Alcohol consumption, which affects the structure and composition of the laryngeal microbiota, is one of the most important risk factors for laryngeal squamous cell cancer (LSCC). Our results demonstrated that high enrichment of Fusobacterium nucleatum (F. nucleatum) in LSCC was associated with poor prognosis. F. nucleatum increased miR-155-5p and miR-205-5p expression to suppress alcohol dehydrogenase 1B (ADH1B) and transforming growth factor β receptor 2 (TGFBR2) expression by activating innate immune signaling, resulting in ethanol metabolism reprogramming to allow F. nucleatum accumulation and PI3K/AKT signaling pathway activation to promote epithelial-mesenchymal transition, further exacerbating the uncontrolled progression and metastasis of LSCC. Therefore, the positive feed-forward loop between F. nucleatum and ethanol metabolism reprogramming promotes cell proliferation, migration, and invasion to affect LSCC patient prognosis. The amount of F. nucleatum is a potential prognostic biomarker, which yields valuable insight into clinical management that may improve the oncologic outcome of patients with LSCC.
24 March 2024 in Proceedings of the AAAI Conference on Artificial Intelligence
Recently, the evaluation of Large Language Models has emerged as a popular area of research. The three crucial questions for LLM evaluation are ``what, where, and how to evaluate''. However, the existing research mainly focuses on the first two questions, which are basically what tasks to give the LLM during testing and what kind of knowledge it should deal with. As for the third question, which is about what standards to use, the types of evaluators, how to score, and how to rank, there hasn't been much discussion. In this paper, we analyze evaluation methods by comparing various criteria with both manual and automatic evaluation, utilizing onsite, crowd-sourcing, public annotators and GPT-4, with different scoring methods and ranking systems. We propose a new dataset, LLMEval and conduct evaluations on 20 LLMs. A total of 2,186 individuals participated, leading to the generation of 243,337 manual annotations and 57,511 automatic evaluation results. We perform comparisons and analyses of different settings and conduct 10 conclusions that can provide some insights for evaluating LLM in the future. The dataset and the results are publicly available at https://github.com/llmeval. The version with the appendix are publicly available at https://arxiv.org/abs/2312.07398.
Primary tumors of the heart are rarely seen. Cardiac angiosarcomas are malignant tumors that almost always have a poor prognosis. Atrium rupture and coronary artery fistula are very rare complications of primary cardiac angiosarcoma. We describe a 57-year-old man suffering from primary cardiac angiosarcoma with spontaneous ruptures of the right atrium and right coronary artery (RCA). Theoretically, either of these ruptures invariably results in pericardial effusion and tamponade that is rare but potentially life threatening. In this instance, however, the patient might have developed fibrous adhesions resulted from previous bloody pericardial effusion. A massive pericardial effusion was localized, which consequently prevented cardiac tamponade and hemodynamic collapse. Echocardiography revealed the tumor progression leading to detectable infiltration of solid mass into the right atrial (RA) wall, which is close to RCA. And color Doppler displayed the flow into the pericardial cavity through a disrupted RA wall and perforated RCA. Echocardiography remains the primary method of choice for evaluation of cardiac masses.
Aims: To explore the clinical characteristics and treatment of malignant minor salivary gland carcinomas of the larynx. Methods: Clinical patient information regarding presentation, pathology, treatment and outcome was obtained through a review of patient charts. Results: Malignant minor salivary carcinomas in the larynx were confirmed pathologically in 15 patients (11 males, 4 females) between 2003 and 2010 in our hospital; 6 patients had mucoepidermoid carcinoma (MEC; 40%), 6 had adenoid cystic carcinoma (ACC; 40%) and 3 had adenocarcinoma (20%). The most common tumour location was the subglottis (60%), followed by the supraglottis (33%). In total, 13 patients underwent surgery, of which 10 (77%) had positive/insufficient resection margins. The mean follow-up time was 42.3 months, with a range of 8-129 months. The 3- and 5-year overall survival rates were 46.7 and 20%, respectively. Conclusion: Malignant minor salivary gland carcinoma of the larynx is a rare disease that showed male predominance in our study. The carcinomas were most often localised in the subglottic region, and the most common histological types were ACC and MEC. Wide-margin surgery with postoperative radiotherapy is advocated. The overall prognosis is poor compared to squamous cell carcinomas of the same location and tumour stage.
Original Article Dual inhibition of autophagy and PI3K/mTOR pathway as a potential therapeutic strategy against laryngeal squamous cell carcinoma Hui-Ying Huang, Ke-Nan Li, Hui-Ching Lau, Chi-Yao Hsueh, Ning Cong, Ming Zhang
Background: Fusobacterium nucleatum (F. nucleatum) is a vital pro-oncogenic bacterium. Our previous study revealed that a high abundance of F. nucleatum in head and neck squamous cell carcinoma (HNSCC) is correlated with poor patient prognosis. However, the impact of F. nucleatum on metabolic reprogramming and tumor progression in HNSCC awaits more exploration. Methods: Liquid chromatography‒mass spectrometry (LC‒MS) was applied to analyze the altered metabolites in a head and neck carcinoma cell line (AMC-HN-8) after coculture with F. nucleatum for 24 hrs and 48 hrs. Both univariate and multivariate analyses were used to screen for differential metabolites. Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway enrichment analysis was further used to explore the metabolic changes. Results: We observed a significantly altered metabolic profile in AMC-HN-8 cells over time after coculture with F. nucleatum. Among the several enriched pathways, the purine metabolic pathway was the most significantly enriched (P = 0.0005), with downregulation of purine degradation. Furthermore, uric acid, the end product of purine metabolism, significantly reversed F. nucleatum-triggered tumor progression and altered the intracellular reactive oxygen species (ROS) level. Moreover, the negative correlation between the serum uric acid level and the abundance of F. nucleatum was verified in 113 HNSCC patients (P = 0.0412, R = − 0.1924). Conclusions: Our study revealed obviously aberrant purine metabolism driven by F. nucleatum in HNSCC, which was closely related to tumor progression and patient prognosis. These findings indicate the possibility of targeting F. nucleatum-induced purine metabolism reprogramming in the future treatment of HNSCC.