Tag: nevin manimala

Phys Med Biol. 2021 May 28. doi: 10.1088/1361-6560/ac0682. Online ahead of print.

ABSTRACT

The use of multi-pinhole collimation has enabled ultra-high-resolution imaging of SPECT and PET tracers in small animals. Key for obtaining high-quality images is the use of statistical iterative image reconstruction with accurate energy-dependent photon transport modelling through collimator and detector. This can be incorporated in a system matrix that contains the probabilities that a photon emitted from a certain voxel is detected at a specific detector pixel. Here we introduce a Fast Monte-Carlo based (FMC-based) matrix generation method for pinhole imaging that is easy to apply to various radionuclides. The method is based on accelerated point-source simulations combined with model-based interpolation to straightforwardly change or combine photon energies of the isotope of interest. The proposed method was evaluated for a VECTor PET-SPECT system with (i) a HE-UHR-M collimator and (ii) an EXIRAD-3D 3D autoradiography collimator. Both experimental scans with^99mTc,¹¹¹In, and¹²³I, and simulated scans with⁶⁷Ga and⁹⁰Y were performed for evaluation. FMC was compared with two currently used approaches, one based on a set of point-source measurements with^99mTc (dubbed traditional method), and the other based on an energy-dependent ray-tracing simulation (ray-tracing method). The reconstruction results show better image quality when using FMC-based matrices than when applying the traditional or ray-tracing matrices in various cases. FMC-based matrices generalise better than the traditional matrices when imaging isotopes with energies deviating too much from the energy used in the calibration and are computationally more efficient for very-high-resolution imaging than the ray-tracing matrices. In addition, FMC has the advantage of easily combining energies in a single matrix which is relevant when imaging isotopes with multiple photopeak energies (e.g.⁶⁷Ga and¹¹¹In) or with a continuous energy spectrum (e.g.⁹⁰Y). To conclude, FMC is an efficient, accurate, and versatile tool for creating system matrices for ultra-high-resolution pinhole SPECT.

PMID:34049291 | DOI:10.1088/1361-6560/ac0682

J Affect Disord. 2021 May 14;291:218-234. doi: 10.1016/j.jad.2021.05.003. Online ahead of print.

ABSTRACT

BACKGROUND: Maternal depression during the perinatal period predicts adverse developmental outcomes for children, via poorly understood mechanisms. One plausible pathway may involve child executive function, a suite of cognitive capacities associated with social, emotional and educational outcomes. Systematic review and meta-analysis are applied to evaluate evidence of association between maternal perinatal depression and child executive function.

METHODS: Medline, Embase, PubMed, PsycInfo, and SCOPUS were searched for relevant articles to August 2020, with hand-search of relevant bibliographies. Original research published in English measuring maternal depressive symptoms during pregnancy and the first year postpartum, and child executive function outcomes at any age was included. 27 studies met criteria for review. 16 studies reporting raw data of the association between depressive symptoms and executive function were used for meta-analysis.

RESULTS: Our systematic review identified inadequate assessment of maternal depression, and unreliable measures of executive function in many studies. Assessment of confounders was also inconsistent. Our meta-analysis identified a small, statistically significant relationship between perinatal depression and child executive function (effect size r = 0.07; 95% CI 0.03-0.10); equivalent to Cohen’s d = 0.14.

LIMITATIONS: Variable quality of available studies leads to cautious interpretation of results.

CONCLUSIONS: This meta-analysis is consistent with the hypothesis that maternal perinatal depression does have an impact on executive function in offspring. Future studies must use robust measurement of depression and executive function, and account for the chronicity of maternal depression, and developmental context to produce meaningful results.

PMID:34049191 | DOI:10.1016/j.jad.2021.05.003

J Mol Graph Model. 2021 May 20;106:107937. doi: 10.1016/j.jmgm.2021.107937. Online ahead of print.

