Category: Nevin Manimala

Sichuan Da Xue Xue Bao Yi Xue Ban. 2021 Mar;52(2):248-258. doi: 10.12182/20210360205.

ABSTRACT

OBJECTIVE: To investigate the significance of stemness-related genes in the diagnosis and treatment of ovarian cancer.

METHODS: Key modules and genes were identified with weighted gene co-expression network analysis (WGCNA). The signal pathways of high expression of key genes were analyzed by gene set enrichment analysis (GSEA) and single cell sequencing data. The chemosensitivity of ovarian cancer to chemotherapy drugs was estimated with pRRophetic. Flow cytometry was used to examine the expression of CD44 ⁺CD117 ⁺in SKOV3 cells and cancer stem cells. The expression of key genes in ovarian cancer stem cells was confirmed by qRT-PCR. The core genes were identified by GeneMANIA analysis.

RESULTS: According to the WGCNA results, 15 key genes were identified at the transcription level, all being highly expressed in many kinds of tumors. They were involved in the cell cycle, DNA repair, E2 target and G2M checkpoint pathway, and had significant correlation with chemosensitivity. The proportion of CD44 ⁺ CD117 ⁺ cells in SKOV3 cells and ovarian cancer stem cells were (1.20±0.34)% and (37.17±1.80)% respectively, with statistically significant difference ( P<0.05). qRT-PCR confirmed that seven key genes ( BUB1, CDC20, CCNB2, DLGAP5, KIF4 A, NEK2, NUSAP1) in the WGCNA results were highly expressed in ovarian cancer stem cells, and BUB1 might have played a core role.

CONCLUSION: Seven hub genes, especially BUB1, were identified by constructing gene co-expression network, which may become potential biomarkers of ovarian cancer gene.

PMID:33829699 | DOI:10.12182/20210360205

Sichuan Da Xue Xue Bao Yi Xue Ban. 2021 Mar;52(2):259-266. doi: 10.12182/20210260302.

ABSTRACT

OBJECTIVE: To explore the individual or combined effects of adiponectin, leptin, and soluble leptin receptor (sOB-R) on risks for premenopausal and postmenopausal breast cancer, and to provide evidence for revealing the molecular mechanism between obesity and breast cancer.

METHODS: 469 newly-diagnosed breast cancer cases were sequentially recruited for the study and 469 age-frequency-matched healthy women were enrolled as the controls over the same period of time. The participant baseline information was collected with questionnaires, and plasmic levels of adiponectin, leptin and sOB-R were checked with ELISA. Multivariate unconditional logistic regression was conducted and the analyses were further stratified according to waist-to-hip ratio (WHR) and body mass index (BMI) to explore the effect of the indicators on the risks for premenopausal and postmenopausal breast cancer.

RESULTS: A total of 480 premenopausal and 458 postmenopausal women were included in the study. Among the premenopausal subjects, 249 were breast cancer patients and 231 were controls. The median BMI was 22.9 kg/m ²and 23.2 kg /m ², respectively, and the median WHR was 0.80 and 0.83, respectively. Among the postmenopausal subjects, 220 were breast cancer patients and 238 were controls. The median BMI was 23.4 kg/m ² and 23.7 kg/m ², respectively, and the median WHR was 0.82 and 0.86, respectively. Multivariate logistic regression analysis showed that before and after model adjustment, the increase in sOB-R and adiponectin levels was correlated to reduced risks of premenopausal and postmenopausal breast cancer ( P<0.05), while the increase in the leptin/sOB-R ratio (also known as free leptin index, FLI) and leptin/adiponectin (L/A) ratio was only correlated to increased risks of postmenopausal breast cancer. After further stratification by WHR and BMI, the association between adiponectin, FLI and postmenopausal breast cancer remained statistically significant in all subgroups. Among subjects with normal-BMI central obesity (18.5 kg/m ²≤BMI<24 kg/m ² & WHR≥0.85) , higher L/A ratio was associated with an increased risk of postmenopausal breast cancer. No clear association between leptin and premenopausal and risks for postmenopausal breast cancer was found in the study.

