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Nevin Manimala Statistics

Metaheuristics for multiple sequence alignment: A systematic review

Comput Biol Chem. 2021 Aug 16;94:107563. doi: 10.1016/j.compbiolchem.2021.107563. Online ahead of print.

ABSTRACT

The Multiple Sequence Alignment (MSA) is a key task in bioinformatics, because it is used in different important biological analysis, such as function and structure prediction of unknown proteins. There are several approaches to perform MSA and the use of metaheuristics stands out because of the search ability of these methods, which generally leads to good results in a reasonable amount of time. This paper presents a Systematic Literature Review (SLR) on metaheuristics for MSA, compiling relevant works published between 2014 and 2019. The results of our SLR show the constant interest in this subject, due to the several recent publications that use different metaheuristics to obtain more accurate alignments. Moreover, the final results of our SLR show a multi-objective and hybrid approaches trends, which generally leads these methods to achieve even better results. Thus, we show in this work how the use of metaheuristics to perform MSA still remains an important and promising open research field.

PMID:34425495 | DOI:10.1016/j.compbiolchem.2021.107563

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Delirium is a good predictor for poor outcomes from coronavirus disease 2019 (COVID-19) pneumonia: A systematic review, meta-analysis, and meta-regression

J Psychiatr Res. 2021 Aug 20;142:361-368. doi: 10.1016/j.jpsychires.2021.08.031. Online ahead of print.

ABSTRACT

AIM: Delirium is a common presenting symptom among older patients. Patients who presented with delirium may have a higher morbidity and mortality rate due to older age, other comorbidities, and atypical COVID-19 presentation. Currently, the evidence supporting delirium as one of the predictors of poor outcome of COVID-19 is still insufficient. This study aims to explore the potential association between delirium and poor outcomes from COVID-19.

METHODS: We systematically searched the PubMed and Google Scholar databases using specific keywords related to our aims until January 30th, 2021. All articles published on COVID-19 and delirium were retrieved. The quality of the study was assessed using the Newcastle Ottawa Scale (NOS) tool for observational studies and Joanna Briggs Institute (JBI) Critical Appraisal Tools for case-series studies. Statistical analysis was done using Review Manager 5.4 software.

RESULTS: Our meta-analysis of 20 studies showed that delirium symptoms on admission was associated with poor outcomes from COVID-19 [OR 2.36 (95% CI 1.80-3.09), p < 0.00001, I2 = 76%, random-effect models] and its subgroup which consist of severe COVID-19 [OR 3.89 (95% CI 1.72-8.75), p = 0.001, I2 = 91%, random-effect models], and mortality from COVID-19 [OR 1.90 (95% CI 1.55-2.33), p < 0.00001, I2 = 36%, random-effect models]. Meta-regression showed that the association was influenced by age (p = 0.005).

CONCLUSIONS: Our study suggests delirium as an important marker to identify patients at higher risk for developing poor COVID-19 outcomes. The physicians should add delirium as one of the common presenting symptoms of COVID-19 in older populations.

PMID:34425488 | DOI:10.1016/j.jpsychires.2021.08.031

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PAX5 haploinsufficiency induced CD8+ T cells dysfunction or exhaustion by high expression of immune inhibitory-related molecules

Cancer Treat Res Commun. 2021 Jul 15;28:100437. doi: 10.1016/j.ctarc.2021.100437. Online ahead of print.

ABSTRACT

PURPOSE: PAX5 haploinsufficiency promoting tumorigenesis is related to immune escape. But the mechanisms of PAX5 mutations inducing tumor immune escape have not been clarified. Our aim was to study how PAX5 haploinsufficiency influences effector CD8 + T cells in tumor microenvironment.

METHODS: We estimated the proportions of 22 immune cell types and the expressions of immune inhibitory-related molecules based on gene expression profiles (GEPs) from children’s B- acute lymphoblastic leukemia(B-ALL) with PAX5 mutations by CIBERSORT, an established algorithm. We constructed the PAX5 haplodeletion A20 cell lines, built allografted A20 tumor models and evaluated the effect of PAX5 haplodeletion on immune inhibitory-related molecules in the tumor microenvironment (TME).

RESULTS: Our results indicated the percentages of T cells in bone marrow of children’s B-ALL with PAX5 mutations were not statistically different from that in bone marrow of B-ALL without PAX5 mutations, except for T follicular helper (Tfh) cells. But a variety of up-regulated immune inhibitory-related molecules in bone marrow of children’s B- ALL with PAX5 mutations were identified. By different approaches, we found that several immune inhibitory-related molecules of CD8+ T cells in TME of PAX5 haplodeletion clones such as TIM3, NR4A1 and BATF, were increased significantly compared with that of PAX5 wild type control. The IFN-ɤ of CD8+ T cells in TME of PAX5 haplodeletion tumors was decreased significantly compared with that of PAX5 wild type control.

