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Challenges and opportunities of next generation therapeutics: A compound management perspective 下一代疗法的挑战与机遇:化合物管理视角。
IF 2.5 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-10-12 DOI: 10.1016/j.slast.2024.100201
In recent years, pharmaceutical research has increased its interest in novel drug modalities beyond small molecules to overcome therapeutic limitations and find more effective cures.
Compound Management teams globally are adapting their processes and equipment to handle such “new modalities” with the same quality and speed as small molecule research.
Here, we share our approach in supporting next-generation therapeutics by introducing solutions for multi-solvent workflows in Compound Management at AstraZeneca.
From sample submission to assay-ready plate generation, we describe the challenges faced and process improvements introduced so far.
Collaborating with our business partners, we are pioneering new best practices and laying solid foundations for future research to bring new efficacious drugs into the clinics.
近年来,制药研究越来越关注小分子药物以外的新型药物模式,以克服治疗上的局限性,找到更有效的治疗方法。全球的化合物管理团队正在调整其流程和设备,以便以与小分子研究相同的质量和速度处理此类 "新模式"。在此,我们通过介绍阿斯利康化合物管理部门的多溶剂工作流程解决方案,分享我们支持下一代疗法的方法。从提交样品到生成可用于检测的平板,我们描述了迄今为止所面临的挑战和所引入的流程改进。通过与业务合作伙伴的合作,我们正在开拓新的最佳实践,为未来的研究奠定坚实的基础,从而将新的高效药物带入临床。
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引用次数: 0
Exploring the mechanisms and current status of acupuncture in alleviating tumor metabolism and associated diseases: Insights from the central nervous system and immune microenvironment 探索针灸缓解肿瘤代谢及相关疾病的机制和现状:中枢神经系统和免疫微环境的启示。
IF 2.5 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-10-11 DOI: 10.1016/j.slast.2024.100208
Acupuncture, as a traditional Chinese medical treatment, has garnered increasing attention in recent years in fields such as tumor metabolism, the central nervous system, and the immune microenvironment. This paper aims to explore the fundamental principles, mechanisms, and research status of acupuncture therapy for tumor-related diseases. Firstly, we introduce the basic principles of acupuncture therapy, including the theories of meridians and its theoretical basis in tumor treatment. Secondly, we systematically review the mechanisms of acupuncture therapy for tumor-related diseases, discussing how acupuncture alleviates side effects such as pain, depression, fatigue, and gastrointestinal discomfort caused by conventional treatments through modulation of the immune microenvironment, central nervous system, and endocrine system. Subsequently, we discuss the current research status of acupuncture therapy for tumor-related diseases, as well as the application of current research methods and technologies in elucidating acupuncture mechanisms. Additionally, by combining clinical practice with different types of tumor-related diseases as experimental subjects, we demonstrate the application effectiveness and clinical practice experience of acupuncture in tumor treatment. Finally, a comprehensive assessment of acupuncture therapy for tumor-related diseases is provided, summarizing its limitations and prospecting future directions, including interdisciplinary collaboration and personalized treatment. In conclusion, acupuncture, as a feasible adjunctive therapy, is closely related to the central nervous system and the immune microenvironment, holding potential significant value in tumor treatment.
