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An integrated deep learning framework leveraging NASNet and vision transformer with MixProcessing for accurate and precise diagnosis of lung diseases 基于混合处理的NASNet和视觉转换器集成深度学习框架用于肺部疾病的准确诊断。
IF 3.7 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-05-01 Epub Date: 2026-01-22 DOI: 10.1016/j.slast.2026.100394
Sajjad Saleem , Muhammad Zaheer Sajid , Abida Sharif , Jarrar Amjad , Anwaar UlHaq , Haya Aldossary
Lung diseases such as pneumonia, tuberculosis, COVID-19, and lung cancer remain significant global health challenges that demand rapid and accurate diagnosis to improve patient outcomes. This study proposes NASNet-ViT, a novel deep learning framework that integrates the powerful convolutional feature extraction of NASNet with the global attention mechanisms of the Vision Transformer (ViT). To enhance diagnostic precision, a multi-stage preprocessing pipeline, termed MixProcessing, is introduced, combining wavelet transform decomposition, adaptive histogram equalization, and morphological filtering to improve image quality and feature clarity. The proposed NASNet-ViT model classifies lung images into five categories, normal, lung cancer, COVID-19, pneumonia, and tuberculosis achieving outstanding performance metrics: 98.9% accuracy, 0.99 sensitivity, 0.988 F1-score, and 0.985 specificity. Compared to established architectures such as MixNet-LD, D-ResNet, MobileNet, and ResNet50, NASNet-ViT demonstrates superior accuracy while maintaining a lightweight model size of only 25.6 MB and fast inference time of 12.4 seconds, making it practical for deployment in real-time, resource-constrained clinical environments. This research advances the field of medical image analysis by offering a robust and scalable AI solution capable of supporting clinicians in timely and precise lung disease diagnosis.
肺炎、结核病、COVID-19和肺癌等肺部疾病仍然是重大的全球卫生挑战,需要快速准确的诊断,以改善患者的治疗结果。本研究提出了一种新的深度学习框架NASNet-ViT,它将NASNet强大的卷积特征提取与视觉转换器(Vision Transformer, ViT)的全局注意机制相结合。为了提高诊断精度,引入了一种称为MixProcessing的多级预处理管道,结合小波变换分解、自适应直方图均衡化和形态滤波来提高图像质量和特征清晰度。所提出的NASNet-ViT模型将肺部图像分为五类:正常、肺癌、COVID-19、肺炎和结核病,获得了出色的性能指标:98.9%的准确率、0.99的灵敏度、0.989的f1评分和0.987的特异性。与MixNet-LD、D-ResNet、MobileNet和ResNet50等现有架构相比,NASNet-ViT在保持轻量级模型大小仅为25.6 MB和快速推理时间12.4秒的同时,具有卓越的准确性,使其在实时、资源受限的临床环境中部署更加实用。这项研究提供了一个强大的、可扩展的人工智能解决方案,能够支持临床医生及时、准确地诊断肺部疾病,从而推动了医学图像分析领域的发展。
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引用次数: 0
Diffusion tensor imaging (DTI) combined with diffusion tensor tractography (DTT) in the brain function and volumetric imaging in children with autism 弥散张量成像(DTI)联合弥散张量束成像(DTT)在自闭症儿童脑功能和体积成像中的应用。
IF 3.7 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-05-01 Epub Date: 2026-01-30 DOI: 10.1016/j.slast.2026.100400
Feifei Huang, Yong Wei, Zidong Lv, Yang Lv, Jie Fu

Objective

To explore the application value of DTI combined with DTT in brain function and volume in children with autism.

Methods

A total of 616 children with autism diagnosed from January 2020 to December 2022 (ASD group) and 91 healthy children with age and gender matching (control group) were included in the study. All subjects underwent DTI and DTT examinations. The DTI-DTT examination was conducted to analyze the Fractional Anisotropy (FA) values of key brain regions such as the corpus callosum and internal capsule, and the correlation and diagnostic efficacy were analyzed with the scores of the Autism Behavior Checklist (ABC).

Results

The total scores of ABC and each factor in the ASD group were significantly higher than those in the control group (p<0.05). The FA values of the knee joint and compressed part of the corpus callosum as well as the anterior and posterior limbs of the internal capsule in the ASD group were significantly higher than those in the control group (p<0.05). Relevant analysis showed that the FA values of the anterior and posterior limbs of the capsule in the ASD group were moderately positively correlated with the scores of sensory and body movement factors in the ABC scale (p<0.01). The FA values of the knee and compression parts of the corpus callosum were also moderately positively correlated with the communication and connection factor scores (p<0.01). ROC curve analysis indicated that the FA values of the above-mentioned brain regions had a high diagnostic value for ASD (AUC values were all >0.64).