ABSTRACT

Class IIa histone deacetylases (HDACs) 5 and 9 play crucial roles in several human disorders such as cancer, making them important targets for drug design. Continuous research is pursed to overcome the cytotoxicity side effect that comes with the currently available broad-spectrum HDACs inhibitors. Herein, common features of active HDACs inhibitors in clinical trials and use have been calculated to generate the best pharmacophore hypothesis. Guner-Henry scoring system was used to validate the generated hypotheses. Hypo1 of HDAC5 and Hypo2 of HDAC9 exhibited the most statistically significance hypotheses. Compounds with fit value of 3 and more were examined by QuickVina 2 docking tool to calculate their binding affinity toward all class IIa HDACs. A total of 6 potential selective compounds were subjected to 100 molecular dynamics (MD) simulation to examine their binding modes. The free binding energy calculations were computed according to the MM-PBSA method. Proposed selective compounds displayed good stability with their targets and thus they may offer potent leads for the designing of HDAC5 and HDAC9 isoform selective inhibitors.

PMID:34049193 | DOI:10.1016/j.jmgm.2021.107937

Dent Med Probl. 2021 May 28. doi: 10.17219/dmp/126304. Online ahead of print.

ABSTRACT

BACKGROUND: The orthodontic removable traction appliance (ORTA) was introduced as an intraoral removable appliance to treat Class III patients, but the pure treatment effects of ORTA have not been established yet.

OBJECTIVES: The aim of the study was to evaluate the skeletal, dental and soft tissue changes following the use of ORTA in treating Class III growing patients, and to compare these changes with those observed in an untreated control group (UCG).

MATERIAL AND METHODS: Forty-two patients with Class III malocclusion (mean age: 9.04 ±0.84 years) were randomly allocated to either the intervention group (ORTA) or UCG with a 1:1 allocation ratio. The patients in the ORTA group were treated until a positive overjet was achieved, whereas those in UCG were observed for an average of 6 months. Lateral cephalograms were obtained before (T1) and at the end of the treatment or observation period (T2). Twenty-six variables were used to evaluate treatment changes. The paired and independent t tests were used to detect significant differences within and between the groups, respectively.

RESULTS: Forty-two patients who met the inclusion criteria were included primarily. Two patients in UCG dropped out of the study. Therefore, 40 patients were included in the statistical analyses (ORTA: 21; UCG: 19). The orthodontic removable traction appliance was able to correct Class III malocclusion in a mean treatment time of 4.34 ±2.02 months. The maxilla moved forward by a mean of 1.31°, which was significantly greater than in the case of UCG (i.e., a mean difference of 1.02°). The mandible moved significantly backward in the ORTA group (the mean change in SNB: -1.85°) and significantly forward in UCG (the mean change in SNB: 0.97°), leaving the overall sagittal skeletal change significantly greater in the ORTA group as compared to UCG (the mean change in ANB: 3.81°) (p < 0.001).

CONCLUSIONS: In the short term, ORTA seemed to be an effective intraoral removable appliance in the treatment of growing Class III patients.

PMID:34048643 | DOI:10.17219/dmp/126304

J Dig Dis. 2021 May 28. doi: 10.1111/1751-2980.13026. Online ahead of print.

ABSTRACT

OBJECTIVE: The current concern exists regarding the efficacy and safety of biological agent monotherapy versus combination therapy with an immunomodulator (IM) in patients with inflammatory bowel disease (IBD). We performed a meta-analysis of results from randomized controlled trials (RCTs) to compare the efficacy and safety of biological and immunosuppressive combination therapy with biological monotherapy in IBD.

METHODS: We comprehensively and systematically identified eligible studies from Embase, PubMed, and Cochrane library and compared the biological and immunomodulator treatment with biological monotherapy. Raw data from RCTs fulfilling inclusion criteria were extracted for meta-analysis, and pooled relative risk (RR) and 95% confidence interval (CI) were performed using fixed-effect and inverse variance methods. Funnel plots were performed to analyze the publication bias.