针灸作为一种传统中医疗法,近年来在肿瘤代谢、中枢神经系统、免疫微环境等领域受到越来越多的关注。本文旨在探讨针灸治疗肿瘤相关疾病的基本原理、机制和研究现状。首先,我们介绍了针灸疗法的基本原理,包括经络学说及其在肿瘤治疗中的理论基础。其次,系统回顾了针灸治疗肿瘤相关疾病的机理,论述了针灸如何通过调节免疫微环境、中枢神经系统和内分泌系统,缓解常规治疗引起的疼痛、抑郁、疲劳和胃肠道不适等副作用。随后,我们讨论了针灸治疗肿瘤相关疾病的研究现状,以及当前研究方法和技术在阐明针灸机制方面的应用。此外,结合临床实践,以不同类型的肿瘤相关疾病为实验对象,论证针灸在肿瘤治疗中的应用效果和临床实践经验。最后,对针灸治疗肿瘤相关疾病进行了全面评估,总结了其局限性,并展望了未来的发展方向,包括跨学科合作和个性化治疗。总之,针灸作为一种可行的辅助疗法,与中枢神经系统和免疫微环境密切相关,在肿瘤治疗中具有潜在的重要价值。
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引用次数: 0
Bio inspired microfluidic-based analysis of Klebsiella pneumoniae virulence factors and antimicrobial resistance 基于生物启发的微流控肺炎克雷伯菌毒力因子和抗菌药耐药性分析
IF 2.5 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-10-11 DOI: 10.1016/j.slast.2024.100209
The objective of this research was to examine the antibiotic resistance and microbiological traits of Klebsiella pneumoniae isolates that were responsible for liver abscesses in Qingdao, China. Between April and September 2022, isolates were taken from 120 patients at three tertiary hospitals. Rapid detection of capsule serotypes (K1, K2) and virulence genes (rmpA, aerobactin) was achieved by using microfluidic-based techniques. Testing for antimicrobial susceptibility was done with the VITEK 2 Compact system. The findings showed that there was a high frequency of extremely virulent K. pneumoniae strains, which are often linked to bacteremia and higher death rates. These strains belonged to the K1 and K2 serotypes and were primarily carrying the aerobactin and rmpA genes. The majority of isolates were antibiotic-sensitive, but the emergence of resistant strains emphasizes the necessity of continuing surveillance. The efficiency of microfluidic platforms for the quick and precise characterization of K. pneumoniae is demonstrated in this work, enabling prompt clinical interventions.
本研究旨在考察中国青岛地区肝脓肿肺炎克雷伯菌分离株的抗生素耐药性和微生物学特征。2022 年 4 月至 9 月期间,研究人员从三家三级医院的 120 名患者中采集了分离菌株。通过微流控技术实现了胶囊血清型(K1、K2)和毒力基因(rmpA、气杆菌素)的快速检测。使用 VITEK 2 Compact 系统对抗菌药敏感性进行了检测。研究结果表明,肺炎克氏菌中毒力极强的菌株出现频率很高,这往往与菌血症和较高的死亡率有关。这些菌株属于 K1 和 K2 血清型,主要携带 aerobactin 和 rmpA 基因。大多数分离菌株对抗生素敏感,但耐药菌株的出现强调了持续监控的必要性。这项工作证明了微流控平台在快速、精确地鉴定肺炎克氏菌方面的高效性,从而能够及时采取临床干预措施。
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引用次数: 0
AI driven interpretable deep learning based fetal health classification 基于人工智能的可解释深度学习胎儿健康分类。
IF 2.5 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-10-11 DOI: 10.1016/j.slast.2024.100206
In this study, a deep learning model is proposed for the classification of fetal health into 3 categories: Normal, suspect, and pathological. The primary objective is to utilize the power of deep learning to improve the efficiency and effectiveness of diagnostic processes. A deep neural network (DNN) model is proposed for fetal health analysis using data obtained from Cardiotocography (CTG). A dataset containing 21 attributes is used to carry out this work. The model incorporates multiple hidden layers, augmented with batch normalization and dropout layers for improved generalization. This study assesses the model's interpretation ability in fetal health classification using explainable deep learning. This enhances transparency in decision-making of the classifier model by leveraging feature importance and feature saliency analysis, fostering trust and facilitating the clinical adoption of fetal health assessments. Our proposed model demonstrates a remarkable performance with 0.99 accuracy, 0.93 sensitivity, 0.93 specificity, 0.96 AUC, 0.93 precision, and 0.93 F1 scores in classifying fetal health. We also performed comparative analysis with six other models including Logistic Regression, KNN, SVM, Naive Bayes, Random Forest, and Gradient Boosting to assess and compare the effectiveness of our model and the accuracies of 0.89, 0.88, 0.90, 081, 0.93, and 0.93 were achieved respectively by these baseline models. The results revealed that our proposed model outperformed all the baseline models in terms of accuracy. This indicates the potential of deep learning in improving fetal health assessment and contributing to the field of obstetrics by providing a robust tool for early risk detection.
