Common endocrine system adverse events associated with immune checkpoint inhibitors

Immune checkpoint inhibitors(ICIs),a novel anti-tumor therapeutic modality,are monoclonal antibodies targeting certain immune checkpoints(ICs)that reactivate T cells to achieve anti-tumor immunity by targeting,binding,and blocking ICs.Targeted inhibitory antibodies against the ICs cytotoxic T-lymphocyte antigen and programmed death receptor-1 have demonstrated efficacy and durable anti-tumor activity in patients with cancer.ICs may prevent autoimmune reactions.However,ICIs may disrupt ICs properties and trigger autoimmune-related adverse reactions involving various organ systems including the cardiovascular,pulmonary,gastrointestinal,renal,musculoskeletal,dermal,and endocrine systems.Approximately 10%of patients with damage to target organs such as the thyroid,pituitary,pancreas,and adrenal glands develop endocrine system immune-related adverse events(irAEs)such as thyroid dysfunction,pituitary gland inflammation,diabetes mellitus,and primary adrenal insufficiency.However,the symptoms of immunotherapy-associated endocrine system irAEs may be nonspecific and similar to those of other treatment-related adverse reactions,and failure to recognize them early may lead to death.Timely detection and treatment of immunotherapy-associated endocrine irAEs is essential to improve the efficacy of immunotherapy,prognosis,and the quality of life of patients.This study aimed to review the mechanisms by which ICIs cause endocrine irAEs providing guidance for the development of appropriate management protocols.Here,we discuss(1)the biological mechanisms of ICs in tumorigenesis and progression,focusing on cytotoxic T-lymphocyte antigen and programmed cell death-1/programmed cell death-ligand 1;and(2)the epidemiology,clinical symptoms,diagnosis,and treatment of four immunotherapy-related endocrine complications.

Cost-Utility Analysis of Screening for Diabetic Retinopathy in China

Background.Diabetic retinopathy(DR)has been primarily indicated to cause vision impairment and blindness,while no studies have focused on the cost-utility of telemedicine-based and community screening programs for DR in China,especially in rural and urban areas,respectively.Methods.We developed a Markov model to calculate the cost-utility of screening programs for DR in DM patients in rural and urban settings from the societal perspective.The incremental cost-utility ratio(ICUR)was calculated for the assessment.Results.In the rural setting,the community screening program obtained 1 QALY with a cost of$4179(95%CI 3859 to 5343),and the telemedicine screening program had an ICUR of$2323(95%CI 1023 to 3903)compared with no screening,both of which satisfied the criterion of a significantly cost-effective health intervention.Likewise,community screening programs in urban areas generated an ICUR of$3812(95%CI 2906 to 4167)per QALY gained,with telemedicine screening at an ICUR of$2437(95%CI 1242 to 3520)compared with no screening,and both were also cost-effective.By further comparison,compared to community screening programs,telemedicine screening yielded an ICUR of 1212(95%CI 896 to 1590)per incremental QALY gained in rural setting and 1141(95%CI 859 to 1403)in urban setting,which both meet the criterion for a significantly cost-effective health intervention.Conclusions.Both telemedicine and community screening for DR in rural and urban settings were cost-effective in China,and telemedicine screening programs were more cost-effective.

Bionic Muscle Control with Adaptive Stiffness for Bionic Parallel Mechanism

As the torso is critical to the coordinated movement and flexibility of vertebrates,a 6-(Degree of Freedom)DOF bionic parallel torso with noteworthy motion space was designed in our previous work.To improve the compliance of the parallel mechanism,a pair of virtual muscle models is constructed on both sides of the rotating joints of each link of the mechanism,and a bionic muscle control algorithm is introduced.By analyzing the control parameters of the muscle model,dynamic characteristics similar to those of biological muscle are obtained.An adaptive stiffness control is proposed to adaptively adjust the stiffness coefficient with the change in the external load of the parallel mechanism.The attitude closed-loop control can effectively keep the attitude angle unchanged when the position of the moving platform changes.The simulations and experiments are undertaken to validate compliant movements and the flexibility and adaptability of the parallel mechanism.

Predicting rice diseases using advanced technologies at different scales: present status and future perspectives

The past few years have witnessed significant progress in emerging disease detection techniques foraccurately and rapidly tracking rice diseases and predicting potential solutions. In this review we focuson image processing techniques using machine learning (ML) and deep learning (DL) models related tomulti-scale rice diseases. Furthermore, we summarize applications of different detection techniques,including genomic, physiological, and biochemical approaches. In addition, we also present the state-ofthe-art in contemporary optical sensing applications of pathogen–plant interaction phenotypes. Thisreview serves as a valuable resource for researchers seeking effective solutions to address the challenges of high-throughput data and model recognition for early detection of issues affecting rice cropsthrough ML and DL models.

