IRAK-M Deficiency Exacerbates Ischemic Neurovascular Injuries in Experimental Stroke Mice

Background: Innate immune response to neuronal death is one of the key events of the pathogenesis of ischemic brain injury. Interleukin-1 receptor-associated kinase (IRAK)-M, encoded by gene Irak3, negatively regulates toll-like receptor signaling by interacting with the MyD88–IRAK-4–IRAK-1 complex and blocking the phosphorylation and dissociation of IRAK-1. Its function in the ischemic stroke is unknown.Objective: This study aims to investigate whether IRAK-M deficiency could exacerbate neuroinflammation and neurovascular injuries during cerebral ischemia and reperfusion.Methods: Male C57BL/6 mice and Irak3 knockout mice were subjected to 45 min of middle cerebral artery occlusion and 4 or 24 h of reperfusion. Transcription of Irak3 gene was evaluated by quantitative real-time PCR (qRT-PCR). Then, infarct volume, neurological score, brain water content, and Evans blue leakage were compared between knock-out and wild-type mice after reperfusion. Through the observation of gross brain specimen after cerebral ischemia, the incidence of hemorrhage transformation was compared between KO and WT mice. To explore underlying signaling pathways involved in IRAK-M deficiency, major proinflammatory cytokines and NF-κB signaling were measured by qRT-PCR and Western blot.Results: The expression of IRAK-M peaked at 1 h after reperfusion, and then gradually decreased within the first 24 h, which was abolished by blocking the expression of hypoxia induced factor 1α. IRAK-M deficiency increased infarct volume, brain edema, the incidence of hemorrhage transformation, and the permeability of blood–brain barrier. In addition, the NF-κB-mediated expressions of proinflammatory cytokines and the activation of microglia in the ipsilateral brain from knock-out mice were much higher than those in wild-type littermates.Conclusion: IRAK-M deletion exacerbates neurovascular damages which are related to the pronounced activation of NF-κB signaling and neuroinflammatory responses during cerebral ischemia-reperfusion in mice. Our study indicates that IRAK-M has neuroprotective effect and has potential to facilitate the development of new pharmaceuticals that reduce neurovascular complications

RJUA-MedDQA: A Multimodal Benchmark for Medical Document Question Answering and Clinical Reasoning

Recent advancements in Large Language Models (LLMs) and Large Multi-modal Models (LMMs) have shown potential in various medical applications, such as Intelligent Medical Diagnosis. Although impressive results have been achieved, we find that existing benchmarks do not reflect the complexity of real medical reports and specialized in-depth reasoning capabilities. In this work, we introduced RJUA-MedDQA, a comprehensive benchmark in the field of medical specialization, which poses several challenges: comprehensively interpreting imgage content across diverse challenging layouts, possessing numerical reasoning ability to identify abnormal indicators and demonstrating clinical reasoning ability to provide statements of disease diagnosis, status and advice based on medical contexts. We carefully design the data generation pipeline and proposed the Efficient Structural Restoration Annotation (ESRA) Method, aimed at restoring textual and tabular content in medical report images. This method substantially enhances annotation efficiency, doubling the productivity of each annotator, and yields a 26.8% improvement in accuracy. We conduct extensive evaluations, including few-shot assessments of 5 LMMs which are capable of solving Chinese medical QA tasks. To further investigate the limitations and potential of current LMMs, we conduct comparative experiments on a set of strong LLMs by using image-text generated by ESRA method. We report the performance of baselines and offer several observations: (1) The overall performance of existing LMMs is still limited; however LMMs more robust to low-quality and diverse-structured images compared to LLMs. (3) Reasoning across context and image content present significant challenges. We hope this benchmark helps the community make progress on these challenging tasks in multi-modal medical document understanding and facilitate its application in healthcare.Comment: 15 pages, 13 figure

RJUA-QA: A Comprehensive QA Dataset for Urology

We introduce RJUA-QA, a novel medical dataset for question answering (QA) and reasoning with clinical evidence, contributing to bridge the gap between general large language models (LLMs) and medical-specific LLM applications. RJUA-QA is derived from realistic clinical scenarios and aims to facilitate LLMs in generating reliable diagnostic and advice. The dataset contains 2,132 curated Question-Context-Answer pairs, corresponding about 25,000 diagnostic records and clinical cases. The dataset covers 67 common urological disease categories, where the disease coverage exceeds 97.6\% of the population seeking medical services in urology. Each data instance in RJUA-QA comprises: (1) a question mirroring real patient to inquiry about clinical symptoms and medical conditions, (2) a context including comprehensive expert knowledge, serving as a reference for medical examination and diagnosis, (3) a doctor response offering the diagnostic conclusion and suggested examination guidance, (4) a diagnosed clinical disease as the recommended diagnostic outcome, and (5) clinical advice providing recommendations for medical examination. RJUA-QA is the first medical QA dataset for clinical reasoning over the patient inquiries, where expert-level knowledge and experience are required for yielding diagnostic conclusions and medical examination advice. A comprehensive evaluation is conducted to evaluate the performance of both medical-specific and general LLMs on the RJUA-QA dataset. Our data is are publicly available at \url{https://github.com/alipay/RJU_Ant_QA}.Comment: An initial versio

