A diRNA-protein scaffold module mediates SMC5/6 recruitment in plant DNA repair.

In eukaryotes, the STRUCTURAL MAINTENANCE OF CHROMOSOME 5/6 (SMC5/6) complex is critical to maintaining chromosomal structures around double-strand breaks (DSBs) in DNA damage repair. However, the recruitment mechanism of this conserved complex at DSBs remains unclear. In this study, using Arabidopsis thaliana as a model, we found that SMC5/6 localization at DSBs is dependent on the protein scaffold containing INVOLVED IN DE NOVO 2 (IDN2), CELL DIVISION CYCLE 5 (CDC5), and ALTERATION/DEFICIENCY IN ACTIVATION 2B (ADA2b), whose recruitment is further mediated by DNA-damage-induced RNAs (diRNAs) generated from DNA regions around DSBs. The physical interactions of protein components including SMC5-ADA2b, ADA2b-CDC5, and CDC5-IDN2 result in formation of the protein scaffold. Further analysis indicated that the DSB localization of IDN2 requires its RNA-binding activity and ARGONAUTE 2 (AGO2), indicating a role for the AGO2-diRNA complex in this process. Given that most of the components in the scaffold are conserved, the mechanism presented here, which connects SMC5/6 recruitment and small RNAs, will improve our understanding of DNA repair mechanisms in eukaryotes.

TNFAIP3 Derived from Skeletal Stem Cells Alleviated Rat Osteoarthritis by Inhibiting the Necroptosis of Subchondral Osteoblasts.

Recent investigations have shown that the necroptosis of tissue cells in joints is important in the development of osteoarthritis (OA). This study aimed to investigate the potential effects of exogenous skeletal stem cells (SSCs) on the necroptosis of subchondral osteoblasts in OA. Human SSCs and subchondral osteoblasts isolated from human tibia plateaus were used for Western blotting, real-time PCR, RNA sequencing, gene editing, and necroptosis detection assays. In addition, the rat anterior cruciate ligament transection OA model was used to evaluate the effects of SSCs on osteoblast necroptosis in vivo. The micro-CT and pathological data showed that intra-articular injections of SSCs significantly improved the microarchitecture of subchondral trabecular bones in OA rats. Additionally, SSCs inhibited the necroptosis of subchondral osteoblasts in OA rats and necroptotic cell models. The results of bulk RNA sequencing of SSCs stimulated or not by tumor necrosis factor α suggested a correlation of SSCs-derived tumor necrosis factor α-induced protein 3 (TNFAIP3) and cell necroptosis. Furthermore, TNFAIP3-derived from SSCs contributed to the inhibition of the subchondral osteoblast necroptosis in vivo and in vitro. Moreover, the intra-articular injections of TNFAIP3-overexpressing SSCs further improved the subchondral trabecular bone remodeling of OA rats. Thus, we report that TNFAIP3 from SSCs contributed to the suppression of the subchondral osteoblast necroptosis, which suggests that necroptotic subchondral osteoblasts in joints may be possible targets to treat OA by stem cell therapy.

Topology-Engineered Orbital Hall Effect in Two-Dimensional Ferromagnets.

Recent advances in the manipulation of the orbital angular momentum (OAM) within the paradigm of orbitronics presents a promising avenue for the design of future electronic devices. In this context, the recently observed orbital Hall effect (OHE) occupies a special place. Here, focusing on both the second-order topological and quantum anomalous Hall insulators in two-dimensional ferromagnets, we demonstrate that topological phase transitions present an efficient and straightforward way to engineer the OHE, where the OAM distribution can be controlled by the nature of the band inversion. Using first-principles calculations, we identify Janus RuBrCl and three septuple layers of MnBi2Te4 as experimentally feasible examples of the proposed mechanism of OHE engineering by topology. With our work, we open up new possibilities for innovative applications in topological spintronics and orbitronics.

Altered intersubject functional variability of brain white-matter in major depressive disorder and its association with gene expression profiles.

