A master list of distinct genes was supplemented with additional genes identified through PubMed searches up to August 15, 2022, with the search criteria being 'genetics' and/or 'epilepsy' and/or 'seizures'. Manual evaluation of evidence backing a singular genetic role for each gene was performed; those possessing limited or contested evidence were removed. Annotation of all genes was performed considering both inheritance patterns and broad epilepsy phenotypes.
Comparing genes included in epilepsy clinical testing panels revealed a substantial disparity in both the number of genes (144 to 511 range) and their respective types. All four clinical panels exhibited a shared set of 111 genes, accounting for 155 percent of the genes examined. Subsequent manual curation of all epilepsy genes yielded more than 900 distinct monogenic etiologies. In nearly 90% of the genes examined, an association with developmental and epileptic encephalopathies was observed. Differing from other factors, a mere 5% of genes were shown to be associated with monogenic origins in common epilepsies, such as generalized and focal epilepsy syndromes. Autosomal recessive genes represented the most frequent type (56%), but their proportion varied according to the epilepsy phenotype(s) involved. Genes responsible for common epilepsy syndromes exhibited a tendency towards dominant inheritance and association with various forms of epilepsy.
Our curated collection of monogenic epilepsy genes, accessible on github.com/bahlolab/genes4epilepsy, is updated routinely. This gene resource provides a pathway to identify genes beyond the scope of conventional clinical gene panels, empowering gene enrichment methods and candidate gene prioritization. Feedback and ongoing contributions from the scientific community are appreciated and can be submitted to [email protected].
A regularly updated, publicly available list of monogenic epilepsy genes can be found on github.com/bahlolab/genes4epilepsy. Gene enrichment and candidate gene prioritization methods can incorporate this gene resource to explore genes outside the typical confines of clinical gene panels. We invite the ongoing contributions and feedback from the scientific community, reaching us at [email protected].
In recent years, massively parallel sequencing, frequently referred to as next-generation sequencing (NGS), has substantially altered both the research and diagnostic fields, fostering the integration of NGS technologies into clinical practice, enhancing analytical processes, and improving the detection of genetic mutations. HIV phylogenetics This paper seeks to review the economic evaluations undertaken on the utilization of next-generation sequencing (NGS) in the diagnosis of genetic diseases. learn more A thorough examination of the economic evaluation of NGS techniques for genetic disease diagnosis was conducted via a systematic review. Databases including PubMed, EMBASE, Web of Science, Cochrane, Scopus, and the CEA registry were screened for pertinent literature from 2005 to 2022. Independent researchers, two in total, executed full-text review and data extraction. With the Checklist of Quality of Health Economic Studies (QHES) as the evaluation framework, all included articles within this study had their quality assessed. Of the 20521 screened abstracts, a mere 36 met the stipulated inclusion criteria. In the analysis of the studies, a mean score of 0.78 was achieved on the QHES checklist, reflecting high quality results. Seventeen studies were designed and executed, with modeling at their core. Employing cost-effectiveness analysis, 26 studies were examined; 13 studies used cost-utility analysis; and 1 study utilized cost-minimization analysis. The available evidence and study results suggest that exome sequencing, a next-generation sequencing technique, might function as a cost-effective genomic test for diagnosing suspected genetic disorders in children. The investigation presented here supports the cost-efficient nature of exome sequencing in the diagnostic process for suspected genetic disorders. However, the use of exome sequencing for initial or secondary diagnostic purposes continues to be a subject of disagreement. While many studies focus on high-income countries, investigating the cost-effectiveness of Next-Generation Sequencing (NGS) methods in low- and middle-income countries is warranted.
Thymic epithelial tumors, or TETs, are a rare category of malignant growths that stem from the thymus gland. Early-stage disease patients still rely heavily on surgery as their primary mode of treatment. Relatively few treatment options exist for unresectable, metastatic, or recurrent TETs, with their clinical efficacy being only modestly beneficial. The development of immunotherapies for solid tumors has fostered a keen interest in understanding their influence on therapies for TET. Nonetheless, the high prevalence of comorbid paraneoplastic autoimmune disorders, specifically in thymoma, has decreased the anticipated effectiveness of immune-based treatment approaches. Immune checkpoint blockade (ICB) clinical trials in thymoma and thymic carcinoma demonstrate a concerning trend of increased immune-related adverse events (IRAEs), alongside disappointing treatment effectiveness. In spite of these difficulties, the developing insight into the thymic tumor microenvironment and the encompassing immune system has contributed to a better grasp of these diseases, creating new potential for novel immunotherapy. In order to enhance clinical efficiency and reduce the possibility of IRAE, ongoing investigations are examining numerous immune-based treatments in TETs. This review will discuss the current understanding of the thymic immune microenvironment, evaluate previous immune checkpoint blockade studies, and provide an overview of currently investigated treatments for TET.