Conclusion

The combination of DTI and DTT effectively reveals the microstructure abnormalities of the main white matter pathways (such as the corpus callosum and internal capsule) in children with autism. These abnormalities are significantly correlated with specific behavioral symptoms. This combined imaging technology provides important neuroimaging evidence for the early objective diagnosis and rehabilitation intervention of children with autism.
目的:探讨DTI联合DTT在自闭症儿童脑功能和脑容量中的应用价值。方法:选取2020年1月~ 2022年12月诊断为自闭症的儿童616例(ASD组)和年龄、性别匹配的健康儿童91例(对照组)作为研究对象。所有受试者均行DTI和DTT检查。采用DTI-DTT检查,分析胼胝体、内囊等脑关键区域分数各向异性(FA)值,并与自闭症行为检查表(ABC)评分进行相关性分析及诊断效果分析。结果:ASD组ABC总分及各因子得分均显著高于对照组(p0.64)。结论:DTI联合DTT能有效揭示自闭症儿童脑白质主要通路(如胼胝体和内囊)的微结构异常。这些异常与特定行为症状显著相关。该联合成像技术为自闭症儿童的早期客观诊断和康复干预提供了重要的神经影像学依据。
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引用次数: 0
Identification of a telomere-aging-related gene as a novel prognostic factor for intrahepatic cholangiocarcinoma: machine learning-aided biomarker discovery and experimental verification. 端粒老化相关基因作为肝内胆管癌新预后因素的鉴定:机器学习辅助生物标志物发现和实验验证。
IF 3.7 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-03-23 DOI: 10.1016/j.slast.2026.100416
Jianjian Yin, Yingying Wang, Hongmei Zhang, Wenhao Qu

Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive hepatobiliary malignancy characterized by a complex pathogenesis and poor prognosis. Telomere dysfunction and cellular senescence are involved in the pathogenesis of various types of cancers. However, the prognostic significance of telomere- and aging-related genes in ICC remains unclear. This study aimed to identify such genes with prognostic significance, and construct a prognostic risk model for ICC.

Methods: We screened prognostic genes associated with telomere-aging in patients using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We then integrated 10 base machine learning algorithms, and generated 101 model configurations via parameter optimization and algorithm combination strategies, to construct and validate a prognostic risk model. The clinical prognostic value was analyzed using a nomogram. Immune infiltration, drug sensitivity, immune responses, and subgroups were analyzed based on telomere-aging-related prognostic genes. We also validated core gene expression in cell lines and tissue samples using the quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and enrolled 76 patients with ICC to identify the prognostic value of key genes.

Results: We constructed a prognostic model using the telomere-aging-related prognostic genes BET1L, RAD50, ANXA1, and AURKA. Survival analysis revealed a significant difference in overall survival between high- and low-risk groups. The expression of these genes was significantly increased in ICC cell lines and tissues. High BET1L expression was significantly associated with lymph node metastasis, tumor-node-metastasis (TNM) stage, tumor differentiation, and a poor prognosis for patients with ICC. Knocking down BET1L significantly reduced the proliferative ability of HUCCT1 cells.

Conclusions: We established a risk model comprising the telomere-aging-related prognostic genes BET1L, RAD50, ANXA1, and AURKA to predict the prognosis of patients with ICC. Elevated BET1L expression indicated a poor prognosis for patients with ICC, and low BET1L expression inhibited HUCCT1 cell proliferation.

背景:肝内胆管癌(ICC)是一种发病复杂、预后差的侵袭性肝胆恶性肿瘤。端粒功能障碍和细胞衰老与各种类型癌症的发病机制有关。然而,端粒和衰老相关基因在ICC中的预后意义尚不清楚。本研究旨在鉴定这些具有预后意义的基因,并构建ICC的预后风险模型。方法:我们使用癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)筛选与患者端粒老化相关的预后基因。然后,我们整合了10种基本机器学习算法,并通过参数优化和算法组合策略生成了101种模型配置,构建并验证了预后风险模型。应用图分析临床预后价值。基于端粒衰老相关预后基因分析免疫浸润、药物敏感性、免疫反应和亚组。我们还利用定量反转录聚合酶链反应(qRT-PCR)验证了核心基因在细胞系和组织样本中的表达,并招募了76名ICC患者,以确定关键基因的预后价值。结果:我们利用端粒衰老相关的预后基因BET1L、RAD50、ANXA1和AURKA构建了预后模型。生存分析显示,高危组和低危组的总生存率有显著差异。这些基因在ICC细胞系和组织中的表达显著增加。BET1L高表达与ICC患者的淋巴结转移、肿瘤-淋巴结转移(TNM)分期、肿瘤分化及不良预后显著相关。敲除BET1L可显著降低HUCCT1细胞的增殖能力。结论:我们建立了端粒老化相关预后基因BET1L、RAD50、ANXA1、AURKA的风险模型,预测ICC患者的预后。升高的BET1L表达提示ICC患者预后不良,低表达的BET1L抑制了HUCCT1细胞的增殖。
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引用次数: 0
HueTools: A modular image processing and ML toolkit for quantitative colorimetric assay development. HueTools:用于定量比色分析开发的模块化图像处理和ML工具包。
IF 3.7 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-03-19 DOI: 10.1016/j.slast.2026.100413
Prava Sharma, David Beery, Adrian Crutchfield, Ayesha Azimuddin, Aaron Lauer, Brianna Wronko-Stevens, Erdi Kara, Nidhi Menon

