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Nevin Manimala Statistics

Assessing the aquatic toxicity and environmental safety of tracer compounds Rhodamine B and Rhodamine WT

Water Res. 2021 Apr 5;197:117109. doi: 10.1016/j.watres.2021.117109. Online ahead of print.

ABSTRACT

Tracer tests represent a well-established method for delineating key environmental processes in various media and engineered systems. Tracers like Rhodamine B and WT are frequently applied due to their strong fluorescence even at low concentrations.. However, due to a lack of ecotoxicological data, limit values for these tracers cannot be determined. This study fills this critical data gap by providing ecotoxicity data for Rhodamine B and WT using a battery of short-term standardized tests, including growth rate inhibition tests with algae (Raphidocelis subcapitata) and lethality tests using crustaceans (Daphnia magna) and zebrafish (Danio rerio) embryos, and estimating EQS for surface water. For Rhodamine B, the effective and lethal concentration (EC50 and LC50) -causing 50% toxicity were in the range of 14-24 mg/L. For Rhodamine WT, no statistically significant effects were observed (p<0.05) at the tsted concentrations (up to 91, 100 and 200 mg/L for algae, crustaceans and fish embryos, respectively). Thus for all tested organisms, Rhodamine B was more toxic than Rhodamine WT (more than 14 times more toxic for R. subcapitata, 5.6 times for D. magna, 15 times for D. rerio embryos,based on EC10 and LC10 values). These results signify that read-across assessments using ecotoxicity data obtained with Rhodamine B is not advisable for estimating the ecotoxicity of Rhodamine WT. The annual-average quality standard (AA-QS) and maximum allowable concentration quality standard (MAC-QS) for Rhodamine B were found to be 14 and 140 µg/L, respectively. For Rhodamine WT, the corresponding values were estimated to >91 µg/L (AA-QS) and >910 µg/L (MAC-QS). Hence, concentrations below 140 µg/L or 910 µg/L for Rhodamine B and WT, respectively, are not expected to pose a risk to aquatic freshwater life in the case of intermittent discharges, e.g. tracer experiments released in streams.

PMID:33857893 | DOI:10.1016/j.watres.2021.117109

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Nevin Manimala Statistics

Characteristics Associated With Functional Changes During Systemic Cancer Treatments: A Systematic Review Focused on Older Adults

J Natl Compr Canc Netw. 2021 Apr 15:1-8. doi: 10.6004/jnccn.2020.7684. Online ahead of print.

ABSTRACT

BACKGROUND: Maintaining functional status is important to older adults with cancer, but data are limited on how systemic treatments affect functional status. We systematically reviewed changes in functional status during systemic cancer treatments and identified characteristics associated with functional decline and improvement.

METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Register of Controlled Trials for articles examining characteristics associated with functional changes in older adults during systemic cancer treatment published in English between database inception and January 11, 2019 (PROSPERO CRD42019123125). Findings were summarized with descriptive statistics. Study characteristics between older adult-specific and non-older adult-specific studies were compared using the Fisher exact test.

RESULTS: We screened 15,244 titles/abstracts and 519 full texts. The final analysis included 44 studies, which enrolled >8,400 patients; 39% of studies focused on older adults (1 study enrolled adults aged ≥60 years, 10 enrolled adults aged ≥65 years, and 6 enrolled adults aged ≥70 years). Almost all studies (98%) used patient-reported outcomes to measure functional status; only 20% used physical performance tests. Reporting of functional change was heterogeneous, with 48% reporting change scores. Older adult-specific studies were more likely to analyze functional change dichotomously (29% vs 4%; P=.008). Functional decline ranged widely, from 6% to 90%. The most common patient characteristics associated with functional decline were older age (n=7 studies), worse performance status (n=4), progressive disease status (n=4), pain (n=4), anemia (n=4), and worse nutritional status (n=4). Twelve studies examined functional improvement and identified 11 unique associated characteristics.

CONCLUSIONS: Functional decline is increasingly recognized as an important outcome in older adults with cancer, but definitions and analyses are heterogeneous, leading to a wide range of prevalence. To identify patients at highest risk of functional decline during systemic cancer treatments, trials need to routinely analyze functional outcomes and measure characteristics associated with decline (eg, nutrition).

