Nevin Manimala

Eur J Cancer. 2021 Sep 8;157:124-131. doi: 10.1016/j.ejca.2021.08.007. Online ahead of print.

ABSTRACT

AIM: Patients with cancer are at an increased risk for severe coronavirus disease of 2019, thus data on the safety and efficacy of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines are essential. We conducted this prospective study of patients with cancer vaccinated with BNT162b2 and monitored for antibody response and safety. The aim was to evaluate the rate of seropositivity and define predictors for non-reactive immune response. Furthermore, we evaluated the frequency and the severity of adverse events.

METHODS: The study included patients with solid tumours undergoing anticancer treatment and immunocompetent health-care workers serving as controls. Serum titres of the receptor-binding domain (RBD) immunoglobulin G (IgG) and neutralising antibodies were measured 2-4 weeks after each vaccine dose.

RESULTS: The analysis included 129 patients, of which 70.5% patients were metastatic. Patients were treated with chemotherapy (55%), immunotherapy (34.1%), biological agents (24.8%), hormonal treatment (8.5%) and radiotherapy (4.6%), that were given either alone or in combinations. The seropositivity rate among patients with cancer and controls was 32.4% versus 59.8% (p < 0.0001) after the first dose and 84.1% versus 98.9% (p < 0.0001) after the second dose, respectively. Median RBD-IgG titre was lower among patients than controls (p < 0.0001). Patients who were seronegative after the second dose had significantly more comorbidities than that with patients with seropositivity (77.8% vs 41.1%, respectively, p = 0.0042).

CONCLUSION: Adequate antibody response after BNT162b2 vaccination was achieved after two doses but not after one dose, in patients with cancer vaccinated during anticancer therapy.

PMID:34508994 | DOI:10.1016/j.ejca.2021.08.007

Eur J Cancer. 2021 Sep 8;157:114-123. doi: 10.1016/j.ejca.2021.08.006. Online ahead of print.

ABSTRACT

AIM: CD73 overexpression has been reported in several malignancies and is considered to be a novel immune checkpoint. However, the role and significance of CD73 in gastric cancer (GC) still remain obscure. We aim to investigate the role of CD73 expression in predicting prognosis, shaping immune contexture and guiding therapeutic strategy in GC.

METHODS: The study enrolled four independent cohorts with a total of 902 patients with GC. CD73 expression and immune contexture were examined by immunohistochemistry, single-sample gene set enrichment analysis and flow cytometry. Clinical outcomes of patient subgroups were evaluated using the Kaplan-Meier curves and Cox proportional hazard analysis. All statistical tests were two-sided.

RESULTS: CD73 was identified as an independent adverse prognostic factor for survival in GC. CD73^high tumours showed a specific microenvironment with more CD8+ T cell infiltration, but these CD8+ T cells displayed a dysfunctional phenotype. Furthermore, the CD73 (NT5E) mRNA level was associated with the Cancer Genome Atlas molecular subtypes, and NT5E high tumours showed significant fibroblast growth factor receptor 2 activation and vascular endothelial growth factor and receptor enrichment. In addition, CD73^high tumours indicated better chemotherapeutic responsiveness to fluorouracil yet a worse objective response rate to pembrolizumab in GC.

CONCLUSIONS: High CD73 expression indicated an immunoevasive contexture with CD8+ T cell dysfunction and represented an independent predictor for adverse clinical outcomes. As a potential immunotherapeutic target, CD73 could potentially be a novel biomarker for adjuvant chemotherapy, targeted therapies and immunotherapy. The crucial role of CD73 in the therapeutic landscape of GC needs further validation retrospectively and prospectively.

PMID:34508993 | DOI:10.1016/j.ejca.2021.08.006

Sleep Med. 2021 Jul 31;87:8-19. doi: 10.1016/j.sleep.2021.07.017. Online ahead of print.

ABSTRACT

BACKGROUND: Recent studies have reported inconclusive results regarding the potential effects of Rosa damascena on sleep quality. Therefore, this review aimed to summarize the findings of parallel-group and cross-over randomized controlled trials (RCTs) on the effects of aromatherapy and oral intake of Rosa damascena on adults’ sleep quality.

METHODS: The electronic data sources of PubMed, Scopus, Web of Science Core Collection, Embase, CENTRAL, ProQuest, CINAHL, SID, and MagIran were searched from inception to June 30, 2021. Out of 1341 publications found in the initial search, 10 RCTs were considered eligible for this review. The Cochrane risk-of-bias assessment tool was used to evaluate the risk of bias. Sufficient data were statistically pooled by a random-effects model using Stata software (version 11.2); otherwise, a narrative summary was presented.

RESULTS: Based on the systematic review, the inhalation and oral intake of Rosa damascena could improve some sleep-related outcomes. The pooled analysis of seven effect sizes revealed that inhalation aromatherapy with Rosa damascena significantly improved sleep quality (standardized mean difference: 2.24; 95% confidence interval: 1.01-3.48; P < 0.001). Most RCTs had fair methodological quality, and two RCTs reported the adverse effects of treatment, including headache, nausea, vomiting, and frequent sneezing.

