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Prompting large language models to extract chemical‒disease relation precisely and comprehensively at the document level: an evaluation study
Given the scarcity of annotated data, current deep learning methods face challenges in the field of document-level chemical-disease relation extraction, making it difficult to achieve precise relation extraction capable of identifying relation types and comprehensive extraction tasks that identify relation-related factors. This study tests the abilities of three large language models (LLMs), GPT3.5, GPT4.0, and Claude-opus, to perform precise and comprehensive extraction in document-level chemical-disease relation extraction on a self-constructed dataset. Firstly, based on the task characteristics, this study designs six workflows for precise extraction and five workflows for comprehensive extraction using prompting engineering strategies. The characteristics of the extraction process are analyzed through the performance differences under different workflows. Secondly, this study analyzes the content bias in LLMs extraction by examining the extraction effectiveness of different workflows on different types of content. Finally, this study analyzes the error characteristics of extracting incorrect examples by the LLMs. The experimental results show that: (1) The LLMs demonstrate good extraction capabilities, achieving the highest F1 scores of 87% and 73% respectively in the tasks of precise extraction and comprehensive extraction; (2) In the extraction process, the LLMs exhibit a certain degree of stubbornness, with limited effectiveness of prompting engineering strategies; (3) In terms of extraction content, the LLMs show a content bias, with stronger abilities to identify positive relations such as induction and acceleration; (4) The essence of extraction errors lies in the LLMs’ misunderstanding of the implicit meanings in biomedical texts. This study provides practical workflows for precise and comprehensive extraction of document-level chemical-disease relations and also indicates that optimizing training data is the key to building more efficient and accurate extraction methods in the future.
MMAgentRec, a personalized multi-modal recommendation agent with large language model
Differential Associations of Cigar, Pipe, and Smokeless Tobacco Use Versus Combustible Cigarette Use With Subclinical Markers of Inflammation, Thrombosis, and Atherosclerosis: The Cross-Cohort Collaboration–Tobacco Working Group
BACKGROUND: Understanding the associations of tobacco product use with subclinical markers is essential in evaluating health effects to inform regulatory policy. This is particularly relevant for noncigarette products (eg, cigars, pipes, and smokeless tobacco), which have been understudied because of their low prevalence in individual cohorts. METHODS: This cross-sectional study included 98 450 participants from the Cross-Cohort Collaboration–Tobacco data set. Associations between the use of tobacco products and subclinical markers (high-sensitivity C-reactive protein, interleukin-6, fibrinogen, D-dimer, coronary artery calcium, carotid intima-media thickness, carotid plaque, and ankle-brachial index) were evaluated. The analyses used multivariable linear and logistic regression models to examine current use status for each product, with additional analyses of “sole” and “exclusive” noncigarette use (versus never use of either cigarettes or specific noncigarette tobacco). Sole use was defined as the current use of a given noncigarette tobacco without concurrent combustible cigarette use, whereas exclusive use was defined as current noncigarette tobacco use without any history of combustible cigarette use. RESULTS: A total of 20.0%, 3.0%, 0.8%, and 1.5% of participants were current cigarette, cigar, pipe, or smokeless tobacco users, respectively. Current cigarette use was linked to higher levels of all markers compared with never cigarette use. Compared with respective reference groups, current, sole, and exclusive cigar use was associated with 10% (95% CI, 1–20), 19% (95% CI, 12–26), and 11% (95% CI, 2–21) higher high-sensitivity C-reactive protein levels on the geometric mean scale. Similar associations were noted for pipe and smokeless tobacco use. For interleukin-6, we observed that sole cigar use was associated with a 15% (95% CI, 6–24) higher level, whereas current, sole, and exclusive pipe use were associated with 22% to 32% (all P values <0.05) higher levels compared with their respective reference groups. Fibrinogen levels were 2% to 6% higher (all P values <0.05) among sole users of cigars, pipes, and smokeless tobacco, compared with their respective reference groups. Additionally, noncigarette tobacco use was moderately associated with carotid plaque and carotid intima-media thickness. CONCLUSIONS: Use of noncigarette tobacco products is linked to subclinical markers related to cardiovascular harm. Inflammatory markers, such as high-sensitivity C-reactive protein and interleukin-6, have the potential for assessing early cardiovascular harm from using these products and aiding regulatory authorities in evaluating their associated risks.