PMID:33857918 | DOI:10.6004/jnccn.2020.7684

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Bioactivity-guided discovery of quality control markers in rhizomes of Curcuma wenyujin based on spectrum-effect relationship against human lung cancer cells

Phytomedicine. 2021 Mar 27;86:153559. doi: 10.1016/j.phymed.2021.153559. Online ahead of print.

ABSTRACT

BACKGROUND: Due to the diversity of the ingredients, the complexity of the mechanism of action, the uncertainty of the effective ingredients, coupled with the multiple species and multiple growing areas, the quality control (QC) of Traditional Chinese Medicines (TCMs) is challenging. Discovering and identifying effective compounds from the complex extracts of TCMs and then establishing a scientific QC method is the key to the holistic QC of TCMs.

PURPOSE: To develop an anti-lung-cancer-guided spectrum-effect relationship approach for the discovery of QC markers of the rhizome of Curcuma wenyujin (WEZ) and establish a bioactive compounds-based holistic QC method.

METHODS: The chemical profiling of the volatile oil (WVO) from 42 batches of WEZ collected from different growing areas was performed by GC-MS. The anti-lung cancer activity of different WVO samples was determined by CCK-8 assay against human lung cancer cells (A549). The apoptosis and cell cycle analysis under different concentrations of WVO were detected by flow cytometry. SIMCA-P software was used to perform multivariate statistical analysis on the chemical composition of different WVO samples and to find the different components. Active compounds were screened using a PLSR model of the spectrum-effect relationship. Bioactive compounds-based fingerprint and quantification of the leading bioactive compounds were developed by GC-MS and GC-FID, respectively.

RESULTS: Seventy-eight compounds were detected in WVO and 54 were successfully identified. The multivariate statistical analysis uncovered that WVO components and the anti-A549 activity of WVO at the concentration of 60 nl/ml differ greatly according to the origin of the plant. The WVO at the concentration of 60 nl/ml (IC50) increased A549 cells apoptosis significantly with late and early apoptosis of 15.61% and 7.80%, and the number of cells in the G2/M phase were also increased significantly under this concentration. The spectrum-effect relationship analysis revealed that 44 compounds were positively correlated with their activities, and the result was verified by A549 cell viability assay. Sixteen positively correlated compounds were further selected as QC markers according to their relative amount > 0.5% and anticancer activity. Finally, the 16 QC markers-based GC-MS fingerprint was established to holistically control the quality of WEZ, and a GC-FID method was developed for the quantification of leading bioactive compounds, β-elemene and β-caryophyllene.

CONCLUSION: Based on an anti-lung-cancer-guided spectrum-effect relationship approach, the bioactive compounds-based holistic QC method was successfully developed for WEZ, which could provide a valuable reference for the QC of TCMs.

PMID:33857848 | DOI:10.1016/j.phymed.2021.153559

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Diagnostic significance of stromal changes in biopsies of prostate adenocarcinoma

Pathol Res Pract. 2021 Apr 8;222:153436. doi: 10.1016/j.prp.2021.153436. Online ahead of print.

