Plasma Resolvin D2 to Leukotriene B4 Ratio Is Reduced in Diabetic Patients with Ischemic Stroke and Related to PrognosisRead the full article
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A Myocardial Segmentation Method Based on Adversarial Learning
Congenital heart defects (CHD) are structural imperfections of the heart or large blood vessels that are detected around birth and their symptoms vary wildly, with mild case patients having no obvious symptoms and serious cases being potentially life-threatening. Using cardiovascular magnetic resonance imaging (CMRI) technology to create a patient-specific 3D heart model is an important prerequisite for surgical planning in children with CHD. Manually segmenting 3D images using existing tools is time-consuming and laborious, which greatly hinders the routine clinical application of 3D heart models. Therefore, automatic myocardial segmentation algorithms and related computer-aided diagnosis systems have emerged. Currently, the conventional methods for automatic myocardium segmentation are based on deep learning, rather than on the traditional machine learning method. Better results have been achieved, however, difficulties still exist such as CMRI often has, inconsistent signal strength, low contrast, and indistinguishable thin-walled structures near the atrium, valves, and large blood vessels, leading to challenges in automatic myocardium segmentation. Additionally, the labeling of 3D CMR images is time-consuming and laborious, causing problems in obtaining enough accurately labeled data. To solve the above problems, we proposed to apply the idea of adversarial learning to the problem of myocardial segmentation. Through a discriminant model, some additional supervision information is provided as a guide to further improve the performance of the segmentation model. Experiment results on real-world datasets show that our proposed adversarial learning-based method had improved performance compared with the baseline segmentation model and achieved better results on the automatic myocardium segmentation problem.
A novel TUBG1 mutation with neurodevelopmental disorder caused by malformations of cortical development
Neurodevelopmental disorder caused by malformations of cortical development is a rare neurological disease. Heterozygous missense variants in the TUBG1 gene lead to malformations of human cortical development, which further result in intellectual disability, developmental retardation, and epilepsy. To the best of our knowledge, only thirteen patients and a total of nine pathogenic TUBG1 variants have been described in the published literature. This study reports the case details and genetic data analysis of a girl (aged 8 years, 9 months) with developmental delay, psychomotor regression, epilepsy, and left external ear deformity. A novel TUBG1 mutation was identified by whole-exome sequencing and Sanger sequencing, confirming that this mutation may be the cause of the neurodevelopmental disorders. This case report characterizes the phenotypic spectrum, molecular genetic findings, and functional consequences of novel pathogenic TUBG1 variants in neurodevelopmental disorders caused by cortical development malformations.
The Polymorphism Analyses of Short Tandem Repeats as a Basis for Understanding the Genetic Characteristics of the Guanzhong Han Population
The short tandem repeat (STR) loci are polymorphic markers in the combined DNA index system (CODIS) and non-CODIS STR loci. Due to the highly polymorphic characteristic of STR loci, they are popular and widely used in forensic DNA typing laboratories. In this study, 22 STR loci (1 CODIS, 21 non-CODIS STR loci) and an Amelogenin locus were genotyped and analyzed in 590 unrelated individuals of the Guanzhong Han population. None of the 22 STR loci deviated from the Hardy–Weinberg equilibrium, and all the loci were in the linkage equilibrium state. We observed 247 alleles, and the corresponding allelic frequencies ranged from 0.0008 to 0.3695 in the Guanzhong Han population. The combined power of discrimination and the cumulative exclusion probability was 0.999 999 999 999 999 999 999 999 999 346 36 and 0.999 999 999 709 74, respectively. The results including Nei’s genetic distance, multidimensional scaling analysis, and principal component analysis showed that the Guanzhong Han population has closer genetic affinities with Northern Han, Chengdu Han, and Xinjiang Hui groups from China based on allelic frequencies of 15 overlapped STR loci from Guanzhong Han and 13 reference groups. The present results indicated that Microreader™ 23sp ID kit included highly polymorphic loci, and it could be well used for individual identification, paternity testing, and population genetics in the Guanzhong Han population.
