Tag: nevin manimala

J Biopharm Stat. 2021 Oct 4:1-14. doi: 10.1080/10543406.2021.1979575. Online ahead of print.

ABSTRACT

This paper investigates the use of a general multi-arm multi-stage (MAMS) approach for time-to-event outcomes that would streamline simultaneous comparison of a large number of promising therapies in clinical trials, thus significantly reducing the time and the number of patients needed to evaluate the treatment. Controlling type I error in this setting is different than regular clinical trials as this approach incorporates both multiple comparison between arms and multiple stages. Historically, pairwise (PWER) and familywise (FWER) type I error rates have been primarily used to regulate the type I error in such designs. This paper will focus on constructing the efficacy and futility boundaries for a MAMS clinical trial in two different scenarios. In the first, it is assumed that the same outcome is used throughout the clinical trial for both intermediate and final assessments. In this scenario, we propose using the generalized Dunnett procedure that controls FWER. In the latter scenario, where intermediate and final outcomes are different in nature, we propose modifications to the existing method that originally concentrated on controlling PWER and extend the method to include FWER in the design. We also explore the performance of the proposed MAMS design in a setting where the proportional hazard assumption is violated in the presence of a delayed treatment effect and demonstrate the loss of power because of that. An alternative test statistic that can help circumvent this problem to maintain the desired power is also suggested.

PMID:34606418 | DOI:10.1080/10543406.2021.1979575

Prague Med Rep. 2021;122(3):201-211. doi: 10.14712/23362936.2021.17.

ABSTRACT

The aim of this study was to evaluate the stomatognathic system of individuals with controlled systemic hypertension through comparison with a disease-free control group. Seventy individuals (44 female and 26 male) were divided into two groups: a controlled systemic hypertension (n=35) and a disease-free control (n=35). The individuals were evaluated on the basis of masticatory cycle efficiency of the value of the ensemble-averaged integrated linear envelope to the electromyographic signal of the masseter and temporalis muscles in the habitual (peanuts and raisins) and non-habitual chewing (Parafilm M); molar bite force (right and left) and ultrasound images from the bilateral masseter and temporal muscles at rest and maximum voluntary contraction. The data obtained were tabulated and submitted to statistical analysis (p<0.05). There was a significant difference between groups in the habitual (peanuts and raisins) and non-habitual (Parafilm M) chewing with reduced muscle activity to controlled systemic hypertension group. Muscle thickness occurred significant difference between groups at rest and maximum voluntary contraction of the temporalis muscles. There was no significant difference between groups in maximum molar bite force. The present study findings indicate that the controlled systemic hypertension promotes functional changes of the masticatory system, especially with respect to its masticatory efficiency and muscle thickness.

PMID:34606432 | DOI:10.14712/23362936.2021.17

RNA Biol. 2021 Oct 4:1-16. doi: 10.1080/15476286.2021.1971382. Online ahead of print.

ABSTRACT

RNA molecules are known to fold into specific structures which often play a central role in their functions and regulation. In silico folding of RNA transcripts, especially when assisted with structure profiling (SP) data, is capable of accurately elucidating relevant structural conformations. However, such methods scale poorly to the swaths of SP data generated by transcriptome-wide experiments, which are becoming more commonplace and advancing our understanding of RNA structure and its regulation at global and local levels. This has created a need for tools capable of rapidly deriving structural assessments from SP data in a scalable manner. One such tool we previously introduced that aims to process such data is patteRNA, a statistical learning algorithm capable of rapidly mining big SP datasets for structural elements. Here, we present a reformulation of patteRNA‘s pattern recognition scheme that sees significantly improved precision without major compromises to computational overhead. Specifically, we developed a data-driven logistic classifier which interprets patteRNA‘s statistical characterizations of SP data in addition to local sequence properties as measured with a nearest neighbour thermodynamic model. Application of the classifier to human structurome data reveals a marked association between detected stem-loops and RNA binding protein (RBP) footprints. The results of our application demonstrate that upwards of 30% of RBP footprints occur within loops of stable stem-loop elements. Overall, our work arrives at a rapid and accurate method for automatically detecting families of RNA structure motifs and demonstrates the functional relevance of identifying them transcriptome-wide.

