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Monitoring treatment response using an ultra-sensitive ctDNA assay in advanced esophagogastric cancer patients. 使用超灵敏ctDNA检测监测晚期食管胃癌患者的治疗反应。
IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-03-23 DOI: 10.1038/s41598-026-43178-4
Andrew B Nixon, Fábio C P Navarro, Katherine I Zhou, Charles W Abbott, Lee McDaniel, Neeraja Ravi, Lauren E Howard, J Christopher Brady, Yingmiao Liu, Jingquan Jia, Donna Niedzwiecki, John H Strickler, Sean M Boyle, Richard O Chen, Hope Uronis

To explore whether ultra-sensitive circulating tumor DNA (ctDNA) profiling enables earlier prediction of treatment response and detection of disease progression, we applied NeXT Personal, an ultra-sensitive bespoke tumor-informed liquid biopsy platform, to profile tumor samples from the KeyLargo study, a phase II trial in which metastatic esophagogastric cancer (mEGC) patients received capecitabine, oxaliplatin, and pembrolizumab. A total of 24 patients were evaluated, and all were ctDNA-positive at baseline. ctDNA levels varied from 406,067 down to 1.5 parts per million (PPM) with a median limit of detection of 2.03 PPM. ctDNA dynamics were highly correlated with changes in tumor size (ρ = 0.59, p = 7.3 × 10- 9). Lack of early molecular response (50% or greater decrease in ctDNA levels at first available time point after 30 days, C2D1 or C4D1) was associated with worse overall survival (OS) (HR 4.5, 95% CI 1.2-16.7, p = 0.02) and progression-free survival (PFS) (HR 10.4, 95% CI 2.2-49.8, p = 0.003). Lack of molecular clearance of ctDNA was associated with worse OS (HR 7.1, 95% CI 1.6-31.7, p = 0.01) and PFS (HR 19.9, 95% CI 2.5-158.2, p = 0.005). Molecular progression (ctDNA increase) preceded imaging-derived progression by a median lead time of 65 days. These results suggest that ultra-sensitive liquid biopsy approaches could improve treatment decision-making for mEGC patients receiving chemotherapy and immunotherapy.

为了探索超敏感循环肿瘤DNA (ctDNA)分析是否能够更早地预测治疗反应和检测疾病进展,我们应用了NeXT Personal,一个超敏感的定制肿瘤信息液体活检平台,来分析来自KeyLargo研究的肿瘤样本,这是一项转移性食管胃癌(mEGC)患者接受卡培他滨、奥沙利铂和派姆单抗治疗的II期试验。共有24名患者接受了评估,所有患者在基线时均为ctdna阳性。ctDNA水平从406067到1.5 PPM不等,中位检测限为2.03 PPM。ctDNA动态与肿瘤大小变化高度相关(ρ = 0.59, p = 7.3 × 10- 9)。缺乏早期分子反应(C2D1或C4D1在30天后第一个可用时间点ctDNA水平下降50%或更多)与总生存期(OS) (HR 4.5, 95% CI 1.2-16.7, p = 0.02)和无进展生存期(PFS) (HR 10.4, 95% CI 2.2-49.8, p = 0.003)相关。缺乏ctDNA分子清除率与较差的OS (HR 7.1, 95% CI 1.6-31.7, p = 0.01)和PFS (HR 19.9, 95% CI 2.5-158.2, p = 0.005)相关。分子进展(ctDNA增加)比影像学进展提前65天。这些结果表明,超敏感液体活检方法可以改善接受化疗和免疫治疗的mEGC患者的治疗决策。
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引用次数: 0
Model test study on the vertical bearing performance of post-grouted piles based on different grouting materials. 基于不同注浆材料的后灌注桩竖向承载性能模型试验研究。
IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-03-23 DOI: 10.1038/s41598-026-44882-x
Chaomin Chu, Tianxing Yi, Yunjie Qin, Xuefei Hou, Guoliang Dai