A New Mutation of the INSR Gene in a 13-Year-Old Girl with Severe Insulin Resistance Syndrome in China
Background. Mutations in insulin receptor genes can cause severe insulin resistance syndrome. Compared with Rabson-Mendenhall Syndrome and Donohue’s Syndrome, type A insulin resistance syndrome is generally not serious. The main manifestations in woman with type A insulin resistance syndrome are hyperinsulinemia, insulin resistance, acanthosis nigricans, hyperandrogenism, and polycystic ovary. Case Presentation. A 13-year-old girl (Han nationality) visited the hospital due to hairiness and acanthosis nigricans. Further examination revealed severe hyperinsulinemia, insulin resistance, elevated blood glucose, hyperandrogenism, and polycystic ovary. Analysis of the insulin receptor gene by sequencing showed the presence of a nucleotide change in intron 7 (c. 1610+1G > A). The mutation was a splicing mutation, which can obviously affect the mRNA splicing of the insulin receptor and cause its function loss. The patient was finally diagnosed with type A insulin resistance syndrome. After 2 months of metformin treatment, the patient had spontaneous menstrual cramps and significantly improved acanthosis nigricans and sex hormones. Conclusion. We report for the first time a new splicing mutation on the insulin receptor gene at the 7th intron (c.1610+1G > A), which leads to type A insulin resistance syndrome. In clinically suspected patients with polycystic ovary syndrome, if there are extremely high blood levels of insulin in the blood, genetic testing should be performed to detect insulin receptor gene mutation of type A insulin resistance syndrome.
Immunoinformatics and Molecular Docking Studies Predicted Potential Multiepitope-Based Peptide Vaccine and Novel Compounds against Novel SARS-CoV-2 through Virtual Screening
Background. Coronaviruses (CoVs) are enveloped positive-strand RNA viruses which have club-like spikes at the surface with a unique replication process. Coronaviruses are categorized as major pathogenic viruses causing a variety of diseases in birds and mammals including humans (lethal respiratory dysfunctions). Nowadays, a new strain of coronaviruses is identified and named as SARS-CoV-2. Multiple cases of SARS-CoV-2 attacks are being reported all over the world. SARS-CoV-2 showed high death rate; however, no specific treatment is available against SARS-CoV-2. Methods. In the current study, immunoinformatics approaches were employed to predict the antigenic epitopes against SARS-CoV-2 for the development of the coronavirus vaccine. Cytotoxic T-lymphocyte and B-cell epitopes were predicted for SARS-CoV-2 coronavirus protein. Multiple sequence alignment of three genomes (SARS-CoV, MERS-CoV, and SARS-CoV-2) was used to conserved binding domain analysis. Results. The docking complexes of 4 CTL epitopes with antigenic sites were analyzed followed by binding affinity and binding interaction analyses of top-ranked predicted peptides with MHC-I HLA molecule. The molecular docking (Food and Drug Regulatory Authority library) was performed, and four compounds exhibiting least binding energy were identified. The designed epitopes lead to the molecular docking against MHC-I, and interactional analyses of the selected docked complexes were investigated. In conclusion, four CTL epitopes (GTDLEGNFY, TVNVLAWLY, GSVGFNIDY, and QTFSVLACY) and four FDA-scrutinized compounds exhibited potential targets as peptide vaccines and potential biomolecules against deadly SARS-CoV-2, respectively. A multiepitope vaccine was also designed from different epitopes of coronavirus proteins joined by linkers and led by an adjuvant. Conclusion. Our investigations predicted epitopes and the reported molecules that may have the potential to inhibit the SARS-CoV-2 virus. These findings can be a step towards the development of a peptide-based vaccine or natural compound drug target against SARS-CoV-2.
Enhanced Biofilm Eradication and Reduced Cytotoxicity of a Novel Polygalacturonic and Caprylic Acid Wound Ointment Compared with Common Antiseptic Ointments
Antiseptic wound ointments are widely used to treat dermal wounds that are microbially contaminated. Polygalacturonic acid (PG)+caprylic acid (CAP) is a novel combination that has been shown to eradicate biofilms. We developed a novel PG+CAP ointment and compared the biofilm eradication capability and cytotoxicity of PG+CAP with that of commercially available antiseptic wound ointments. We used a well-established biofilm model to quantitatively assess the eradication of organisms following exposure to the wound ointments for 2 hours. PG+CAP ointment completely eradicated Candida albicans, multidrug-resistant Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus biofilms, whereas MediHoney, polyhexamethylene biguanide (PHMB), and benzalkonium chloride (BZK) ointments failed to eradicate all biofilms within 2 hours. We assessed cytotoxicity by exposing L-929 fibroblasts to extracts of each ointment; Trypan blue exclusion was used to assess cell viability, and Alamar blue conversion was used to assess metabolic function. After exposure to PG+CAP and MediHoney, fibroblast viability was 96.23% and 95.23%, respectively (Trypan blue), and was comparable to untreated cells (98.77%). PHMB and BZK showed reduced viability (83.25% and 77.83%, respectively, ). Metabolic activity results followed a similar pattern. Cytotoxicity of PG+CAP ointment towards erythrocytes was comparable to saline. PG+CAP ointment seems to be safe and can rapidly eradicate microbial biofilm; thus, PG+CAP ointment merits further in vivo testing as a potential antimicrobial wound ointment.