Colorimetric assays offer a low-cost, accessible means of diagnostic testing but often suffer from subjective interpretation and variability caused by inconsistent imaging conditions. To address these challenges, we present HueTools, a comprehensive image processing software that enables quantitative development of paper-based colorimetric assays using smartphone imaging. HueTools integrates a mobile app, and a web platform to standardize image capture, apply precise color correction, and predictive modeling of analyte concentration using interpretable machine learning. The system supports a complete workflow: from image acquisition and color calibration to region-of-interest (ROI) selection, signal extraction, and statistical analysis. The system enables perceptually grounded color analysis using the CIELAB space and provides quantitative metrics, including LoB, LoD, and LoQ via interpretable ensemble-based customization models. HueTools was validated using a lateral flow dipstick luteinizing hormone (LH) and vertical-flow alanine transaminase (ALT) assays. The results demonstrate HueTools' ability to reduce human error, improve assay reproducibility, and provide feedback for optimizing assay design. It also supports seamless transitions between field testing and lab analysis, allowing researchers to capture images on-site and perform in-depth analysis remotely. HueTools offers a hardware-independent, cloud-based solution for assay developers, streamlining workflows while minimizing costs associated with dedicated readers. Its accessibility, automation, and cross-platform compatibility make it well-suited for research and development of colorimetric point-of-care diagnostics, especially in resource-limited settings.

比色分析提供了一种低成本、可获得的诊断测试手段,但往往存在主观解释和不一致的成像条件引起的可变性。为了应对这些挑战,我们提出了HueTools,这是一种全面的图像处理软件,可以使用智能手机成像进行基于纸张的比色分析的定量开发。HueTools集成了一个移动应用程序和一个web平台,用于标准化图像捕获,应用精确的色彩校正,并使用可解释的机器学习对分析物浓度进行预测建模。该系统支持完整的工作流程:从图像采集和颜色校准到感兴趣区域(ROI)选择,信号提取和统计分析。该系统可以使用CIELAB空间进行感知基础颜色分析,并通过可解释的基于集成的定制模型提供定量指标,包括LoB、LoD和LoQ。采用侧流黄体生成素(LH)测试和垂直流丙氨酸转氨酶(ALT)测试对HueTools进行验证。结果表明,HueTools能够减少人为错误,提高检测重复性,并为优化检测设计提供反馈。它还支持现场测试和实验室分析之间的无缝过渡,允许研究人员在现场捕获图像并远程执行深入分析。HueTools为分析开发人员提供了独立于硬件的基于云的解决方案,简化了工作流程,同时最大限度地降低了与专用阅读器相关的成本。它的可访问性、自动化和跨平台兼容性使其非常适合于比色法即时诊断的研究和开发,特别是在资源有限的环境中。
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引用次数: 0
Development and Validation of a Novel Ion-pair Hydrophilic Interaction Liquid Chromatography Method for the Separation and Quantification of Oligonucleotide Therapeutics. 一种新型离子对亲水性相互作用液相色谱法用于寡核苷酸治疗药物的分离和定量的开发和验证。
IF 3.7 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-03-17 DOI: 10.1016/j.slast.2026.100415
Qian Zhang, Xinjie Li, Yalin Jiang, Zhen Wang

Background: This study developed and systematically optimized an ion-pair hydrophilic interaction liquid chromatography (IP-HILIC) system for oligonucleotide medicine analysis, aiming to the issues of insufficient resolution and prolonged retention times commonly encountered in traditional hydrophilic interaction liquid chromatography (HILIC) and ion-pair reversed-phase liquid chromatography (IP-RPLC). Therefore, this study aimed to optimize and validate a TEAA-based IP-HILIC analytical system for both the effective separation and quantitative analysis of oligonucleotides, including evaluations of linearity, sensitivity, precision, and robustness.

Methods: By synthesizing an amino/hexadecyl-bifunctionalized silica matrix and systematically optimizing mobile phase parameters (including ion-pair reagent type and concentration, organic solvent, and buffer pH), a highly efficient separation system was established. To validate the separation efficiency, a 21-mer oligonucleotide Fomivirsen and its truncated impurities (5'-21-1 and 3'-21-1) were synthesized, along with Food and Drug Administration(FDA)-approved Kynamro (20-mer), Macugen (28-mer), and Exondys 51 (30-mer) for method evaluation.