CONCLUSION: Our study showed that PAX5 haploinsufficiency induced CD8+ T cells dysfunction or exhaustion by high expression of TIM3, NR4A1 and BATF in the CD8+ T cells of TME.

PMID:34425470 | DOI:10.1016/j.ctarc.2021.100437

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Combination of Hua Shi Bai Du granule (Q-14) and standard care in the treatment of patients with coronavirus disease 2019 (COVID-19): A single-center, open-label, randomized controlled trial

Phytomedicine. 2021 Jul 17;91:153671. doi: 10.1016/j.phymed.2021.153671. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of Hua Shi Bai Du Granule (Q-14) plus standard care compared with standard care alone in adults with coronavirus disease (COVID-19).

STUDY DESIGN: A single-center, open-label, randomized controlled trial.

SETTING: Wuhan Jinyintan Hospital, Wuhan, China, February 27 to March 27, 2020.

PARTICIPANTS: A total of 204 patients with laboratory-confirmed COVID-19 were randomized into the treatment group and control group, consisting of 102 patients in each group.

INTERVENTIONS: In the treatment group, Q-14 was administered at 10 g (granules) twice daily for 14 days, plus standard care. In the control group, patients were provided standard care alone for 14 days.

MAIN OUTCOME MEASURE: The primary outcome was the conversion time for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral assay. Adverse events were analyzed in the safety population.

RESULTS: Among the 204 patients, 195 were analyzed according to the intention-to-treat principle. A total of 149 patients (71 vs. 78 in the treatment and control groups, respectively) tested negative via the SARS-CoV-2 viral assay. There was no statistical significance in the conversion time between the treatment group and control group (Full analysis set: Median [interquartile range]: 10.00 [9.00-11.00] vs. 10.00 [9.00-11.00]; Mean rank: 67.92 vs. 81.44; P = 0.051). The recovery time for fever was shorter in the treatment group than in the control group. The disappearance rate of symptoms like cough, fatigue, and chest discomfort was significantly higher in the treatment group. In chest computed tomography (CT) examinations, the overall evaluation of chest CT examination after treatment compared with baseline showed that more patients improved in the treatment group. There were no significant differences in the other outcomes.

CONCLUSION: The combination of Q-14 and standard care for COVID-19 was useful for the improvement of symptoms (such as fever, cough, fatigue, and chest discomfort), but did not result in a significantly higher probability of negative conversion in the SARS-CoV-2 viral assay. No serious adverse events were observed.

TRIAL REGISTRATION: ChiCTR2000030288.

PMID:34425471 | DOI:10.1016/j.phymed.2021.153671

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Do group-based mindfulness meditation programs enhance executive functioning? A systematic review and meta-analysis of the evidence

Conscious Cogn. 2021 Aug 20;95:103195. doi: 10.1016/j.concog.2021.103195. Online ahead of print.

ABSTRACT

Research examining the effects of group-based mindfulness interventions on executive functioning have yielded inconsistent findings, with some reports of enhanced performance and other reports of null findings. Inconsistencies in the literature may be due to methodological differences across studies, including the type of control group employed and sample characteristics (e.g., clinical vs. non-clinical samples). The current systematic review and meta-analysis examined the effect of group-based mindfulness programs on executive functioning in persons 18+ years of age. Following the standards for systematic review, a total of 29 studies were included in the meta-analysis, of which 21 comparisons contributed to the analysis of inhibition; nine to working memory; nine to attention shifting; and four to the analysis of verbal fluency. After removing outliers, random effects models suggested a small but significant synthesized effect of group-mindfulness training on overall executive functioning (95% CI = 0.256, 0.725). Examination of executive subdomains after removing outliers suggested a small, statistically significant effect for inhibition (95% CI = 0.055, 0.387), working memory (95% CI = 0.010, 0.437), and verbal fluency (95% CI = 0.071, 1.931). No significant pooled effects were found for attention shifting. A priori subgroup analysis by randomization, type of control group, and sample cohort revealed inconsistent results. Overall, the current review suggests that the effect of group-based mindfulness training on executive functioning is not robust.