Major depressive disorder (MDD) is a clinically heterogeneous disorder. Its mechanism is still unknown. Although the altered intersubject variability in functional connectivity (IVFC) within gray-matter has been reported in MDD, the alterations to IVFC within white-matter (WM-IVFC) remain unknown. Based on the resting-state functional MRI data of discovery (145 MDD patients and 119 healthy controls [HCs]) and validation cohorts (54 MDD patients, and 78 HCs), we compared the WM-IVFC between the two groups. We further assessed the meta-analytic cognitive functions related to the alterations. The discriminant WM-IVFC values were used to classify MDD patients and predict clinical symptoms in patients. In combination with the Allen Human Brain Atlas, transcriptome-neuroimaging association analyses were further conducted to investigate gene expression profiles associated with WM-IVFC alterations in MDD, followed by a set of gene functional characteristic analyses. We found extensive WM-IVFC alterations in MDD compared to HCs, which were associated with multiple behavioral domains, including sensorimotor processes and higher-order functions. The discriminant WM-IVFC could not only effectively distinguish MDD patients from HCs with an area under curve ranging from 0.889 to 0.901 across three classifiers, but significantly predict depression severity (r = 0.575, p = 0.002) and suicide risk (r = 0.384, p = 0.040) in patients. Furthermore, the variability-related genes were enriched for synapse, neuronal system, and ion channel, and predominantly expressed in excitatory and inhibitory neurons. Our results obtained good reproducibility in the validation cohort. These findings revealed intersubject functional variability changes of brain WM in MDD and its linkage with gene expression profiles, providing potential implications for understanding the high clinical heterogeneity of MDD.

Multitask Deep Learning-Based Whole-Process System for Automatic Diagnosis of Breast Lesions and Axillary Lymph Node Metastasis Discrimination from Dynamic Contrast-Enhanced-MRI: A Multicenter Study.

BACKGROUND: Accurate diagnosis of breast lesions and discrimination of axillary lymph node (ALN) metastases largely depend on radiologist experience. PURPOSE: To develop a deep learning-based whole-process system (DLWPS) for segmentation and diagnosis of breast lesions and discrimination of ALN metastasis. STUDY TYPE: Retrospective. POPULATION: 1760 breast patients, who were divided into training and validation sets (1110 patients), internal (476 patients), and external (174 patients) test sets. FIELD STRENGTH/SEQUENCE: 3.0T/dynamic contrast-enhanced (DCE)-MRI sequence. ASSESSMENT: DLWPS was developed using segmentation and classification models. The DLWPS-based segmentation model was developed by the U-Net framework, which combined the attention module and the edge feature extraction module. The average score of the output scores of three networks was used as the result of the DLWPS-based classification model. Moreover, the radiologists' diagnosis without and with the DLWPS-assistance was explored. To reveal the underlying biological basis of DLWPS, genetic analysis was performed based on RNA-sequencing data. STATISTICAL TESTS: Dice similarity coefficient (DI), area under receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and kappa value. RESULTS: The segmentation model reached a DI of 0.828 and 0.813 in the internal and external test sets, respectively. Within the breast lesions diagnosis, the DLWPS achieved AUCs of 0.973 in internal test set and 0.936 in external test set. For ALN metastasis discrimination, the DLWPS achieved AUCs of 0.927 in internal test set and 0.917 in external test set. The agreement of radiologists improved with the DLWPS-assistance from 0.547 to 0.794, and from 0.848 to 0.892 in breast lesions diagnosis and ALN metastasis discrimination, respectively. Additionally, 10 breast cancers with ALN metastasis were associated with pathways of aerobic electron transport chain and cytoplasmic translation. DATA CONCLUSION: The performance of DLWPS indicates that it can promote radiologists in the judgment of breast lesions and ALN metastasis and nonmetastasis. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 3.

High-Precision Atom Interferometer-Based Dynamic Gravimeter Measurement by Eliminating the Cross-Coupling Effect.