CONCLUSION: Postmenopausal women with decreased levels of sOB-R and adiponectin, and increased FLI and L/A, and premenopausal women with decreased levels of sOB-R and adiponectin were found to be at high risks for breast cancer.

PMID:33829700 | DOI:10.12182/20210260302

Sci Rep. 2021 Apr 7;11(1):7617. doi: 10.1038/s41598-021-87081-6.

ABSTRACT

Postbiotic RS5, produced by Lactiplantibacillus plantarum RS5, has been identified as a promising alternative feed supplement for various livestock. This study aimed to lower the production cost by enhancing the antimicrobial activity of the postbiotic RS5 by improving the culture density of L. plantarum RS5 and reducing the cost of growth medium. A combination of conventional and statistical-based approaches (Fractional Factorial Design and Central Composite Design of Response Surface Methodology) was employed to develop a refined medium for the enhancement of the antimicrobial activity of postbiotic RS5. A refined medium containing 20 g/L of glucose, 27.84 g/L of yeast extract, 5.75 g/L of sodium acetate, 1.12 g/L of Tween 80 and 0.05 g/L of manganese sulphate enhanced the antimicrobial activity of postbiotic RS5 by 108%. The cost of the production medium was reduced by 85% as compared to the commercially available de Man, Rogosa and Sharpe medium that is typically used for Lactobacillus cultivation. Hence, the refined medium has made the postbiotic RS5 more feasible and cost-effective to be adopted as a feed supplement for various livestock industries.

PMID:33828119 | DOI:10.1038/s41598-021-87081-6

Sci Rep. 2021 Apr 7;11(1):7647. doi: 10.1038/s41598-021-86716-y.

ABSTRACT

Unemployment shocks from the COVID-19 pandemic have reignited concerns over the long-term effects of job loss on population health. Past research has highlighted the corrosive effects of unemployment on health and health behaviors. This study examines whether the effects of job loss on changes in body mass index (BMI) are moderated by genetic predisposition using data from the U.S. Health and Retirement Study (HRS). To improve detection of gene-by-environment (G × E) interplay, we interacted layoffs from business closures-a plausibly exogenous environmental exposure-with whole-genome polygenic scores (PGSs) that capture genetic contributions to both the population mean (mPGS) and variance (vPGS) of BMI. Results show evidence of genetic moderation using a vPGS (as opposed to an mPGS) and indicate genome-wide summary measures of phenotypic plasticity may further our understanding of how environmental stimuli modify the distribution of complex traits in a population.

PMID:33828129 | DOI:10.1038/s41598-021-86716-y

Cancer Epidemiol Biomarkers Prev. 2021 Apr 7:cebp.1568.2020. doi: 10.1158/1055-9965.EPI-20-1568. Online ahead of print.

ABSTRACT

BACKGROUND: The role of progestogens in colorectal cancer development are poorly characterized. To address this, our group developed a highly sensitive assay to measure concentrations of seven markers of endogenous progestogen metabolism among postmenopausal women.

METHODS: The markers were measured in baseline serum collected from postmenopausal women in a case-cohort study within the Breast and Bone Follow-up to the Fracture Intervention Trial (B~FIT). We followed women not using exogenous hormones at baseline (1992-1993) for up to twelve years: 187 women with incident colorectal cancer diagnosed during follow-up and a subcohort of 495 women selected on strata of age and clinical center. We used adjusted Cox regression models with robust variance to estimate risk for colorectal cancer (hazard ratios [HR], 95% confidence intervals [CI]).

RESULTS: High concentrations of pregnenolone and progesterone were not associated with colorectal cancer (quintile(Q)5 vs. Q1: pregnenolone HR 0.71, CI 0.40-1.25; progesterone HR 1.25, CI 0.71-2.22). A trend of increasing risk was suggested, but statistically imprecise across quintiles of 17-hydroxypregnenolone (Q2 to Q5 HRs 0.75 to 1.44, p-trend 0.06).

CONCLUSIONS: We used sensitive and reliable assays to measure multiple circulating markers of progestogen metabolism. Progestogens were generally unassociated with colorectal cancer risk in postmenopausal women.