Results: Experimental results demonstrated that under pH 8.0 conditions, a mobile phase system composed of 50 mM triethylamine acetate (TEAA) and acetonitrile enabled baseline separation of 20-30-mer oligonucleotides with a resolution ≥1.5. Using Fomivirsen impurities (e.g., 5'-21-1 and 5'-21-3) as examples, the retention times were optimized to between 3.76 and 6.76 minutes, achieving a resolution of 3.82. Acetonitrile shortened the analysis time by 34% compared with methanol, while 50 mM TEAA maintained resolution in the range of 2.58-3.71 and avoided the excessive retention seen at 100 mM, where the peak time extended to 7.57 minutes.Method validation demonstrated that the method exhibited good linearity (R²>0.999) over the concentration range of 0.05-10 μg/mL, with a limit of detection (LOD) of 0.2 μM and a limit of quantitation (LOQ) of 0.6 μM. The method also showed satisfactory precision (intra-day RSD < 1.5%, inter-day RSD < 2.1%) and was robust against minor variations in mobile phase composition, column temperature, and flow rate. Compared to traditional methods, IP-HILIC demonstrated significantly superior resolution (1.50-2.09) for long-chain oligonucleotides (e.g., 30-mer Exondys 51) over IP-RPLC (1.30) and HILIC (1.20), with better peak symmetry (tailing factor <1.2).

Conclusion: This study provides an systematically optimized and validated analytical platform for the quality control of oligonucleotide medicines, particularly showing significant advantages in the separation of key impurities (e.g., n-1 sequences) for long-chain oligonucleotides (20-30 mer), laying a technical foundation for the precise analysis of hydrophilic biopolymers.