A dynamic gravimeter with an atomic interferometer (AI) can perform absolute gravity measurements with high precision. AI-based dynamic gravity measurement is a type of joint measurement that uses an AI sensor and a classical accelerometer. The coupling of the two sensors may degrade the measurement precision. In this study, we analyzed the cross-coupling effect and introduced a recovery vector to suppress this effect. We improved the phase noise of the interference fringe by a factor of 1.9 by performing marine gravity measurements using an AI-based gravimeter and optimizing the recovery vector. Marine gravity measurements were performed, and high gravity measurement precision was achieved. The external and inner coincidence accuracies of the gravity measurement were ±0.42 mGal and ±0.46 mGal after optimizing the cross-coupling effect, which was improved by factors of 4.18 and 4.21 compared to the cases without optimization.

Robust Second-Order Topological Insulators with Giant Valley Polarization in Two-Dimensional Honeycomb Ferromagnets.

Magnetic topological states have attracted great attention that provide exciting platforms for exploring prominent physical phenomena and applications of topological spintronics. Here, using a tight-binding model and first-principles calculations, we put forward that, in contrast to previously reported magnetic second-order topological insulators (SOTIs), robust SOTIs can emerge in two-dimensional ferromagnets regardless of magnetization directions. Remarkably, we identify intrinsic ferromagnetic 2H-RuCl2 and Janus VSSe monolayers as experimentally feasible candidates of predicted robust SOTIs with the emergence of nontrivial corner states along different magnetization directions. Moreover, under out-of-plane magnetization, we unexpectedly point out that the valley polarization of SOTIs can be huge and much larger than that of the known ferrovalley materials, opening up a technological avenue to bridge the valleytronics and higher-order topology with high possibility of innovative applications in topological spintronics and valleytronics.

Multimodal and multiscale evidence for network-based cortical thinning in major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is associated with widespread, irregular cortical thickness (CT) reductions across the brain. However, little is known regarding mechanisms that govern spatial distribution of the reductions. METHODS: We combined multimodal MRI and genetic, cytoarchitectonic and chemoarchitectonic data to examine structural covariance, functional synchronization, gene co-expression, cytoarchitectonic similarity and chemoarchitectonic covariance between regions atrophied in MDD. RESULTS: Regions atrophied in MDD were associated with significantly higher structural covariance, functional synchronization, gene co-expression and chemoarchitectonic covariance. These results were robust against methodological variations in brain parcellation and null model, reproducible in patients and controls, and independent of age at onset of MDD. Despite no significant differences in the cytoarchitectonic similarity, MDD-related CT reductions were susceptible to specific cytoarchitectonic class of association cortex. Further, we found that nodal shortest path lengths to disease epicenters derived from structural (right supramarginal gyrus) and chemoarchitectonic covariance (right sulcus intermedius primus) networks of healthy brains were correlated with the extent to which a region was atrophied in MDD, supporting the transneuronal spread hypothesis that regions closer to the epicenters are more susceptible to MDD. Finally, we showed that structural covariance and functional synchronization among regions atrophied in MDD were mainly related to genes enriched in metabolic and membrane-related processes, driven by genes in excitatory neurons, and associated with specific neurotransmitter transporters and receptors. CONCLUSIONS: Altogether, our findings provide empirical evidence for and genetic and molecular insights into connectivity-constrained CT thinning in MDD.

Attention-based deep learning for breast lesions classification on contrast enhanced spectral mammography: a multicentre study.

BACKGROUND: This study aims to develop an attention-based deep learning model for distinguishing benign from malignant breast lesions on CESM. METHODS: Preoperative CESM images of 1239 patients, which were definitely diagnosed on pathology in a multicentre cohort, were divided into training and validation sets, internal and external test sets. The regions of interest of the breast lesions were outlined manually by a senior radiologist. We adopted three conventional convolutional neural networks (CNNs), namely, DenseNet 121, Xception, and ResNet 50, as the backbone architectures and incorporated the convolutional block attention module (CBAM) into them for classification. The performance of the models was analysed in terms of the receiver operating characteristic (ROC) curve, accuracy, the positive predictive value (PPV), the negative predictive value (NPV), the F1 score, the precision recall curve (PRC), and heat maps. The final models were compared with the diagnostic performance of conventional CNNs, radiomics models, and two radiologists with specialised breast imaging experience. RESULTS: The best-performing deep learning model, that is, the CBAM-based Xception, achieved an area under the ROC curve (AUC) of 0.970, a sensitivity of 0.848, a specificity of 1.000, and an accuracy of 0.891 on the external test set, which was higher than those of other CNNs, radiomics models, and radiologists. The PRC and the heat maps also indicated the favourable predictive performance of the attention-based CNN model. The diagnostic performance of two radiologists improved with deep learning assistance. CONCLUSIONS: Using an attention-based deep learning model based on CESM images can help to distinguishing benign from malignant breast lesions, and the diagnostic performance of radiologists improved with deep learning assistance.

