Ten-Year Change in Disorders of Consciousness: A Bibliometric Analysis

Objectives: Disorders of consciousness (DoC) is a dynamic and challenging discipline, presenting intriguing challenges to clinicians and neurorehabilitation specialists for the lack of reliable assessment methods and interventions. Understanding DoC keeps pace with scientific research is urgent to need. We quantitively analyzed publications on DoC over the recent 10 years via bibliometrics analysis, to summarize the intellectual structure, current research hotspots, and future research trends in the field of DoC. Methods: Literature was obtained from the Science Citation Index Expanded of Web of Science Core Collection (WoSCC). To illustrate the knowledge structure of DoC, CiteSpace 5.8.R3 was used to conduct a co-occurrence analysis of countries, institutions, and keywords, and a co-citation analysis of references and journals. Also, Gephi 0.9.2 contributed to the author and co-cited author analysis. We found the most influential journals, authors, and countries and the most talked about keywords in the last decade of research. Results: A total of 1919 publications were collected. Over the past 10 years, the total number of annual publications has continued to increase, with the largest circulation in 2018. We found most DoC research and close cooperation originated from developed countries, e.g., the USA, Canada, and Italy. Academics from Belgium appear to have a strong presence in the field of DoC. The most influential journals were also mainly distributed in the USA and some European countries. Conclusions: This bibliometric study sheds light on the knowledge architecture of DoC research over the past decade, reflecting current hotspots and emerging trends, and providing new insights for clinicians and academics interested in DoC. The hot issues in DoC were diagnosing and differentiating the level of consciousness, and detecting covert awareness in early severe brain-injured patients. New trends focus on exploring the recovery mechanism of DoC and neuromodulation techniques

Atypical features and de novo heterozygous mutations in two siblings with Cockayne syndrome

Abstract Background Cockayne syndrome (CS) is a rare autosomal recessive disorder which displays multiorgan dysfunction, especially within the nervous system including psychomotor retardation, cerebral atrophy, microcephaly, cognitive dysfunction, mental retardation, and seizures. Many genetic variations reported were related to this syndrome, but splicing mutations with cardiac anomalies have not been found in previous studies. Methods Herein, we described a pair of brothers and sisters who present essential manifestations of CS including premature feature, developmental delay, growth failure, microcephaly, and characteristic facial features, such as sunken eyes and a beaked nose. Interestingly, the brother also presented with atypical features which included cardiac anomalies such as left atrioventricular enlargement and cardiac dysfunction such as dilated cardiomyopathy. In addition, whole exome sequencing and RNA sequencing were employed to analyze their genetic landscape. Results WES analysis showed that these two cases carried double unreported heterozygous spliced mutations in the excision repair cross‐complementing group 8 (ERCC8, also known as CSA, NM_000082) gene, which were c.78‐2 (IVS1) A>T and c.1042‐1 (IVS10) G>A, respectively. Moreover, transcript sequencing analysis validated these mutation sites. In this study, Gene Ontology enrichment and KEGG pathway analyses from RNA sequencing demonstrated similarities but some differences when compared with previous studies. Conclusion For patients with Cockayne syndrome, cardiac changes need to be monitored carefully, especially for cases with splicing mutations of the ERCC8 gene

BRD4 PROTAC degrader MZ1 exhibits anti-B-cell acute lymphoblastic leukemia effects via targeting CCND3

ABSTRACTIntroduction B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent malignant tumor affecting children. While the majority of B-ALL patients (90%) experience successful recovery, early relapse cases of B-ALL continue to exhibit high mortality rates. MZ1, a novel inhibitor of Bromodomains and extra-terminal (BET) proteins, has demonstrated potent antitumor activity against hematological malignancies. The objective of this study was to examine the role and therapeutic potential of MZ1 in the treatment of B-ALL.Methods In order to ascertain the fundamental mechanism of MZ1, a sequence of in vitro assays was conducted on B-ALL cell lines, encompassing Cell Counting Kit 8 (CCK8) assay, Propidium iodide (PI) staining, and Annexin V/PI staining. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to examine protein and mRNA expression levels. Transcriptomic RNA sequencing (RNA-seq) was utilized to screen the target genes of MZ1, and lentiviral transfection was employed to establish stably-expressing/knockdown cell lines.Results MZ1 has been observed to induce the degradation of Bromodomain Containing 4 (BRD4), Bromodomain Containing 3 (BRD3), and Bromodomain Containing 2 (BRD2) in B-ALL cell strains, leading to inhibited cell growth and induction of cell apoptosis and cycle arrest in vitro. These findings suggest that MZ1 exhibits cytotoxic effects on two distinct molecular subtypes of B-ALL, namely 697 (TCF3/PBX1) and RS4;11 (MLL-AF4) B-ALL cell lines. Additionally, RNA-sequencing analysis revealed that MZ1 significantly downregulated the expression of Cyclin D3 (CCND3) gene in B-ALL cell lines, which in turn promoted cell apoptosis, blocked cell cycle, and caused cell proliferation inhibition.Conclusion Our results suggest that MZ1 has potential anti-B-ALL effects and might be a novel therapeutic target

BRD4 PROTAC degrader MZ1 exhibits anti-B-cell acute lymphoblastic leukemia effects via targeting CCND3

B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent malignant tumor affecting children. While the majority of B-ALL patients (90%) experience successful recovery, early relapse cases of B-ALL continue to exhibit high mortality rates. MZ1, a novel inhibitor of Bromodomains and extra-terminal (BET) proteins, has demonstrated potent antitumor activity against hematological malignancies. The objective of this study was to examine the role and therapeutic potential of MZ1 in the treatment of B-ALL. In order to ascertain the fundamental mechanism of MZ1, a sequence of in vitro assays was conducted on B-ALL cell lines, encompassing Cell Counting Kit 8 (CCK8) assay, Propidium iodide (PI) staining, and Annexin V/PI staining. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to examine protein and mRNA expression levels. Transcriptomic RNA sequencing (RNA-seq) was utilized to screen the target genes of MZ1, and lentiviral transfection was employed to establish stably-expressing/knockdown cell lines. MZ1 has been observed to induce the degradation of Bromodomain Containing 4 (BRD4), Bromodomain Containing 3 (BRD3), and Bromodomain Containing 2 (BRD2) in B-ALL cell strains, leading to inhibited cell growth and induction of cell apoptosis and cycle arrest in vitro. These findings suggest that MZ1 exhibits cytotoxic effects on two distinct molecular subtypes of B-ALL, namely 697 (TCF3/PBX1) and RS4;11 (MLL-AF4) B-ALL cell lines. Additionally, RNA-sequencing analysis revealed that MZ1 significantly downregulated the expression of Cyclin D3 (CCND3) gene in B-ALL cell lines, which in turn promoted cell apoptosis, blocked cell cycle, and caused cell proliferation inhibition. Our results suggest that MZ1 has potential anti-B-ALL effects and might be a novel therapeutic target.</p