背景:针对传统亲水相互作用液相色谱(HILIC)和离子对反相液相色谱(IP-RPLC)分析中存在的分辨率不足、保留时间长等问题,建立并系统优化了一种用于寡核苷酸药物分析的离子对亲水相互作用液相色谱(IP-HILIC)系统。因此,本研究旨在优化和验证基于teaa的IP-HILIC分析系统,对寡核苷酸进行有效分离和定量分析,包括线性、灵敏度、精密度和鲁棒性评价。方法:通过合成氨基/十六烷基双功能化二氧化硅基质,系统优化流动相参数(离子对试剂类型及浓度、有机溶剂、缓冲液pH),建立高效分离体系。为了验证分离效率,合成了21聚体寡核苷酸Fomivirsen及其截短杂质(5’-21-1和3’-21-1),以及FDA批准的Kynamro(20聚体)、Macugen(28聚体)和Exondys 51(30聚体)进行方法评估。结果:实验结果表明,在pH 8.0条件下,由50 mM醋酸三乙胺(TEAA)和乙腈组成的流动相体系可以基线分离20-30-mer的寡核苷酸,分辨率≥1.5。以Fomivirsen杂质(如5′-21-1和5′-21-3)为例,优化保留时间为3.76 ~ 6.76 min,分辨率为3.82。与甲醇相比,乙腈的分析时间缩短了34%,而50 mM TEAA的分辨率保持在2.58-3.71范围内,避免了100 mM时的过度保留,峰值时间延长至7.57 min。方法验证表明,该方法在0.05 ~ 10 μg/mL范围内线性良好(R²>0.999),检出限为0.2 μM,定量限为0.6 μM。该方法还具有令人满意的精密度(日内RSD < 1.5%,日间RSD < 2.1%),并且对流动相组成、柱温和流速的微小变化具有较强的稳定性。与传统方法相比,IP-HILIC对长链寡核苷酸(如30-mer Exondys 51)的分辨率(1.50-2.09)明显优于IP-RPLC(1.30)和HILIC(1.20),且具有更好的峰对称性(尾因子)。本研究为寡核苷酸类药物的质量控制提供了一个系统优化和验证的分析平台,特别是在长链寡核苷酸(20- 30mer)关键杂质(如n-1序列)的分离方面具有显著优势,为亲水生物聚合物的精确分析奠定了技术基础。
{"title":"Development and Validation of a Novel Ion-pair Hydrophilic Interaction Liquid Chromatography Method for the Separation and Quantification of Oligonucleotide Therapeutics.","authors":"Qian Zhang, Xinjie Li, Yalin Jiang, Zhen Wang","doi":"10.1016/j.slast.2026.100415","DOIUrl":"https://doi.org/10.1016/j.slast.2026.100415","url":null,"abstract":"<p><strong>Background: </strong>This study developed and systematically optimized an ion-pair hydrophilic interaction liquid chromatography (IP-HILIC) system for oligonucleotide medicine analysis, aiming to the issues of insufficient resolution and prolonged retention times commonly encountered in traditional hydrophilic interaction liquid chromatography (HILIC) and ion-pair reversed-phase liquid chromatography (IP-RPLC). Therefore, this study aimed to optimize and validate a TEAA-based IP-HILIC analytical system for both the effective separation and quantitative analysis of oligonucleotides, including evaluations of linearity, sensitivity, precision, and robustness.</p><p><strong>Methods: </strong>By synthesizing an amino/hexadecyl-bifunctionalized silica matrix and systematically optimizing mobile phase parameters (including ion-pair reagent type and concentration, organic solvent, and buffer pH), a highly efficient separation system was established. To validate the separation efficiency, a 21-mer oligonucleotide Fomivirsen and its truncated impurities (5'-21-1 and 3'-21-1) were synthesized, along with Food and Drug Administration(FDA)-approved Kynamro (20-mer), Macugen (28-mer), and Exondys 51 (30-mer) for method evaluation.</p><p><strong>Results: </strong>Experimental results demonstrated that under pH 8.0 conditions, a mobile phase system composed of 50 mM triethylamine acetate (TEAA) and acetonitrile enabled baseline separation of 20-30-mer oligonucleotides with a resolution ≥1.5. Using Fomivirsen impurities (e.g., 5'-21-1 and 5'-21-3) as examples, the retention times were optimized to between 3.76 and 6.76 minutes, achieving a resolution of 3.82. Acetonitrile shortened the analysis time by 34% compared with methanol, while 50 mM TEAA maintained resolution in the range of 2.58-3.71 and avoided the excessive retention seen at 100 mM, where the peak time extended to 7.57 minutes.Method validation demonstrated that the method exhibited good linearity (R²>0.999) over the concentration range of 0.05-10 μg/mL, with a limit of detection (LOD) of 0.2 μM and a limit of quantitation (LOQ) of 0.6 μM. The method also showed satisfactory precision (intra-day RSD < 1.5%, inter-day RSD < 2.1%) and was robust against minor variations in mobile phase composition, column temperature, and flow rate. Compared to traditional methods, IP-HILIC demonstrated significantly superior resolution (1.50-2.09) for long-chain oligonucleotides (e.g., 30-mer Exondys 51) over IP-RPLC (1.30) and HILIC (1.20), with better peak symmetry (tailing factor <1.2).</p><p><strong>Conclusion: </strong>This study provides an systematically optimized and validated analytical platform for the quality control of oligonucleotide medicines, particularly showing significant advantages in the separation of key impurities (e.g., n-1 sequences) for long-chain oligonucleotides (20-30 mer), laying a technical foundation for the precise analysis of hydrophilic biopolymers.</p>","PeriodicalId":54248,"journal":{"name":"SLAS Technology","volume":" ","pages":"100415"},"PeriodicalIF":3.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147488536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrative transcriptomic profiling reveals molecular signatures of disease progression from gastroesophageal reflux disease to Barrett's esophagus: A foundation for single-cell resolution studies. 综合转录组学分析揭示了从胃食管反流病到巴雷特食管疾病进展的分子特征:单细胞分辨率研究的基础。
IF 3.7 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-03-14 DOI: 10.1016/j.slast.2026.100412
Shanshan Jiang, Xiumin Wang, Yujun Chen, Weihua Dong, Jing Xu, Chunlan Zhang, Chun Zhou, Chun Yu
<p><strong>Background: </strong>Barrett's esophagus (BE) represents a critical precancerous lesion arising from chronic gastroesophageal reflux disease (GERD), with significant risk of progression to esophageal adenocarcinoma. Despite advances in transcriptomic technologies, including single-cell RNA sequencing (scRNA-seq), the molecular mechanisms underlying the GERD-to-BE transition remain incompletely understood. Comprehensive transcriptomic profiling at both bulk and, prospectively, single-cell resolution is essential for identifying disease-driving molecular signatures and cellular heterogeneity. This study aimed to systematically characterize the transcriptomic landscape of GERD and Barrett's esophagus through integrative bulk RNA-sequencing analysis, with the goal of establishing a foundational framework for future single-cell transcriptomic investigations.</p><p><strong>Methods: </strong>A balanced cohort of N=40 patients (n=20 GERD, n=20 Barrett's esophagus) was enrolled. Esophageal tissue samples were collected via endoscopic biopsy and subjected to high-throughput RNA sequencing. Rigorous quality control, read alignment (HISAT2), and gene expression quantification (StringTie) were performed. DESeq2 was employed for differential expression analysis with stringent criteria (|log2FC| ≥ 1.0, FDR < 0.05). Functional enrichment analysis was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Integration of gene expression data with clinical parameters enabled comprehensive clinical-molecular association analyses. Multi-dimensional visualization approaches, including volcano plots, heatmaps, principal component analysis (PCA), and network diagrams, were utilized to present the transcriptomic landscape.