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67. Predictive and prognostic role of early apolipoprotein A‐I alteration in recurrent or metastatic nasopharyngeal carcinoma patients treated with anti‐PD‐1 therapy

Author

Bi Jing Xiao, Xiao Xian Sima, Gang Chen, Haimiti Gulizeba, Ting Zhou, and Yan Huang

Subjects
anti‐PD‐1 therapy, apolipoprotein A‐I, nasopharyngeal carcinoma, prognosis, recurrent or metastatic stage, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The primary objective of this study was to evaluate the predictive and prognostic value of serum lipids in recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients received anti‐PD‐1 therapy. Materials and Methods Patients treated with anti‐PD‐1 therapy (monotherapy or combined with chemotherapy) from two clinical trials (CAPTAIN and CAPTAIN‐1st study) were included. Serum lipids were measured at baseline and after two cycles of treatment. We examined the impact of both baseline and post‐treatment lipid levels on objective response rate (ORR), progression‐free survival (PFS), and duration of response (DOR). Results Of 106 patients, 89 patients (84%) were male. The patients' median age was 49 years. An early elevated (after two cycles of treatment) cholesterol (CHO), low‐density lipoprotein cholesterol (LDL‐C), apolipoprotein A‐I (ApoA‐I), and apolipoprotein B (ApoB) were significantly associated with better ORR. Moreover, early elevated CHO, LDL‐C, and ApoA‐I were also positively correlated with DOR and PFS. Further multivariate analysis showed that only early change in ApoA‐I could independently predict PFS (HR, 2.27; 95% CI, 1.11–4.61; p = 0.034). The median PFS for patients with early elevated and reduced ApoA‐I was 11.43 and 1.89 months, respectively. However, baseline lipids levels do not play a significant role in the prognosis and prediction of patients with anti‐PD‐1 treatment. Conclusion Collectively, an early elevation in ApoA‐I was correlated with better outcomes for anti‐PD‐1 therapy in patients with R/M NPC, suggesting that clinicians should consider the early alteration of ApoA‐I as a useful marker in treating R/M NPC patients with anti‐PD‐1.

Published
2023
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68. Cubic Spline Smoothing Compensation for Irregularly Sampled Sequences

Author

Shi, Jing, Bi, Jing, Liu, Yingru, and Xu, Chenliang

Subjects
Computer Science - Machine Learning, Statistics - Machine Learning
Abstract

The marriage of recurrent neural networks and neural ordinary differential networks (ODE-RNN) is effective in modeling irregularly-observed sequences. While ODE produces the smooth hidden states between observation intervals, the RNN will trigger a hidden state jump when a new observation arrives, thus cause the interpolation discontinuity problem. To address this issue, we propose the cubic spline smoothing compensation, which is a stand-alone module upon either the output or the hidden state of ODE-RNN and can be trained end-to-end. We derive its analytical solution and provide its theoretical interpolation error bound. Extensive experiments indicate its merits over both ODE-RNN and cubic spline interpolation.

Published
2020

70. Learning from Interventions using Hierarchical Policies for Safe Learning

Author

Bi, Jing, Dhiman, Vikas, Xiao, Tianyou, and Xu, Chenliang

Subjects
Computer Science - Robotics, Computer Science - Artificial Intelligence, Computer Science - Computer Vision and Pattern Recognition, Computer Science - Human-Computer Interaction, Computer Science - Machine Learning
Abstract

Learning from Demonstrations (LfD) via Behavior Cloning (BC) works well on multiple complex tasks. However, a limitation of the typical LfD approach is that it requires expert demonstrations for all scenarios, including those in which the algorithm is already well-trained. The recently proposed Learning from Interventions (LfI) overcomes this limitation by using an expert overseer. The expert overseer only intervenes when it suspects that an unsafe action is about to be taken. Although LfI significantly improves over LfD, the state-of-the-art LfI fails to account for delay caused by the expert's reaction time and only learns short-term behavior. We address these limitations by 1) interpolating the expert's interventions back in time, and 2) by splitting the policy into two hierarchical levels, one that generates sub-goals for the future and another that generates actions to reach those desired sub-goals. This sub-goal prediction forces the algorithm to learn long-term behavior while also being robust to the expert's reaction time. Our experiments show that LfI using sub-goals in a hierarchical policy framework trains faster and achieves better asymptotic performance than typical LfD., Comment: Accepted for publication at the Thirty-Fourth AAAI Conference on Artificial Intelligence (AAAI-20)

Published
2019

88. Deletion of large-conductance calcium-activated potassium channels promotes vascular remodelling through the CTRP7-mediated PI3K/Akt signaling pathway

Author

Bi Jing, Duan Yanru, Wang Meili, He Chunyu, Li Xiaoyue, Zhang Xi, Tao Yan, Du Yunhui, and Liu Huirong

Subjects
large-conductance calcium-activated potassium channel, vascular remodelling, vascular smooth muscle cell, C1q/tumor necrosis factor-related protein 7, Biochemistry, QD415-436, Genetics, QH426-470
Abstract

The large-conductance calcium-activated potassium (BK) channel is a critical regulator and potential therapeutic target of vascular tone and architecture, and abnormal expression or dysfunction of this channel is linked to many vascular diseases. Vascular remodelling is the early pathological basis of severe vascular diseases. Delaying the progression of vascular remodelling can reduce cardiovascular events, but the pathogenesis remains unclear. To clarify the role of BK channels in vascular remodelling, we use rats with BK channel α subunit knockout (BK α ‒/‒). The results show that BK α ‒/‒ rats have smaller inner and outer diameters, thickened aortic walls, increased fibrosis, and disordered elastic fibers of the aortas compared with WT rats. When the expression and function of BK α are inhibited in human umbilical arterial smooth muscle cells (HUASMCs), the expressions of matrix metalloproteinase 2 (MMP2), MMP9, and interleukin-6 are enhanced, while the expressions of smooth muscle cell contractile phenotype proteins are reduced. RNA sequencing, bioinformatics analysis and qPCR verification show that C1q/tumor necrosis factor-related protein 7 ( CTRP7) is the downstream target gene. Furthermore, except for that of MMPs, a similar pattern of IL-6, smooth muscle cell contractile phenotype proteins expression trend is observed after CTRP7 knockdown. Moreover, knockdown of both BK α and CTRP7 in HUASMCs activates PI3K/Akt signaling. Additionally, CTRP7 is expressed in vascular smooth muscle cells (VSMCs), and BK α deficiency activates the PI3K/Akt pathway by reducing CTRP7 level. Therefore, we first show that BK channel deficiency leads to vascular remodelling. The BK channel and CTRP7 may serve as potential targets for the treatment of cardiovascular diseases.

Published
2022
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