Engineering Second-Order Corner States in 2D Multiferroics.

The understanding and manipulate of the second-order corner states are central to both fundamental physics and future topotronics applications. Despite the fact that numerous second-order topological insulators (SOTIs) are achieved, the efficient engineering in a given material remains elusive. Here, the emergence of 2D multiferroics SOTIs in SbAs and BP5 monolayers is theoretically demonstrated, and an efficient and straightforward way for engineering the nontrivial corner states by ferroelasticity and ferroelectricity is remarkably proposed. With ferroelectric polarization of SbAs and BP5 monolayers, the nontrivial corner states emerge in the mirror symmetric corners and are perpendicular to orientations of the in-plane spontaneous polarization. And remarkably the spatial distribution of the corner states can be effectively tuned by a ferroelastic switching. At the intermediate states of both ferroelectric and ferroelastic switchings, the corner states disappear. These finding not only combines exotic SOTIs with multiferroics but also pave the way for experimental discovery of 2D tunable SOTIs.

Enhancing nutritional niche and host defenses by modifying the gut microbiome.

The gut microbiome is essential for processing complex food compounds and synthesizing nutrients that the host cannot digest or produce, respectively. New model systems are needed to study how the metabolic capacity provided by the gut microbiome impacts the nutritional status of the host, and to explore possibilities for altering host metabolic capacity via the microbiome. Here, we colonized the nematode Caenorhabditis elegans gut with cellulolytic bacteria that enabled C. elegans to utilize cellulose, an otherwise indigestible substrate, as a carbon source. Cellulolytic bacteria as a community component in the worm gut can also support additional bacterial species with specialized roles, which we demonstrate by using Lactobacillus plantarum to protect C. elegans against Salmonella enterica infection. This work shows that engineered microbiome communities can be used to endow host organisms with novel functions, such as the ability to utilize alternate nutrient sources or to better fight pathogenic bacteria.

Diagnosis of Major Depressive Disorder Using Machine Learning Based on Multisequence MRI Neuroimaging Features.

BACKGROUND: Previous studies have found qualitative structural and functional brain changes in major depressive disorder (MDD) patients. However, most studies ignored the complementarity of multisequence MRI neuroimaging features and cannot determine accurate biomarkers. PURPOSE: To evaluate machine-learning models combined with multisequence MRI neuroimaging features to diagnose patients with MDD. STUDY TYPE: Prospective. SUBJECTS: A training cohort including 111 patients and 90 healthy controls (HCs) and a test cohort including 28 patients and 22 HCs. FIELD STRENGTH/SEQUENCE: A 3.0 T/T1-weighted imaging, resting-state functional MRI with echo-planar sequence, and single-shot echo-planar diffusion tensor imaging. ASSESSMENT: Recruitment and integration were used to reflect the dynamic changes of functional networks, while gray matter volume and fractional anisotropy were used to reflect the changes in the morphological and anatomical network. We then fused features with significant differences in functional, morphological, and anatomical networks to evaluate a random forest (RF) classifier to diagnose patients with MDD. Furthermore, a support vector machine (SVM) classifier was used to verify the stability of neuroimaging features. Linear regression analyses were conducted to investigate the relationships among multisequence neuroimaging features and the suicide risk of patients. STATISTICAL TESTS: The comparison of functional network attributes between patients and controls by two-sample t-test. Network-based statistical analysis was used to identify structural and anatomical connectivity changes between MDD and HCs. The performance of the model was evaluated by receiver operating characteristic (ROC) curves. RESULTS: The performance of the RF model integrating multisequence neuroimaging features in the diagnosis of depression was significantly improved, with an AUC of 93.6%. In addition, we found that multisequence neuroimaging features could accurately predict suicide risk in patients with MDD (r = 0.691). DATA CONCLUSION: The RF model fusing functional, morphological, and anatomical network features performed well in diagnosing patients with MDD and provided important insights into the pathological mechanisms of MDD. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.