</p><p><strong>Results: </strong>Transcriptomic profiling identified 1,247 significantly differentially expressed genes (673 upregulated, 574 downregulated) between GERD and Barrett's esophagus, with balanced distribution of upregulated and downregulated genes. Functional enrichment analysis revealed significant involvement of DEGs in critical biological processes including extracellular matrix remodeling, epithelial cell proliferation, inflammatory response, and immune regulation. KEGG pathway analysis highlighted activation of cancer-related signaling cascades, including PI3K-Akt, cell cycle regulation, and ECM-receptor interaction pathways, suggesting that Barrett's esophagus exhibits partial molecular characteristics of malignant transformation. Correlation analysis demonstrated that specific genes (MMP7 (matrix metalloproteinase 7) and CDH17 (cadherin 17)) showed dose-response relationships with disease severity, while CXCL8 (interleukin-8) expression was significantly associated with treatment resistance. Longitudinal monitoring revealed heterogeneous disease progression trajectories among patients, with inflammation scores ranging from 3.0-6.5 points and exhibiting variable temporal dynamics. T
背景:巴雷特食管(BE)是一种由慢性胃食管反流病(GERD)引起的严重癌前病变,具有进展为食管腺癌的显著风险。尽管转录组学技术取得了进步,包括单细胞RNA测序(scRNA-seq),但gerd -to- to转变的分子机制仍然不完全清楚。整体和单细胞分辨率的综合转录组分析对于识别疾病驱动的分子特征和细胞异质性至关重要。本研究旨在通过整体rna测序分析系统地表征GERD和Barrett食管的转录组学特征,目的是为未来的单细胞转录组学研究建立基础框架。方法:纳入均衡队列N=40例患者(N= 20例胃食管反流,N= 20例巴雷特食管)。通过内镜活检收集食管组织样本,并进行高通量RNA测序。进行了严格的质量控制、读取比对(HISAT2)和基因表达定量(StringTie)。采用DESeq2进行差异表达分析,标准严格(|log2FC|≥1.0,FDR < 0.05)。使用基因本体(GO)和京都基因与基因组百科全书(KEGG)数据库进行功能富集分析。基因表达数据与临床参数的整合使全面的临床-分子关联分析成为可能。利用多维可视化方法,包括火山图、热图、主成分分析(PCA)和网络图来呈现转录组景观。结果:转录组学分析鉴定出1247个基因在GERD和Barrett食管中显著差异表达(673个上调,574个下调),且上调和下调基因分布均衡。功能富集分析显示,DEGs在细胞外基质重塑、上皮细胞增殖、炎症反应和免疫调节等关键生物过程中具有重要作用。KEGG通路分析强调了癌症相关信号级联的激活,包括PI3K-Akt、细胞周期调节和ecm受体相互作用通路,表明Barrett食管具有恶性转化的部分分子特征。相关分析显示,特异性基因(MMP7(基质金属蛋白酶7)和CDH17(钙粘蛋白17))与疾病严重程度呈剂量反应关系,而CXCL8(白细胞介素-8)表达与治疗耐药性显著相关。纵向监测显示,患者的疾病进展轨迹具有异质性,炎症评分在3.0-6.5分之间,并表现出可变的时间动态。三维临床特征空间分析证实了GERD和Barrett食管患者之间可区分的分布模式,尽管部分重叠表明疾病连续特征。结论:这项全面的转录组学研究揭示了gerd到barrett食管进展的分子复杂性,确定了驱动病理转化的关键基因和途径。
{"title":"Integrative transcriptomic profiling reveals molecular signatures of disease progression from gastroesophageal reflux disease to Barrett's esophagus: A foundation for single-cell resolution studies.","authors":"Shanshan Jiang, Xiumin Wang, Yujun Chen, Weihua Dong, Jing Xu, Chunlan Zhang, Chun Zhou, Chun Yu","doi":"10.1016/j.slast.2026.100412","DOIUrl":"10.1016/j.slast.2026.100412","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Barrett's esophagus (BE) represents a critical precancerous lesion arising from chronic gastroesophageal reflux disease (GERD), with significant risk of progression to esophageal adenocarcinoma. Despite advances in transcriptomic technologies, including single-cell RNA sequencing (scRNA-seq), the molecular mechanisms underlying the GERD-to-BE transition remain incompletely understood. Comprehensive transcriptomic profiling at both bulk and, prospectively, single-cell resolution is essential for identifying disease-driving molecular signatures and cellular heterogeneity. This study aimed to systematically characterize the transcriptomic landscape of GERD and Barrett's esophagus through integrative bulk RNA-sequencing analysis, with the goal of establishing a foundational framework for future single-cell transcriptomic investigations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A balanced cohort of N=40 patients (n=20 GERD, n=20 Barrett's esophagus) was enrolled. Esophageal tissue samples were collected via endoscopic biopsy and subjected to high-throughput RNA sequencing. Rigorous quality control, read alignment (HISAT2), and gene expression quantification (StringTie) were performed. DESeq2 was employed for differential expression analysis with stringent criteria (|log2FC| ≥ 1.0, FDR &lt; 0.05). Functional enrichment analysis was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Integration of gene expression data with clinical parameters enabled comprehensive clinical-molecular association analyses. Multi-dimensional visualization approaches, including volcano plots, heatmaps, principal component analysis (PCA), and network diagrams, were utilized to present the transcriptomic landscape.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Transcriptomic profiling identified 1,247 significantly differentially expressed genes (673 upregulated, 574 downregulated) between GERD and Barrett's esophagus, with balanced distribution of upregulated and downregulated genes. Functional enrichment analysis revealed significant involvement of DEGs in critical biological processes including extracellular matrix remodeling, epithelial cell proliferation, inflammatory response, and immune regulation. KEGG pathway analysis highlighted activation of cancer-related signaling cascades, including PI3K-Akt, cell cycle regulation, and ECM-receptor interaction pathways, suggesting that Barrett's esophagus exhibits partial molecular characteristics of malignant transformation. Correlation analysis demonstrated that specific genes (MMP7 (matrix metalloproteinase 7) and CDH17 (cadherin 17)) showed dose-response relationships with disease severity, while CXCL8 (interleukin-8) expression was significantly associated with treatment resistance. Longitudinal monitoring revealed heterogeneous disease progression trajectories among patients, with inflammation scores ranging from 3.0-6.5 points and exhibiting variable temporal dynamics. T","PeriodicalId":54248,"journal":{"name":"SLAS Technology","volume":" ","pages":"100412"},"PeriodicalIF":3.7,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
OT2Eye: Detection of labware conditions to monitor and extend affordable liquid-handling robots. OT2Eye:检测实验室条件,以监测和扩展负担得起的液体处理机器人。
IF 3.7 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-03-13 DOI: 10.1016/j.slast.2026.100410
Koki Tachibana, Haruka Ozaki