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Concrete Dam Displacement Prediction Based on an ISODATA-GMM Clustering and Random Coefficient Model

Displacement data modelling is of great importance for the safety control of concrete dams. The commonly used artificial intelligence method modelled the displacement data at each monitoring point individually, i.e., the data correlations between the monitoring points are overlooked, which leads to the over-fitting problem and the limitations in the generalization of model. A novel model combines Gaussian mixture model and Iterative self-organizing data analysing (ISODATA-GMM) clustering and the random coefficient method is proposed in this article, which takes the temporal-spatial correlation among the monitoring points into account. By taking the temporal-spatial correlation among the monitoring points into account and building models for all the points simultaneously, the random coefficient model improves the generalization ability of the model through reducing the number of free model variables. Since the random coefficient model supposed the data follows normal distributions, we use an ISODATA-GMM clustering algorithm to classify the measuring points into several groups according to its temporal and spatial characteristics, so that each group follows one distribution. Our model has the advantage of having a stronger generalization ability

Improve the Model Stability of Dam's Displacement Prediction Using a Numerical-Statistical Combined Model

In most studies of dam's displacement prediction based on monitoring data, emphasis was given on improving the prediction accuracy, while the model stability was merely considered. This study proposed a numerical-statistical combined model which aims to improve the model stability. The displacement was modelled within three modules: recoverable displacement (i.e., displacement induced by the external load including the water pressure and temperature), non-recoverable displacement (i.e., displacement due to the inherent variations of the materials such as the creep and fatigue of the concrete), and measurement errors (i.e., instrument error and human error). To reduce the random errors and increase the model stability, we used the numerical simulation to constrain the coefficients of explanatory variables for the recoverable displacement. The non-recoverable displacement was estimated by empirical equations, and the measurement errors were given by Gaussian distributions. The randomness of coefficients in the model among all monitoring points are constrained further by random coefficient model. We adopted the root mean square error (RMSE) at varying time and the change ratio of the coefficients (CRC) to evaluate the model stability. Results indicated that the proposed model not only has better prediction accuracy but also has better model stability compared with the statistical model and coordinates-included statistical model proposed in previous studies

Integrating the Finite Element Method with a Data-Driven Approach for Dam Displacement Prediction

Both numerical simulations and data-driven methods have been applied in dam's displacement modeling. For monitored displacement data-driven methods, the physical mechanism and structural correlations were rarely discussed. In order to take the spatial and temporal correlations among all monitoring points into account, we took the first step toward integrating the finite element method into a data-driven model. As the data-driven method, we selected the random coefficient model, which can make each explanatory variable coefficient of all monitoring points following one or several normal distributions. In this way, explanatory variables are constrained. Another contribution of the proposed model is that the actual elastic modulus at each monitoring point can be back-calculated. Moreover, with a Lagrange polynomial interpolation, we can obtain the distribution field of elastic modulus, rather than gaining one value for the whole dam in previous studies. The proposed model was validated by a case study of the concrete arch dam in Jinping-I hydropower station. It has a better prediction precision than the random coefficient model without the finite element method

A Data-Driven Approach Based on Multivariate Copulas for Quantitative Risk Assessment of Concrete Dam

Risk assessment of dam's running status is an important part of dam management. A data-driven method based on monitored displacement data has been applied in risk assessment, owing to its easy operation and real-time analysis. However, previous data-driven methods considered displacement data series at each monitoring point as an independent variable and assessed the running status of each monitoring point separately, without considering the correlation between displacement of different monitoring points. In addition, previous studies assessed the dam's running status qualitatively, without quantifying the risk probability. To solve the above two issues, a displacement-data driven method based on a multivariate copula function is proposed in this paper. Multivariate copula functions can construct a joint distribution which reveals the relevance structure of random variables. We assumed that the risk probability of each dam section is independent and took monitoring points at one dam section as examples. Starting from the risk assessment of single monitoring points, we calculated the residual between the monitored displacement data and the modelled data estimated by the statistical model, and built a risk ratio function based on the residual. Then, using the multivariate copula function, we obtained a combined risk ratio of multi-monitoring points which took the correlation between each monitoring point into account. Finally, a case study was provided. The proposed method not only quantitatively assessed the probability of the real-time dam risk but also considered the correlation between the displacement data of different monitoring points

Application of Spatiotemporal Hybrid Model of Deformation in Safety Monitoring of High Arch Dams: A Case Study

As an important feature, deformation analysis is of great significance to ensure the safety and stability of arch dam operation. In this paper, Jinping-I arch dam with a height of 305 m, which is the highest dam in the world, is taken as the research object. The deformation data representation method is analyzed, and the processing method of deformation spatiotemporal data is discussed. A deformation hybrid model is established, in which the hydraulic component is calculated by the finite element method, and other components are still calculated by the statistical model method. Since the relationship among the measuring points is not taken into account and the overall situation cannot be fully reflected in the hybrid model, a spatiotemporal hybrid model is proposed. The measured values and coordinates of all the typical points with pendulums of the arch dam are included in one spatiotemporal hybrid model, which is feasible, convenient, and accurate. The model can predict the deformation of any position on the arch dam. This is of great significance for real-time monitoring of deformation and stability of Jinping-I arch dam and ensuring its operation safety