PMID:34425456 | DOI:10.1016/j.concog.2021.103195

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Diseases of affluence? A systematic review of the literature on socioeconomic diversity in eating disorders

Eat Behav. 2021 Aug 11;43:101548. doi: 10.1016/j.eatbeh.2021.101548. Online ahead of print.

ABSTRACT

The stereotype that eating disorders (ED) primarily present among individuals of higher socioeconomic status (SES) has long persisted in popular and professional perception. This belief has likely contributed to disparities in ED identification and treatment, particularly among those of lower SES backgrounds. The objective of this article was to systematically review the literature investigating socioeconomic diversity in distinct ED diagnoses. A PRISMA search was conducted to identify studies that empirically assessed the association between ED pathology and indicators of SES via PubMed and PsycINFO. This search generated 13,538 articles, of which 62 articles published between 1973 and August 2020 met criteria for inclusion in the review. Included studies were primarily cross-sectional and covered diagnoses of anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED), with quality ratings of poor, fair, and good. Results are examined in the context of studies’ sampling methods, operationalization of SES, and statistical analyses. There is no consistent pattern of evidence to suggest a relationship between high SES and ED. Instead, all ED present across a wide range of socioeconomic backgrounds. Limitations included the predominance of cross-sectional study designs and poor to fair quality ratings. Future research should include adequately powered, community-based longitudinal studies that examine how sociocultural factors, including SES, intersect to influence ED risk and treatment outcome. The existing data suggest an urgent need to prioritize affordable and accessible ED treatment.

PMID:34425457 | DOI:10.1016/j.eatbeh.2021.101548

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Biomonitoring of glyphosate and AMPA in the urine of Spanish lactating mothers

Sci Total Environ. 2021 Aug 17;801:149688. doi: 10.1016/j.scitotenv.2021.149688. Online ahead of print.

ABSTRACT

The objectives of this study were to evaluate the urinary levels of Glyphosate (Gly) and its metabolite aminomethylphosphonic acid (AMPA) in Spanish breastfeeding mothers (n = 97), to identify the main predictors of exposure and to perform a risk assessment. Urine samples were analyzed using a method based on solid phase extraction and liquid chromatography tandem mass spectrometry (LC-MS/MS) determination. The developed method showed limits of quantification of 0.1 μg/L for both analytes. The detection frequencies (DFs) were 54% for Gly and 60% for AMPA, with geometric means (GMs) of 0.12 μg/L and 0.14 μg/L, respectively. In the statistical analysis, no relationship was found between the urinary levels of Gly and AMPA. Multiple regression analysis showed a significant relationship between the intake of eggs and fruits and Gly levels in urine. Estimated daily intakes (EDIs), hazard quotients (HQs), and a hazard index (HI) were calculated to analyze the obtained data from a health risk perspective. The GMs of the EDIs were 0.31 and 0.37 μg/kg of body weight (BW)/day for Gly and AMPA, respectively. The HQs were calculated considering 0.5 mg/kg BW/day as an acceptable daily intake (ADI), which EFSA has established as a health-based reference value for both analytes. The values obtained were lower than 1, and thus, low health risk due to Gly and AMPA exposure was expected for the population under study.

PMID:34425442 | DOI:10.1016/j.scitotenv.2021.149688

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Novel multimethod approach for the determination of the colloidal stability of nanomaterials in complex environmental mixtures using a global stability index: TiO2 as case study

Sci Total Environ. 2021 Aug 17;801:149607. doi: 10.1016/j.scitotenv.2021.149607. Online ahead of print.

ABSTRACT

A systematic study on the colloidal behavior of uncoated and polyvinylpyrrolidone (PVP) coated TiO2 engineered nanomaterials (ENMs) in simulated aqueous media is herein reported, in which conditions representative for natural waters (pH, presence of divalent electrolytes (i.e. Ca2+/Mg2+ and SO42-), of natural organic matter (NOM) and of suspended particulate matter (SPM)) were systematically varied. The colloidal stability of the different dispersions was investigated by means of Dynamic and Electrophoretic Light Scattering (DLS and ELS) and Centrifugal Separation Analysis (CSA), and a global stability index based on these three techniques was developed. The index allows to quantitatively classify the nano-based dispersions according to their colloidal stability affected by the different parameters studied. This multimethod approach clearly identifies inorganic SPM followed by divalent electrolytes as the main natural components destabilizing TiO2 ENMs upon entering in simulated natural waters, while it highlights a moderate stabilization induced by NOM, depending mainly on pH. Moreover, the PVP coating was found to attenuate the influence of these parameters on the colloidal stability. The obtained results show how the global stability index developed is influenced by the complexity of the system, suggesting the importance of combining the information gathered from all the techniques employed to better elucidate the fate and behavior of ENMs in natural surface waters.