Classification of Major Depressive Disorder Based on Integrated Temporal and Spatial Functional MRI Variability Features of Dynamic Brain Network.

BACKGROUND: Characterization of the dynamics of functional brain network has gained increased attention in the study of depression. However, most studies have focused on single temporal dimension, while ignoring spatial dimensional information, hampering the discovery of validated biomarkers for depression. PURPOSE: To integrate temporal and spatial functional MRI variability features of dynamic brain network in machine-learning techniques to distinguish patients with major depressive disorder (MDD) from healthy controls (HCs). STUDY TYPE: Prospective. POPULATION: A discovery cohort including 119 patients and 106 HCs and an external validation cohort including 126 patients and 124 HCs from Rest-meta-MDD consortium. FIELD STRENGTH/SEQUENCE: A 3.0 T/resting-state functional MRI using the gradient echo sequence. ASSESSMENT: A random forest (RF) model integrating temporal and spatial variability features of dynamic brain networks with separate feature selection method (MSFS ) was implemented for MDD classification. Its performance was compared with three RF models that used: temporal variability features (MTVF ), spatial variability features (MSVF ), and integrated temporal and spatial variability features with hybrid feature selection method (MHFS ). A linear regression model based on MSFS was further established to assess MDD symptom severity, with prediction performance evaluated by the correlations between true and predicted scores. STATISTICAL TESTS: Receiver operating characteristic analyses with the area under the curve (AUC) were used to evaluate models' performance. Pearson's correlation was used to assess relationship of predicted scores and true scores. P < 0.05 was considered statistically significant. RESULTS: The model with MSFS achieved the best performance, with AUCs of 0.946 and 0.834 in the discovery and validation cohort, respectively. Additionally, altered temporal and spatial variability could significantly predict the severity of depression (r = 0.640) and anxiety (r = 0.616) in MDD. DATA CONCLUSION: Integration of temporal and spatial variability features provides potential assistance for clinical diagnosis and symptom prediction of MDD. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Attention-based Deep Learning for the Preoperative Differentiation of Axillary Lymph Node Metastasis in Breast Cancer on DCE-MRI.

BACKGROUND: Previous studies have explored the potential on radiomics features of primary breast cancer tumor to identify axillary lymph node (ALN) metastasis. However, the value of deep learning (DL) to identify ALN metastasis remains unclear. PURPOSE: To investigate the potential of the proposed attention-based DL model for the preoperative differentiation of ALN metastasis in breast cancer on dynamic contrast-enhanced MRI (DCE-MRI). STUDY TYPE: Retrospective. POPULATION: A total of 941 breast cancer patients who underwent DCE-MRI before surgery were included in the training (742 patients), internal test (83 patients), and external test (116 patients) cohorts. FIELD STRENGTH/SEQUENCE: A 3.0 T MR scanner, DCE-MRI sequence. ASSESSMENT: A DL model containing a 3D deep residual network (ResNet) architecture and a convolutional block attention module, named RCNet, was proposed for ALN metastasis identification. Three RCNet models were established based on the tumor, ALN, and combined tumor-ALN regions on the images. The performance of these models was compared with ResNet models, radiomics models, the Memorial Sloan-Kettering Cancer Center (MSKCC) model, and three radiologists (W.L., H.S., and F. L.). STATISTICAL TESTS: Dice similarity coefficient for breast tumor and ALN segmentation. Accuracy, sensitivity, specificity, intercorrelation and intracorrelation coefficients, area under the curve (AUC), and Delong test for ALN classification. RESULTS: The optimal RCNet model, that is, RCNet-tumor+ALN , achieved an AUC of 0.907, an accuracy of 0.831, a sensitivity of 0.824, and a specificity of 0.837 in the internal test cohort, as well as an AUC of 0.852, an accuracy of 0.828, a sensitivity of 0.792, and a specificity of 0.853 in the external test cohort. Additionally, with the assistance of RCNet-tumor+ALN , the radiologists' performance was improved (external test cohort, P < 0.05). DATA CONCLUSION: DCE-MRI-based RCNet model could provide a noninvasive auxiliary tool to identify ALN metastasis preoperatively in breast cancer, which may assist radiologists in conducting more accurate evaluation of ALN status. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Artificial intelligence-based prediction of cervical lymph node metastasis in papillary thyroid cancer with CT.

