Nevin Manimala

Head Neck. 2022 Apr 20. doi: 10.1002/hed.27062. Online ahead of print.

ABSTRACT

Recurrent salivary gland carcinomas (RSCs) are poorly characterized and their clinical features and treatment options have not yet been fully described. The goal of this study was to analyze the therapeutic strategies and oncological outcomes of RSC patients through a literature review analysis. This systematic review was performed according to the PRISMA statements. Inclusion criteria for the systematic review were based on the population, intervention, comparison, and outcomes according to (PICO) framework. Two thousand seven hundred and four records were selected and 1817 recurrences were studied. Three hundred and sixty-five patients underwent salvage surgery (20.1%) and their 5-year mortality rate, overall survival and disease-free survival were 35%, 70%, and 42%, respectively. RSCs are aggressive neoplasms with a high rate of distant metastases (28.9%). Salvage surgery can be considered in patients with limited local and/or regional recurrences, even in case of single distant relapse, appearing within the first 3 years of follow-up.

PMID:35441406 | DOI:10.1002/hed.27062

J Bone Miner Res. 2022 Apr 20. doi: 10.1002/jbmr.4548. Online ahead of print.

ABSTRACT

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to have weak but beneficial effects on bone health, including fracture risk, but many epidemiological studies are likely confounded. We explored the relationship between NSAIDs and fracture risk in a post hoc analysis of a well-documented, randomized, placebo-controlled study of the bisphosphonate, clodronate, in which treatment reduced osteoporotic fracture risk by 23%. Concurrent medication use at baseline was used to identify those prescribed oral NSAIDs. Only verified, incident fractures were included in the analysis. A total of 1082 (20.8%) women reported use of NSAIDs at baseline. They were slightly, but significantly, younger (mean 79 versus 80 years, p = 0.004), heavier (mean 66.7 versus 64.7 kg, p < 0.001) than nonusers, with slightly higher femoral neck bone mineral density (FN-BMD, 0.66 versus 0.64 g/cm² , p < 0.001). In an adjusted model, NSAID use was associated with a significant increase in osteoporotic fracture risk over the 3-year study period (hazard ratio [HR] 1.27; 95% confidence interval [CI], 1.01-1.62; p = 0.039). However, this increase in risk was not statistically significant in the placebo group (HR 1.11; 95% CI, 0.81-1.52). In women receiving clodronate, the effect of the bisphosphonate to reduce osteoporotic fracture risk was not observed in those receiving NSAIDs (HR 0.95; 95% CI, 0.65-1.41; p = 0.81) in contrast to those not using NSAIDs (HR 0.71; 95% CI, 0.58-0.89; p = 0.002). In a subset with hip BMD repeated at 3 years, BMD loss during clodronate therapy was greater in those women receiving NSAIDs than in nonusers (eg, total hip -2.75% versus -1.27%, p = 0.078; femoral neck -3.06% versus -1.12%, p = 0.028), and was not significantly different from that observed in women receiving placebo. The efficacy of the bisphosphonate, clodronate, to reduce fracture risk was largely negated in those receiving NSAIDs. Although the mechanism is unclear, this clinically significant observation requires exploration in studies of commonly used bisphosphonates. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

PMID:35441396 | DOI:10.1002/jbmr.4548

Proteins. 2022 Apr 20. doi: 10.1002/prot.26349. Online ahead of print.

ABSTRACT

Protein structural classification (PSC) is a supervised problem of assigning proteins into pre-defined structural (e.g., CATH or SCOPe) classes based on the proteins’ sequence or 3D structural features. We recently proposed PSC approaches that model protein 3D structures as protein structure networks (PSNs) and analyze PSN-based protein features, which performed better than or comparable to state-of-the-art sequence or other 3D structure-based PSC approaches. However, existing PSN-based PSC approaches model the whole 3D structure of a protein as a static (i.e., single-layer) PSN. Because folding of a protein is a dynamic process, where some parts (i.e., sub-structures) of a protein fold before others, modeling the 3D structure of a protein as a PSN that captures the sub-structures might further help improve the existing PSC performance. Here, we propose to model 3D structures of proteins as multi-layer sequential PSNs that approximate 3D sub-structures of proteins, with the hypothesis that this will improve upon the current state-of-the-art PSC approaches that are based on single-layer PSNs (and thus upon the existing state-of-the-art sequence and other 3D structural approaches). Indeed, we confirm this on 72 datasets spanning ∼44,000 CATH and SCOPe protein domains.

PMID:35441395 | DOI:10.1002/prot.26349

J Clin Lab Anal. 2022 Apr 20:e24442. doi: 10.1002/jcla.24442. Online ahead of print.

ABSTRACT

BACKGROUND: Renal cell carcinoma is difficult to diagnose and unpredictable in disease course and severity. There are no specific biomarkers for diagnosis and prognosis estimation feasible in clinical practice. Long non-coding RNAs (lncRNAs) have emerged as potent regulators of gene expression in recent years. Aside from their cellular role, their expression patterns could be used as a biomarker of ongoing pathology.