Post-grouting is an effective engineering technique for enhancing the bearing performance of pile foundations, and the grouting material is a key factor determining the performance of post-grouted piles. In this study, different grouting materials (fly ash-cement, geopolymer, cement, and cement-sodium silicate) were adopted in laboratory tests. Model tests of post-grouted piles were conducted under simulated groundwater flow conditions and long-term loading scenarios to investigate the influence of various grouting materials on pile bearing performance under vertical loading. The research focuses on the characteristics of load- settlement curves, the axial force transfer along the pile, and the mobilization behavior of side resistance and tip resistance, and employs scanning electron microscopy (SEM) tests to reveal the action mechanisms of different grouting materials. The test results indicate that the grouting process significantly enhances the pile-soil interaction. Compared with the ungrouted piles, the bearing capacity of the grouted piles increases markedly. Under flowing-water conditions, the cement-sodium silicate double-liquid grout provides the best reinforcement effect around the pile due to its short gel time, rapid solidification, and dense hydration products, whereas the fly ash-cement and geopolymer grouts mainly improve the soil via permeation grouting, with the hydration reaction of fly ash proceeding relatively slowly.

后注浆是提高桩基承载性能的有效工程技术,而后注浆材料是决定后注浆桩性能的关键因素。本研究采用不同的注浆材料(粉煤灰-水泥、地聚合物、水泥、水泥-水玻璃)进行室内试验。在模拟地下水流动条件和长期荷载情景下,对后注浆桩进行模型试验,研究竖向荷载作用下不同注浆材料对桩承载性能的影响。研究了桩身荷载沉降曲线特征、桩身轴向力传递特征以及侧阻力和端阻力的动员行为,并通过扫描电镜(SEM)试验揭示了不同注浆材料的作用机理。试验结果表明,注浆过程显著增强了桩土相互作用。与未灌浆桩相比,灌浆桩的承载力显著提高。流动水条件下,水泥-水玻璃双液浆液凝胶时间短、固化快、水化产物致密,对桩周加固效果最好,而粉煤灰-水泥和地聚合物浆液主要通过渗透灌浆对土体进行改善,粉煤灰水化反应进行相对缓慢。
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引用次数: 0
Multiscale microscopic pore structure characterization and storage-flow coupling mechanisms in ultra-low permeability tight sandstone reservoirs. 特低渗透致密砂岩储层多尺度微观孔隙结构表征及储流耦合机制
IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-03-23 DOI: 10.1038/s41598-026-42495-y
Cun-Lei Li, Dong-Rui Su, Pan-Pan Chen, Tuan-Tuan Qu, Cheng-Ming Wang, Cheng-Chi Wang
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引用次数: 0
Temporal dynamics in barrier-involved crashes: Determining shifts in driving behavior and injury risk across multi-year periods. 涉及障碍的碰撞的时间动态:确定多年期间驾驶行为和伤害风险的变化。
IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-03-23 DOI: 10.1038/s41598-026-45273-y
Swastika Barua, Monire Jafari, Michael Starewich, Reuben Tamakloe, Nawaf Alnawmasi, Subasish Das

Barrier-involved crashes are shaped by evolving behavioral patterns, roadway conditions, and systemic changes in transportation environments. This study investigates temporal shifts in the factors influencing injury severity in barrier-related traffic crashes over three multi-year periods: 2017-2018, 2019-2020, and 2021-2022. A Multinomial Logit (MNL) model and its extensions, including the Random Parameter Logit (RPL), Random Parameter Logit with Heterogeneity in Means (RPLHM), Correlated Random Parameter Logit with Heterogeneity in Means (CRPLHM), and Random Parameter Logit with Heterogeneity in Means and Variance (RPLHMV), are employed to capture unobserved heterogeneity and temporal changes in predictor effects. The analysis reveals that contextual factors such as roadway alignment, posted speed limits, weather, lighting, and vehicle type exhibit time-varying associations with crash outcomes. Moderate speed zones (35-55 mph), previously not significant, became increasingly associated with lower severity in later periods. Meanwhile, the influence of lane departure, marked lanes, positive median barriers, and collisions with fixed objects also varied across periods. Notably, crashes outside intersections that initially corresponded with lower injury risk began to show elevated severity in the later years. Driver failure to maintain a single lane consistently emerged as a strong predictor of severity, with its effect intensifying over time. These findings highlight the importance of capturing temporal instability in crash determinants and support the need for adaptive, evidence-driven safety policies that reflect shifting roadway and behavioral dynamics.