In chronic obstructive pulmonary disease (COPD), lung fibroblasts are central to the disruption of tissue repair processes. The details of the underlying processes are yet to be determined, and a detailed analysis comparing COPD- and control fibroblasts is absent. Unbiased proteomic and transcriptomic analyses are employed in this study to explore the role of lung fibroblasts within the pathophysiology of chronic obstructive pulmonary disease. From cultured parenchymal lung fibroblasts of 17 Stage IV COPD patients and 16 healthy controls, protein and RNA were extracted. The method of protein analysis was LC-MS/MS, and RNA sequencing was used to examine RNA. In COPD, differential protein and gene expression were examined through linear regression, subsequent pathway enrichment analysis, correlation analysis, and immunohistological staining of pulmonary tissue. An investigation into the overlap and correlation between proteomic and transcriptomic data was undertaken by comparing the two. The study of COPD and control fibroblasts yielded a finding of 40 differentially expressed proteins, but no genes exhibited differential expression. The DE proteins of greatest importance were HNRNPA2B1 and FHL1. From the total of 40 proteins assessed, 13 were previously reported in association with chronic obstructive pulmonary disease (COPD), exemplified by FHL1 and GSTP1. The six proteins amongst forty that were related to telomere maintenance pathways were positively correlated with the senescence marker LMNB1. Analysis of the 40 proteins demonstrated no significant relationship between gene and protein expression. In this report, we describe 40 DE proteins in COPD fibroblasts, including already documented COPD proteins (FHL1 and GSTP1), as well as emerging COPD research targets, including HNRNPA2B1. The divergence and lack of correlation between gene and protein data advocates for the use of unbiased proteomic approaches, revealing that each method generates a unique data type.
A crucial attribute of solid-state electrolytes for lithium metal batteries is their high room-temperature ionic conductivity, together with their compatibility with lithium metal and cathode materials. Solid-state polymer electrolytes (SSPEs) are fabricated through the innovative fusion of two-roll milling technology and interface wetting. High room-temperature ionic conductivity (4610-4 S cm-1), excellent electrochemical oxidation stability (up to 508 V), and improved interface stability characterize the as-prepared electrolytes consisting of an elastomer matrix and a high mole loading of LiTFSI salt. These phenomena find their rationale in the formation of continuous ion conductive paths, a consequence of refined structural characterization, incorporating methodologies like synchrotron radiation Fourier-transform infrared microscopy and wide- and small-angle X-ray scattering. Regarding the LiSSPELFP coin cell, at room temperature, it exhibits high capacity (1615 mAh g-1 at 0.1 C), an extended lifespan (50% capacity and 99.8% Coulombic efficiency maintained after 2000 cycles), and good performance with various C-rates, up to 5 C. bioheat equation This study, consequently, presents a robust solid-state electrolyte, satisfying both the electrochemical and mechanical demands of viable lithium metal batteries.
The catenin signaling pathway exhibits abnormal activation within the context of cancer. A human genome-wide library is employed in this study to assess the mevalonate metabolic pathway enzyme PMVK's impact on the stability of β-catenin signaling. MVA-5PP, manufactured by PMVK, displays competitive binding to CKI, which, in turn, stops -catenin's Ser45 phosphorylation and subsequent degradation. Unlike other enzymes, PMVK acts as a protein kinase, specifically phosphorylating -catenin at serine 184, consequently increasing its nuclear presence. A combined effect of PMVK and MVA-5PP stimulates -catenin signaling. Additionally, the ablation of PMVK impedes mouse embryonic development, resulting in embryonic fatality. The detrimental effects of DEN/CCl4-induced hepatocarcinogenesis are mitigated in liver tissue where PMVK is deficient. This observation spurred the development of PMVKi5, a small-molecule inhibitor of PMVK, which was found to inhibit carcinogenesis in both liver and colorectal tissues.