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1.
《Molecular therapy》2022,30(8):2856-2867
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尽管嵌合抗原受体(CAR)T细胞治疗在血液系统恶性肿瘤患者中取得了显著的临床疗效,但需要进一步优化。脂质纳米粒(LNP)-信使核糖核酸(mRNA)递送系统作为一种非病毒性基因载体运用于CAR-T细胞治疗研究中,一方面通过LNP将密封蛋白-6 mRNA靶向递送至抗原提呈细胞,从而实现抗原提呈细胞辅助性增强密封蛋白-6靶向的CAR-T细胞的功能,以进一步诱导对实体瘤的清除;另一方面,通过LNP将成纤维细胞激活蛋白(FAP)CARmRNA靶向递送至T细胞,实现体内FAP靶向的CAR-T细胞的制备,以通过阻断心脏纤维化过程达到治疗急性心肌损伤的目的。在CAR-T细胞研究和治疗中,LNP-mRNA递送系统具有不与细胞基因组整合、价格便宜、毒副作用小及可修饰等优点,亦存在蛋白瞬时表达导致调控细胞功能的持久性不足及制备等方面的技术局限性。本文综述了LNP-mRNA递送系统及其在CAR-T细胞治疗中的应用研究。  相似文献   
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《Value in health》2022,25(3):350-358
ObjectivesWe propose a framework of health outcomes modeling with dynamic decision making and real-world data (RWD) to evaluate the potential utility of novel risk prediction models in clinical practice. Lung transplant (LTx) referral decisions in cystic fibrosis offer a complex case study.MethodsWe used longitudinal RWD for a cohort of adults (n = 4247) from the Cystic Fibrosis Foundation Patient Registry to compare outcomes of an LTx referral policy based on machine learning (ML) mortality risk predictions to referral based on (1) forced expiratory volume in 1 second (FEV1) alone and (2) heterogenous usual care (UC). We then developed a patient-level simulation model to project number of patients referred for LTx and 5-year survival, accounting for transplant availability, organ allocation policy, and heterogenous treatment effects.ResultsOnly 12% of patients (95% confidence interval 11%-13%) were referred for LTx over 5 years under UC, compared with 19% (18%-20%) under FEV1 and 20% (19%-22%) under ML. Of 309 patients who died before LTx referral under UC, 31% (27%-36%) would have been referred under FEV1 and 40% (35%-45%) would have been referred under ML. Given a fixed supply of organs, differences in referral time did not lead to significant differences in transplants, pretransplant or post-transplant deaths, or overall survival in 5 years.ConclusionsHealth outcomes modeling with RWD may help to identify novel ML risk prediction models with high potential real-world clinical utility and rule out further investment in models that are unlikely to offer meaningful real-world benefits.  相似文献   
4.
Radiomics is the quantitative analysis of standard-of?care medical imaging; the information obtained can be applied within clinical decision support systems to create diagnostic, prognostic, and/or predictive models. Radiomics analysis can be performed by extracting hand-crafted radiomics features or via deep learning algorithms. Radiomics has evolved tremendously in the last decade, becoming a bridge between imaging and precision medicine. Radiomics exploits sophisticated image analysis tools coupled with statistical elaboration to extract the wealth of information hidden inside medical images, such as computed tomography (CT), magnetic resonance (MR), and/or Positron emission tomography (PET) scans, routinely performed in the everyday clinical practice. Many efforts have been devoted in recent years to the standardization and validation of radiomics approaches, to demonstrate their usefulness and robustness beyond any reasonable doubts. However, the booming of publications and commercial applications of radiomics approaches warrant caution and proper understanding of all the factors involved to avoid “scientific pollution” and overly enthusiastic claims by researchers and clinicians alike. For these reasons the present review aims to be a guidebook of sorts, describing the process of radiomics, its pitfalls, challenges, and opportunities, along with its ability to improve clinical decision-making, from oncology and respiratory medicine to pharmacological and genotyping studies.  相似文献   
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检验医学作为医学科学的重要支撑学科,在疾病早期诊断、病情监测、预后判断与风险评估等方面发挥着重要作用。21世纪是数字信息时代,高新检测技术、计算机科学及互联网大数据等,为检验医学的发展带来巨大的机遇与挑战,新时代下如何借助信息科技革命实现检验医学新发展是检验工作者面临的重要课题。该文回顾检验医学的发展历程,重点关注检验医学在新时代的发展定位及未来发展方向,以求开创检验医学发展新局面。  相似文献   
7.
