scholar, Proquest Dissertation and Theses, and relevant bibliographic articles. Primary and secondary outcome measures were the efficacy of skin asepsis protocols using chlorhexidine versus povidone-iodine on SSI incidence and skin bacterial colonization, respectively. A meta-analysis was performed with a random-effect model, with effect size calculated as risk ratio (RR) or mean standard deviation (MSD) with 95% CI. Statistical significance was set at P < .05.

RESULTS: Among 1067 publications that met the initial search criteria, 9 relevant studies were eligible for analysis. No difference in the incidence of postoperative SSI or skin bacterial colonization between preoperative asepsis protocols using chlorhexidine versus povidone-iodine was found. Insufficient information and detail were frequent among studies and precluded a clear assessment of bias.

CONCLUSION: This study showed that asepsis protocols using chlorhexidine were comparable to povidone-iodine in preventing postoperative SSI and reducing skin bacterial colonization.

CLINICAL SIGNIFICANCE: Given the limitations of the studies that were included in terms of both quality and quantity, more high-quality randomized controlled trials are needed to confirm these conclusions.

PMID:35437786 | DOI:10.1111/vsu.13810

Ann Hum Genet. 2022 Apr 18. doi: 10.1111/ahg.12467. Online ahead of print.

ABSTRACT

BACKGROUND: The circadian locomotor output cycles kaput (CLOCK) gene and the alcohol dehydrogenase 4 (ADH4) gene are promising candidates for susceptibility to cluster headaches (CH). Associations of the three single nucleotide polymorphisms (SNPs)-CLOCK SNP rs1801260 and ADH4 SNPs rs1800759, and rs1126671-with CH were studied previously, but the results were inconsistent.

METHODS: Associations between the three SNPs (rs1801260, rs1126671, and rs1800759) and CH risk were separately assessed by pooled odds ratios (ORs) along with 95% confidence intervals (95% CIs) based on five different genetic models. Methodological quality was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). All statistical analyses were carried out with RevMan 5.3 software.

RESULTS: Eight studies involving 1437 CH patients and 2541 healthy controls were selected for quantitative synthesis, from five studies on CLOCK rs1801260, five on ADH4 rs1800759, and three on ADH4 rs1126671. Our pooled data did not support associations between the three SNPs (rs1801260 in the CLOCK gene, rs1800759 and rs1126671 in the ADH4 gene) and susceptibility to CH (rs1801260: OR 1.10, 95% CI: 0.95-1.28; p = 0.19; rs1800759: OR 1.06, 95% CI: 0.93-1.22; p = 0.37; and rs1126671: OR 1.09, 95% CI: 0.92-1.28; p = 0.32).

CONCLUSION: We found no significant associations between the three SNPs (rs1801260 in the CLOCK gene and rs1800759 and rs1126671 in the ADH4 gene) and the susceptibility to CH across both Caucasian and Asian ethnicities in our meta-analysis.

PMID:35437765 | DOI:10.1111/ahg.12467