Design,analysis,and neural control of a bionic parallel mechanism

Although the torso plays an important role in the movement coordination and versatile locomotion of mammals,the structural design and neuromechanical control of a bionic torso have not been fully addressed.In this paper,a parallel mechanism is designed as a bionic torso to improve the agility,coordination,and diversity of robot locomotion.The mechanism consists of 6-degree of freedom actuated parallel joints and can perfectly simulate the bending and stretching of an animal’s torso during walking and running.The overall spatial motion performance of the parallel mechanism is improved by optimizing the structural parameters.Based on this structure,the rhythmic motion of the parallel mechanism is obtained by supporting state analysis.The neural control of the parallel mechanism is realized by constructing a neuromechanical network,which merges the rhythmic signals of the legs and generates the locomotion of the bionic parallel mechanism for different motion patterns.Experimental results show that the complete integrated system can be controlled in real time to achieve proper limb-torso coordination.This coordination enables several different motions with effectiveness and good performance.

早期筛查老年人群糖尿病视网膜病变的卫生经济学分析

目的从社会角度和卫生系统角度探讨中国50岁以上人群行糖尿病视网膜病变(DR)筛查的经济学效益。方法检索中国知网、万方数据库、PubMed及Medline等数据库,检索日期为自建库之始至2020年12月,搜集中国50岁以上人群DR的患病率、转归率、筛查依从性、治疗依从性、筛查敏感性、筛查特异性、DR不同分期的效用值及死亡率等指标。按照国际分级系统将DR分为不威胁视力DR、威胁视力DR,糖尿病性黄斑水肿及DR致盲等4个阶段。筛查项目、转诊检查及治疗费用来源于邯郸眼病研究和2020年首都医科大学附属北京同仁医院住院系统。使用TreeAge Pro软件构建DR筛查的马尔可夫模型,以社区筛查、远程筛查及人工智能(AI)辅助筛查为研究策略,以无筛查为对照策略,以我国农村和城市50岁以上人群为队列人群,比较不同策略的成本效益,并比较1~5年筛查间隔的成本效益。2020年中国农村和城市人均生产总值(GDP)分别为49000元和84000元。经济学效益以增量成本-效用比(ICUR)和增量成本-效果比(ICER)表示。成本效益阈值按照世界卫生组织规定的ICER或ICUR<3倍人均GDP为具有成本效益,<1倍人均GDP为具有高成本效益,>3倍人均GDP则不具备经济性。通过敏感性分析评价模型的稳健性。结果农村和城市人群的成本效益阈值分别为147000元和252000元。从社会角度看,对农村50岁以上人群进行社区、远程及AI辅助筛查的ICUR分别为4214元、2772元及3206元;每避免1个致盲年导致的ICER分别为216524元、152726元及164745元;对城市人群筛查的ICUR分别为7133元、5061元及5894元;每避免1个致盲年导致的ICER分别为57792元、37632元及55839元。与无筛查人群相比,农村和城市的ICUR以及城市人群的ICER均<1倍人均GDP;3种筛查方式对农村50岁以上人群的ICER均略高于成本效益阈值。从卫生系统角度看,3种筛查方式对农村和城市老年人群的ICUR和ICER均低于成本效益阈值。社区或AI辅助筛查对城市老年人群间隔2年以上具有成本效益,远程筛查间隔1年以上已具有成本效益;而对农村人群各筛查间隔均不具有成本效益。经概率敏感性分析,当成本效益阈值为3倍人均GDP时,农村老年人群社区、远程及AI辅助筛查成本效益概率分别为87.34%、87.56%及87.54%;城市老年人群筛查的成本效益概率分别为89.19%、89.48%及89.61%。当成本效益阈值为1倍人均GDP时,3种筛查方式对农村老年人群筛查有成本效益的概率分别为86.03%、86.84%及86.55%;城市老年人群的成本效益概率分别为87.83%、88.55%及88.62%。说明构建马尔可夫模型的设计和结果稳健,对参数的浮动不敏感。结论对我国50岁以上老年人群进行DR筛查具有成本效益,因农村和城市的经济发展水平和疾病负担不同,应制定适宜当地的DR筛查模式。