Integration of experiences of contingency in patients with advanced cancer supported by a multimodal art approach
To support patients with cancer in a palliative treatment phase with the integration of experiences of contingency into their life narrative, we developed a multi-modal approach: In Search of Stories (ISOS). ISOS consists of the following elements: filling out the self-report RE-LIFE questionnaire, drawing of Rich Pictures, and reading an exemplary story with a spiritual counselor, followed by a co-creation process with a professional artist. In the current article we illustrate how patients moved through the process of integration of experiences of contingency during the meetings of ISOS by presenting two case descriptions. All meetings of the first two patients who completed the ISOS project were audio recorded, imported into Atlas-Ti and analyzed by applying a phenomenological approach to deepen our understanding of the patient’s experiences throughout the meetings. The two cases showed distinct differences on how the experience of contingency was dealt with and how the integration of experiences of contingency into the life narrative unfolded. Patients focused on life goals and values concerning connection with loved ones, and on leaving a legacy behind, which was expressed through creating a work of art. The current study provides preliminary insight into how patients can go through a process of integration of experiences of contingency into their life narrative, which could inform the development of future support for patients with advanced cancer dealing with experiences of contingency. Specifically, offering patients possibilities to express themselves through materials within an artistic setting could support these patients to find new words and additional non-linguistic ways of expressing their experiences, and thereby facilitate the integration of experiences of contingency into their life narrative.
Unveiling the mechanism of amelioration of adjuvant-induced rheumatoid arthritis by Drynaria quercifolia rhizome extract using network pharmacology and gene expression-based studies
Nrf3-Mediated Mitochondrial Superoxide Promotes Cardiomyocyte Apoptosis and Impairs Cardiac Functions by Suppressing Pitx2
BACKGROUND: Myocardial infarction (MI) elicits mitochondria reactive oxygen species (ROS) production and cardiomyocyte (CM) apoptosis. Nrf3 (nuclear factor erythroid 2-related factor 3) has an established role in regulating redox signaling and tissue homeostasis. Here, we aimed to evaluate the role and mechanism of Nrf3 in injury-induced pathological cardiac remodeling. METHODS: Global (Nrf3-KO) and CM-specific (Nrf3 △CM ) Nrf3 knockout mice were subjected to MI or ischemia/reperfusion injury, followed by functional and histopathological analysis. Primary neonatal mouse and rat ventricular myocytes and CMs derived from human induced pluripotent stem cells were used to evaluate the impact of Nrf3 on CM apoptosis and mitochondrial ROS production. Chromatin immunoprecipitation sequencing and immunoprecipitation–mass spectrometry analysis were used to uncover potential targets of Nrf3. MitoParaquat administration and CM-specific adeno-associated virus vectors were used to further confirm the i n vivo relevance of the identified signal pathways. RESULTS: Nrf3 was expressed mainly in CMs in healthy human hearts, and an increased level of Nrf3 was observed in CMs within the border zone of infarcted human hearts and murine cardiac tissues after MI. Both global and CM-specific Nrf3 knockout significantly decreased injury-induced mitochondrial ROS production, CM apoptosis, and pathological cardiac remodeling, consequently improving cardiac functions. In addition, cardiac-specific Nrf3 overexpression reversed the ameliorative cardiac phenotypes observed in Nrf3-KO mice. Functional studies showed that Nrf3 promoted neonatal mouse ventricular myocyte, neonatal rat ventricular myocyte, and CMs derived from human induced pluripotent stem cell apoptosis by increasing mitochondrial ROS production. Critically, augmenting mitochondrial ROS with MitoParaquat blunted the beneficial effects of Nrf3 deletion on cardiac function and remodeling. Mechanistically, a redox regulator Pitx2 (paired-like homeodomain transcription factor 2) was identified as one of the main target genes of Nrf3. Specifically, Nrf3 binds to Pitx2 promoter, where it increases DNA methylation through recruiting heterogeneous nuclear ribonucleoprotein K and DNA-methyltransferase 1 complex, thereby inhibiting Pitx2 expression. CM-specific knockdown of Pitx2 blunted the beneficial effects of Nrf3 deletion on cardiac function and remodeling, and cardiac-specific Pitx2 overexpression attenuated MI-induced mitochondrial ROS production and CM apoptosis, as well as preserved cardiac functions after MI. CONCLUSIONS: Nrf3 promotes injury-induced CM apoptosis and deteriorates cardiac functions by increasing mitochondrial ROS production through suppressing Pitx2 expression. Targeting the Nrf3–Pitx2–mitochondrial ROS signal axis may therefore represent a novel therapeutic approach for MI treatment.
