147 research outputs found
Immunochemotherapy achieved a complete response for metastatic adenocarcinoma of unknown primary based on gene expression profiling: a case report and review of the literature
BackgroundCancer of unknown primary (CUP) is a malignant and aggressive tumor whose primary origin is still unknown despite thorough evaluation. CUP can be life-threatening with a median overall survival of less than 1 year based on empirical chemotherapy. Gene detection technology advances the driver gene detection of malignant tumors and the appropriate precise therapy. Immunotherapy has ushered in a new era in cancer therapy, changing the way advanced tumors, including CUP, are treated. Combined with comprehensive clinical and pathological investigations, molecular analysis of the original tissue and detection of potential driver mutations may provide therapeutic recommendations for CUP.Case presentationA 52-year-old female was admitted to hospital for dull abdominal pain, with peripancreatic lesions below the caudate lobe of the liver and posterior peritoneal lymph nodes enlargement. Conventional biopsy under endoscopic ultrasonography and laparoscopic biopsy both revealed poorly differentiated adenocarcinoma based on immunohistochemical series. To help identify tumor origin and molecular characteristics, 90-gene expression assay, tumor gene expression profiling with Next-generation sequencing (NGS) method and Immunohistochemical expression of PD-L1 were employed. Although no gastroesophageal lesions discovered by gastroenteroscopy, the 90-gene expression assay yielded a similarity score and prompted the most likely primary site was gastric/esophagus cancer. NGS revealed high TMB (19.3mutations/Mb) but no druggable driver genes identified. The Dako PD-L1 22C3 assay IHC assay for PD-L1 expression revealed a tumor proportion score (TPS) of 35%. Given the presence of negative predictive biomarkers for immunotherapy, including adenomatous polyposis coli (APC) c.646C>T mutation at exon 7 and Janus kinase 1(JAK1), the patient received immunochemotherapy instead of immunotherapy alone. She was successfully treated with nivolumab plus carboplatin and albumin-bound nanoparticle paclitaxel for six cycles and nivolumab maintenance, which achieved a complete response (CR) maintained for 2 years without severe adverse events.ConclusionsThis case highlights the value of multidisciplinary diagnosis and individual precision treatment in CUP. Further investigation is needed as an individualized treatment approach combining immunotherapy and chemotherapy based on tumor molecular characteristics and immunotherapy predictors is expected to improve the outcome of CUP therapy
Interaction of autophagy with microRNAs and their potential therapeutic implications in human cancers
AbstractAutophagy is a tightly regulated intracellular self-digestive process involving the lysosomal degradation of cytoplasmic organelles and proteins. A number of studies have shown that autophagy is dysregulated in cancer initiation and progression, or cancer cells under various stress conditions. As a catabolic pathway conserved among eukaryotes, autophagy is regulated by the autophagy related genes and pathways. MicroRNAs (miRNAs) are small, non-coding endogenous RNAs that may regulate almost every cellular process including autophagy. And autophagy is also involved in the regulation of miRNAs expression and homeostasis. Here we reviewed some literatures on the interaction of miRNAs with autophagy and the application of miRNAs-mediated autophagic networks as a promising target in pre-clinical cancer models. Furthermore, strategies of miRNAs delivery for miRNAs-based anti-cancer therapy will also be summarized and discussed
Thrust: Adaptively Propels Large Language Models with External Knowledge
Although large-scale pre-trained language models (PTLMs) are shown to encode
rich knowledge in their model parameters, the inherent knowledge in PTLMs can
be opaque or static, making external knowledge necessary. However, the existing
information retrieval techniques could be costly and may even introduce noisy
and sometimes misleading knowledge. To address these challenges, we propose the
instance-level adaptive propulsion of external knowledge (IAPEK), where we only
conduct the retrieval when necessary. To achieve this goal, we propose
measuring whether a PTLM contains enough knowledge to solve an instance with a
novel metric, Thrust, which leverages the representation distribution of a
small number of seen instances. Extensive experiments demonstrate that thrust
is a good measurement of PTLM models' instance-level knowledgeability.
Moreover, we can achieve significantly higher cost-efficiency with the Thrust
score as the retrieval indicator than the naive usage of external knowledge on
88% of the evaluated tasks with 26% average performance improvement. Such
findings shed light on the real-world practice of knowledge-enhanced LMs with a
limited knowledge-seeking budget due to computation latency or costs.Comment: 13 pages, 6 figure
Chain-of-Note: Enhancing Robustness in Retrieval-Augmented Language Models
Retrieval-augmented language models (RALMs) represent a substantial
advancement in the capabilities of large language models, notably in reducing
factual hallucination by leveraging external knowledge sources. However, the
reliability of the retrieved information is not always guaranteed. The
retrieval of irrelevant data can lead to misguided responses, and potentially
causing the model to overlook its inherent knowledge, even when it possesses
adequate information to address the query. Moreover, standard RALMs often
struggle to assess whether they possess adequate knowledge, both intrinsic and
retrieved, to provide an accurate answer. In situations where knowledge is
lacking, these systems should ideally respond with "unknown" when the answer is
unattainable. In response to these challenges, we introduces Chain-of-Noting
(CoN), a novel approach aimed at improving the robustness of RALMs in facing
noisy, irrelevant documents and in handling unknown scenarios. The core idea of
CoN is to generate sequential reading notes for retrieved documents, enabling a
thorough evaluation of their relevance to the given question and integrating
this information to formulate the final answer. We employed ChatGPT to create
training data for CoN, which was subsequently trained on an LLaMa-2 7B model.
