The diversity of mesenchymal cell types in the lung that influence epithelial homeostasis and regeneration is poorly defined. We used genetic lineage tracing, single-cell RNA sequencing, and organoid ...culture approaches to show that Lgr5 and Lgr6, well-known markers of stem cells in epithelial tissues, are markers of mesenchymal cells in the adult lung. Lgr6+ cells comprise a subpopulation of smooth muscle cells surrounding airway epithelia and promote airway differentiation of epithelial progenitors via Wnt-Fgf10 cooperation. Genetic ablation of Lgr6+ cells impairs airway injury repair in vivo. Distinct Lgr5+ cells are located in alveolar compartments and are sufficient to promote alveolar differentiation of epithelial progenitors through Wnt activation. Modulating Wnt activity altered differentiation outcomes specified by mesenchymal cells. This identification of region- and lineage-specific crosstalk between epithelium and their neighboring mesenchymal partners provides new understanding of how different cell types are maintained in the adult lung.
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•Lgr5 and Lgr6 mark mesenchymal cells in adult lungs•Single-cell transcriptome analysis defines mesenchymal heterogeneity•Distinct mesenchymal niches drive airway and alveolar differentiation•Wnt activity affects epithelial differentiation specified by mesenchymal cells
Heterogeneous mesenchymal cell populations in the lung play a central role in epithelial maintenance and alveolar differentiation.
One of the artificial intelligence applications in the biomedical field is knowledge-intensive question-answering. As domain expertise is particularly crucial in this field, we propose a method for ...efficiently infusing biomedical knowledge into pretrained language models, ultimately targeting biomedical question-answering. Transferring all semantics of a large knowledge graph into the entire model requires too many parameters, increasing computational cost and time. We investigate an efficient approach that leverages adapters to inject Unified Medical Language System knowledge into pretrained language models, and we question the need to use all semantics in the knowledge graph. This study focuses on strategies of partitioning knowledge graph and either discarding or merging some for more efficient pretraining. According to the results of three biomedical question answering finetuning datasets, the adapters pretrained on semantically partitioned group showed more efficient performance in terms of evaluation metrics, required parameters, and time. The results also show that discarding groups with fewer concepts is a better direction for small datasets, and merging these groups is better for large dataset. Furthermore, the metric results show a slight improvement, demonstrating that the adapter methodology is rather insensitive to the group formulation.
There are two kinds of hostilities on the Korean Peninsula: hostility between the U.S. and North Korea; hostility between the two Koreas. The nature of North Korea's nuclear crisis is a mixture of ...those two hostilities. The crisis was exacerbated by misinterpretation and wishful thinking regarding its intentions. Another reason for North Korea's nuclear crisis is the failure of the international community to speak with one voice on how to resolve it. Every country is different in its threat perceptions, national interests, and strategic calculations. In the grand scheme of things, however, the North Korea problem seems to be a strategic conflict between the U.S. and China. South Korea's internal friction prevented any policy from being implemented effectively.
It is not only unfair but unrealistic to handle the two hostilities separately. Any efforts to denuclearize North Korea should not undermine the security of South Korea. For example, the withdrawal of the U.S. forces from the Korean peninsula may be even worse for peace and stability on the Korean Peninsula than a nuclear North Korea, if it keeps the current political system and there is no fundamental change in inter-Korean relations.
Like the front and rear wheels in an automobile, the U.S.-North Korean dialogue and inter-Korean dialogue began to operate as two driving forces for a breakthrough in the nuclear crisis. The wheels should be aligned with a strong U.S.-R.O.K. alliance. Then a multilateral format like the Six-Party Talks can resume for a sustainable peace and stability on the Korean Peninsula.
Although renal hyperfiltration (RHF) or an abnormal increase in GFR has been associated with many lifestyles and clinical conditions, including diabetes, its clinical consequence is not clear. RHF is ...frequently considered to be the result of overestimating true GFR in subjects with muscle wasting. To evaluate the association between RHF and mortality, 43,503 adult Koreans who underwent voluntary health screening at Seoul National University Hospital between March of 1995 and May of 2006 with baseline GFR≥60 ml/min per 1.73 m(2) were followed up for mortality until December 31, 2012. GFR was estimated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation, and RHF was defined as GFR>95th percentile after adjustment for age, sex, muscle mass, and history of diabetes and/or hypertension medication. Muscle mass was measured with bioimpedance analysis at baseline. During the median follow-up of 12.4 years, 1743 deaths occurred. The odds ratio of RHF in participants with the highest quartile of muscle mass was 1.31 (95% confidence interval 95% CI, 1.11 to 1.54) compared with the lowest quartile after adjusting for confounding factors, including body mass index. The hazard ratio of all-cause mortality for RHF was 1.37 (95% CI, 1.11 to 1.70) by Cox proportional hazards model with adjustment for known risk factors, including smoking. These data suggest RHF may be associated with increased all-cause mortality in an apparently healthy population. The possibility of RHF as a novel marker of all-cause mortality should be confirmed.