CONCLUSIONS: The administration of Rosa damascena seems to be a promising approach in complementary and alternative medicine for the improvement of adults’ sleep quality. However, considering the fair methodological quality of most RCTs and reported adverse effects, it is required to perform further high-quality RCTs to draw an evidence-based conclusion on the use of Rosa damascena for the improvement of adults’ sleep quality.

PROSPERO NO: CRD42020211778.

PMID:34508987 | DOI:10.1016/j.sleep.2021.07.017

Comput Biol Med. 2021 Sep 4;137:104829. doi: 10.1016/j.compbiomed.2021.104829. Online ahead of print.

ABSTRACT

Glioma is the most pernicious cancer of the nervous system, with histological grade influencing the survival of patients. Despite many studies on the multimodal treatment approach, survival time remains brief. In this study, a novel two-stage ensemble of an ensemble-type machine learning-based predictive framework for glioma detection and its histograde classification is proposed. In the proposed framework, five characteristics belonging to 135 subjects were considered: human telomerase reverse transcriptase (hTERT), chitinase-like protein (YKL-40), interleukin 6 (IL-6), tissue inhibitor of metalloproteinase-1 (TIMP-1) and neutrophil/lymphocyte ratio (NLR). These characteristics were examined using distinctive ensemble-based machine learning classifiers and combination strategies to develop a computer-aided diagnostic system for the non-invasive prediction of glioma cases and their grade. In the first stage, the analysis was conducted to classify glioma cases and control subjects. Machine learning approaches were applied in the second stage to classify the recognised glioma cases into three grades, from grade II, which has a good prognosis, to grade IV, which is also known as glioblastoma. All experiments were evaluated with a five-fold cross-validation method, and the classification results were analysed using different statistical parameters. The proposed approach obtained a high value of accuracy and other statistical parameters compared with other state-of-the-art machine learning classifiers. Therefore, the proposed framework can be utilised for designing other intervention strategies for the prediction of glioma cases and their grades.

PMID:34508971 | DOI:10.1016/j.compbiomed.2021.104829

Vision Res. 2021 Sep 8;189:11-26. doi: 10.1016/j.visres.2021.08.006. Online ahead of print.

ABSTRACT

The current study investigated how people summarize and represent objects with multiple features to cope with the complexity due to the number of objects and feature dimensions. We presented a set of circles whose color and size were either correlated perfectly (r = 1) or not correlated at all (r = 0). Using a membership identification task, we found that participants formed a statistical representation that included information about conjunctions as well as each color and size dimensions. In addition, we found that participants represented different set boundaries depending on the correlation between features of a set. Lastly, a pair-matching task revealed that participants predicted one feature value from the other feature value based on the correlation between features of a set. Our findings suggest that people represent a multi-feature ensemble statistically as a multivariate feature distribution, which is an efficient strategy to cope with scene complexity.

PMID:34508940 | DOI:10.1016/j.visres.2021.08.006

Autoimmun Rev. 2021 Sep 8:102941. doi: 10.1016/j.autrev.2021.102941. Online ahead of print.

ABSTRACT

Although vaccination represents the most promising way to stop or contain the coronavirus disease 2019 (COVID-19) pandemic and safety and effectiveness of available vaccines were proven, a small number of individuals who received anti-SARS-CoV-2 vaccines developed a prothrombotic syndrome. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can be triggered by the adenoviral vector-based vaccine, whereas lipid nanoparticle-mRNA-based vaccines can induce rare cases of deep vein thrombosis (DVT). Although the main pathogenic mechanisms behind this rare phenomenon have not yet been identified, both host and vaccine factors might be involved, with pathology at least in part being related to the vaccine-triggered autoimmune reaction. In this review, we are considering some aspects related to pathogenesis, major risk factors, as well as peculiarities of diagnosis and treatment of this rare condition.

PMID:34508917 | DOI:10.1016/j.autrev.2021.102941

J Natl Cancer Inst. 2021 Sep 11:djab177. doi: 10.1093/jnci/djab177. Online ahead of print.

ABSTRACT

Some concerns have been raised about potential bias in patient-reported outcome (PRO) results from open-label cancer randomized controlled trials (RCTs). We investigated if open-label trials favor the experimental treatment over the standard treatment more frequently than blinded trials. We also examined if the effect of treatment concealment differs for distal vs more proximal PROs. We assessed 538 RCTs with a PRO endpoint conducted in the most prevalent cancers, of which 366 (68.0%) were open-label, 148 (27.5%) were blinded, and 24 (4.5%) were categorized as unclear. In our multivariable logistic regression model, we did not observe a statistically significant association of the independent variable treatment concealment (open-label vs blinded) on the dependent variable measuring the proportion of trials favoring the experimental treatment (adjusted odds ratio = 1.19, 95% confidence interval = 0.79 to 1.79, 2-sided P = .40. This was also the case when comparing distal and proximal PROs. Our findings provide novel evidence-based data that support the validity of PRO results from open label cancer RCTs.