IMPACT: Our findings are consistent with most prior research on circulating endogenous sex hormones, which taken together, suggest sex hormones may not be major drivers of colorectal carcinogenesis in postmenopausal women.

PMID:33827983 | DOI:10.1158/1055-9965.EPI-20-1568

Dent Mater J. 2021 Apr 7. doi: 10.4012/dmj.2020-293. Online ahead of print.

ABSTRACT

The effects of space setting values and restorative materials on the bonding of metal-free CAD/CAM onlay restoration were examined quantitatively and qualitatively. Seventy-two standardized MODB onlay cavities, prepared using human molars were restored under nine conditions, based on three space setting values, Increased (IC), Standard (SC, control), Decreased (DC), and three restorative block materials, resin-composites (RC), lithium disilicate glass-ceramics (LD), Feldspar ceramics (FC, control). All the restored specimens were subjected to cyclic loading and thereafter the microtensile bond strength (µ-TBS) was measured and analyzed statistically. The effect of space setting value on the µ-TBS varied with the restorative material. The bonding reliability of RC and the bonding durability of LD were significantly superior to FC. The bonding characteristics of RC under IC and DC were similar to those under SC. LD under DC and FC under IC were effective in obtaining an excellent bonding reliability relative to their SC.

PMID:33827999 | DOI:10.4012/dmj.2020-293

Sci Rep. 2021 Apr 7;11(1):7641. doi: 10.1038/s41598-021-87066-5.

ABSTRACT

This paper presents the assessment of water resource security in the Guizhou karst area, China. A mean impact value and back-propagation (MIV-BP) neural network was used to understand the influencing factors. Thirty-one indices involving five aspects, the water quality subsystem, water quantity subsystem, engineering water shortage subsystem, water resource vulnerability subsystem, and water resource carrying capacity subsystem, were selected to establish an evaluation index of water resource security. In addition, a genetic algorithm and back-propagation (GA-BP) neural network was constructed to assess the water resource security of Guizhou Province from 2001 to 2015. The results show that water resource security in Guizhou was at a moderate warning level from 2001 to 2006 and a critical safety level from 2007 to 2015, except in 2011 when a moderate warning level was reached. For protection and management of water resources in a karst area, the modes of development and utilization of water resources must be thoroughly understood, along with the impact of engineering water shortage. These results are a meaningful contribution to regional ecological restoration and socio-economic development and can promote better practices for future planning.

PMID:33828114 | DOI:10.1038/s41598-021-87066-5

J Immunother Cancer. 2021 Apr;9(4):e002421. doi: 10.1136/jitc-2021-002421.

ABSTRACT

BACKGROUND: Some concomitant medications including antibiotics (ATB) have been reproducibly associated with worse survival following immune checkpoint inhibitors (ICIs) in unselected patients with non-small cell lung cancer (NSCLC) (according to programmed death-ligand 1 (PD-L1) expression and treatment line). Whether such relationship is causative or associative is matter of debate.

METHODS: We present the outcomes analysis according to concomitant baseline medications (prior to ICI initiation) with putative immune-modulatory effects in a large cohort of patients with metastatic NSCLC with a PD-L1 expression ≥50%, receiving first-line pembrolizumab monotherapy. We also evaluated a control cohort of patients with metastatic NSCLC treated with first-line chemotherapy. The interaction between key medications and therapeutic modality (pembrolizumab vs chemotherapy) was validated in pooled multivariable analyses.