In the automation of life science experiments, verifying and recording the types, positions, and states of labware are essential for quality assurance and traceability of experimental results. To achieve this, researchers often record static images or videos within lab automation instruments and workstations. However, the absence of specialized open-source software for labware detection significantly hinders the efficient utilization of these images and videos in automated life science experiments. To address this issue, we developed OT2Eye, a labware detection tool tailored for the images and videos of the Opentrons OT-2, an affordable liquid-handling robot. OT2Eye demonstrated high accuracy in identifying various labware types, including microwell plates and tip racks, and precisely locating them within the OT-2 workspace. Additionally, OT2Eye accurately detected the presence or absence of tips on tip racks. OT2Eye renders labware states machine-readable, streamlining labware status management and logging, and enabling integration with AI-driven laboratory automation systems using cost-effective automated pipetting robots.

在生命科学实验自动化中,验证和记录实验仪器的类型、位置和状态是保证实验结果质量和可追溯性的必要条件。为了实现这一点,研究人员经常在实验室自动化仪器和工作站中记录静态图像或视频。然而,缺乏专门的开源软件用于实验室软件检测,严重阻碍了这些图像和视频在自动化生命科学实验中的有效利用。为了解决这个问题,我们开发了OT2Eye,这是一款为Opentrons OT-2(一款价格合理的液体处理机器人)的图像和视频量身定制的实验室软件检测工具。OT2Eye在识别各种实验室设备类型(包括微孔板和尖端架)以及在OT-2工作空间内精确定位方面表现出了很高的准确性。此外,OT2Eye还能准确检测到小费架上的小费是否存在。OT2Eye使实验室软件状态机器可读,简化了实验室软件状态管理和记录,并使用具有成本效益的自动移液机器人与人工智能驱动的实验室自动化系统集成。
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引用次数: 0
Experience from an HTS campaign: Investigation of susceptibility and rescue of SARS-CoV-2 nsp3 protease assay from metal contamination. HTS运动的经验:SARS-CoV-2 nsp3蛋白酶测定对金属污染的敏感性和抢救调查。
IF 3.7 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-03-13 DOI: 10.1016/j.slast.2026.100409
Irene Georgiou, Sandra O'Neill, Colin Robinson, Fraser Cunningham, Sean N O'Byrne, David Gray, Ian H Gilbert, Duncan E Scott

Different biochemical assays yield different rates of false positives than others either due to the nature of the enzyme, the technology associated with the bioassay, or properties of the compounds being screened. Ensuring that the right counter-screens are in place to identify false positives without wasting time and resources on them is of great importance. Herein we describe the results of a high throughput screen (HTS) against non-structural protein 3 (nsp3) protease PLPro, which resulted exclusively in false-positive hits. By triaging hit compounds through purification of metal chelating resin, we identified contamination by either copper or palladium as the most likely source of false positives from the library screening campaign. We then performed a systematic assessment of the vulnerability of nsp3 protease screening to metal contamination and evaluated common additives to combat the inhibitory effects of different metal salts. We further conducted a thorough survey of the literature reports of nsp3 HTS campaigns with a focus on the presence of additives and what metal susceptibility was likely, given the results of our work. We conclude that the majority of reported nsp3 screens are susceptible to copper contamination with a smaller proportion also potentially susceptible to palladium contamination.