Correction: Comprehensive techno-environmental evaluation of an isolated PV/wind/biomass hybrid microgrid employing various battery technologies: A comparative analysis
Author Correction: Advanced predictive machine and deep learning models for round-ended CFST column
Correction to: 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines
Edge-enhanced interaction graph network for protein-ligand binding affinity prediction
Protein-ligand interactions are crucial in drug discovery. Accurately predicting protein-ligand binding affinity is essential for screening potential drugs. Graph neural networks have proven highly effective in modeling spatial relationships and three-dimensional structures within intermolecular. In this paper, we introduce a graph neural network-based model named EIGN to predict protein-ligand binding affinity. The model consists of three main components: the normalized adaptive encoder, the molecular information propagation module, and the output module. Experimental results indicate that EIGN achieves root mean squared error of 1.126 and Pearson correlation coefficient of 0.861 on CASF-2016. Additionally, our model outperforms state-of-the-art methods on CASF-2013, CASF-2016, and the CSAR-NRC set, showing exceptional accuracy and robust generalization ability. To further validate the effectiveness of EIGN, we conducted several experiments, including ablation studies, feature importance analysis, data similarity analysis, and others, to evaluate its performance and applicability.
The effective-compound compatibility of JHF inhibits fibroblast activation in pulmonary fibrosis by enhancing PINK1/PARK2-mediated mitophagy
Correction to: Targeting NPM1 Epigenetically Promotes Postinfarction Cardiac Repair by Reprogramming Reparative Macrophage Metabolism
The impact pathway of new quality productive forces on regional green technology innovation: A spatial mediation effect based on intellectual property protection
Against the backdrop of global economic transformation and sustainable development, green technological innovation has become a core driver for enhancing national competitiveness and addressing environmental challenges. With the profound changes in production methods and technological innovation, new quality productive forces (NQPF) have emerged as a key driver of green technological innovation. This study aims to explore the mechanisms through which NQPF influence Regional Green Technology Innovation (RGTI), with a particular focus on the mediating role of intellectual property protection (IPP). Using panel data from 31 provinces in China from 2011 to 2022, we conduct an empirical analysis employing a spatial Durbin model and a spatial mediation effect model. The results indicate that NQPF significantly promote RGTI, particularly in enhancing resource utilization efficiency and greening production processes. However, the study also identifies an inverted U-shaped relationship between NQPF and green technological innovation, primarily driven by local dynamics, where the positive effect diminishes after reaching a certain threshold. Further analysis reveals that IPP plays a crucial mediating role, not only directly fostering green innovation but also amplifying the positive effects of NQPF by enhancing the efficiency of innovation outcomes. Based on these findings, this study offers policy recommendations for promoting RGTI, emphasizing the need to strengthen support for NQPF, improve IPP mechanisms, and build a regional collaborative innovation system.