RESULTS: Of 3625 identified studies, 12 were eligibly included in this meta-analysis. Overall, there was statistical benefit for combination treatment over anti-TNF monotherapy in inducing clinical remission and preventing the relapse in both UC and CD patients (RR = 0.89; 95% CI = 0.80-0.98). There were benefits for combination treatment over monotherapy in further subgroup analysis of active CD patients (RR = 0.83, 95% CI = 0.73-0.94) but not quiescent CD (RR = 1.01; 95% CI = 0.84-1.22), active UC (RR = 0.82; 95% CI = 0.56-1.19), and quiescent UC patients (RR = 0.61; 95% CI = 0.12-3.00). There were significant benefits for combination therapy in subgroup of infliximab treatment (RR = 0.83; 95% CI = 0.70-0.97) but not in adalimumab treatment (RR = 0.95; 95% CI = 0.83-1.07). For safety analysis, no significant differences were observed in the overall pooled summary for adverse events (RR = 1.05; 95% CI = 0.89-1.23), opportunistic infections (RR = 1.13; 95% CI = 0.94-1.36), and serious infections (RR = 1.20; 95% CI = 0.83-1.73) of combination therapy versus monotherapy. However, an increase of risk of liver enzyme abnormality (RR = 3.47; 95% CI = 1.67-7.21) and a decrease of infusion reactions (RR = 0.43; 95% CI = 0.23-0.80) were seen in combination therapy.

CONCLUSION: The current study suggest that combination therapy among active CD patients shows slight benefits in inducing clinical remission compared with anti-TNF monotherapy. IBD patients who receive therapy with infliximab and IMs also have mild advantage in comparison to those with infliximab monotherapy. Further studies are warranted to define the efficacy and safety of combination therapy versus biological monotherapy in IBD.

PMID:34048629 | DOI:10.1111/1751-2980.13026

Mol Biol Evol. 2021 May 28:msab165. doi: 10.1093/molbev/msab165. Online ahead of print.

ABSTRACT

To address the void in the availability of high-quality proteomic data traversing the animal tree, we have implemented a pipeline for generating de novo assemblies based on publicly available data from the NCBI Sequence Read Archive, yielding a comprehensive collection of proteomes from 100 species spanning 21 animal phyla. We have also created the Animal Proteome Database (AniProtDB), a resource providing open access to this collection of high-quality metazoan proteomes, along with information on predicted proteins and protein domains for each taxonomic classification and the ability to perform sequence similarity searches against all proteomes generated using this pipeline. This solution vastly increases the utility of these data by removing the barrier to access for research groups who do not have the expertise or resources to generate these data themselves and enables the use of data from non-traditional research organisms that have the potential to address key questions in biomedicine.

PMID:34048573 | DOI:10.1093/molbev/msab165

J Natl Cancer Inst. 2021 May 28:djab111. doi: 10.1093/jnci/djab111. Online ahead of print.

ABSTRACT

BACKGROUND: Loss of ovarian function is a recognized adverse effect of chemotherapy for breast cancer, and of great importance to patients. Little is known about the ovarian toxicity of newer cancer treatments. This study examined whether breast cancer clinical trials include assessment of the impact of trial interventions on ovarian function.

METHODS: Eligible trials were phase 3 (neo)adjuvant trials of pharmacologic treatments for breast cancer recruiting between June 2008-October 2019, which included premenopausal women. MEDLINE, EMBASE, Clinicaltrials.gov, EudraCT were searched. Data were extracted from trial publications, protocols, databases, and a survey sent to all trial chairs. Tests of statistical significance were two-sided. PROSPERO registration CRD42019134551.

RESULTS: Of 2,354 records identified, 141 trials were eligible. Investigational treatments included chemotherapy (36.9%), HER2-targeted (24.8%), endocrine (12.8%), immunotherapy (7.8%), CDK4/6-inhibitors (5.0%), PARP-inhibitors (2.8%). Ovarian function was a pre-specified endpoint in 13 (9.2%) trials. Forty-five (31.9%) trials collected ovarian function data, but only 33 (23.4%) collected post-trial-intervention data. Common post-intervention data collected included menstruation (15.6%), pregnancy (13.5%), estradiol (9.9%) and follicle-stimulating hormone levels (8.5%). Only four (2.8%) trials collected post-intervention anti-mullerian hormone levels and three (2.1%) trials collected antral follicle count. Of 22 trials investigating immunotherapy, CDK4/6-inhibitors or PARP-inhibitors, none specified ovarian function as an endpoint, but four (18.2%) collected post-intervention ovarian function data.

CONCLUSIONS: The impact of pharmacologic interventions on ovarian function is infrequently assessed in phase 3 breast cancer (neo)adjuvant trials that include premenopausal women. Trialists should consider inclusion of ovarian function endpoints when designing clinical trials, given its importance for informed decision-making.

PMID:34048575 | DOI:10.1093/jnci/djab111

Nucleic Acids Res. 2021 May 28:gkab405. doi: 10.1093/nar/gkab405. Online ahead of print.