本研究提出了一种深度学习模型,用于将胎儿健康状况分为 3 类:正常、可疑和病理。其主要目的是利用深度学习的力量来提高诊断过程的效率和有效性。我们提出了一种深度神经网络(DNN)模型,利用从心脏排畸(CTG)获得的数据进行胎儿健康分析。这项工作使用了一个包含 21 个属性的数据集。该模型包含多个隐藏层,并增加了批量归一化和剔除层,以提高泛化能力。本研究利用可解释深度学习评估了模型在胎儿健康分类中的解释能力。这通过利用特征重要性和特征显著性分析,提高了分类器模型决策的透明度,增强了信任度,促进了胎儿健康评估的临床应用。我们提出的模型在胎儿健康分类方面表现出了卓越的性能,准确率为 0.99,灵敏度为 0.93,特异性为 0.93,AUC 为 0.96,精确度为 0.93,F1 分数为 0.93。我们还与其他六个模型进行了比较分析,包括逻辑回归、KNN、SVM、Naive Bayes、随机森林和梯度提升,以评估和比较我们模型的有效性。结果显示,我们提出的模型在准确率方面优于所有基线模型。这表明了深度学习在改善胎儿健康评估方面的潜力,并通过提供早期风险检测的强大工具为产科领域做出了贡献。
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引用次数: 0
Automation of biochemical assays using an open-sourced, inexpensive robotic liquid handler 使用开源、廉价的机器人液体处理装置实现生化测定自动化
IF 2.5 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-10-11 DOI: 10.1016/j.slast.2024.100205
High Throughput Screening is crucial in pharmaceutical companies for efficient testing in drug discovery and development. Our Vaccines Analytical Research and Development (V-AR&D) department extensively uses robotic liquid handlers in their High Throughput Analytics (HTA) group for assay development and sample screening. However, these instruments are expensive and require extensive training. Opentrons' OT-2 liquid handler offers a more affordable option (<∼ $10,000) with Python programming language and open-source flexibility, reducing training requirements. OT-2 allows broadening of testing capabilities and method transfer without significant capital investments. Two biochemical assays were conducted to assess OT-2′s performance, and it demonstrated accurate pipetting with low covariance compared to Tecan EVO liquid handlers. Though OT-2 has some limitations such as lack of a crash detection system and limited deck space, it is a cost-effective, medium-throughput, and accurate liquid handling tool suitable for early-stage development and method transfer.
高通量筛选是制药公司在药物发现和开发过程中进行高效测试的关键。我们的疫苗分析研发部门(V-AR&D)在其高通量分析 (HTA) 小组中广泛使用机器人液体处理机进行检测开发和样品筛选。然而,这些仪器价格昂贵,而且需要大量培训。Opentrons的OT-2液体处理机提供了一种更经济实惠的选择(小于10,000美元),采用Python编程语言,具有开源灵活性,减少了培训要求。OT-2 可扩大测试能力和方法转移,无需大量资金投入。为了评估 OT-2 的性能,我们进行了两项生化测定,与 Tecan-EVO 液体处理仪相比,OT-2 的移液准确度高,协方差小。虽然 OT-2 有一些局限性,如缺乏碰撞检测系统和甲板空间有限,但它是一款经济高效、中等通量和精确的液体处理工具,适合早期开发和方法转让。
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引用次数: 0
HTS Library Plate Rejuvenation Using a DMSO-Rich Atmosphere. 使用富含二甲基亚砜的气氛使 HTS 库板恢复活力。
IF 2.5 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-10-11 DOI: 10.1016/j.slast.2024.100204
Fraser Hughes, Alex Cookson, Fabio Tamaki, Christopher Bailey, David W Gray, Karolina Wrobel, Kirsty Cookson, Steve Bell, Gary Tarver

Dry DMSO can rapidly pull water vapor out of the air due to its hygroscopic nature. This is a well-documented problem within drug discovery, particularly within high-throughput screening (HTS). This hydration is caused by atmospheric moisture being absorbed each time a compound library is used. This effect becomes increasingly pronounced when a compound library is used routinely. The result of this hydration is a change to both the total volume of solution and the concentration of sample still in solution. This can result in a large amount of variability in the measured biological activity of a sample depending on the library usage. In this paper, we show the detrimental effects the hydration of sample libraries has on the reproducibility of biological data and present a novel way to remove it from HTS library plates. Our approach involves creating a DMSO-rich environment, created by placing anhydrous DMSO in compound storage pods purged with nitrogen, and incubating library plates in this environment for up to 3 days. Quantification via evaporative light scattering detection (ELSD) showed that removing water greatly increased the molarity of solutions, with a greater effect being seen for compounds with poor solubility. We also demonstrated how this approach can restore the inhibitory activity of stock solutions of compounds (pIC50) of samples containing ∼30% water from >30 µM to sub-micromolar after moisture removal. This method improves the reliability of tested compounds in HTS by potentially saving pharmaceutical companies hundreds of thousands of dollars in screening campaigns and increasing the quality of data.

