NAA10 gene related Ogden syndrome with obstructive hypertrophic cardiomyopathy: A rare case report.

RATIONALE: Ogden syndrome is an exceptionally rare X-linked disease caused by mutations in the NAA10 gene. Reported cases of this syndrome are approximately 20 children and are associated with facial dysmorphism, growth delay, developmental disorders, congenital heart disease, and arrhythmia. PATIENT CONCERNS: We present the clinical profile of a 3-year-old girl with Ogden syndrome carrying a de novo NAA10 variant [NM_003491:c.247C>T, p.(Arg83Cys)]. During infancy, she exhibited features such as left ventricular hypertrophy, protruding eyeballs, and facial deformities. DIAGNOSIS: Clinical diagnosis included Ogden syndrome, congenital heart disease (obstructive hypertrophic cardiomyopathy, left ventricular outflow tract obstruction, mitral valve disease, tricuspid valve regurgitation), tonsillar and adenoidal hypertrophy, and speech and language delay. INTERVENTIONS: The girl was considered to have hypertrophic cardiomyopathy (HCM) and received oral metoprolol as a treatment for HCM at our hospital. The drug treatment effect was not ideal, and her hypertrophy myocardial symptoms were aggravated and she had to be hospitalized for surgery. OUTCOMES: The girl underwent a modified Morrow procedure under cardiopulmonary bypass and experienced a favorable postoperative recovery. No pulmonary infections or significant complications were observed during this period. The patient's family expressed satisfaction with the treatment process. LESSONS: The case emphasizes the HCM of Odgen syndrome, and early surgery should be performed if drug treatment is ineffective.

OncoCTMiner: streamlining precision oncology trial matching via molecular profile analysis.

By establishing omics sequencing of patient tumors as a crucial element in cancer treatment, the extensive implementation of precision oncology necessitates effective and prompt execution of clinical studies for approving molecular-targeted therapies. However, the substantial volume of patient sequencing data, combined with strict clinical trial criteria, increasingly complicates the process of matching patients to precision oncology studies. To streamline enrollment in these studies, we developed OncoCTMiner, an automated pre-screening platform for molecular cancer clinical trials. Through manual tagging of eligibility criteria for 2227 oncology trials, we identified key bio-concepts such as cancer types, genes, alterations, drugs, biomarkers and therapies. Utilizing this manually annotated corpus along with open-source biomedical natural language processing tools, we trained multiple named entity recognition models specifically designed for precision oncology trials. These models analyzed 460 952 clinical trials, revealing 8.15 million precision medicine concepts, 9.32 million entity-criteria-trial triplets and a comprehensive precision oncology eligibility criteria database. Most significantly, we developed a patient-trial matching system based on cancer patients' clinical and genetic profiles, which can seamlessly integrate with the omics data analysis platform. This system expedites the pre-screening process for potentially suitable precision oncology trials, offering patients swifter access to promising treatment options. Database URL  https://oncoctminer.chosenmedinfo.com.

Global burden of atrial fibrillation/atrial flutter and its attributable risk factors from 1990 to 2019.

AIMS: The aim of this study was to estimate the global burden of atrial fibrillation (AF)/atrial flutter (AFL) and its attributable risk factors from 1990 to 2019. METHODS AND RESULTS: The data on AF/AFL were retrieved from the Global Burden of Disease Study (GBD) 2019. Incidence, disability-adjusted life years (DALYs), and deaths were metrics used to measure AF/AFL burden. The population attributable fractions (PAFs) were used to calculate the percentage contributions of major potential risk factors to age-standardized AF/AFL death. The analysis was performed between 1990 and 2019. Globally, in 2019, there were 4.7 million [95% uncertainty interval (UI): 3.6 to 6.0] incident cases, 8.4 million (95% UI: 6.7 to 10.5) DALYs cases, and 0.32 million (95% UI: 0.27 to 0.36) deaths of AF/AFL. The burden of AF/AFL in 2019 and their temporal trends from 1990 to 2019 varied widely due to gender, Socio-Demographic Index (SDI) quintile, and geographical location. Among all potential risk factors, age-standardized AF/AFL death worldwide in 2019 were primarily attributable to high systolic blood pressure [34.0% (95% UI: 27.3 to 41.0)], followed by high body mass index [20.2% (95% UI: 11.2 to 31.2)], alcohol use [7.4% (95% UI: 5.8 to 9.0)], smoking [4.3% (95% UI: 2.9 to 5.9)], diet high in sodium [4.2% (95% UI: 0.8 to 10.5)], and lead exposure [2.3% (95% UI: 1.3 to 3.4)]. CONCLUSION: Our study showed that AF/AFL is still a major public health concern. Despite the advancements in the prevention and treatment of AF/AFL, especially in regions in the relatively SDI quintile, the burden of AF/AFL in regions in lower SDI quintile is increasing. Since AF/AFL is largely preventable and treatable, there is an urgent need to implement more cost-effective strategies and interventions to address modifiable risk factors, especially in regions with high or increased AF/AFL burden.