Our experiments across four open-domain QA benchmarks show that RALMs equipped
with CoN significantly outperform standard RALMs. Notably, CoN achieves an
average improvement of +7.9 in EM score given entirely noisy retrieved
documents and +10.5 in rejection rates for real-time questions that fall
outside the pre-training knowledge scope.Comment: Preprin
PIVOINE: Instruction Tuning for Open-world Information Extraction
We consider the problem of Open-world Information Extraction (Open-world IE),
which extracts comprehensive entity profiles from unstructured texts. Different
from the conventional closed-world setting of Information Extraction (IE),
Open-world IE considers a more general situation where entities and relations
could be beyond a predefined ontology. More importantly, we seek to develop a
large language model (LLM) that is able to perform Open-world IE to extract
desirable entity profiles characterized by (possibly fine-grained) natural
language instructions. We achieve this by finetuning LLMs using instruction
tuning. In particular, we construct INSTRUCTOPENWIKI, a substantial instruction
tuning dataset for Open-world IE enriched with a comprehensive corpus,
extensive annotations, and diverse instructions. We finetune the pretrained
BLOOM models on INSTRUCTOPENWIKI and obtain PIVOINE, an LLM for Open-world IE
with strong instruction-following capabilities. Our experiments demonstrate
that PIVOINE significantly outperforms traditional closed-world methods and
other LLM baselines, displaying impressive generalization capabilities on both
unseen instructions and out-of-ontology cases. Consequently, PIVOINE emerges as
a promising solution to tackle the open-world challenge in IE effectively
Knowledge-in-Context: Towards Knowledgeable Semi-Parametric Language Models
Fully-parametric language models generally require a huge number of model
parameters to store the necessary knowledge for solving multiple natural
language tasks in zero/few-shot settings. In addition, it is hard to adapt to
the evolving world knowledge without the costly model re-training. In this
paper, we develop a novel semi-parametric language model architecture,
Knowledge-in-Context (KiC), which empowers a parametric text-to-text language
model with a knowledge-rich external memory. Specifically, the external memory
contains six different types of knowledge: entity, dictionary, commonsense,
event, script, and causality knowledge. For each input instance, the KiC model
adaptively selects a knowledge type and retrieves the most helpful pieces of
knowledge. The input instance along with its knowledge augmentation is fed into
a text-to-text model (e.g., T5) to generate the output answer, where both the
input and the output are in natural language forms after prompting.
Interestingly, we find that KiC can be identified as a special
mixture-of-experts (MoE) model, where the knowledge selector plays the role of
a router that is used to determine the sequence-to-expert assignment in MoE.
This key observation inspires us to develop a novel algorithm for training KiC
with an instance-adaptive knowledge selector. As a knowledge-rich
semi-parametric language model, KiC only needs a much smaller parametric part
to achieve superior zero-shot performance on unseen tasks. By evaluating on 40+
different tasks, we show that KiC_Large with 770M parameters easily outperforms
large language models (LMs) that are 4-39x larger by a large margin. We also
demonstrate that KiC exhibits emergent abilities at a much smaller model scale
compared to the fully-parametric models
From Cluster Assumption to Graph Convolution: Graph-based Semi-Supervised Learning Revisited
Graph-based semi-supervised learning (GSSL) has long been a hot research
topic. Traditional methods are generally shallow learners, based on the cluster
assumption. Recently, graph convolutional networks (GCNs) have become the
predominant techniques for their promising performance. In this paper, we
theoretically discuss the relationship between these two types of methods in a
unified optimization framework. One of the most intriguing findings is that,
unlike traditional ones, typical GCNs may not jointly consider the graph
structure and label information at each layer. Motivated by this, we further
propose three simple but powerful graph convolution methods. The first is a
supervised method OGC which guides the graph convolution process with labels.
The others are two unsupervised methods: GGC and its multi-scale version GGCM,
both aiming to preserve the graph structure information during the convolution
process. Finally, we conduct extensive experiments to show the effectiveness of
our methods
Numerical simulation and experimental investigation of diesel fuel reforming over a Pt/CeO<sub>2</sub>-Al<sub>2</sub>O<sub>3</sub> catalyst
In order to benefit from a realistic hydrogen production device equipped on a vehicle, issues with the effects of the process parameters on H2 and CO yield need to be resolved. In this study, a reduced mechanism for n-heptane (as a surrogate diesel) reforming over a Pt/CeO2-Al2O3 catalyst is adopted to investigate the effects of the process parameters on H2 and CO yield, and the preferred process parameters are concluded. In addition, the comparison of reforming bench tests of diesel fuel and n-heptane under typical diesel engine operating conditions is conducted. The n-heptane reforming simulation results show that the maximum H2 and CO yield moves toward unity with the decreased GHSV and increased reaction temperature, and the GHSV of 10,000 1/h, O2/C ratio of 0.6 and reaction temperature of 500 °C is preferable. The contrast experiments reveal that the change trend of H2 and CO yield displays consistence, although the difference of the average H2 and CO yield results is obvious. The characteristics of n-heptane reforming can represent H2 and CO yield features of diesel fuel reforming at typical reaction temperatures in a way
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