OBJECTIVES: To develop an artificial intelligence (AI) system for predicting cervical lymph node metastasis (CLNM) preoperatively in patients with papillary thyroid cancer (PTC) based on CT images. METHODS: This multicenter retrospective study included the preoperative CT of PTC patients who were divided into the development, internal, and external test sets. The region of interest of the primary tumor was outlined manually on the CT images by a radiologist who has eight years of experience. With the use of the CT images and lesions masks, the deep learning (DL) signature was developed by the DenseNet combined with convolutional block attention module. One-way analysis of variance and least absolute shrinkage and selection operator were used to select features, and a support vector machine was used to construct the radiomics signature. Random forest was used to combine the DL, radiomics, and clinical signature to perform the final prediction. The receiver operating characteristic curve, sensitivity, specificity, and accuracy were used by two radiologists (R1 and R2) to evaluate and compare the AI system. RESULTS: For the internal and external test set, the AI system achieved excellent performance with AUCs of 0.84 and 0.81, higher than the DL (p = .03, .82), radiomics (p < .001, .04), and clinical model (p < .001, .006). With the aid of the AI system, the specificities of radiologists were improved by 9% and 15% for R1 and 13% and 9% for R2, respectively. CONCLUSIONS: The AI system can help predict CLNM in patients with PTC, and the radiologists' performance improved with AI assistance. CLINICAL RELEVANCE STATEMENT: This study developed an AI system for preoperative prediction of CLNM in PTC patients based on CT images, and the radiologists' performance improved with AI assistance, which could improve the effectiveness of individual clinical decision-making. KEY POINTS: • This multicenter retrospective study showed that the preoperative CT image-based AI system has the potential for predicting the CLNM of PTC. • The AI system was superior to the radiomics and clinical model in predicting the CLNM of PTC. • The radiologists' diagnostic performance improved when they received the AI system assistance.

Intra- and peritumoral radiomics for predicting malignant BiRADS category 4 breast lesions on contrast-enhanced spectral mammography: a multicenter study.

OBJECTIVE: To construct and test a nomogram based on intra- and peritumoral radiomics and clinical factors for predicting malignant BiRADS 4 lesions on contrast-enhanced spectral mammography. METHODS: A total of 884 patients with BiRADS 4 lesions were enrolled from two centers. For each lesion, five ROIs were defined using the intratumoral region (ITR), peritumoral regions (PTRs) of 5 and 10 mm around the tumor, and ITR plus PTRs of 5 mm and 10 mm. Five radiomics signatures were established by LASSO after selecting features. A nomogram was built using selected signatures and clinical factors by multivariable logistic regression analysis. The performance of the nomogram was assessed with the AUC, decision curve analysis, and calibration curves, and also compared with the radiomics model, clinical model, and radiologists. RESULTS: The nomogram built by three radiomics signatures (constructed from ITR, 5 mm PTR, and ITR + 10 mm PTR) and two clinical factors (age and BiRADS category) showed powerful predictive ability in internal and external test sets with AUCs of 0.907 and 0.904, respectively. The calibration curves, decision curve analysis, showed favorable predictive performance of the nomogram. In addition, radiologists improved the diagnostic performance with the help of nomogram. CONCLUSION: The nomogram established via intratumoral and peritumoral radiomics features and clinical risk factors had the best performance in distinguishing benign and malignant BiRADS 4 lesions, which could help radiologists improve diagnostic capabilities. KEY POINTS: • Radiomics features from peritumoral regions in contrast-enhanced spectral mammography images may provide valuable information for the diagnosis of benign and malignant breast imaging reporting and data system category 4 breast lesions. • The nomogram incorporated intra- and peritumoral radiomics features and clinical variables have good application prospects in assisting clinical decision-makers.

