Hypersensitivity Reactions Induced by Iodinated Contrast Media in Radiological Diagnosis: A Disproportionality Analysis Based on the FAERS Database.

PURPOSE: This study aimed to evaluate the Pharmacovigilance (PV) and severity of hypersensitivity reactions induced by non-ionic Iodinated Contrast Media (ICM) in the radiology diagnosis reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We retrospectively reviewed the reports of ICM-induced hypersensitivity reactions submitted to the FAERS database between January 2015 and January 2023 and conducted a disproportionality analysis. The seven most common non-ionic ICM, including iohexol, iopamidol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol, were chiefly analyzed. Our primary endpoint was the PV of non-ionic ICM-induced total hypersensitivity events. STATA 17.0 MP was used for statistical analysis. RESULTS: In total, 35357 reports of adverse reaction events in radiology diagnosis were retrieved from the FAERS database. Among them, 6181 reports were on hypersensitivity reaction events (mean age: 57.1 ± 17.8 years). The hypersensitivity reaction-related PV signal was detected for iohexol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol, but not for iopamidol. The proportion of iomeprol-induced hypersensitivity reactions and the probability of ioversol-induced severe hypersensitivity reactions have been found to be significantly increased. CONCLUSION: The probability and severity of hypersensitivity reaction events in non-ionic ICM are different. Iohexol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol have higher risks compared to iopamidol. In addition, the constituent ratio of hypersensitivity reactions induced by iomeprol is significantly increased, and the associated probability induced by ioversol is significantly increased.

Different functional connectivity optimal frequency in autism compared with healthy controls and the relationship with social communication deficits: Evidence from gene expression and behavior symptom analyses.

Studies have reported that different brain regions/connections possess distinct frequency properties, which are related to brain function. Previous studies have proposed altered brain activity frequency and frequency-specific functional connectivity (FC) patterns in autism spectrum disorder (ASD), implying the varied dominant frequency of FC in ASD. However, the difference of the dominant frequency of FC between ASD and healthy controls (HCs) remains unclear. In the present study, the dominant frequency of FC was measured by FC optimal frequency, which was defined as the intermediate of the frequency bin at which the FC strength could reach the maximum. A multivariate pattern analysis was conducted to determine whether the FC optimal frequency in ASD differs from that in HCs. Partial least squares regression (PLSR) and enrichment analyses were conducted to determine the relationship between the FC optimal frequency difference of ASD/HCs and cortical gene expression. PLSR analyses were also performed to explore the relationship between FC optimal frequency and the clinical symptoms of ASD. Results showed a significant difference of FC optimal frequency between ASD and HCs. Some genes whose cortical expression patterns are related to the FC optimal frequency difference of ASD/HCs were enriched for social communication problems. Meanwhile, the FC optimal frequency in ASD was significantly related to social communication symptoms. These results may help us understand the neuro-mechanism of the social communication deficits in ASD.

AGODB: a comprehensive domain annotation database of argonaute proteins.

Argonaute (Ago) proteins are widely expressed in almost all organisms. Eukaryotic Ago (eAgo) proteins bind small RNA guides forming RNA-induced silencing complex that silence gene expression, and prokaryotic Ago (pAgo) proteins defend against invading nucleic acids via binding small RNAs or DNAs. pAgo proteins have shown great potential as a candidate 'scissors' for gene editing. Protein domains are fundamental units of protein structure, function and evolution; however, the domains of Ago proteins are not well annotated/curated currently. Therefore, full functional domain annotation of Ago proteins is urgently needed for researchers to understand the function and mechanism of Ago proteins. Herein, we constructed the first comprehensive domain annotation database of Ago proteins (AGODB). The database curates detailed information of 1902 Ago proteins, including 1095 eAgos and 807 pAgos. Especially for long pAgo proteins, all six domains are annotated and curated. Gene Ontology (GO) enrichment analysis revealed that Ago genes in different species were enriched in the following GO terms: biological processes (BPs), molecular function and cellular compartment. GO enrichment analysis results were integrated into AGODB, which provided insights into the BP that Ago genes may participate in. AGODB also allows users to search the database with a variety of options and download the search results. We believe that the AGODB will be a useful resource for understanding the function and domain components of Ago proteins. This database is expected to cater to the needs of scientific community dedicated to the research of Ago proteins. DATABASE URL: http://i.uestc.edu.cn/agodb/.