PMID:34606413 | DOI:10.1080/15476286.2021.1971382

Bioengineered. 2021 Oct 4. doi: 10.1080/21655979.2021.1988365. Online ahead of print.

ABSTRACT

Glioblastoma is malignant intracranial tumor with indispensable growth. Identification of biomarkers associated with the progression of tumors could benefit the clinical therapy o and improve patient’s survival. miR-411 has been reported to play role in other cancers, while its function in glioblastoma was explored in the present study. The expression of miR-411 was evaluated in glioblastoma tissues (collected from 108 glioblastoma patients) and cells by polymerase chain reaction. The clinical significance of miR-411 was estimated with a series of statistical analyses. The biological function of miR-411 in the cellular processes of glioblastoma was assessed by cell counting kit 8 and Transwell assay. The expression of miR-411 was significantly reduced in glioblastoma, which was associated with the Karnofsky Performance Score (KPS) and Isocitrate dehydrogenase 1 (IDH1) status of patients. miR-411 was identified as an independent prognostic indicator that correlated with the poor prognosis of patients. miR-411 suppressed the growth, migration, and invasion of glioblastoma cells via modulating signal transducer and activator of transcription 3 (STAT3). miR-411 participated in the development of glioblastoma and function as a prognostic biomarker. miR-411 functions as a tumor suppressor, which provides a novel potential therapeutic target of glioblastoma.

PMID:34606414 | DOI:10.1080/21655979.2021.1988365

JCO Oncol Pract. 2021 Oct 4:OP2100407. doi: 10.1200/OP.21.00407. Online ahead of print.

ABSTRACT

PURPOSE: Health-related quality of life (HRQOL) is an established prognostic factor for mortality; however, it is unclear if HRQOL is predictive of time to disease progression, a particularly meaningful outcome for patients. We examined the association between HRQOL and progression-free survival (PFS) in SWOG Cancer Research Network clinical trials.

METHODS: For this secondary analysis, we reviewed all completed SWOG clinical trials to identify those for patients with advanced cancer that incorporated Functional Assessment of Cancer Therapy (FACT) questionnaires at baseline. FACT-Trial Outcome Index (FACT-TOI) was the primary independent variable. Associations between FACT-TOI and other FACT subscores with PFS and overall survival were evaluated via log-rank test and multivariable Cox regression analysis.

RESULTS: Three clinical trials met our inclusion criteria: S0027 and S9509 for advanced non-small-cell lung cancer and S0421 for hormone-refractory prostate cancer. Of the 1,527 enrolled patients, 1,295 (85%) had both HRQOL and survival outcomes data available and were included in this analysis. In univariable analysis, we observed a statistically significant gradient effect in all three trials, with higher baseline FACT-TOI scores corresponding to better PFS (S0027, P < .001; S9509, P = .02; and S0421, P < .001). In multivariable analysis, FACT-TOI was significantly associated with PFS in S0027 (hazard ratio [HR] = 0.64; 95% CI, 0.42 to 1.00) but not in S9509 (HR = 0.77; 95% CI, 0.56 to 1.05) or S042 (HR = 0.86; 95% CI, 0.73 to 1.01). FACT-TOI was significantly associated with overall survival in multivariable analysis (P < .005 in all three trials).

CONCLUSION: The association between baseline FACT-TOI scores and survival underscores their potential as a stratification factor in clinical trials.

PMID:34606328 | DOI:10.1200/OP.21.00407

Public Health Rep. 2021 Oct 4:333549211047552. doi: 10.1177/00333549211047552. Online ahead of print.

ABSTRACT

OBJECTIVES: Although data on the prevalence of current asthma among adults and children are available at national, regional, and state levels, such data are limited at the substate level (eg, urban-rural classification and county). We examined the prevalence of current asthma in adults and children across 6 levels of urban-rural classification in each state.