RESULTS: 950 and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Corticosteroid and proton pump inhibitor (PPI) therapy but not ATB therapy was associated with poorer performance status at baseline in both the cohorts. No association with clinical outcomes was found according to baseline statin, aspirin, β-blocker and metformin within the pembrolizumab cohort. On the multivariable analysis, ATB emerged as a strong predictor of worse overall survival (OS) (HR=1.42 (95% CI 1.13 to 1.79); p=0.0024), and progression free survival (PFS) (HR=1.29 (95% CI 1.04 to 1.59); p=0.0192) in the pembrolizumab but not in the chemotherapy cohort. Corticosteroids were associated with shorter PFS (HR=1.69 (95% CI 1.42 to 2.03); p<0.0001), and OS (HR=1.93 (95% CI 1.59 to 2.35); p<0.0001) following pembrolizumab, and shorter PFS (HR=1.30 (95% CI 1.08 to 1.56), p=0.0046) and OS (HR=1.58 (95% CI 1.29 to 1.94), p<0.0001), following chemotherapy. PPIs were associated with worse OS (HR=1.49 (95% CI 1.26 to 1.77); p<0.0001) with pembrolizumab and shorter OS (HR=1.12 (95% CI 1.02 to 1.24), p=0.0139), with chemotherapy. At the pooled analysis, there was a statistically significant interaction with treatment (pembrolizumab vs chemotherapy) for corticosteroids (p=0.0020) and PPIs (p=0.0460) with respect to OS, for corticosteroids (p<0.0001), ATB (p=0.0290), and PPIs (p=0.0487) with respect to PFS, and only corticosteroids (p=0.0033) with respect to objective response rate.

CONCLUSION: In this study, we validate the significant negative impact of ATB on pembrolizumab monotherapy but not chemotherapy outcomes in NSCLC, producing further evidence about their underlying immune-modulatory effect. Even though the magnitude of the impact of corticosteroids and PPIs is significantly different across the cohorts, their effects might be driven by adverse disease features.

PMID:33827906 | DOI:10.1136/jitc-2021-002421

mSphere. 2021 Apr 7;6(2):e01019-20. doi: 10.1128/mSphere.01019-20.

ABSTRACT

Shannon’s entropy is a popular alpha diversity metric because it estimates both richness and evenness in a single equation. However, since its value is dependent on both those parameters, there is theoretically an infinite number of richness/evenness value combinations translating into the same index score. By decoupling both components measured by Shannon’s entropy, two communities having identical indices can be differentiated by mapping richness and evenness coordinates on a scatter plot. In such graphs, confidence ellipses would allow testing significant differences between groups of samples. Multivariate statistical tests such as permutational multivariate analysis of variance (PERMANOVA) can be performed on distance matrices calculated from richness and evenness coordinates and detect statistically significant differences that would have remained unforeseen otherwise. Therefore, plotting richness and evenness on two-dimensional (2D) graphs gives a more thorough understanding of how alpha diversity differs between groups of samples.

PMID:33827912 | DOI:10.1128/mSphere.01019-20

Pediatrics. 2021 Apr 7:e20201634. doi: 10.1542/peds.2020-1634. Online ahead of print.

ABSTRACT

BACKGROUND: Clinicians commonly obtain endotracheal aspirate cultures (EACs) in the evaluation of suspected ventilator-associated infections. However, bacterial growth in EACs does not distinguish bacterial colonization from infection and may lead to overtreatment with antibiotics. We describe the development and impact of a clinical decision support algorithm to standardize the use of EACs from ventilated PICU patients.

METHODS: We monitored EAC use using a statistical process control chart. We compared the rate of EACs using Poisson regression and a quasi-experimental interrupted time series model and assessed clinical outcomes 1 year before and after introduction of the algorithm.

RESULTS: In the preintervention year, there were 557 EACs over 5092 ventilator days; after introduction of the algorithm, there were 234 EACs over 3654 ventilator days (an incident rate of 10.9 vs 6.5 per 100 ventilator days). There was a 41% decrease in the monthly rate of EACs (incidence rate ratio [IRR]: 0.59; 95% confidence interval [CI] 0.51-0.67; P < .001). The interrupted time series model revealed a preexisting 2% decline in the monthly culture rate (IRR: 0.98; 95% CI 0.97-1.0; P = .01), immediate 44% drop (IRR: 0.56; 95% CI 0.45-0.70; P = .02), and stable rate in the postintervention year (IRR: 1.03; 95% CI 0.99-1.07; P = .09). In-hospital mortality, hospital length of stay, 7-day readmissions, and All Patients Refined Diagnosis Related Group severity and mortality scores were stable. The estimated direct cost savings was $26 000 per year.

CONCLUSIONS: A clinical decision support algorithm standardizing EAC obtainment from ventilated PICU patients was associated with a sustained decline in the rate of EACs, without changes in mortality, readmissions, or length of stay.

PMID:33827937 | DOI:10.1542/peds.2020-1634