PDL1Binder: Identifying programmed cell death ligand 1 binding peptides by incorporating next-generation phage display data and different peptide descriptors.

Monoclonal antibody drugs targeting the PD-1/PD-L1 pathway have showed efficacy in the treatment of cancer patients, however, they have many intrinsic limitations and inevitable drawbacks. Peptide inhibitors as alternatives might compensate for the drawbacks of current PD-1/PD-L1 interaction blockers. Identifying PD-L1 binding peptides by random peptide library screening is a time-consuming and labor-intensive process. Machine learning-based computational models enable rapid discovery of peptide candidates targeting the PD-1/PD-L1 pathway. In this study, we first employed next-generation phage display (NGPD) biopanning to isolate PD-L1 binding peptides. Different peptide descriptors and feature selection methods as well as diverse machine learning methods were then incorporated to implement predictive models of PD-L1 binding. Finally, we proposed PDL1Binder, an ensemble computational model for efficiently obtaining PD-L1 binding peptides. Our results suggest that predictive models of PD-L1 binding can be learned from deep sequencing data and provide a new path to discover PD-L1 binding peptides. A web server was implemented for PDL1Binder, which is freely available at http://i.uestc.edu.cn/pdl1binder/cgi-bin/PDL1Binder.pl.

BBPpredict: A Web Service for Identifying Blood-Brain Barrier Penetrating Peptides.

Blood-brain barrier (BBB) is a major barrier to drug delivery into the brain in the treatment of central nervous system (CNS) diseases. Blood-brain barrier penetrating peptides (BBPs), a class of peptides that can cross BBB through various mechanisms without damaging BBB, are effective drug candidates for CNS diseases. However, identification of BBPs by experimental methods is time-consuming and laborious. To discover more BBPs as drugs for CNS disease, it is urgent to develop computational methods that can quickly and accurately identify BBPs and non-BBPs. In the present study, we created a training dataset that consists of 326 BBPs derived from previous databases and published manuscripts and 326 non-BBPs collected from UniProt, to construct a BBP predictor based on sequence information. We also constructed an independent testing dataset with 99 BBPs and 99 non-BBPs. Multiple machine learning methods were compared based on the training dataset via a nested cross-validation. The final BBP predictor was constructed based on the training dataset and the results showed that random forest (RF) method outperformed other classification algorithms on the training and independent testing dataset. Compared with previous BBP prediction tools, the RF-based predictor, named BBPpredict, performs considerably better than state-of-the-art BBP predictors. BBPpredict is expected to contribute to the discovery of novel BBPs, or at least can be a useful complement to the existing methods in this area. BBPpredict is freely available at http://i.uestc.edu.cn/BBPpredict/cgi-bin/BBPpredict.pl.

A database of anti-coronavirus peptides.

Since 2019, the novel coronavirus (SARS-COV-2) disease (COVID-19) has caused a worldwide epidemic. Anti-coronavirus peptides (ACovPs), a type of antimicrobial peptides (AMPs), have demonstrated excellent inhibitory effects on coronaviruses. However, state-of-the-art AMP databases contain only a small number of ACovPs. Additionally, the fields of these databases are not uniform, and the units or evaluation standards of the same field are inconsistent. Most of these databases have not included the target domains of ACovPs and description of in vitro and in vivo assays to measure the inhibitory effects of ACovPs. Here, we present a database focused on ACovPs (ACovPepDB), which contains comprehensive and precise ACovPs information of 518 entries with 214 unique ACovPs manually collected from public databases and published peer-reviewed articles. We believe that ACovPepDB is of great significance for facilitating the development of new peptides and improving treatment for coronavirus infection. The database will become a portal for ACovPs and guide and help researchers perform further studies. The ACovPepDB is available at http://i.uestc.edu.cn/ACovPepDB/ .