METHODS: We estimated current asthma prevalence among adults for urban-rural categories in the 50 states and the District of Columbia and among children for urban-rural categories in 27 states by analyzing 2016-2018 Behavioral Risk Factor Surveillance System survey data. We used the 2013 National Center for Health Statistics 6-level urban-rural classification scheme to define urban-rural status of counties.

RESULTS: During 2016-2018, the current asthma prevalence among US adults in medium metropolitan (9.5%), small metropolitan (9.5%), micropolitan (10.0%), and noncore (9.6%) areas was higher than the asthma prevalence in large central metropolitan (8.6%) and large fringe metropolitan (8.7%) areas. Current asthma prevalence in adults differed significantly among the 6 levels of urban-rural categories in 19 states. In addition, the prevalence of current asthma in adults was significantly higher in the Northeast (9.9%) than in the South (8.7%) and the West (8.8%). The current asthma prevalence in children differed significantly by urban-rural categories in 7 of 27 states. For these 7 states, the prevalence of asthma in children was higher in large central metropolitan areas than in micropolitan or noncore areas, except for Oregon, in which the prevalence in the large central metropolitan area was the lowest.

CONCLUSIONS: Knowledge about county-level current asthma prevalence in adults and children may aid state and local policy makers and public health officers in establishing effective asthma control programs and targeted resource allocation.

PMID:34606402 | DOI:10.1177/00333549211047552

J Proteome Res. 2021 Oct 4. doi: 10.1021/acs.jproteome.1c00537. Online ahead of print.

ABSTRACT

Anorexia nervosa (AN), a pathological restriction of food intake, leads to metabolic dysregulation. We conducted a metabolomics study to reveal changes caused by AN and the effect of hospital realimentation on metabolism. Both stool and serum from patients with AN and healthy controls were analyzed by NMR and MS. Statistical analysis revealed several altered biochemical and anthropometric parameters and 50 changed metabolites, including phospholipids, acylcarnitines, amino acids, derivatives of nicotinic acid, nucleotides, and energy metabolism intermediates. Biochemical and anthropometric parameters were correlated with metabolomic data. Metabolic changes in patients with AN described in our study imply serious system disruption defects, such as the development of inflammation and oxidative stress, changed free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels, a deficit of vitamins, muscle mass breakdown, and a decrease in ketone bodies as an important source of energy for the brain and heart. Furthermore, our data indicate only a very slight improvement after treatment. However, correlations of metabolomic results with body weight, interleukin 6, tumor necrosis factor α, fT4, and TSH might entail better prognoses and treatment effectiveness in patients with better system parameter status. Data sets are deposited in MassIVE: MSV000087713, DOI: 10.25345/C57R7X.

PMID:34606283 | DOI:10.1021/acs.jproteome.1c00537

Int J Numer Method Biomed Eng. 2021 Oct 4:e3535. doi: 10.1002/cnm.3535. Online ahead of print.

ABSTRACT

Quantitative estimation of local mechanical properties remains critically important in the ongoing effort to elucidate how blood vessels establish, maintain, or lose mechanical homeostasis. Recent advances based on panoramic digital image correlation (pDIC) have made high-fidelity 3D reconstructions of small-animal (e.g., murine) vessels possible when imaged in a variety of quasi-statically loaded configurations. While we have previously developed and validated inverse modeling approaches to translate pDIC-measured surface deformations into biomechanical metrics of interest, our workflow did not heretofore include a methodology to quantify uncertainties associated with local point estimates of mechanical properties. This limitation has compromised our ability to infer biomechanical properties on a subject-specific basis, such as whether stiffness differs significantly between multiple material locations on the same vessel or whether stiffness differs significantly between multiple vessels at a corresponding material location. In the present study, we have integrated a novel uncertainty quantification and propagation pipeline within our inverse modeling approach, relying on empirical and analytic Bayesian techniques. To demonstrate the approach, we present illustrative results for the ascending thoracic aorta from three mouse models, quantifying uncertainties in constitutive model parameters as well as circumferential and axial tangent stiffness. Our extended workflow not only allows parameter uncertainties to be systematically reported, but also facilitates both subject-specific and group-level statistical analyses of the mechanics of the vessel wall. This article is protected by copyright. All rights reserved.