PMID:34425449 | DOI:10.1016/j.scitotenv.2021.149607

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Real-world efficacy and safety of axitinib in combination with anti-programmed cell death-1 antibody for advanced mucosal melanoma

Eur J Cancer. 2021 Aug 20;156:83-92. doi: 10.1016/j.ejca.2021.07.018. Online ahead of print.

ABSTRACT

PURPOSE: The combination of vascular endothelial growth factor receptor (VEGFR) inhibitor and programmed cell death-1 (PD-1) blockade provides promising therapeutic opportunities for advanced mucosal melanoma in early phase trials. The aim of this retrospective study was to evaluate the efficacy and safety of the combination regimen for advanced mucosal melanoma in the real world.

METHODS: Patients with advanced mucosal melanoma received an anti-PD-1 antibody plus the VEGFR inhibitor axitinib until confirmed disease progression or unacceptable toxicity. In addition, those with liver metastasis were allowed to take hepatic transcatheter arterial chemoembolisation (TACE). The primary endpoint was overall response rate (ORR). Secondary endpoints included disease control rate (DCR), time to treatment failure (TTF), duration of response (DOR), overall survival (OS) and treatment-related adverse events (TRAEs).

RESULTS: Eighty-one and sixty-six patients received axitinib plus immunotherapy as first-line and salvage therapy, respectively. Overall, ORR was 24.5% (95% CI, 17.3-31.6), DCR was 72.7% (95% CI, 65.3-80.1). Median TTF, DOR and OS were 5.2 months (95% CI, 3.7-6.6), 9.2 months (95% CI, 7.2-11.2) and 11.1 months (95% CI, 7.2-15.0). ORR was 30.0% (95% CI, 19.7-40.3) and 17.5% (95% CI, 7.8-27.1) as first-line and salvage therapy, respectively. No statistical difference among the primary sites was noted for ORR. The ORR of patients with liver metastasis with or without hepatic TACE was 26.1% (95% CI, 6.7-45.5) and 15.0% (95% CI, 2.1-32.1), respectively (P = 0.467). Elevated LDH and poor ECOG status are negative predictive factors.

CONCLUSION: This is the largest analysis of anti-PD-1 plus VEGFR inhibitor therapy for mucosal melanoma to date. Immunotherapy plus anti-angiogenesis is applicable for advanced mucosal melanoma, especially as front-line. Hepatic TACE might act synergistically with systemic immunotherapy and anti-angiogenesis.

PMID:34425407 | DOI:10.1016/j.ejca.2021.07.018

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The Association Between Sex and Survival for Anal Squamous Cell Carcinoma

J Surg Res. 2021 Aug 20;268:474-484. doi: 10.1016/j.jss.2021.07.015. Online ahead of print.

ABSTRACT

BACKGROUND: The incidence of anal squamous cell carcinoma (SCC) is rising, despite the introduction of a vaccine against human papillomavirus (HPV), the most common etiology of anal SCC. The rate of anal SCC is higher among women and sex-based survival differences may exist. We aimed to examine the association between sex and survival for stage I-IV anal SCC.

MATERIALS AND METHODS: The National Cancer Database was used to identify patients with stage I-IV anal SCC from 2004-2016. Outcomes were assessed utilizing log rank tests, Kaplan-Meier statistics, and Cox proportional-hazard modeling. Subgroup analyses by disease stage and by HPV status were performed. Outcomes of interest were median, 1-, and 5-year survival by sex.

RESULTS: There were 31,185 patients with stage I-IV anal SCC. 10,714 (34.3%) were male and 20,471 (65.6%) were female. 1- and 5- year survival was 90.2% (95% CI 89.8 – 90.7) and 67.7% (95% CI 66.9 – 68.5) for females compared to 85.8% (95% CI 85.1 – 86.5) and 55.9% (95% CI 54.7 – 57.0) for males. In subgroup analysis, females demonstrated improved unadjusted and adjusted survival for all stages of disease. Female sex was an independent predictor of improved survival (HR 0.68, 95% CI 0.65 – 0.71, P < 0.001).

CONCLUSIONS: We demonstrate better overall survival for females compared to males for stage I-IV anal SCC. It is not clear why women have a survival advantage over men, though exposure to prominent risk factors may play a role. High-risk men may warrant routine screening for anal cancer.

PMID:34425409 | DOI:10.1016/j.jss.2021.07.015