涉及障碍物的碰撞是由不断变化的行为模式、道路状况和交通环境的系统性变化所决定的。本研究研究了2017-2018年、2019-2020年和2021-2022年三个多年期障碍相关交通事故伤害严重程度影响因素的时间变化。采用多项Logit (MNL)模型及其扩展,包括随机参数Logit (RPL)、随机参数Logit with Heterogeneity in Means (RPLHM)、相关随机参数Logit with Heterogeneity in Means (CRPLHM)和随机参数Logit with Heterogeneity in Means and Variance (RPLHMV),来捕捉未观测到的异质性和预测效应的时间变化。分析显示,道路线形、车速限制、天气、照明和车辆类型等环境因素与碰撞结果表现出随时间变化的关联。中速区(35-55英里/小时),以前不明显,在后期变得越来越轻。与此同时,车道偏离、车道标记、正中间障碍物和与固定物体碰撞的影响也在不同时期有所不同。值得注意的是,在十字路口外发生的车祸,最初的伤害风险较低,但在后来的几年里,事故的严重程度开始上升。司机未能持续保持单车道是严重程度的一个强有力的预测指标,其影响随着时间的推移而加剧。这些发现强调了在碰撞决定因素中捕捉时间不稳定性的重要性,并支持了适应性、证据驱动的安全政策的需求,这些政策反映了道路和行为动态的变化。
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引用次数: 0
Blockchain-empowered unified services for streamlined traceability implementation in food supply chain: a demonstration in Australian seafood traceability. 在食品供应链中简化可追溯性实施的区块链授权统一服务:澳大利亚海鲜可追溯性示范。
IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-03-23 DOI: 10.1038/s41598-026-36778-7
H T Thien Pham, Chen Huang, Frank Jiang, Rose Elphick-Darling, Alessio Bonti, Lei Pan, Mohamed Abdelrazek

Traceability is a key requirement for compliance in food supply chains, ensuring transparency, safety, and product authenticity across all stages of production and distribution. Although advanced technologies have been introduced to support compliance efforts, blockchain stands out for its potential to provide secure, tamper-proof, and verifiable traceability. However, adoption of blockchain remains limited due to technical complexity, high implementation costs, and fragmented integration between supply chains. To address these challenges, this study proposes a unified blockchain-enabled services framework for the implementation of streamlined, standardized, and accessible traceability. The framework includes a network architecture, traceability-driven operational rules, a UML sequence diagram defining system interactions, and algorithms to record and verify data. Demonstrated through an Australian seafood traceability scenario, the framework was validated by deploying a prototype digital platform and smart contracts on the blockchain. The results show that the framework enables reliable traceability with minimal integration effort while supporting interoperability and data integrity. Although not required, the study highlights the potential role of regulatory bodies as service providers to strengthen compliance alignment. In general, this approach presents a scalable, cost-effective, and practical solution to improve traceability in supply chains through blockchain technology.