The deubiquitinating enzyme ATXN3 promotes the progression of anaplastic thyroid carcinoma by stabilizing EIF5A2.

Ataxin-3 (ATXN3) is a ubiquitous deubiquitinating enzyme that plays an essential role in the carcinogenesis of numerous tumors and stabilizes the expression of substrates by deubiquitination. However, the functional role of ATXN3 in anaplastic thyroid carcinoma (ATC) remains unknown. In this research, we report that ATXN3 was overexpressed in ATC compared to that in paracancerous samples. Moreover, various gain/loss functional assays were performed to indicate that ATXN3 overexpression enhanced ATC cell proliferation and metastasis. We also found that ATXN3 and eukaryotic translation initiation factor 5A2 (EIF5A2) protein levels in ATC tissues are positively correlated, and ATXN3 promotes the proliferation and metastasis of ATC cells through EIF5A2. Mechanistically, ATXN3 promotes EIF5A2 expression by directly binding to EIF5A2 to reduce its ubiquitination and degradation. Therefore, for the first time, we clarified the role of ATXN3 in the carcinogenesis of ATC cells, which provides novel insights into potential therapeutic targets for ATC progression.

Transcriptomic analysis of interstock-induced dwarfism in Sweet Persimmon (Diospyros kaki Thunb.).

Growth monitoring indicated that the height of 'Kanshu' plants with 'Nantong-xiaofangshi' as an interstock was significantly shorter than that of 'Kanshu' plants with no interstock. A transcriptome analysis of the two graft combinations ('Kanshu'/Diospyros lotus and 'Kanshu'/'Nantong-xiaofangshi'/Diospyros lotus) was conducted to explore the dwarfing genes related to the use of the 'Nantong-xiaofangshi' interstock. Hormone levels and water conductance were also measured in these two graft combinations. The results indicated that the levels of both IAA and GA were lower in 'Kanshu' that had been grafted onto the 'Nantong-xiaofangshi' interstock than in 'Kanshu' with no interstock; additionally, the water conductance was lower in grafts with interstocks than in grafts without interstocks. The expression of AUX/IAA and auxin-responsive GH3 genes was enhanced in scions grafted on the interstock and was negatively correlated with the IAA content and growth of scions. The expression of GA2ox, DELLA, and SPINDLY genes were also upregulated and associated with a decrease in the level of GA in scions grafted on the interstock. Since one of the GA2ox unigenes was annotated as DkGA2ox1 in Diospyros kaki, but was not functionally validated, a functional analysis was conducted in transgenic tobacco. Overexpression of DkGA2ox1 in transgenic plants resulted in a dwarf phenotype that could be recovered by the exogenous application of GA3. We conclude that the 'Nantong-xiaofangshi' interstock affects the water conductance and expression of genes related to the metabolism and transduction of IAA and GA in the grafted scion and thus regulates phytohormone levels, producing dwarfing.

[Expression and significance of VEGF, VEGF-C, and VEGF-D in papillary thyroid carcinoma].

BACKGROUND & OBJECTIVE: Vascular endothelial growth factor-C and -D (VEGF-C, VEGF-D) are related to lymphangiogenesis. Papillary thyroid carcinoma is characterized by regional lymph node metastasis. This study was designed to determine the expression and significance of VEGF, VEGF-C, and VEGF-D in papillary thyroid carcinoma. METHODS: The expression of VEGF, VEGF-C, and VEGF-D in 115 specimens of papillary thyroid carcinoma and 20 specimens of nodular goiter were detected by SP immunohistochemistry. RESULTS: Positive rates of VEGF, VEGF-C, and VEGF-D were significantly higher in papillary thyroid carcinoma than in nodular goiter (79.1% vs. 30.0%, 87.0% vs. 15.0%, and 72.2% vs. 20.0%, P<0.01). The expression of VEGF was closely related to the size of papillary thyroid carcinoma. Positive rates of VEGF were 84.7% in lymph node positive group, and 73.2% in lymph node negative group. Positive rates of VEGF-C and VEGF-D were significantly higher in lymph node positive group than in lymph node negative group (93.2% vs. 80.4%, P<0.05; 83.1% vs. 60.7%, P<0.01). CONCLUSION: VEGF is closely related to tumor growth of papillary thyroid carcinoma; while VEGF-C and VEGF-D are closely related to lymph node metastasis of papillary thyroid carcinoma, and may be predictors of lymph node metastasis.