METHODS: In this work, we used next-generation sequencing for global lncRNA expression profiling in tumor and non-tumor tissue of RCC patients. The four candidate lncRNAs have been further validated on an independent cohort. PVT1, as the most promising lncRNA, has also been studied using functional in vitro tests.

RESULTS: Next-generation sequencing showed significant dysregulation of 1163 lncRNAs; among them top 20 dysregulated lncRNAs were AC061975.7, AC124017.1, AP000696.1, AC148477.4, LINC02437, GATA3-AS, LINC01762, LINC01230, LINC01271, LINC01187, LINC00472, AC007849.1, LINC00982, LINC01543, AL031710.1, and AC019197.1 as down-regulated lncRNAs; and SLC16A1-AS1, PVT1, LINC0887, and LUCAT1 as up-regulated lncRNAs. We observed statistically significant dysregulation of PVT1, LUCAT1, and LINC00982. Moreover, we studied the effect of artificial PVT1 decrease in renal cell line 786-0 and observed an effect on cell viability and migration.

CONCLUSION: Our results show not only the diagnostic but also the therapeutic potential of PVT1 in renal cell carcinoma.

PMID:35441392 | DOI:10.1002/jcla.24442

Aust Occup Ther J. 2022 Apr 19. doi: 10.1111/1440-1630.12803. Online ahead of print.

ABSTRACT

INTRODUCTION: Current research evidence suggests that people with schizophrenia have sensory processing difficulties. Sensory modulation has growing evidence for use in this population. This study aimed to evaluate the extent to which health, social, cognitive, and occupational functioning outcomes were impacted by sensory modulation interventions for people with schizophrenia.

METHODS: A prospective observational cohort study using a waitlist control design was used in two large hospital and health services in Queensland, Australia. The study recruited patients who used sensory modulation (n = 30) across the two hospitals and those who did not use sensory modulation interventions as a control (n = 11). Results were analysed using a series of planned comparisons including independent and paired t-tests, and mixed ANOVA was used whenever statistically indicated. The analysed measures were pre- and post-intervention scores.

RESULTS: This study found no statically significant differences between the control and intervention groups at both pre- and post-intervention. However, analysis of results from within the intervention group showed statistically significant improvements between pre- and post-test scores on distress, occupational functioning, and health and social functioning but not on sensory processing and global cognitive processing. Further analysis of results from this study, compared with those from an earlier study on the general population showed significant differences in Low Registration and Sensation Avoiding, as measured by the Adult/Adolescent Sensory Profile, between participants with schizophrenia and those without schizophrenia.

CONCLUSION: This study provides evidence to suggest that sensory modulation interventions can be complementary to standard care when utilised appropriately in clinical settings. Findings also suggest that the sensory profile of people with schizophrenia is different to that of the general population and this may have clinical implications. Further longitudinal research is needed with larger and randomised samples, using more targeted measures to better explore effectiveness of sensory modulation interventions.

PMID:35441391 | DOI:10.1111/1440-1630.12803

Stat Med. 2022 Apr 19. doi: 10.1002/sim.9369. Online ahead of print.

ABSTRACT

Cluster/group randomized controlled trials (CRTs) have a long history in the study of health sciences. CRT is a special type of intervention trial in which a complete group is randomly assigned to a study condition (or intervention). It is typically performed when individual randomization is difficult/impossible without substantial risk of contamination across study arms or prohibitive from the cost or group dynamics point of view. In this article, the aim is to design and analyze four-level longitudinal cluster randomized trials. The main interest here is to study the difference between treatment groups over time for such a four-level hierarchical data structure. This work is motivated by a real-life study for education based HIV prevention. Such trials are not only popular for administrative convenience, ethical considerations, subject compliance, but also help to reduce contamination bias. A random intercept mixed effects linear regression including a time by intervention interaction is used for modeling. Closed form expression of the power function to detect the interaction effect is determined. Sample size equations depend on correlation among schools but not on correlations among classes or students while, the power function depends on the product of number of units at different levels. Optimal allocation of units under a fixed cost by minimizing the expected standardized variance is also determined and are shown to be independent of correlations among units in any level. Results of detailed simulation studies find the theoretical power estimates based on the derived formulae close to the empirical estimates.

PMID:35441378 | DOI:10.1002/sim.9369

Behav Res Methods. 2022 Apr 19. doi: 10.3758/s13428-022-01845-0. Online ahead of print.

ABSTRACT

Research demonstrates that IATs are fakeable. Several indices [either slowing down or speeding up, and increasing errors or reducing errors in congruent and incongruent blocks; Combined Task Slowing (CTS); Ratio 150-10000] have been developed to detect faking. Findings on these are inconclusive, but previous studies have used small samples, suggesting they were statistically underpowered. Further, the stability of the results, the unique predictivity of the indices, the advantage of combining indices, and the dependency on how faking success is computed have yet to be examined. Therefore, we reanalyzed a large data set (N = 750) of fakers and non-fakers who completed an extraversion IAT. Results showed that faking strategies depend on the direction of faking. It was possible to detect faking of low scores due to slowing down on the congruent block, and somewhat less with CTS-both strategies led to faking success. In contrast, the strategy of increasing errors on the congruent block was observed but was not successful in altering the IAT effect in the desired direction. Fakers of high scores could be detected due to slowing down on the incongruent block, increasing errors on the incongruent block, and with CTS-all three strategies led to faking success. The results proved stable in subsamples and generally across different computations of faking success. Using regression analyses and machine learning, increasing errors had the strongest impact on the classification. Apparently, fakers use various goal-dependent strategies and not all are successful. To detect faking, we recommend combining indices depending on the context (and examining convergence).