PMID:34508610 | DOI:10.1093/jnci/djab177

J Natl Cancer Inst. 2021 Sep 11:djab186. doi: 10.1093/jnci/djab186. Online ahead of print.

ABSTRACT

BACKGROUND: Incidence of estrogen receptor (ER)-negative breast cancer, an aggressive subtype, is highest in United States (US) African American women and in southern residents but has decreased overall since 1992. We assessed whether ER-negative breast cancer is decreasing in all age groups and cancer registries among non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic White (HW) women.

METHODS: We analyzed 17 Surveillance, Epidemiology, and End-Results Program registries (twelve for 1992-2016; five for 2000-2016) to assess NHW, NHB, and HW trends by ER status and age group (30-39, 40-49, 50-69, 70-84 years). We used hierarchical age-period-cohort models that account for sparse data, which improve estimates to quantify between-registry heterogeneity in mean incidence rates and age-adjusted trends versus SEER overall.

RESULTS: Overall, ER-negative incidence was highest in NHB, then NHW and HW women, and decreased from 1992-2016 in each age group and racial/ethnic group. The greatest decrease was for HW women ages 40-49 years with an annual percent change of -3.5%/year (95% credible interval = -4.4%, -2.7%), averaged over registries. The trend heterogeneity was statistically significant in every race/ethnic and age group. Furthermore, the incidence relative risks by race/ethnicity compared to the race-specific SEER average were also statistically significantly heterogeneous across the majority of registries and age groups (62 of 68 strata). The greatest heterogeneity was seen in HW women, followed by NHB women, and the least in NHW women.

CONCLUSION: Decreasing ER-negative breast cancer incidence differs meaningfully by US region and age among NHB and HW women. Analytical studies including minority women from higher and lower incidence areas may provide insights into breast cancer racial disparities.

PMID:34508608 | DOI:10.1093/jnci/djab186

Syst Biol. 2021 Sep 11:syab075. doi: 10.1093/sysbio/syab075. Online ahead of print.

ABSTRACT

The historical signal in nucleotide sequences becomes eroded over time by substitutions occurring repeatedly at the same sites. This phenomenon, known as substitution saturation, is recognized as one of the primary obstacles to deep-time phylogenetic inference using genome-scale data sets. We present a new test of substitution saturation and demonstrate its performance in simulated and empirical data. For some of the 36 empirical phylogenomic data sets that we examined, we detect substitution saturation in around 50% of loci. We found that saturation tends to be flagged as problematic in loci with highly discordant phylogenetic signals across sites. Within each data set, the loci with smaller numbers of informative sites are more likely to be flagged as containing problematic levels of saturation. The entropy saturation test proposed here is sensitive to high evolutionary rates relative to the evolutionary timeframe, while also being sensitive to several factors known to mislead phylogenetic inference, including short internal branches relative to external branches, short nucleotide sequences, and tree imbalance. Our study demonstrates that excluding loci with substitution saturation can be an effective means of mitigating the negative impact of multiple substitutions on phylogenetic inferences.

PMID:34508605 | DOI:10.1093/sysbio/syab075

J Natl Cancer Inst. 2021 Sep 11:djab171. doi: 10.1093/jnci/djab171. Online ahead of print.

ABSTRACT

BACKGROUND: Trials of immune checkpoint inhibitors (ICIs) have published patient-reported quality of life (QOL), but the size and heterogeneity of this literature can make patient education difficult. This meta-analysis aimed to describe change in QOL and symptomatology in patients receiving ICIs for cancer.

METHODS: Following PRISMA guidelines, databases were searched through November 2019 for articles or abstracts of prospective, original studies reporting longitudinal QOL in adult cancer patients treated with ICIs. The prespecified primary outcomes were change in global QOL among patients treated with ICIs and difference in change since baseline in global QOL between patients treated with ICI vs. non-ICI active treatment. Secondary outcomes included physical functioning and symptomatology. All statistical tests were 2-sided.

RESULTS: Twenty-six of 20,323 publications met inclusion criteria. Global QOL did not change over time in patients treated with ICIs (k = 26, n = 6,974, P = .19). Larger improvements in global QOL was observed in patients receiving ICI vs. non-ICI regimens (k = 16, ICI n = 3,588, non-ICI n = 2,948, P < .001). Physical functioning did not change in patients treated with ICIs (k = 14, n = 3,169, P=.47); there were no differences in mean change between ICI vs. non-ICI regimens (k = 11, n = 4,630, P=.94. Regarding symptoms, appetite loss, insomnia, and pain severity decreased but dyspnea severity increased in patients treated with ICIs (k = 14, n = 3,243-3,499) (Ps < 0.001). Insomnia severity was higher in patients treated with ICIs than non-ICI regimens (k = 11, n = 4,791) (P < .001).

CONCLUSIONS: This study is among the first to quantitatively summarize QOL in patients treated with ICIs. Findings suggest ICI recipients report no change in global QOL and higher QOL than patients treated with non-ICI regimens.

PMID:34508604 | DOI:10.1093/jnci/djab171