可追溯性是食品供应链合规的关键要求,确保生产和分销各个阶段的透明度、安全性和产品真实性。尽管已经引入了先进的技术来支持遵从性工作,但区块链因其提供安全、防篡改和可验证的可追溯性的潜力而脱颖而出。然而,由于技术复杂性、高实施成本和供应链之间的分散集成,区块链的采用仍然有限。为了应对这些挑战,本研究提出了一个统一的支持区块链的服务框架,用于实现简化、标准化和可访问的可追溯性。该框架包括网络体系结构、可追溯性驱动的操作规则、定义系统交互的UML序列图,以及记录和验证数据的算法。通过澳大利亚海鲜可追溯性场景演示,该框架通过在区块链上部署原型数字平台和智能合约进行了验证。结果表明,该框架在支持互操作性和数据完整性的同时,以最小的集成工作实现可靠的可跟踪性。虽然不是必需的,但该研究强调了监管机构作为服务提供商在加强合规一致性方面的潜在作用。一般来说,这种方法提供了一种可扩展的、具有成本效益的、实用的解决方案,可以通过区块链技术改善供应链中的可追溯性。
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引用次数: 0
A security-oriented four-factor spatio-temporal framework for assessing and mitigating traffic congestion risks. 面向安全的交通拥堵风险评估与缓解四因子时空框架。
IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-03-23 DOI: 10.1038/s41598-026-41451-0
Yunxia Li, Yuman Xu, Xiangyang He, Dan Zhu, Yichen Zhang, Jiquan Zhang
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引用次数: 0
Atomistic and electronic insights into Ca2+ and Li+ intercalation in TiS2: a first-principles approach supported by electrochemical validation. 在TiS2中Ca2+和Li+插入的原子和电子见解:电化学验证支持的第一原理方法。
IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-03-23 DOI: 10.1038/s41598-026-42087-w
Seunga Yang, Sangyup Lee, Paul Maldonado Nogales, Yangsoo Kim, Soon-Ki Jeong
{"title":"Atomistic and electronic insights into Ca<sup>2+</sup> and Li<sup>+</sup> intercalation in TiS<sub>2</sub>: a first-principles approach supported by electrochemical validation.","authors":"Seunga Yang, Sangyup Lee, Paul Maldonado Nogales, Yangsoo Kim, Soon-Ki Jeong","doi":"10.1038/s41598-026-42087-w","DOIUrl":"https://doi.org/10.1038/s41598-026-42087-w","url":null,"abstract":"","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147505008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Voltage-gated calcium channels as key regulators of neuronal differentiation in the immortalized dorsal root ganglion neuronal cell line F11. 电压门控钙通道作为永生化背根神经节神经元细胞系F11神经元分化的关键调控因子。
IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-03-23 DOI: 10.1038/s41598-026-44595-1
D López, J Brea, M Barro, M I Loza, A L Martínez
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引用次数: 0
Attention re-alignment in multimodal large language models via intermediate-layer guidance. 基于中间层引导的多模态大型语言模型的注意力重新对齐。
IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-03-23 DOI: 10.1038/s41598-026-44935-1
Yanming Chen, Pandong Wang, Guofeng Qin, Wei Wu, Ming Chen, Yongtao Hao

Multimodal large language models (MLLMs) have achieved impressive performance in understanding and describing visual content, setting new state-of-the-art results on a variety of visual question answering (VQA) benchmarks. However, during decoding, these models often fail to attend to fine-grained visual details in the input image. Our analysis of intermediate attention layers reveals that MLLMs are not inherently incapable of perceiving target objects; rather, attention to visual details becomes diluted in deeper layers due to the dominance of language priors. To address this limitation, we propose a plug-and-play attention re-alignment module (ARA) that enhances suppressed visual grounding. ARA conducts a layer-wise analysis of the relative attention distribution of image-centric attention heads. It incorporates a confidence-aware layer selection mechanism based on attention peak and entropy, enabling the dynamic aggregation of attention maps from the most informative layers. These aggregated maps are subsequently leveraged to guide the generation of semantic masks, enabling the model to emphasize salient visual regions while suppressing irrelevant or noisy content. ARA can be seamlessly integrated into existing MLLMs and demonstrates consistent improvements across multiple VQA benchmarks, validating its effectiveness in enhancing visual detail sensitivity.

多模态大型语言模型(mllm)在理解和描述视觉内容方面取得了令人印象深刻的表现,在各种视觉问答(VQA)基准上设置了新的最先进的结果。然而,在解码过程中,这些模型往往无法处理输入图像中的细粒度视觉细节。我们对中间注意层的分析表明,mllm并非天生无法感知目标物体;相反,由于语言先验的主导地位,对视觉细节的关注在更深层次上被稀释了。为了解决这一限制,我们提出了一个即插即用的注意力重新对准模块(ARA),以增强被抑制的视觉基础。ARA对以图像为中心的注意头的相对注意分布进行了分层分析。它结合了基于注意力峰值和熵的自信感知层选择机制,实现了来自最具信息量层的注意力图的动态聚合。随后利用这些聚合的地图来指导语义掩码的生成,使模型能够强调突出的视觉区域,同时抑制不相关或有噪声的内容。ARA可以无缝集成到现有的mllm中,并在多个VQA基准测试中表现出一致的改进,验证了其在增强视觉细节灵敏度方面的有效性。
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引用次数: 0
Syninclusions reveal "ant mosaic" in the Eocene amber forest. 始新世琥珀林中的同包体揭示了“蚂蚁镶嵌”现象。
IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-03-23 DOI: 10.1038/s41598-026-44622-1
Dmitry M Zharkov, Dmitry A Dubovikoff, Vadim M Khaitov, Evgeny V Abakumov
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引用次数: 0
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