由于具有吸湿性,干燥的二甲基亚砜能迅速从空气中吸附水蒸气。这是药物发现领域,尤其是高通量筛选(HTS)领域一个有据可查的问题。每次使用化合物库时,大气中的水分都会被吸收,从而导致这种水化现象。当化合物库被常规使用时,这种影响会变得越来越明显。水化的结果是改变溶液的总体积和溶液中的样品浓度。根据化合物库的使用情况,这可能会导致测得的样品生物活性存在很大差异。在本文中,我们展示了样品库水合对生物数据重现性的不利影响,并提出了一种从 HTS 库板中去除水合的新方法。我们的方法是通过将无水二甲基亚砜置于氮气吹扫的化合物存储舱中来创造富含二甲基亚砜的环境,并将库板在此环境中培养长达 3 天。通过蒸发光散射检测(ELSD)进行的定量分析显示,除去水分可大大提高溶液的摩尔浓度,对溶解度低的化合物影响更大。我们还展示了这种方法如何在去除水分后将含水量在 30% 以下的样品的化合物储备溶液的抑制活性(pIC50)从大于 30 µM 恢复到亚微摩级。这种方法提高了 HTS 中测试化合物的可靠性,有可能为制药公司节省数十万美元的筛选费用,并提高数据质量。
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引用次数: 0
Bio inspired technological performance in color Doppler ultrasonography and echocardiography for enhanced diagnostic precision in fetal congenital heart disease 彩色多普勒超声和超声心动图的生物启发技术性能可提高胎儿先天性心脏病的诊断精度。
IF 2.5 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-10-11 DOI: 10.1016/j.slast.2024.100207
The aim of this experiment is to investigate the bioinspired diagnostic performance of color Doppler ultrasound (CDUS) and two-dimensional (2D) echocardiography (ECG) for fetal congenital heart disease (FCHD). The research subjects were 33 expectant mothers with a diagnosis of FCHD at Xiangyang No. 1 People's Hospital between January 2017 and January 2021. The accuracy, sensitivity, and specificity of the two detection techniques were computed to ascertain and compare the diagnostic efficiency after CDUS and ECG examinations of all pregnant women. According to the findings, the prenatal CDUS detection rate was 92.61% higher than the 2D ECG detection rate (64.32%). The CDUS had an accuracy of 93.94%, sensitivity of 93.55%, and specificity of 100%, detecting 29 true positives, 0 false positives, 2 false negatives, and 2 true negatives. At 84.85% accuracy, 88.89% sensitivity, and 80% specificity, the 2D ECG identified 16 true positives, 3 false positives, 2 false positives, and 12 true negatives. There was a statistically significant (P < 0.05) difference between the accuracy, sensitivity, and specificity of 2D ECG and CDUS. In summary, CDUS was more effective than 2D ECG in diagnosing prenatal FCHD, and it also had a lower rate of missed and incorrect diagnoses.
本实验旨在研究彩色多普勒超声(CDUS)和二维超声心动图(ECG)对胎儿先天性心脏病(FCHD)的生物启发诊断性能。研究对象为2017年1月至2021年1月期间在襄阳市第一人民医院确诊为FCHD的33名准妈妈。计算两种检测技术的准确性、敏感性和特异性,以确定和比较所有孕妇在接受CDUS和心电图检查后的诊断效率。结果显示,产前 CDUS 检测率为 92.61%,高于二维心电图检测率(64.32%)。CDUS 的准确率为 93.94%,灵敏度为 93.55%,特异性为 100%,检测出 29 个真阳性、0 个假阳性、2 个假阴性和 2 个真阴性。二维心电图的准确性为 84.85%,灵敏度为 88.89%,特异性为 80%,可发现 16 个真阳性、3 个假阳性、2 个假阴性和 12 个真阴性。二维心电图和 CDUS 的准确性、灵敏度和特异性之间的差异具有统计学意义(P < 0.05)。总之,在诊断产前 FCHD 方面,CDUS 比二维心电图更有效,漏诊率和误诊率也更低。
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引用次数: 0
Diagnostic value of rEBUS-TBLB combined distance measurement method based on ultrasound images in bronchoscopy for peripheral lung lesions 基于超声图像的 rEBUS-TBLB 组合距离测量法在支气管镜检查肺周边病变中的诊断价值。
IF 2.5 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-10-11 DOI: 10.1016/j.slast.2024.100198
Traditional imaging methods have limitations in the diagnosis of peripheral lung lesions. The aim of this study is to evaluate the diagnostic value of the distance measurement method based on ultrasound image-based inverted electrostrain (rEBUS) combined with thoracoscopic lung biopsy (TBLB) for peripheral lung lesions. A group of patients with peripheral lung lesions were recruited for the study, and rEBUS examination was performed simultaneously during TBLB. Using rEBUS ultrasound images combined with electrostrain information, evaluate the morphological characteristics of peripheral lung lesions and the elastic properties of internal tissues. By comparing with pathological examination results, both rEBUS-D-TBLB and rEBUS-GS-TBLB have a higher positive diagnostic rate for PPL under bronchoscopy. However, rEBUS-D-TBLB is more effective in diagnosing benign PPL with ≥ 3 cm PPL than rEBUS-GS-TBLB. The rEBUS-TBLB combined ranging method has shown high accuracy and sensitivity in diagnosing peripheral lung lesions. Ultrasound images provide clear morphological features of the tumor, while the electrical strain information of rEBUS provides elastic information of the internal tissue of the tumor, further improving the accuracy of diagnosis.
