Hepatocellular Carcinoma:from Liquid Biopsy to Immunotherapy

In this thesis we aim to optimize existing immunotherapy for hepatocellular carcinoma (HCC) with a strong emphasis on checkpoint inhibition. We aim to detect tumor-associated mutations in paired circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in a western cohort of HCC patients

ConcEPT: Concept-Enhanced Pre-Training for Language Models

Pre-trained language models (PLMs) have been prevailing in state-of-the-art methods for natural language processing, and knowledge-enhanced PLMs are further proposed to promote model performance in knowledge-intensive tasks. However, conceptual knowledge, one essential kind of knowledge for human cognition, still remains understudied in this line of research. This limits PLMs' performance in scenarios requiring human-like cognition, such as understanding long-tail entities with concepts. In this paper, we propose ConcEPT, which stands for Concept-Enhanced Pre-Training for language models, to infuse conceptual knowledge into PLMs. ConcEPT exploits external taxonomies with entity concept prediction, a novel pre-training objective to predict the concepts of entities mentioned in the pre-training contexts. Unlike previous concept-enhanced methods, ConcEPT can be readily adapted to various downstream applications without entity linking or concept mapping. Results of extensive experiments show the effectiveness of ConcEPT in four tasks such as entity typing, which validates that our model gains improved conceptual knowledge with concept-enhanced pre-training.Comment: 12pages. Work completed in 2023.0

Does building smart cities necessarily enhance urban ICT development? Insights from a quasi-natural experiment based on Chinese pilot policy

Purpose – With the help of a quasi-natural experiment on Chinese policies, this study aims to understand the actual contribution of Smart City (SC) policies to the development of information and communications technology (ICT) in different cities. It also discusses the social and digital differences that such policies may generate, with a particular focus on the potential for exacerbating urban inequalities. Design/methodology/approach – To achieve this, the study employs a principal component analysis (PCA) to develop an ICT development indicator system. It then employs a difference-in-differences (DID) model to analyze panel data from 209 Chinese cities over the period from 2007 to 2019, examining the impact of SC policies on ICT development across various urban settings. Findings – Our findings show that SC policies have significantly contributed to the enhancement of ICT development, especially in ICT usage. However, SC policies may inadvertently reinforce developmental disparities among cities. Compared to less developed areas, the benefits of SC policies are more pronounced in economically booming cities. This is likely due to the agglomeration of the ICT industry and the strong allure of developed urban centers for high-caliber talent. Originality/value – This study contributes to the related literature by explaining the role of SC policies in driving ICT development and by focusing on the often-overlooked impact of SC policies on urban inequality. These findings can provide guidance to policymakers on the need to recognize and address existing urban inequalities

Beyond the Obvious: Evaluating the Reasoning Ability In Real-life Scenarios of Language Models on Life Scapes Reasoning Benchmark~(LSR-Benchmark)

This paper introduces the Life Scapes Reasoning Benchmark (LSR-Benchmark), a novel dataset targeting real-life scenario reasoning, aiming to close the gap in artificial neural networks' ability to reason in everyday contexts. In contrast to domain knowledge reasoning datasets, LSR-Benchmark comprises free-text formatted questions with rich information on real-life scenarios, human behaviors, and character roles. The dataset consists of 2,162 questions collected from open-source online sources and is manually annotated to improve its quality. Experiments are conducted using state-of-the-art language models, such as gpt3.5-turbo and instruction fine-tuned llama models, to test the performance in LSR-Benchmark. The results reveal that humans outperform these models significantly, indicating a persisting challenge for machine learning models in comprehending daily human life

Xiezhi: An Ever-Updating Benchmark for Holistic Domain Knowledge Evaluation

New Natural Langauge Process~(NLP) benchmarks are urgently needed to align with the rapid development of large language models (LLMs). We present Xiezhi, the most comprehensive evaluation suite designed to assess holistic domain knowledge. Xiezhi comprises multiple-choice questions across 516 diverse disciplines ranging from 13 different subjects with 220,000 questions and accompanied by Xiezhi-Specialty and Xiezhi-Interdiscipline, both with 15k questions. We conduct evaluation of the 47 cutting-edge LLMs on Xiezhi. Results indicate that LLMs exceed average performance of humans in science, engineering, agronomy, medicine, and art, but fall short in economics, jurisprudence, pedagogy, literature, history, and management. We anticipate Xiezhi will help analyze important strengths and shortcomings of LLMs, and the benchmark is released in https://github.com/MikeGu721/XiezhiBenchmark .Comment: Under review of NeurIPS 202

Restructuring the interfacial active sites to generalize the volcano curves for platinum-cobalt synergistic catalysis

Computationally derived volcano curve has become the gold standard in catalysis, whose practical application usually relies on empirical interpretations of composition or size effects by the identical active site assumption. Here, we present a proof-of-concept study on disclosing both the support- and adsorbate-induced restructuring of Pt-Co bimetallic catalysts, and the related interplays among different interfacial sites to propose the synergy-dependent volcano curves. Multiple characterizations, isotopic kinetic investigations, and multiscale simulations unravel that the progressive incorporation of Co into Pt catalysts, driven by strong Pt-C bonding (metal-support interfaces) and Co-O bonding (metal-adsorbate interfaces), initiates the formation of Pt-rich alloys accompanied by isolated Co species, then Co segregation to epitaxial CoOx overlayers and adjacent Co3O4 clusters, and ultimately structural collapse into amorphous alloys. Accordingly, three distinct synergies, involving lattice oxygen redox from Pt-Co alloy/Co3O4 clusters, dual-active sites engineering via Pt-rich alloy/CoOx overlayer, and electron coupling within exposed alloy, are identified and quantified for CO oxidation (gas-phase), ammonia borane hydrolysis (liquid-phase), and hydrogen evolution reaction (electrocatalysis), respectively. The resultant synergy-dependent volcano curves represent an advancement over traditional composition-/size-dependent ones, serving as a bridge between theoretical models and experimental observations in bimetallic catalysis.publishedVersio

Expression of cancer testis antigens in tumor-adjacent normal liver is associated with post-resection recurrence of hepatocellular carcinoma

High recurrence rates after resection of hepatocellular carcinoma (HCC) with curative intent impair clinical outcomes of HCC. Cancer/testis antigens (CTAs) are suitable targets for cancer immunotherapy if selectively expressed in tumor cells. The aims were to identify CTAs that are frequently and selectively expressed in HCC-tumors, and to investigate whether CTAs could serve as biomarkers for occult metastasis. Tumor and paired tumor-free liver (TFL) tissues of HCC-patients and healthy tissues were assessed for mRNA expression of 49 CTAs by RT-qPCR and protein expression of five CTAs by immunohistochemistry. Twelve CTA-mRNAs were expressed in ≥10% of HCC-tumors and not in healthy tissues except testis. In tumors, mRNA and protein of ≥ 1 CTA was expressed in 78% and 71% of HCC-patients, respectively. In TFL, CTA mRNA and protein was found in 45% and 30% of HCC-patients, respectively. Interestingly, CTA-expression in TFL was an independent negative prognostic factor for post-resection HCC-recurrence and survival. We established a panel of 12 testis-restricted CTAs expressed in tumors of most HCC-patients. The increased risk of HCC-recurrence in patients with CTA expression in TFL, suggests that CTA-expressing (pre-)malignant cells may be a source of HCC-recurrence, reflecting the relevance of targeting these to prevent HCC-recurrence