Nomogram Using CT Radiomics Features for Differentiation of Pneumonia-Type Invasive Mucinous Adenocarcinoma and Pneumonia: Multicenter Development and External Validation Study.

BACKGROUND. Pneumonia-type invasive mucinous adenocarcinoma (IMA) and pneumonia show overlapping chest CT features as well as overlapping clinical characteristics. OBJECTIVE. The purpose of our study was to develop and validate a nomogram combining clinical and CT-based radiomics features to differentiate pneumonia-type IMA and pneumonia. METHODS. This retrospective study included 314 patients (172 men, 142 women; mean age, 60.3 ± 14.5 [SD] years) from six hospitals who underwent noncontrast chest CT showing consolidation and were diagnosed with pneumonia-type IMA (n = 106) or pneumonia (n = 208). Patients from three hospitals formed a training set (n = 195) and a validation set (n = 50), and patients from the other three hospitals formed the external test set (n = 69). A model for predicting pneumonia-type IMA was built using clinical characteristics that were significant independent predictors of this diagnosis. Radiomics features were extracted from CT images by placing ROIs on areas of consolidation, and a radiomics signature of pneumonia-type IMA was constructed. A nomogram for predicting pneumonia-type IMA was constructed that combined features in the clinical model and the radiomics signature. Two cardiothoracic radiologists independently reviewed CT images in the external test set to diagnose pneumonia-type IMA. Diagnostic performance was compared among models and radiologists. Decision curve analysis (DCA) was performed. RESULTS. The clinical model included fever and family history of lung cancer. The radiomics signature included 15 radiomics features. DCA showed higher overall net benefit from the nomogram than from the clinical model. In the external test set, AUC was higher for the nomogram (0.85) than for the clinical model (0.71, p = .01), radiologist 1 (0.70, p = .04), and radiologist 2 (0.67, p = .01). In the external test set, the nomogram had sensitivity of 46.9%, specificity of 94.6%, and accuracy of 72.5%. CONCLUSION. The nomogram combining clinical variables and CT-based radiomics features outperformed the clinical model and two cardiothoracic radiologists in differentiating pneumonia-type IMA from pneumonia. CLINICAL IMPACT. The findings support potential clinical use of the nomogram for diagnosing pneumonia-type IMA in patients with consolidation on chest CT.

Review of animal transmission experiments of respiratory viruses: Implications for transmission risk of SARS-COV-2 in humans via different routes.

Exploring transmission risk of different routes has major implications for epidemic control. However, disciplinary boundaries have impeded the dissemination of epidemic information, have caused public panic about "air transmission," "air-conditioning transmission," and "environment-to-human transmission," and have triggered "hygiene theater." Animal experiments provide experimental evidence for virus transmission, but more attention is paid to whether transmission is driven by droplets or aerosols and using the dichotomy to describe most transmission events. Here, according to characteristics of experiment setups, combined with patterns of human social interactions, we reviewed and grouped animal transmission experiments into four categories-close contact, short-range, fomite, and aerosol exposure experiments-and provided enlightenment, with experimental evidence, on the transmission risk of severe acute respiratory syndrome coronavirus (SARS-COV-2) in humans via different routes. When referring to "air transmission," context should be showed in elaboration results, rather than whether close contact, short or long range is uniformly described as "air transmission." Close contact and short range are the major routes. When face-to-face, unprotected, horizontally directional airflow does promote transmission, due to virus decay and dilution in air, the probability of "air conditioning transmission" is low; the risk of "environment-to-human transmission" highly relies on surface contamination and human behavior based on indirect path of "fomite-hand-mucosa or conjunctiva" and virus decay on surfaces. Thus, when discussing the transmission risk of SARS-CoV-2, we should comprehensively consider the biological basis of virus transmission, environmental conditions, and virus decay. Otherwise, risk of certain transmission routes, such as long-range and fomite transmission, will be overrated, causing public excessive panic, triggering ineffective actions, and wasting epidemic prevention resources.