ABSTRACT

The diagnostic value of stromal changes in carcinomas, including prostate, is under debate; in terms of limited sample tissue of biopsy, in addition to glandular alterations, the stromal changes could have additional diagnostic value, but the results in clinical settings are controversial. The research aims to evaluate the potential of stromal changes as a supplementary tool to predict the presence of higher grade carcinomas in the prostate using Masson’s trichrome and Fanconi anemia complementation group M (FANCM) antibody stainings. 385 biopsies and corresponding radical prostatectomy specimens were analyzed to evaluate the rates of the diversity of ISUP grades. Of 128 upgraded prostatectomy cases, 82 were diagnosed with ISUP Gleason Grade 1 (GG1) in a biopsy. All 82 cancerous samples were stained with Masson’s trichrome and FACNM antibody and compared with 82 samples without cancer to see if there was a difference in stromal composition. Additionally, 50 GG1 samples without the upgrade were stained to demonstrate if stromal changes can predict less differentiated carcinomas in the prostate. In FANCM stained samples, the average percentage of positively staining stroma over the total in non-upgraded GG1 biopsies was 36 % (13-59 %, SD = 11); 34 % (9-58, SD = 13) in samples from the upgraded cancerous group, and 44 % (22-69, SD = 11) in samples without cancer. In Masson’s trichrome stained samples, with collagen quantified, the percentage in non-upgraded GG1 biopsies was 41 % (20-78 %, SD = 11); 44 % (23-89, SD = 15) in samples from upgraded cancerous group and 37 % (15-57, SD = 9) in samples without cancer. In both FANCM and Masson’s trichrome, no statistical significance was found between upgraded and non-upgraded groups (p = 0.84 and p = 0.5, respectively), although some upgrades from GG1 to GG4 showed extreme values. The statistical significance was found in cancerous vs. benign samples with both FANCM (p < 0.01) and Masson’s trichrome (p = 0.012). The main limiting factor is a significant overlap in staining intensity between cancerous and cancer-free groups.

PMID:33857855 | DOI:10.1016/j.prp.2021.153436

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Nevin Manimala Statistics

Actin cytoskeletal structure and the statistical variations of the mechanical properties of non-tumorigenic breast and triple-negative breast cancer cells

J Mech Behav Biomed Mater. 2021 Apr 9;119:104505. doi: 10.1016/j.jmbbm.2021.104505. Online ahead of print.

ABSTRACT

This paper presents the results of a study of the actin cytoskeletal structures and the statistical variations in the actin fluorescence intensities and viscoelastic properties of non-tumorigenic breast cells and triple-negative breast cancer cells at different stages of tumor progression. The variation in the actin content of the cell cytoskeletal structures is shown to be consistent with the viscoelastic properties of the cell as it progresses from non-tumorigenic to more metastatic states. The corresponding viscoelastic properties of the nuclei and the cytoplasm (Young’s moduli, viscosities, and relaxation times) of the cells are also measured using Digital Image Correlation (DIC) and shear assay techniques. These properties are shown to exhibit statistical variations that are well characterized by normal distributions. The changes in the mean properties of individual cancer cells are tested using Fisher pairwise comparisons and the analysis of variance (ANOVA). The implications of the results are then discussed for the development of shear assay techniques and mechanical biomarkers for the detection of triple-negative breast cancer at different stages of tumor progression.

PMID:33857875 | DOI:10.1016/j.jmbbm.2021.104505

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Nevin Manimala Statistics

Histogram analysis of quantitative parameters from synthetic MRI: Correlations with prognostic factors and molecular subtypes in invasive ductal breast cancer

Eur J Radiol. 2021 Apr 8;139:109697. doi: 10.1016/j.ejrad.2021.109697. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate intra-tumoral heterogeneity through a histogram analysis of quantitative parameters obtained from synthetic MRI (magnetic resonance imaging), and determine correlations of these histogram characteristics with prognostic factors and molecular subtypes of invasive ductal carcinoma (IDC).

METHODS: A total of 122 IDC from 122 women who underwent preoperative synthetic MRI and DCE (dynamic contrast enhancement)-MRI were investigated. The synthetic MRI parameters (T1, T2, and PD (proton density)) were obtained. For each parameter, the minimum, 10th percentile, mean, median, 90th percentile, maximum, skewness, and kurtosis values of tumor were calculated, and correlations with prognostic factors and subtypes were assessed. The Mann-Whitney U test or the Students t test were utilized to analyze the association between the histogram features of synthetic MRI parameters and prognostic factors. The Kruskal-Wallis test followed by the post-hoc test was used to analyze differences of synthetic MRI parameters among molecular subtypes.

RESULTS: IDC with high histopathologic grade showed statistically higher PDmaxium, T1mean and T1median values than those with low grade (p = 0.003, p = 0.007, p = 0.003). The T110th were significantly higher in cancers with PR (progesterone receptor) negativity than those with PR positivity (p = 0.005). ER-negative cancers had significant higher values of T210th, T2mean, and T2median than ER-positive cancers (p = 0.006, 0.002, and 0.006, respectively). The values of PDmedian were significantly higher in IDC with HER2 (human epidermal growth factor receptor 2) positivity than those with HER2 negativity (p = 0.001). When discriminating molecular subtypes of IDC, the T2mean achieved the highest performance. The T2mean values of TN (triple-negative), luminal B and luminal A types are arranged in descending order (p < 0.0001).