PMID:34605615 | DOI:10.1002/cnm.3535

J Adv Nurs. 2021 Oct 4. doi: 10.1111/jan.15052. Online ahead of print.

ABSTRACT

AIMS: To evaluate the effects of the implementation of a professional practice model based on Magnet principles on the nurse work environment in a Dutch teaching hospital.

DESIGN: A quasi-experimental study.

METHODS: Data were collected from registered nurses working on the clinical wards and outpatient clinics of the hospital in June/July 2016 (baseline) and in June/September 2019 (measurement of effects). Participants completed the Dutch Essentials of Magnetism II survey, which was used to measure their perception of their work environment. After baseline measurements were collected, interventions based on a professional practice model incorporating Magnet principles were implemented to improve the nurse work environment. Descriptive statistics and independent t-tests were conducted to examine differences between survey outcomes in 2016 and 2019.

RESULTS: Survey outcomes revealed significant changes in the nurse work environment between 2016 and 2019. Seven of the eight subscales (essentials of magnetism) improved significantly. Score for overall job satisfaction increased from 7.3 to 8.0 and score for quality of care increased from 7.0 to 7.6. On unit level, 17 of the 19 units showed improvement in the nurse work environment.

CONCLUSION: The implementation of a professional practice model positively affects the nurse work environment, job satisfaction and quality of care.

IMPACT: Nowadays, the quality of care is threatened by workload pressure and the low autonomy experienced by nurses. Considering the global shortage of nurses and growing complexity of healthcare, it is important to invest in improving the nurse work environment. The Magnet concept created a work environment in which nurses can deliver optimal quality of care. Knowledge of how Magnet principles affect the nurse work environment in the Netherlands is missing. These study results, including the description of how the interventions were implemented, will assist other hospitals to develop improvement strategies by focusing on the nurse work environment.

PMID:34605566 | DOI:10.1111/jan.15052

J Cell Biochem. 2021 Oct 4. doi: 10.1002/jcb.30155. Online ahead of print.

ABSTRACT

Remodelin is a small molecule inhibitor of N-acetyltransferase 10 (NAT10), reported to reverse the effect of cancer conditions such as epithelial to mesenchymal transition, hypoxia, and drug resistance. We analysed RNA seq data of siNAT10 and found many metabolic pathways were altered, this made us perform unbiased metabolic analysis. Here we performed untargeted metabolomics in Remodelin treated cancer cells using high-performance liquid chromatography-tandem mass spectrometry. Statistical analysis revealed a total number of 138 of which 52 metabolites were significantly modified in Remodelin treated cells. Among the most significantly altered metabolites, we identified metabolites related with mitochondrial fatty acid elongation (MFAE) and mitochondrial beta-oxidation such as lauroyl-CoA, cholesterol, triglycerides, (S)-3-hydroxyhexadecanoyl-CoA, and NAD⁺ . Furthermore, assessment showed alteration in expression of Enoyl-CoA hydratase, short chain 1, mitochondrial (ECHS1), and Mitochondrial trans-2-enoyl-CoA reductase (MECR) genes, associated with MFAE pathway. We also found statistically significant decrease in total cholesterol and triglycerides in Remodelin treated cancer cells. Overall, our results showed that Remodelin alters mitochondrial fatty acid metabolism and lipid accumulation in cancer cells. Finally, we validated these results in NAT10 knockdown cancer cells and found that NAT10 reduction results in alteration in gene expression associated with mitochondrial fatty acid metabolism, clearly suggesting the possible role of NAT10 in maintaining mitochondrial fatty acid metabolism.

PMID:34605570 | DOI:10.1002/jcb.30155