Radiomics of contrast-enhanced spectral mammography for prediction of pathological complete response to neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been regarded as one of the standard treatments for patients with locally advanced breast cancer. No previous study has investigated the feasibility of using a contrast-enhanced spectral mammography (CESM)-based radiomics nomogram to predict pathological complete response (pCR) after NAC. OBJECTIVE: To develop and validate a CESM-based radiomics nomogram to predict pCR after NAC in breast cancer. METHODS: A total of 118 patients were enrolled, which are divided into a training dataset including 82 patients (with 21 pCR and 61 non-pCR) and a testing dataset of 36 patients (with 9 pCR and 27 non-pCR). The tumor regions of interest (ROIs) were manually segmented by two radiologists on the low-energy and recombined images and radiomics features were extracted. Intraclass correlation coefficients (ICCs) were used to assess the intra- and inter-observer agreements of ROI features extraction. In the training set, the variance threshold, SelectKBest method, and least absolute shrinkage and selection operator regression were used to select the optimal radiomics features. Radiomics signature was calculated through a linear combination of selected features. A radiomics nomogram containing radiomics signature score (Rad-score) and clinical risk factors was developed. The receiver operating characteristic (ROC) curve and calibration curve were used to evaluate prediction performance of the radiomics nomogram, and decision curve analysis (DCA) was used to evaluate the clinical usefulness of the radiomics nomogram. RESULTS: The intra- and inter- observer ICCs were 0.769-0.815 and 0.786-0.853, respectively. Thirteen radiomics features were selected to calculate Rad-score. The radiomics nomogram containing Rad-score and clinical risk factor showed an encouraging calibration and discrimination performance with area under the ROC curves of 0.906 (95% confidence interval (CI): 0.840-0.966) in the training dataset and 0.790 (95% CI: 0.554-0.952) in the test dataset. CONCLUSIONS: The CESM-based radiomics nomogram had good prediction performance for pCR after NAC in breast cancer; therefore, it has a good clinical application prospect.

Applying a nomogram based on preoperative CT to predict early recurrence of laryngeal squamous cell carcinoma after surgery.

PURPOSE: To identify the value of a computed tomography (CT)-based radiomics model to predict probability of early recurrence (ER) in patients diagnosed with laryngeal squamous cell carcinoma (LSCC) after surgery. MATERIALS AND METHOD: Pre-operative CT scans of 140 LSCC patients treated by surgery are reviewed and selected. These patients are randomly split into the training set (n = 97) and test set (n = 43). The regions of interest of each patient were delineated manually by two senior radiologists. Radiomics features are extracted from CT images acquired in non-enhanced, arterial, and venous phases. Variance threshold, one-way ANOVA, and least absolute shrinkage and selection operator algorithm are used for feature selection. Then, radiomics models are built with five algorithms namely, k-nearest neighbor (KNN), logistic regression (LR), linear support vector machine (LSVM), radial basis function SVM (RSVM), and polynomial SVM (PSVM). Clinical factors are selected using univariate and multivariate logistic regressions. Last, a radiomics nomogram incorporating the radiomics signature and clinical factors is built to predict ER and its efficiency is evaluated by receiver operating characteristic (ROC) curve and calibration curve. Decision curve analysis (DCA) is also used to evaluate clinical usefulness. RESULTS: Four features are remarkably associated with ER in patients with LSCC. Applying to test set, the area under the ROC curves (AUCs) of KNN, LR, LSVM, RSVM, and PSVM are 0.936, 0.855, 0.845, 0.829, and 0.794, respectively. The radiomics nomogram shows better discrimination (with AUC: 0.939, 95% CI: 0.867-0.989) than the best radiomics model and the clinical model. Predicted and actual ERs in the calibration curves are in good agreement. DCA shows that the radiomics nomogram is clinically useful. CONCLUSION: The radiomics nomogram, as a noninvasive prediction tool, exhibits favorable performance for ER prediction of LSCC patients after surgery.