A dual layer wideband angular stable frequency selective surface for linear to circular and circular to linear polarization conversion for 5G applications
Direct-to-Consumer Genetic Testing for Cardiovascular Disease: A Scientific Statement From the American Heart Association
Despite insufficient evidence to support direct-to-consumer genetic testing in routine clinical care, cardiovascular clinicians increasingly face questions about its utility and interpretation because individuals can purchase these tests directly from laboratories. A burgeoning marketplace offers an expanding array of testing options. In many cases, direct-to-consumer genetic testing advertises information that could inform one’s risk of heritable disease, including insight into having a genetic predisposition to cardiovascular disease or data about gene-drug interactions that could affect response to cardiovascular medications. Navigating clinical questions about direct-to-consumer genetic testing involves understanding the evolution and oversight of the marketplace; the scope of direct-to-consumer genetic testing offerings; and the risks, benefits, and limitations of said testing. In this American Heart Association scientific statement, we summarize the state of the direct-to-consumer genetic testing industry, review types of cardiovascular genetic information that may be included in direct-to-consumer genetic testing, describe approaches to evaluate test quality, and provide resources for clinicians navigating questions about direct-to-consumer genetic testing. If direct-to-consumer genetic test information is used in clinical care, care should be taken to assess the limitations of the test, to contextualize the information specifically to the patient, and to corroborate potentially actionable monogenic findings.
Advancing non-human primate welfare: An automated facial recognition system for unrestrained cynomolgus monkeys
Cynomolgus monkeys (Macaca fascicularis) are vital in biomedical research, particularly for drug development and studying neurological diseases. However, accurately identifying individuals in group housing environments remains a significant challenge. This paper presents a near real-time facial recognition system tailored for cynomolgus monkeys, utilizing a fine-tuned Detectron2 model for face detection, followed by eigenface-based classification with Support Vector Machine (SVM) and radial basis function (RBF) kernel. The system achieved an accuracy of 97.65% in 10-fold cross-validation and identified individuals in under 1 minute under ideal conditions. This method eliminates the need for invasive identification techniques, potentially reducing stress and improving animal welfare, and has the potential to reduce the need for individualized housing or specialized enclosures. Additionally, as the system reduces the time and labor required for identifying monkeys, it might benefit research facilities with high turnover rates. This method could improve identification in non-human primate research while minimizing stress associated with traditional techniques.
Study on flame fractal characteristics of coal dust explosion at the decompression position of Hartmann tube
Abstract The explosion of coal dust is powerful and has a wide range of spread, which can easily cause mass death and injury. In this paper, the flame microstructure and propagation characteristics of coal dust explosion are recorded by high-speed photography schlieren technique. The experimental results show that the flame shape of Hartmann outlet is mushroom cloud with obvious fractal characteristics, and the fractal dimension can measure its complexity. When the particle size of coal dust is constant, the fractal dimension increases first and then decreases with the increase of concentration. When the coal dust particle size is less than 53 μm and the initial concentration is 300 g/m3, the flame fractal dimension reaches the maximum value of 1.71. The fractal dimension decreases with the increase of coal dust particle size. The coal dust explosion flame has a cellular structure, and its instability is caused by the combined action of hydrodynamic instability and unequal diffusion instability. These instabilities make the flame front structure develop from wrinkles to cell bodies and change continuously. This study can reveal the complexity of coal dust explosion flame propagation at the outlet position, and provide a new perspective for in-depth understanding of coal dust explosion propagation behavior.