TUPDB: Target-Unrelated Peptide Data Bank.

The isolation of target-unrelated peptides (TUPs) through biopanning remains as a major problem of phage display selection experiments. These TUPs do not have any actual affinity toward targets of interest, which tend to be mistakenly identified as target-binding peptides. Therefore, an information portal for storing TUP data is urgently needed. Here, we present a TUP data bank (TUPDB), which is a comprehensive, manually curated database of approximately 73 experimentally verified TUPs and 1963 potential TUPs collected from TUPScan, the BDB database, and public research articles. The TUPScan tool has been integrated in TUPDB to facilitate TUP analysis. We believe that TUPDB can help identify and remove TUPs in future reports in the biopanning community. The database is of great importance to improving the quality of phage display-based epitope mapping and promoting the development of vaccines, diagnostics, and therapeutics. The TUPDB database is available at http://i.uestc.edu.cn/tupdb .

Atypical Functional Covariance Connectivity Between Gray and White Matter in Children With Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder with atypical gray matter (GM) and white matter (WM) functional developmental course. However, the functional co-developmental pattern between GM and WM in ASD is unclear. Here, we utilized a functional covariance connectivity method to explore the concordance pattern between GM and WM function in individuals with ASD. A multi-center resting-state fMRI dataset composed of 105 male children with ASD and 102 well-matched healthy controls (HCs) from six sites of the ABIDE dataset was utilized. GM and WM ALFF maps were calculated for each subject. Voxel by voxel functional covariance connectivity of the ALFF values across subjects was calculated between GM and WM for children with ASD and HCs. A Z-test combining FDR multi-comparison correction was then employed to determine whether the functional covariance is significantly different between the two groups. A "bundling" strategy was utilized to ensure that the GM/WM clusters showing atypical functional covariance were larger than 5 voxels. Finally, canonical correlation analysis was conducted to explore whether the atypical GM/WM functional covariance is related to ASD symptoms. Results showed atypical functional covariance connections between specific GM and WM regions, whereas the ALFF values of these regions indicated no significant difference between the two groups. Canonical correlation analysis revealed a significant relationship between the atypical functional covariance and stereotyped behaviors of ASD. The results indicated an altered functional co-developmental pattern between WM and GM in ASD. LAY SUMMARY: White matter (WM) and gray matter (GM) are two major human brain organs supporting brain function. WM and GM functions show a specific co-developmental pattern in typical developed individuals. This study showed that this GM/WM co-developmental pattern was altered in children with ASD, while this altered GM/WM co-developmental pattern was related to stereotyped behaviors. These findings may help understand the GM/WM functional development of ASD.

Parcellation of the thalamus by using a dual-segment method based on resting-state functional connectivity: An application on autism spectrum disorder.

BACKGROUND: Evidence suggests thalamus is a key "information relay" center and all cortical areas receive inputs from the thalamus and each of the main nuclei of thalamus connects a single one or a few cortical areas. The traditional "winner-takes-all" thalamus parcellation method was then proposed based on this assumption. However, this method is based on the structural segments of the cortex which is not suitable for the functional parcellation of the thalamus. METHOD: Here we proposed a dual-segment method for thalamus functional parcellation based on the resting-state fMRI data. The traditional "winner-takes-all" and the proposed dual-segment methods were both applied to the dataset of 76 healthy controls (HCs) and 34 subjects with autism spectrum disorder. RESULTS: The results showed that the thalamus was subdivided into two sub-regions by using the dual-segment method: one is located in the dorsomedial part of thalamus which connects the high-level cognitive cortical regions; the other is located in the ventrolateral part of thalamus which connects the low-level sensory cortical areas. The functional connectivity strength between thalamus sub-regions and the corresponding cortical regions based on the dual-segment method was higher than that of results from the traditional "winner-takes-all" method. The thalamo-cortical functional connectivity based on our proposed method also showed higher classification ability to distinguish subjects with autism spectrum disorder from HCs. CONCLUSION: Our study will provide a new method for functional thalamus parcellation which might help understand the sub-regions functions of thalamus in neuroscience studies.