ObjectiveAddress model drift in a machine learning (ML) model for predicting diagnostic imaging follow-up using data augmentation with more recent data versus retraining new predictive models.MethodsThis institutional review board–approved retrospective study was conducted January 1, 2016, to December 31, 2020, at a large academic institution. A previously trained ML model was trained on 1,000 radiology reports from 2016 (old data). An additional 1,385 randomly selected reports from 2019 to 2020 (new data) were annotated for follow-up recommendations and randomly divided into two sets: training (n = 900) and testing (n = 485). Support vector machine and random forest (RF) algorithms were constructed and trained using 900 new data reports plus old data (augmented data, new models) and using only new data (new data, new models). The 2016 baseline model was used as comparator as is and trained with augmented data. Recall was compared with baseline using McNemar’s test.ResultsFollow-up recommendations were contained in 11.3% of reports (157 or 1,385). The baseline model retrained with new data had precision = 0.83 and recall = 0.54; none significantly different from baseline. A new RF model trained with augmented data had significantly better recall versus the baseline model (0.80 versus 0.66, P = .04) and comparable precision (0.90 versus 0.86).DiscussionML methods for monitoring follow-up recommendations in radiology reports suffer model drift over time. A newly developed RF model achieved better recall with comparable precision versus simply retraining a previously trained original model with augmented data. Thus, regularly assessing and updating these models is necessary using more recent historical data.  相似文献   
8.
PurposeAccording to the social determinants of health framework, income inequality is a potential risk factor for adverse mental health. However, few studies have explored the mechanisms suspected to mediate this relationship. The current study addresses this gap through a mediation analysis to determine if social support and community engagement act as mediators linking neighbourhood income inequality to maternal anxiety and depressive symptoms within a cohort of new mothers living in the City of Calgary, Canada.MethodsData collected at three years postpartum from mothers belonging to the All Our Families (AOF) cohort were used in the current study. Maternal data were collected between 2012 and 2015 and linked to neighbourhood socioeconomic data from the 2006 Canadian Census. Income inequality was measured using Gini coefficients derived from 2006 after-tax census data. Generalized structural equation models were used to quantify the associations between income inequality and mental health symptoms, and to assess the potential direct and indirect mediating effects of maternal social support and community engagement.ResultsIncome inequality was not significantly associated with higher depressive symptoms (β = 0.32, 95%CI = −0.067, 0.70), anxiety symptoms (β = 0.11, 95%CI = −0.39, 0.60), or lower social support. Income inequality was not associated with community engagement. For the depression models, higher social support was significantly associated with lower depressive symptoms (β = −0.13, 95%CI = −0.15, −0.097), while community engagement was not significantly associated with depressive symptoms (β = 0.059, 95%CI = −0.15, 0.27). Similarly, for the anxiety models, lower anxiety symptoms were significantly associated with higher levels of social support (β = −0.17, 95%CI = −0.20, −0.13) but not with higher levels of community engagement (β = 0.14, 95%CI = −0.14, 0.41).ConclusionThe current study did not find clear evidence for social support or community engagement mediating the relationship between neighbourhood income inequality and maternal mental health. Future investigations should employ a broader longitudinal approach to capture changes in income inequality, potential mediators, and mental health symptomatology over time.  相似文献   
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目的 构建家庭正向行为支持(positive behavior support,PBS)方案,并探讨其在学龄前恶性肿瘤患儿情绪行为影响中的应用效果。方法 以家庭系统理论为框架构建家庭PBS方案,选取2019年3月—2020年2月于重庆市某三级甲等儿童医院就诊的100例学龄前恶性肿瘤患儿为研究对象,采用随机数字表法分为试验组(n=50)和对照组(n=50)。试验组在常规护理基础上接受为期3个月的家庭PBS方案,对照组实施常规护理。比较两组干预前后家庭亲密度与适应性量表得分、养育心理灵活性问卷得分及长处与困难问卷得分。结果 两组干预后长处与困难问卷得分低于干预前(均P<0.001),家庭亲密度与适应性量表得分高于干预前(均P<0.001);试验组干预后养育心理灵活性问卷得分高于干预前(P<0.001);干预后试验组长处与困难问卷得分低于对照组(P<0.001),家庭亲密度与适应性量表得分和养育心理灵活性问卷得分高于对照组(均P<0.05)。结论 应用家庭PBS方案可减少学龄前恶性肿瘤患儿情绪行为问题的发生,改善家庭亲密度与适应性,提高父母养育心理灵活性。  相似文献   
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