Evidence-Based Application of Natriuretic Peptides in the Evaluation of Chronic Heart Failure With Preserved Ejection Fraction in the Ambulatory Outpatient Setting
BACKGROUND: Plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) is commonly used to diagnose heart failure with preserved ejection fraction (HFpEF), but its diagnostic performance in the ambulatory/outpatient setting is unknown because previous studies lacked objective reference standards. METHODS: Among patients with chronic dyspnea, diagnosis of HFpEF or noncardiac dyspnea was determined conclusively by exercise catheterization in a derivation cohort (n=414), multicenter validation cohort 1 (n=560), validation cohort 2 (n=207), and a nonobese Japanese validation cohort 3 (n=77). Optimal NT-proBNP cut points for HFpEF rule out (optimizing sensitivity) and rule in (optimizing specificity) were derived and tested, stratified by obesity and atrial fibrillation. Derived cut points were tested in 3 additional validation cohorts (cohorts 4–6) in whom HFpEF was diagnosed by resting catheterization only (n=260), previous hospitalization for heart failure (n=447), or exercise echocardiography (n=517), respectively. RESULTS: Current recommended rule-out NT-proBNP threshold <125 pg/mL had 82% sensitivity (95% CI, 77%–88%) with a body mass index (BMI) <35 kg/m 2 , decreasing to 67% (95% CI, 58%–77%) with a BMI ≥35 kg/m 2 . A lower rule-out NT-proBNP threshold <50 pg/mL displayed good sensitivity with a BMI <35 kg/m 2 (97% [95% CI, 95%–99%]), with a modest decline in sensitivity with a BMI ≥35 kg/m 2 (86% [95% CI, 79%–93%]); diagnostic thresholds were confirmed in validation cohorts 1 and 2 (91% [95% CI, 88%–95%] and 86% [95% CI, 80%–93%] with a BMI <35 kg/m 2 ; 80% [95% CI, 74%–87%] and 84% [95% CI, 74%–93%] with a BMI ≥35 kg/m 2 ). Current consensus age- and BMI-stratified rule-in thresholds demonstrated only 65% specificity (95% CI, 57%–72%). Rule-in NT-proBNP threshold ≥500 pg/mL had 85% specificity (95% CI, 78%–91%) with a BMI <35 kg/m 2 (87% [95% CI, 80%–94%] and 90% [95% CI, 81%–99%] in validation cohorts), with 100% specificity at a BMI ≥35 kg/m 2 (93% [95% CI, 81%–100%] and 100% in validation cohorts). With a BMI ≥35 kg/m 2 , lower rule-in thresholds (≥220 pg/mL) provided good specificity (88% [95% CI, 73%–100%]; 93% [95% CI, 81%–100%] and 100% in validation cohorts). Findings were consistent in validation cohorts 3 through 6 (sensitivity of <50 pg/mL, 93%–98%; specificity of ≥500 pg/mL, 82%–89%). NT-proBNP provided no incremental discrimination among patients with history of AF; ≥98% of patients with AF and dyspnea were found to have HFpEF in our cohorts. CONCLUSIONS: In patients with chronic unexplained dyspnea, current rule-in and rule-out NT-proBNP diagnostic thresholds lead to unacceptably high error rates, with important interactions by obesity and AF status. In our study, NT-proBNP provided little value in those with AF and dyspnea because the presence of AF is by itself a robust biomarker of HFpEF. Use of separate rule-in and rule-out diagnostic thresholds stratified by BMI reduces miscategorization and can guide more appropriate use of exercise testing for possible HFpEF.
Ptgds downregulation protect vestibular hair cells from aminoglycoside-induced vestibulotoxicity
The clinical use of aminoglycosides often results in injury to vestibular hair cells and subsequent vestibular dysfunction. Thus, clarifying the targets and mechanisms underlying aminoglycoside-mediated damage is of urgent importance. Prostaglandin D2 synthase (Ptgds) is a glycoprotein that plays dual roles in lipid transport regulation and prostaglandin metabolism. However, the role of Ptgds in aminoglycoside-induced vestibular dysfunction remains unclear. This study aimed to explore the function of Ptgds in the utricle and HEI-OC1 cells. Neomycin injury induced high levels of Ptgds expression in utricle explants. Moreover, Ptgds knockdown protected against neomycin injury by enhancing cellular proliferation and viability while suppressing reactive oxygen species production, inflammation, and apoptosis. These findings suggest that Ptgds may serve as a novel therapeutic target for treating vestibular dysfunction caused by aminoglycoside-induced damage.