PMID:35441359 | DOI:10.3758/s13428-022-01845-0

Clin Transl Oncol. 2022 Apr 19. doi: 10.1007/s12094-022-02808-9. Online ahead of print.

ABSTRACT

OBJECTIVE: There is a gap in knowledge regarding the ideal management of patients with early-stage cervical cancer and intermediate-risk features. Here, we present a meta-analysis of the published literature on oncological outcomes in these patients and determine trends in postoperative management.

METHODS: MEDLINE and PubMed were used for literature searches. The inclusion criteria were: English language articles including ≥ 10 patients, patients who underwent radical hysterectomy, nodes negative, studies reporting oncological outcomes and complications treatment-related and compare a surgery-only cohort with a radiotherapy cohort. The PRISMA guidelines were followed. Combined relative risk was calculated using DerSimonian-Laird random-effects model and a forest plot was drawn.

RESULTS: We collected 183 manuscripts on early-stage cervical cancer treated with radical hysterectomy alone or with adjuvant radiotherapy after surgery. A total of eight studies met the inclusion criteria. Regarding oncological outcomes, survival was reported in five studies. The relative risk of recurrence and the relative risk of mortality was similar in both groups independently whether receive or not adjuvant therapy. Most of the studies did not report significant differences regarding morbidity treatment related between the groups, except for a higher rate of lymphedema after radiotherapy.

CONCLUSION: We found that the relative risk of recurrence and mortality was similar in both groups not depending on adjuvant therapy. Therefore, whether radiotherapy adjuvant treatment is indicated remains a topic of debate.

PMID:35441353 | DOI:10.1007/s12094-022-02808-9

AAPS PharmSciTech. 2022 Apr 19;23(5):116. doi: 10.1208/s12249-022-02269-x.

ABSTRACT

Topical drug delivery systems are interesting and popular dosage forms for formulation development. Thai herbs are used in alternative medicine to treat patients suffering from severe illnesses. They have significant economic and cultural value in Thailand. This work prepared Thai herbal topical patches of Lysiphyllum strychnifolium stem extracts using pectin and Eudragit^® NM 30D, and glycerin as a plasticizer. Astilbin was selected as a chemical marker in L. strychnifolium stem extracts. The L. strychnifolium stem extracts showed a statistically significant decrease in nitrate accumulation. The various properties of Thai herbal topical patches were not significantly different from blank patches. However, the trends of the properties depended on the amount of Eudragit^® NM 30D. All ingredients were homogeneously mixed in Thai herbal topical patches and showed a smooth and compact film. The astilbin content was found in a range of 52.72-63.36 μg/cm². The in vitro release of astilbin depended on the amount of Eudragit^® NM 30D. The kinetics of astilbin release were fitted to the Korsmeyer-Peppas model. The astilbin showed low permeation; thus, polyethylene glycol 400 was used as a permeation enhancer. Polyethylene glycol 400 could increase the permeation rates of astilbin and the cumulative amount of astilbin in pig skin. This would be suitable for preparing the Thai herbal topical patches and could be developed for pharmaceutical and herbal products.

PMID:35441285 | DOI:10.1208/s12249-022-02269-x

Res Synth Methods. 2022 Apr 19. doi: 10.1002/jrsm.1561. Online ahead of print.

ABSTRACT

The meta-analytic-predictive (MAP) approach is a Bayesian meta-analytic method to synthesize and incorporate information from historical controls in the analysis of a new trial. Classically, only a single parameter, typically the intercept or rate, is assumed to vary across studies, which may not be realistic in more complex models. Analysis of covariance (ANCOVA) is often used to analyze trials with a pretest-posttest design, where both the intercept and the baseline effect (coefficient of the outcome at baseline) affect the estimated treatment effect. We extended the MAP approach to ANCOVA, to allow for variation in the intercept and the baseline effect across studies, and possibly also correlation between these parameters. The method was illustrated using data from the Alzheimer’s Disease Cooperative Study (ADCS) and assessed with a simulation study. In the ADCS data, the proposed multivariate MAP approach yielded a prior effective sample size of 79 and 58 for the intercept and the baseline effect respectively and reduced the posterior standard deviation of the treatment effect by 12.6%. The result was robust to the choice of prior for the between-study variation. In the simulations, the proposed approach yielded power gains with a good control of the type I error rate. Ignoring the between-study correlation of the parameters or assuming no variation in the baseline effect generally led to less power gain. In conclusion, the MAP approach can be extended to a multivariate version for ANCOVA, which may improve the estimation of the treatment effect. This article is protected by copyright. All rights reserved.

PMID:35439840 | DOI:10.1002/jrsm.1561