Although several studies have attempted to develop a model for predicting 30-day re-hospitalization, few attempts have been made for sufficient verification and multi-center expansion for clinical ...use. In this study, we developed a model that predicts unplanned hospital readmission within 30 days of discharge; the model is based on a common data model and considers weather and air quality factors, and can be easily extended to multiple hospitals. We developed and compared four tree-based machine learning methods: decision tree, random forest, AdaBoost, and gradient boosting machine (GBM). Above all, GBM showed the highest AUC performance of 75.1 in the clinical model, while the clinical and W-score model showed the best performance of 73.9 for musculoskeletal diseases. Further, PM10, rainfall, and maximum temperature were the weather and air quality variables that most impacted the model. In addition, external validation has confirmed that the model based on weather and air quality factors has transportability to adapt to other hospital systems.
This study explores the progression of intracerebral hemorrhage (ICH) in patients with mild to moderate traumatic brain injury (TBI). It aims to predict the risk of ICH progression using initial CT ...scans and identify clinical factors associated with this progression. A retrospective analysis of TBI patients between January 2010 and December 2021 was performed, focusing on initial CT evaluations and demographic, comorbid, and medical history data. ICH was categorized into intraparenchymal hemorrhage (IPH), petechial hemorrhage (PH), and subarachnoid hemorrhage (SAH). Within our study cohort, we identified a 22.2% progression rate of ICH among 650 TBI patients. The Random Forest algorithm identified variables such as petechial hemorrhage (PH) and countercoup injury as significant predictors of ICH progression. The XGBoost algorithm, incorporating key variables identified through SHAP values, demonstrated robust performance, achieving an AUC of 0.9. Additionally, an individual risk assessment diagram, utilizing significant SHAP values, visually represented the impact of each variable on the risk of ICH progression, providing personalized risk profiles. This approach, highlighted by an AUC of 0.913, underscores the model's precision in predicting ICH progression, marking a significant step towards enhancing TBI patient management through early identification of ICH progression risks.
This paper presents a conditional random fields (CRF) method that enables the capture of specific high-order label transition factors to improve clinical named entity recognition performance. ...Consecutive clinical entities in a sentence are usually separated from each other, and the textual descriptions in clinical narrative documents frequently indicate causal or posterior relationships that can be used to facilitate clinical named entity recognition. However, the CRF that is generally used for named entity recognition is a first-order model that constrains label transition dependency of adjoining labels under the Markov assumption.
Based on the first-order structure, our proposed model utilizes non-entity tokens between separated entities as an information transmission medium by applying a label induction method. The model is referred to as precursor-induced CRF because its non-entity state memorizes precursor entity information, and the model's structure allows the precursor entity information to propagate forward through the label sequence.
We compared the proposed model with both first- and second-order CRFs in terms of their F
-scores, using two clinical named entity recognition corpora (the i2b2 2012 challenge and the Seoul National University Hospital electronic health record). The proposed model demonstrated better entity recognition performance than both the first- and second-order CRFs and was also more efficient than the higher-order model.
The proposed precursor-induced CRF which uses non-entity labels as label transition information improves entity recognition F
score by exploiting long-distance transition factors without exponentially increasing the computational time. In contrast, a conventional second-order CRF model that uses longer distance transition factors showed even worse results than the first-order model and required the longest computation time. Thus, the proposed model could offer a considerable performance improvement over current clinical named entity recognition methods based on the CRF models.
Dental panoramic radiographs (DPRs) provide information required to potentially evaluate bone density changes through a textural and morphological feature analysis on a mandible. This study aims to ...evaluate the discriminating performance of deep convolutional neural networks (CNNs), employed with various transfer learning strategies, on the classification of specific features of osteoporosis in DPRs. For objective labeling, we collected a dataset containing 680 images from different patients who underwent both skeletal bone mineral density and digital panoramic radiographic examinations at the Korea University Ansan Hospital between 2009 and 2018. Four study groups were used to evaluate the impact of various transfer learning strategies on deep CNN models as follows: a basic CNN model with three convolutional layers (CNN3), visual geometry group deep CNN model (VGG-16), transfer learning model from VGG-16 (VGG-16_TF), and fine-tuning with the transfer learning model (VGG-16_TF_FT). The best performing model achieved an overall area under the receiver operating characteristic of 0.858. In this study, transfer learning and fine-tuning improved the performance of a deep CNN for screening osteoporosis in DPR images. In addition, using the gradient-weighted class activation mapping technique, a visual interpretation of the best performing deep CNN model indicated that the model relied on image features in the lower left and right border of the mandibular. This result suggests that deep learning-based assessment of DPR images could be useful and reliable in the automated screening of osteoporosis patients.