传统的成像方法在诊断肺周围病变方面存在局限性。本研究旨在评估基于超声图像的倒置电应变距离测量法(rEBUS)结合胸腔镜肺活检术(TBLB)对肺周围病变的诊断价值。研究招募了一组肺周围病变患者,在进行 TBLB 时同时进行了 rEBUS 检查。利用 rEBUS 超声图像结合电应变信息,评估肺外周病变的形态特征和内部组织的弹性特性。与病理检查结果相比,rEBUS-D-TBLB 和 rEBUS-GS-TBLB 在支气管镜下对 PPL 的诊断阳性率更高。不过,rEBUS-D-TBLB 在诊断 PPL≥ 3 厘米的良性 PPL 方面比 rEBUS-GS-TBLB 更有效。rEBUS-TBLB 联合测距法在诊断肺外周病变方面具有较高的准确性和灵敏度。超声图像提供了清晰的肿瘤形态特征,而 rEBUS 的电应变信息提供了肿瘤内部组织的弹性信息,进一步提高了诊断的准确性。
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引用次数: 0
Evaluation of microplate handling accuracy for applying robotic arms in laboratory automation 评估在实验室自动化中应用机械臂的微孔板处理精度。
IF 2.5 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-10-11 DOI: 10.1016/j.slast.2024.100200
An inexpensive single-arm robot is widely utilized for recent laboratory automation solutions. The integration of a single-arm robot as a transfer system into a semi-automatic liquid dispenser without a transfer system can be realized as an inexpensive alternative to a fully automated liquid handling system. However, there has been no quantitative investigation of the positional accuracy of robot arms required to transfer microplates. In this study, we constructed a platform comprising aluminum frames and digital gauges to facilitate such measurements. We measured the position repeatability of a robot arm equipped with a custom-made finger by repeatedly transferring microplates. Further, the acceptable misalignment of plate transfer was evaluated by adding an artificial offset to the microplate position using this platform. The results of these experiments are expected to serve as benchmarks for the selection of robot arms for laboratory automation in biology. Furthermore, all information for replicating this device will be made publicly available, thereby allowing many researchers to collaborate and accumulate knowledge, hopefully contributing to advances in this field.
廉价的单臂机器人被广泛应用于最新的实验室自动化解决方案中。将单臂机器人作为传送系统集成到不带传送系统的半自动液体分配器中,可作为全自动液体处理系统的廉价替代方案。然而,目前还没有对传送微孔板所需的机械臂位置精度进行定量研究。在本研究中,我们构建了一个由铝制框架和数字量规组成的平台,以方便进行此类测量。通过反复转移微孔板,我们测量了配备定制手指的机械臂的位置重复性。此外,我们还利用该平台为微孔板位置添加了一个人工偏移量,从而评估了可接受的微孔板转移偏差。这些实验结果有望成为选择生物实验室自动化机械臂的基准。此外,复制该装置的所有信息都将公开发布,从而使许多研究人员能够合作并积累知识,希望能对该领域的进步做出贡献。
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引用次数: 0
Advances in synthetic biology 合成生物学的进展。
IF 2.5 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-10-01 DOI: 10.1016/j.slast.2024.100197
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引用次数: 0
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SLAS Technology
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