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关键词： Cardiac magnetic resonance   coronary computerized tomography angiography   revascularizations   health economic   cost effective   cost saving   I10   I19  

摘要： AimsWhile the clinical benefits of non-invasive modalities to diagnose coronary artery disease (CAD) are well recognized, the economic implications of their use over invasive options remain unclear. This review aims to understand the health economic consequences of using non-invasive versus invasive modalities in symptomatic patients with low-to-intermediate pre-test probability (PTP) of CAD, and to explore whether economic and humanistic data can inform future investment decisions around non-invasive and invasive diagnostic *** and methodsWe performed a systematic review of MEDLINE and Embase, MEDLINE In-process, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials. Studies from January 1992 to January 2023 were included, if they were based in the UK, France, Germany, Italy, Japan, China, and/or the USA (published in any language). Risk of bias was assessed using the Drummond *** evaluated invasive techniques, including invasive catheterization angiography (ICA) and ICA with fractional flow reserve (ICA-FFR), as well as non-invasive modalities, including coronary computerized tomography angiography (CCTA), CCTA-FFR, cardiovascular magnetic resonance (CMR), stress electrocardiogram, myocardial perfusion scintigraphy-single photon emission computed tomography, positron emission tomography, and stress *** and methodsWe performed a systematic review of MEDLINE and Embase, MEDLINE In-process, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials. Studies from January 1992 to January 2023 were included, if they were based in the UK, France, Germany, Italy, Japan, China, and/or the USA (published in any language). Risk of bias was assessed using the Drummond *** evaluated invasive techniques, including invasive catheterization angiography (ICA) and ICA with fractional flow reserve (ICA-FFR), as well as non-invasive modaliti

关键词： Coronary artery disease   ischemic heart disease   cardiovascular magnetic resonance   myocardial perfusion scintigraphy by single photon emission computed tomography   health economic analysis   cost-effectiveness   I10   I19  

摘要： AimsThe health economic impacts of cardiovascular magnetic resonance (CMR) imaging and myocardial perfusion scintigraphy by single photon emission computed tomography (MPS-SPECT) as diagnostic modalities are not well understood. This review is based on a wider systematic review and aims to compare CMR and MPS-SPECT as first-line, non-invasive modalities for the diagnosis of symptomatic individuals with a low-to-intermediate pre-test probability (PTP) of coronary artery disease (CAD).Materials and methodsWe performed a systematic review of MEDLINE and Embase, MEDLINE In-process, the Cochrane Database of Systematic reviews and the Cochrane Central Register of Controlled Trials. Studies from January 1992 to January 2023 were included, if they were based in the UK, France, Germany, Italy, Japan, China, and/or the USA (published in any language). Risk of bias was assessed using the Drummond *** relevant reports were identified. In the USA, CMR was consistently cost-effective compared with MPS-SPECT for patients with a low-to-intermediate PTP of CAD;resource use and associated costs, as well as total costs, were lower. For patients with a low-to-intermediate PTP of CAD in Europe, CMR was cost-effective in Germany, while in the UK increases in quality-adjusted life-years were found but cost savings were mixed. This review found only 13 reports on the economic benefits of CMR over MPS-SPECT, with just three providing cost-effectiveness outcomes, highlighting the need for further research across different settings and ***, findings suggest that the cost savings from using CMR compared with MPS-SPECT for patients with a low-to-intermediate PTP of CAD support prioritized investment;however, confirmatory research is needed given the limited number of cost-effectiveness analyses identified in this review.

标准号: GB/T 17678-2025

摘要： 本文件规定了CAD电子文件归档与管理的总体要求、职责划分和CAD电子文件形成、收集、整理、归档移交与档案管理的一般要求和方法。 本文件适用于机械CAD电子文件归档与管理,其他CAD电子文件归档与管理参照执行。

关键词： lative distribution function (CDF) [53   54   map-level infer  

摘要： We present a joint cosmological analysis of the two-point correlation function and the aperture-mass skewness measured from the Year 3 data of the Hyper Suprime-Cam Subaru Strategic Program. The aperture-mass skewness is a compressed representation of three-point shear information, designed to capture non-Gaussian features while keeping the data vector computationally tractable. We find that including the aperture-mass skewness improves the S8−Ωm figure of merit by 80% compared to the two-point-correlation-function-only case, primarily due to the breaking of degeneracies. Our joint analysis yields a constraint of S8=0.736±0.020, which is slightly lower than the two-point-only result and increases the tension with Planck 2018 to 3.2σ in the S8−Ωm plane. The two- and three-point statistics are found to be internally consistent across redshift bins and angular scales, and we detect no significant intrinsic alignment signal. We also explore extensions to the w cold dark matter model and find no evidence for deviations from a cosmological constant. This work demonstrates the feasibility and scientific value of incorporating third-order shear statistics into weak lensing cosmology and provides a practical pathway for similar analyses in future Stage-IV surveys such as LSST, Euclid, and Roman.