由于酶的性质、与生物测定相关的技术或被筛选化合物的性质,不同的生化测定产生不同的假阳性率。确保正确的反筛查措施到位,以识别误报,而不浪费时间和资源,这一点非常重要。在这里,我们描述了针对非结构蛋白3 (nsp3)蛋白酶PLPro的高通量筛选(HTS)的结果,该结果仅导致假阳性命中。通过金属螯合树脂的纯化对命中的化合物进行分类,我们确定了铜或钯的污染是文库筛选活动中最可能的假阳性来源。然后,我们对nsp3蛋白酶筛选对金属污染的脆弱性进行了系统的评估,并评估了常见的添加剂来对抗不同金属盐的抑制作用。根据我们的工作结果,我们进一步对nsp3 HTS活动的文献报告进行了彻底的调查,重点关注添加剂的存在以及可能的金属敏感性。我们得出的结论是,大多数报道的nsp3屏幕容易受到铜污染,而较小比例的nsp3屏幕也可能受到钯污染。
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引用次数: 0
Engineering integrated evaporation solutions: Harmonizing manual approaches with automated laboratory workflows. 工程集成蒸发解决方案:协调人工方法与自动化实验室工作流程。
IF 3.7 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-03-13 DOI: 10.1016/j.slast.2026.100411
Pranav Bende, Anthony Garrison, Manan Luthra, Vijaya Krishna Veerisetty, Meghav Verma, Alexander G Godfrey, Dave Calabrese, Cullen Klein, Aco Radujevic, Thierry Masquelin, Savannah Wood, Victoria Ujah, Samarjit Patnaik, Vidushi Sharma, Samuel G Michael, Carleen Klumpp-Thomas

Solvent evaporation, a ubiquitous yet often limiting step in chemical synthesis, routinely creates critical bottlenecks in research workflows. We introduce a novel benchtop solvent evaporation platform engineered to dramatically accelerate this process within a standard fume hood. Designed with flexible hardware and software architecture, this system is primed for autonomous control via Python scripting, transitioning from its current manual operation to fully automated capabilities. The platform offers two versatile configurations: a single-container evaporator for individual sample precision and a batch evaporator for high-throughput, simultaneous processing of multiple vials. Both variants feature a custom-designed, chemically inert 3D-printed adapter, equipped with precise compressed nitrogen and air inlet ports, alongside an efficient exhaust. Rapid and uniform solvent removal is achieved through a synergistic approach: integrated heating pads maintain optimal temperature in the vial block, while pressurized nitrogen is directed through uniquely helical channels within the adapter, generating a powerful vortex that significantly accelerates evaporation. Rigorous studies confirm the platform's robust and uniform solvent removal performance, conclusively demonstrating its potential to fundamentally alleviate key bottlenecks in chemical synthesis, thereby enhancing productivity and accelerating discovery. This innovative system represents a vital step towards fully automated and efficient chemical laboratories.

溶剂蒸发是化学合成中普遍存在的一个限制步骤,通常会在研究工作流程中造成关键瓶颈。我们推出了一种新型的台式溶剂蒸发平台,可在标准通风柜内显着加速这一过程。该系统采用灵活的硬件和软件架构设计,可通过Python脚本进行自主控制,从目前的手动操作过渡到全自动功能。该平台提供两种多功能配置:单个样品精度的单容器蒸发器和批量蒸发器,用于高通量,同时处理多个小瓶。这两种型号都采用了定制设计的化学惰性3d打印适配器,配备了精确的压缩氮气和空气入口端口,以及高效排气。通过协同方法实现快速均匀的溶剂去除:集成加热垫在小瓶块中保持最佳温度,而加压氮气通过适配器内独特的螺旋通道定向,产生强大的涡流,显著加速蒸发。严格的研究证实了该平台强大而均匀的溶剂去除性能,最终证明了它有可能从根本上缓解化学合成的关键瓶颈,从而提高生产率并加速发现。这个创新的系统代表了迈向全自动和高效化学实验室的重要一步。
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引用次数: 0
Life sciences and anxiety – Between enlightenment and uncertainty 生命科学与焦虑——在启蒙与不确定性之间。
IF 3.7 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-03-01 Epub Date: 2025-11-14 DOI: 10.1016/j.slast.2025.100366
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引用次数: 0
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SLAS Technology
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