CONCLUSIONS: Histogram features derived from synthetic MRI quantifies the distributions of tissue relaxation time and proton density, and may serve as a potential biomarker for discriminating histopathological grade, hormone receptor status, HER2 expression status and breast cancer subtypes.

PMID:33857828 | DOI:10.1016/j.ejrad.2021.109697

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3D dissimilar-siamese-u-net for hyperdense Middle cerebral artery sign segmentation

Comput Med Imaging Graph. 2021 Mar 14;90:101898. doi: 10.1016/j.compmedimag.2021.101898. Online ahead of print.

ABSTRACT

The hyperdense middle cerebral artery sign (HMCAS) representing a thromboembolus has been declared as a vital CT finding for intravascular thrombus in the diagnosis of acute ischemia stroke. Early recognition of HMCAS can assist in patient triage and subsequent thrombolysis or thrombectomy treatment. A total of 624 annotated head non-contrast-enhanced CT (NCCT) image scans were retrospectively collected from multiple public hospitals in Hong Kong. In this study, we present a deep Dissimilar-Siamese-U-Net (DSU-Net) that is able to precisely segment the lesions by integrating Siamese and U-Net architectures. The proposed framework consists of twin sub-networks that allow inputs of left and right hemispheres in head NCCT images separately. The proposed Dissimilar block fully explores the feature representation of the differences between the bilateral hemispheres. Ablation studies were carried out to validate the performance of various components of the proposed DSU-Net. Our findings reveal that the proposed DSU-Net provides a novel approach for HMCAS automatic segmentation and it outperforms the baseline U-Net and many state-of-the-art models for clinical practice.

PMID:33857830 | DOI:10.1016/j.compmedimag.2021.101898

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Cognitive training with fully immersive virtual reality in patients with neurological and psychiatric disorders: A systematic review of randomized controlled trials

Psychiatry Res. 2021 Apr 6;300:113928. doi: 10.1016/j.psychres.2021.113928. Online ahead of print.

ABSTRACT

Cognitive impairment occurs across several neuropsychiatric diseases and impede everyday functioning and quality of life. Fully immersive Virtual Reality (VR) aid motivation and engagement and therefore has a potential to help overcome the obstacles in the field of cognitive rehabilitation. The aim of this systematic review is to investigate whether VR can be a useful intervention in cognitive rehabilitation transdiagnostically. We identified nine studies with randomized controlled trials following the PRISMA guidelines in databases Pubmed, Embase and PsychInfo. The trials were all evaluated through Cochrane Collaboration’s Risk of Bias. The studies were conducted in patients with mild cognitive impairment (k=4), schizophrenia (k=3), ADHD (k=1), or stroke (k=1) and involved 6-12 weeks of training. Overall, results showed improvement in some domains of cognition, primarily executive function and attention. The studies were pilot studies with 6-34 participants per treatment group. Risk of bias was either high (k=3) or moderate (some concerns) (k=6). Key reasons were suboptimal statistical analyses and lack of clarification on randomization and blinding of participants and assessors. In conclusion, this review found promising evidence for VR cognitive rehabilitation for neuropsychiatric illnesses. However, larger and methodologically stronger studies are warranted to establish the full potential of VR.

PMID:33857847 | DOI:10.1016/j.psychres.2021.113928

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Effect of a Virtual Reality-Enhanced Exercise and Education Intervention on Patient Engagement and Learning in Cardiac Rehabilitation: Randomized Controlled Trial

J Med Internet Res. 2021 Apr 15;23(4):e23882. doi: 10.2196/23882.

ABSTRACT

BACKGROUND: Cardiac rehabilitation (CR) is clinically proven to reduce morbidity and mortality; however, many eligible patients do not enroll in treatment. Furthermore, many enrolled patients do not complete their full course of treatment. This is greatly influenced by socioeconomic factors but is also because of patients’ lack of understanding of the importance of their care and a lack of motivation to maintain attendance.