关键词： breast cancer   EfficientNet V2   CBAM   CLAHE   explainable artificial intelligence   Grad CAM  

摘要： Background: Breast cancer remains a leading cause of mortality among women worldwide, underscoring the need for timely and accurate detection. Conventional mammographic diagnosis, while widely used, is limited by subjectivity and variability in interpretation. Recent advances in deep learning (DL) have improved automated detection;however, the black-box nature of these models raises concerns regarding clinical trust and interpretability. Methods: To address this, we propose an explainable DL framework for breast cancer classification using mammographic images. The approach employs contrast limited adaptive histogram equalization (CLAHE)-based preprocessing to enhance lesion contrast, EfficientNetV2 for feature extraction, and the convolutional block attention module (CBAM) to refine salient features. For interpretability, gradient-weighted class activation mapping++ (Grad-CAM++) is used to highlight discriminative regions influencing predictions. Results: The framework is evaluated on three publicly available datasets-MIAS, DDSM, and InBreast-individually and under cross-dataset settings. Results demonstrate superior performance over existing methods, achieving classification accuracies of 99.85%, 99.40%, and 99.70% on MIAS, DDSM, and InBreast, respectively, with corresponding F1-scores of 99.75%, 99.10%, and 99.55%. Confusion matrix analysis confirms excellent sensitivity for malignant cases, and time complexity assessments show reduced training and inference overhead compared to conventional deep models. Conclusions: The framework thus provides a robust and interpretable solution for mammogram-based breast cancer screening.

关键词： cinnamyl alcohol dehydrogenase7   histamine   Phytophthora parasitica   plant susceptibility   small-molecule aldehyde reductase  

摘要： Negative immune regulator CAD7 is a non-canonical member of the CAD (cinnamyl alcohol dehydrogenase) family in plants. However, little is known on its biochemical functions and underlying mechanisms of immune regulation. Here, we show that Arabidopsis thaliana AtCAD7 harbours substrate-binding residues divergent from lignin-forming CADs (AtCAD4/5), being conserved with bacterial alcohol dehydrogenases EcYahK and EcYjgB. Comparative enzymatic analysis revealed that AtCAD7 exhibits a broad substrate preference for diverse small-molecule aldehydes, including histamine-derived intermediates, being distinct from the canonical lignin-forming AtCAD5. Metabolomic analyses revealed that AtCAD7-overexpression transformants were affected in the biosynthesis and metabolism of amino acids, whereas AtCAD7-silencing lines were activated in the phenylpropanoid pathway and increased in flavonoid accumulation. Histamine was elevated in AtCAD7-overexpression lines and functional validation revealed its promoted effect on plant susceptibility to Phytophthora parasitica. In contrast, phytoalexins scopolin and chlorogenic acid were enriched in AtCAD7-silencing lines, accompanied by upregulated expression of phenylpropanoid pathway-related genes. Functional validation demonstrated that scopolin and chlorogenic acid enhanced plant resistance to P. parasitica. Collectively, our study uncovers that CAD7 functions as a metabolic hub linking small-molecule aldehyde reductase activity to immune suppression, providing a potential novel target for developing crops with enhanced resistance to Phytophthora pathogens.

关键词： gearbox design   evolutionary algorithm   computer-aided design   CAD journaling   NSGA-II  

摘要： This paper investigates global optimization methods applied to the design of a one-stage gearbox, aiming to partially automate the design using artificial intelligence. The developed software autonomously determines the gearbox parameters (number of teeth, gear width, modulus, etc.), optimizes them, and then models the assembly in Siemens NX CAD (computer-aided design). The direct connection between optimization and CAD leads to a faster designing process. The literature review reveals that the field of machine design is quite conservative, and only a few articles with some similarities to our research have been found. The paper describes gear dimensioning and the application of the Ipopt algorithm to the optimization of gear-pair parameters. Then, it addresses shaft design and bearing selection through multi-objective optimization using the NSGA-II algorithm, balancing cost, weight, and volume while meeting strength and durability constraints. The paper also describes the transfer of the optimized parameters and the creation of a CAD model. The last part is dedicated to the problems encountered, their potential solutions, and the advantages of the new approach. The proposed approach delivers a functional, optimized CAD model in about 10 min, providing a notable speed advantage over typical manual workflows.

