The value of machine learning based on CT radiomics in the preoperative identification of peripheral nerve invasion in colorectal cancer: a two-center study.

BACKGROUND: We aimed to explore the application value of various machine learning (ML) algorithms based on multicenter CT radiomics in identifying peripheral nerve invasion (PNI) of colorectal cancer (CRC). METHODS: A total of 268 patients with colorectal cancer who underwent CT examination in two hospitals from January 2016 to December 2022 were considered. Imaging and clinicopathological data were collected through the Picture Archiving and Communication System (PACS). The Feature Explorer software (FAE) was used to identify the peripheral nerve invasion of colorectal patients in center 1, and the best feature selection and classification channels were selected. Finally, the best feature selection and classifier pipeline were verified in center 2. RESULTS: The six-feature models using RFE feature selection and GP classifier had the highest AUC values, which were 0.610, 0.699, and 0.640, respectively. FAE generated a more concise model based on one feature (wavelet-HLL-glszm-LargeAreaHighGrayLevelEmphasis) and achieved AUC values of 0.614 and 0.663 on the validation and test sets, respectively, using the "one standard error" rule. Using ANOVA feature selection, the GP classifier had the best AUC value in a one-feature model, with AUC values of 0.611, 0.663, and 0.643 on the validation, internal test, and external test sets, respectively. Similarly, when using the "one standard error" rule, the model based on one feature (wave-let-HLL-glszm-LargeAreaHighGrayLevelEmphasis) achieved AUC values of 0.614 and 0.663 on the validation and test sets, respectively. CONCLUSIONS: Combining artificial intelligence and radiomics features is a promising approach for identifying peripheral nerve invasion in colorectal cancer. This innovative technique holds significant potential for clinical medicine, offering broader application prospects in the field. CRITICAL RELEVANCE STATEMENT: The multi-channel ML method based on CT radiomics has a simple operation process and can be used to assist in the clinical screening of patients with CRC accompanied by PNI. KEY POINTS: • Multi-channel ML in the identification of peripheral nerve invasion in CRC. • Multi-channel ML method based on CT-radiomics can detect the PNI of CRC. • Early preoperative identification of PNI in CRC is helpful to improve the formulation of treatment strategies and the prognosis of patients.

Individualized driver amplitude in liver MR elastography: a linear regression study.

BACKGROUND: Current liver magnetic resonance elastography (MRE) scans often require adjustments to driver amplitude to produce acceptable images. This could lead to time wastage and the potential loss of an opportunity to capture a high-quality image. PURPOSE: To construct a linear regression model of individualized driver amplitude to improve liver MRE image quality. MATERIAL AND METHODS: Data from 95 liver MRE scans of 61 participants, including abdominal missing volume ratio (AMVR), breath-holding status, the distance from the passive driver on the skin surface to the liver edge (Dd-l), body mass index (BMI), and lateral deflection of the passive driver with respect to the human sagittal plane (Angle α), were continuously collected. The Spearman correlation analysis and lasso regression were conducted to screen the independent variables. Multiple linear regression equations were developed to determine the optimal amplitude prediction model. RESULTS: The optimal formula for linear regression models: driver amplitude (%) = -16.80 + 78.59 × AMVR - 11.12 × breath-holding (end of expiration = 1, end of inspiration = 0) + 3.16 × Dd-l + 1.94 × BMI + 0.34 × angle α, with the model passing the F test (F = 22.455, P <0.001) and R2 value of 0.558. CONCLUSION: The individualized amplitude prediction model based on AMVR, breath-holding status, Dd-l, BMI, and angle α is a valuable tool in liver MRE examination.

Acidosis activates breast cancer ferroptosis through ZFAND5/SLC3A2 signaling axis and elicits M1 macrophage polarization.

Acidosis is involved in multiple pathways in tumor cells and immune cells among the tumor microenvironment (TME). Ferroptosis is a nonapoptotic and iron-dependent form of cell death characterized by accumulation of lipid peroxidation involved in various cancers. The role of ferroptosis in the breast cancer (BC) acidic microenvironment remains unrevealed. Here, we reported that short-term acidosis induced ferroptosis of BC cells in the zinc finger AN1-type domain 5 (ZFAND5)/solute carrier family 3 member 2 (SLC3A2) dependent manner to suppress tumor growth using in silico and multiple biological methods. Mechanistically, we demonstrated that short-term acidosis increased total/lipid reactive oxygen species (ROS) level, decreased glutathione (GSH) level and induced the morphological changes of mitochondria. Specifically, acidosis restrained the protein stability of SLC3A2 by promoting its ubiquitination process. The prognostic analysis showed that higher expression of ZFAND5 and lower expression of SLC3A2 were correlated with longer overall survival of BC patients, respectively. Furthermore, in combination with ferroptosis agonist metformin, short-term acidosis could synergistically inhibit viability and enhance the ferroptosis of BC cells. Meanwhile, by the exploration of immune cells, short-term acidosis also induced M1 macrophage polarization, triggering processes of phagocytosis and ferroptosis in BC cells. This study demonstrated that short-term acidosis induced BC cell ferroptosis through ZFAND5/SLC3A2 signaling axis and promoted phagocytosis and ferroptosis of BC cells with M1 macrophage polarization, which might be a new mechanism for BC therapy.