ABSTRACT

The Mergeomics web server is a flexible online tool for multi-omics data integration to derive biological pathways, networks, and key drivers important to disease pathogenesis and is based on the open source Mergeomics R package. The web server takes summary statistics of multi-omics disease association studies (GWAS, EWAS, TWAS, PWAS, etc.) as input and features four functions: Marker Dependency Filtering (MDF) to correct for known dependency between omics markers, Marker Set Enrichment Analysis (MSEA) to detect disease relevant biological processes, Meta-MSEA to examine the consistency of biological processes informed by various omics datasets, and Key Driver Analysis (KDA) to identify essential regulators of disease-associated pathways and networks. The web server has been extensively updated and streamlined in version 2.0 including an overhauled user interface, improved tutorials and results interpretation for each analytical step, inclusion of numerous disease GWAS, functional genomics datasets, and molecular networks to allow for comprehensive omics integrations, increased functionality to decrease user workload, and increased flexibility to cater to user-specific needs. Finally, we have incorporated our newly developed drug repositioning pipeline PharmOmics for prediction of potential drugs targeting disease processes that were identified by Mergeomics. Mergeomics is freely accessible at http://mergeomics.research.idre.ucla.edu and does not require login.

PMID:34048577 | DOI:10.1093/nar/gkab405

Genome Biol Evol. 2021 May 28:evab121. doi: 10.1093/gbe/evab121. Online ahead of print.

ABSTRACT

Sex chromosomes are generally derived from a pair of autosomes that have acquired a locus controlling sex. Sex chromosomes may evolve reduced recombination around this locus and undergo a long process of molecular divergence. At that point, the original loci controlling sex may be difficult to pinpoint. This difficulty has affected many model species from mammals to birds to flies, which present highly diverged sex chromosomes. Identifying sex-controlling loci is easier in species with molecularly similar sex chromosomes. Here we aimed at pinpointing the sex-determining region (SDR) of Armadillidium vulgare, a terrestrial isopod with female heterogamety (ZW females and ZZ males) and whose sex chromosomes appear to show low genetic divergence. To locate the SDR, we assessed SNP allele frequencies in F1 daughters and sons sequenced in pools (pool-seq) in several families. We developed a Bayesian method that uses the SNP genotypes of individually sequenced parents and poolseq data from F1 siblings to estimate the genetic distance between a given genomic region (contig) and the SDR. This allowed us to assign more than 43 Megabases of contigs to sex chromosomes, and to demonstrate extensive recombination and very low divergence between these chromosomes. By taking advantage of multiple F1 families, we delineated a very short genomic region (∼65 kilobases) that presented no evidence of recombination with the SDR. In this short genomic region, the comparison of sequencing depths between sexes highlighted female-specific genes that have undergone recent duplication, and which may be involved in sex determination in A. vulgare.

PMID:34048551 | DOI:10.1093/gbe/evab121

Nucleic Acids Res. 2021 May 28:gkab410. doi: 10.1093/nar/gkab410. Online ahead of print.

ABSTRACT

Genetic association studies are frequently used to study the genetic basis of numerous human phenotypes. However, the rapid interrogation of how well a certain genomic region associates across traits as well as the interpretation of genetic associations is often complex and requires the integration of multiple sources of annotation, which involves advanced bioinformatic skills. We developed snpXplorer, an easy-to-use web-server application for exploring Single Nucleotide Polymorphisms (SNP) association statistics and to functionally annotate sets of SNPs. snpXplorer can superimpose association statistics from multiple studies, and displays regional information including SNP associations, structural variations, recombination rates, eQTL, linkage disequilibrium patterns, genes and gene-expressions per tissue. By overlaying multiple GWAS studies, snpXplorer can be used to compare levels of association across different traits, which may help the interpretation of variant consequences. Given a list of SNPs, snpXplorer can also be used to perform variant-to-gene mapping and gene-set enrichment analysis to identify molecular pathways that are overrepresented in the list of input SNPs. snpXplorer is freely available at https://snpxplorer.net. Source code, documentation, example files and tutorial videos are available within the Help section of snpXplorer and at https://github.com/TesiNicco/snpXplorer.

PMID:34048563 | DOI:10.1093/nar/gkab410