关键词： End-of-life dreams and visions   end-of-life experiences   delirium   CAM   palliative care  

摘要： Objectives End-of-life dreams and visions (ELDVs) and delirium frequently occur near death but differ in core features. Clinical differentiation becomes challenging when they co-occur. This case report illustrates the interplay between ELDVs and delirium, examines the limits of current diagnostic criteria in mixed cases, and outlines a nuanced approach to *** We report the case of an elderly Brazilian woman with metastatic cancer who exhibited both ELDVs and delirium. Mental status was serially assessed using the Confusion Assessment Method (CAM). ELDV accounts were prospectively triangulated across patient, family, and clinician reports to enhance reliability and contextual *** The patient's experiences showed ELDV hallmarks - vivid, realistic encounters with deceased relatives, biographical relevance, and preparatory themes - yet many were affectively distressing and occurred alongside fluctuating attention and consciousness consistent with delirium. CAM effectively identified delirium but could not, on its own, distinguish ELDVs within delirious states. When co-occurring, ELDVs often emerged during "windows of lucidity" marked by preserved autobiographical context, intact recall with subsequent coherent narration, and insight, despite intense emotional valence. Distress alone was not discriminatory, probably being shaped by psychosocial and cultural factors. These observations indicate the need to supplement CAM with qualitative and phenomenological criteria, including content, vividness, biographical meaning, insight, cultural fit, and acuity/*** To our knowledge, this is the first case to map evolving end-of-life mental status using serial CAM while prospectively documenting ELDVs via triangulated reports. The findings highlight the complexity of differentiating co-occurring ELDVs and delirium and challenge the sufficiency of CAM alone. An integrated approach - combining CAM screening with structured ELDV assess

关键词： CAD   miR-18b-5p   Liver cancer   Icaritin   De novo synthesis of pyrimidine  

摘要： Cancer cells show abnormal nucleotide metabolism and prefer the de novo synthesis pathway. As the key enzymes, Carbamoyl-phosphate synthetase 2, Aspartate transcarbamoylase, and Dihydroorotase (CAD) is overactivated in cancer and promotes pyrimidine de novo synthesis, supplying cancer cells with DNA and RNA biosynthesis precursors. Therefore, the development of drugs targeting CAD might inhibit cancer progression and transformation. Icaritin (ICT) is an isoprenoid flavonoid derivative with a wide range of anticancer activities, however, the mechanism of ICT in regulating pyrimidine biosynthesis in cancer remains unclear. MicroRNAs are involved in carcinogenesis by regulating the expression of target genes, and ICT has been shown to regulate the expression of miRNAs leading to suppressing cancer progression. Using both human normal hepatocytes and liver cancer cells, we found that CAD expression was significantly elevated in cancer cells. Interestingly, although ICT treatment reduced CAD protein levels in liver cancer cells, it increased CAD transcriptional activity. Dual-luciferase reporter assays confirmed miR-18b-5p as a direct regulator of CAD. By transfecting miR-18b-5p mimics or inhibitors, we showed ICT upregulates miR-18b-5p to suppress CAD, inhibiting liver cancer cell proliferation, migration, and colony formation. Furthermore, in a human liver cancer xenograft mouse model, ICT treatment markedly reduced tumor growth and decreased Ki-67 expression, consistent with the in vitro results, CAD protein expression was downregulated, while its mRNA level was upregulated, further supporting a post-transcriptional regulatory mechanism. Overall, ICT plays an anti-liver cancer role by increasing miR-18b-5p at the post-transcriptional level to inhibit CAD expression, which may interfere with the de novo synthesis of pyrimidine and development of liver cancer.

关键词： Conformations  

摘要： Cytochrome P450cam exhibits striking conformational heterogeneity and substrate-dependent allostery, yet a unifying mechanism has remained elusive. Here, we reveal the I-helix (αI) as the master regulator of the P450 function. Multimicrosecond MD simulations, NMR pseudocontact shifts, and ensemble analysis of more than 100 crystal structures show that glycines G248 and G249 confer intrinsic flexibility, enabling reversible transitions betweenstraightandkinked αI. Substrate binding stabilizes thestraightconformation, closing solvent channels 1 and 2 while enlarging the distal allosteric site, thereby establishing reciprocal allosteric coupling. This I-helix-centric mechanism resolves decades of structural discrepancies and explains cooperativity, with G249 conserved across human P450s. Proof-of-concept mutants locked in constitutively open or closed states validate αI as a tunable allosteric switch. By overturning the conventional FG-lid focus, this work provides an immediate structural blueprint for the rational engineering of P450 reactivity and selectivity.