OBJECTIVE: This study aims to explore the potential benefits of virtual reality (VR) walking trails within CR treatment, specifically with regard to patient knowledge retention, satisfaction with treatment, and the overall attendance of treatment sessions.

METHODS: New CR patients were enrolled and randomized on a rolling basis to either the control group or intervention group. Intervention patients completed their time on the treadmill with VR walking trails, which included audio-recorded education, whereas control patients completed the standard of care therapy. Both groups were assisted by nursing staff for all treatment sessions. Primary outcomes were determined by assessing 6-minute walk test improvement. In addition, secondary outcomes of patients’ cardiac knowledge and satisfaction were assessed via a computer-based questionnaire; patient adherence to the recommended number of sessions was also monitored. Cardiac knowledge assessment included a prerehabilitation education quiz, and the same quiz was repeated at patients’ final visit and again at the 2-month follow-up. The satisfaction questionnaire was completed at the final visit.

RESULTS: Between January 2018 and May 2019, 72 patients were enrolled-41 in the intervention group and 31 in the control group. On the basis of the results of the prerehabilitation and postrehabilitation 6-minute walk test, no significant differences were observed between the intervention and control groups (P=.64). No statistical differences were observed between groups in terms of education (P=.86) or satisfaction (P=.32) at any time point. The control group had statistically more favorable rates of attendance, as determined by the risk group comparison (P=.02) and the comparison of the rates for completing the minimum number of sessions (P=.046), but no correlation was observed between the study group and reasons for ending treatment.

CONCLUSIONS: Although no improvements were seen in the VR intervention group over the control group, it is worth noting that limitations in the study design may have influenced these outcomes, not the medium itself. Furthermore, the qualitative information suggests that patients may have indeed enjoyed their experience with VR, even though quantitative satisfaction data did not capture this. Further considerations for how and when VR should be applied to CR are suggested in this paper.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03945201; https://clinicaltrials.gov/ct2/show/NCT03945201.

PMID:33856355 | DOI:10.2196/23882

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Sutured Versus Mesh-Augmented Hiatus Hernia Repair: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Ann Surg. 2021 Apr 7. doi: 10.1097/SLA.0000000000004902. Online ahead of print.

ABSTRACT

OBJECTIVE: This meta-analysis systematically reviewed published randomized control trials (RCTs) comparing sutured versus mesh-augmented hiatus hernia (HH) repair. Our primary endpoint was HH recurrence at short- and long-term follow-up. Secondary endpoints were: surgical complications, operative times, dysphagia and quality of life.

SUMMARY BACKGROUND DATA: Repair of large hiatus hernias is increasingly being performed. However, there is no consensus for the optimal technique for hiatal closure between sutured versus mesh-augmented (absorbable or non-absorbable) repair.

METHODS: A systematic review of Medline, Scopus (which encompassed Embase), Cochrane Central Register of Controlled Trials, Web of Science and PubMed was performed to identify relevant studies comparing mesh-augmented versus sutured HH repair. Data were extracted and compared by meta-analysis, using odds ratio and mean differences with 95% confidence intervals.

RESULTS: Seven RCTs were found which compared mesh-augmented (non-absorbable mesh: n = 296; absorbable mesh: n = 92) with sutured repair (n = 347). There were no significant differences for short-term hernia recurrence (defined as 6-12 months, 10.1% mesh versus 15.5% sutured, P = 0.22), long-term hernia recurrence (defined as 3-5 years, 30.7% mesh vs 31.3% sutured, P = 0.69), functional outcomes and patient satisfaction. The only statistically significant difference was that the mesh repair required a longer operation time (P = 0.05, OR 2.33, 95% CI 0.03-24.69).

CONCLUSIONS: Mesh repair for hiatus hernia does not offer any advantage over sutured hiatal closure. As both techniques deliver good and comparable clinical outcomes, a suture only technique is still an appropriate approach.

PMID:33856379 | DOI:10.1097/SLA.0000000000004902