Effects of morality and reputation on sharing behaviors in human-robot teams.

Introduction: The relationship between robots and humans is becoming increasingly close and will become an inseparable part of work and life with humans and robots working together. Sharing, which involves distributing goods between individuals and others, involves individuals as potential beneficiaries and the possibility of giving up the interests of others. In human teams, individual sharing behaviors are influenced by morality and reputation. However, the impact on individuals' sharing behaviors in human-robot collaborative teams remains unclear-individuals may consider morality and reputation differently when sharing with robot or human partners. In this study, three experiments were conducted using the dictator game paradigm, aiming to compare the effects and mechanisms of morality and reputation on sharing behaviors in human and human-robot teams. Methods: Experiment 1 involving 18 participants was conducted. Experiment 2 involving 74 participants was conducted. Experiment 3 involving 128 participants was conducted. Results: Experiment 1 validated the differences in human sharing behaviors when the agents were robots and humans. Experiment 2 verifies that moral constraints and reputation constraints affect sharing behaviors in human-robot teams. Experiment 3 further reveals the mechanism of differences in sharing behaviors in human-robot teams, where reputation concern plays a mediating role in the impact of moral constraint on sharing behaviors, and the agent type plays a moderating role in the impact of moral constraint on reputation concern and sharing behaviors. Discussion: The results of this study contribute to a better understanding of the interaction mechanism of human-robot teams. In the future, the formulation of human-robot collaborative team rules and the setting of interaction environments can consider the potential motivation of human behavior from both morality and reputation perspectives and achieve better work performance.

Covalent Organic Framework-Based Nanomotor for Multimodal Cancer Photo-Theranostics.

Developing efficient integrated diagnosis and treatment agents based on fuel-free self-movement nanomotors remains challenging in antitumor therapy. In this study, a covalent organic framework (COF)-based biomimetic nanomotor composed of polypyrrole (PPy) core, porphyrin-COF shell, and HCT116 cancer cell membrane coating is reported. Under near-infrared (NIR) light irradiation, the obtained mPPy@COF-Por can overcome Brownian motion and achieves directional motion through self-thermophoretic force generated from the PPy core. The HCT116 cancer cell membrane coating enables the nanomotor to selectively recognize the source cell lines and reduces the bio-adhesion of mPPy@COF-Por in a biological medium, endowing with this NIR light-powered nanomotor good mobility. More importantly, such multifunctional integration allows the COF-based nanomotor to be a powerful nanoagent for cancer treatment, and the high infrared thermal imaging/photoacoustic imaging/fluorescence trimodal imaging-guided combined photothermal/photodynamic therapeutic effect on HCT116 tumor cell is successfully achieved. The results offer considerable promise for the development of COF nanomotors with integrated imaging/therapy modalities in biomedical applications.

Development and validation of a robot social presence measurement dimension scale.

Robots that can exhibit human-like behaviour, build social relationships with humans, and carry out social interaction that can be considered to have a social presence. Measuring the social presence of robots can provide an important basis for optimizing the design of robots' human-like behaviour, but until now, there has been no research and discussion on the presence of robots from the perspective of social interaction. Based on related studies, such as the theory of the presence of interpersonal interaction society, the mechanism of network social presence measurement and human-computer interaction, this study constructs a theoretical model of robot social presence, and develops corresponding measurement scales with five dimensions, namely, the presence, attention distribution, interactive expression and information understanding, perceived emotional interdependence, and interaction behaviour perception. The 5-dimensional robot social presence model was finalized, and a 17-question questionnaire scale was developed. The validation of the model and the development of the scale includes one expert assessment (involving three experts), one user interview (involving five interviewees), and two questionnaire surveys (involving 172 valid questionnaires and 494 valid questionnaires respectively). The final model shows good reliability of the measurement questionnaire, high inter-factor correlation, high model fit, high internal consistency of the dimensions, high reliability of the scale, and high convergent validity of all dimensions. This study provides a theoretical basis for the study of robot social presence and human-robot collaboration and provides a reference measurement tool for social robot-related development and research.

Prevalence and risk prediction value of tricuspid regurgitation by echocardiography in precapillary pulmonary hypertension.

BACKGROUND: In precapillary pulmonary hypertension (PH), the incidence of different tricuspid regurgitation (TR) degree is poorly defined. The impact of TR severity on pulmonary artery pressure (PAP) assessment and clinical risk stratification in precapillary PH remains unclear. METHODS: A total of 207 patients diagnosed precapillary PH who underwent right heart catheterization (RHC) and echocardiography within 3 days were included. The severity of TR was graded as trace, mild, moderate and severe. Pearson correlation analysis was performed to evaluate the correlation between systolic PAP by echocardiography (sPAPECHO) and mean PAP by RHC (mPAPRHC) in different TR degree groups. The impact factors on risk stratification of precapillary PH were analyzed by logistic regression analysis. RESULTS: The proportion of None, Trace, Mild, Moderate and Severe TR group was 2.4%, 23.7%, 39.1%, 28.5% and 6.3% respectively. Right atrium (RA) area increased gradually with TR aggravation (p < 0.001). Moderate and Severe TR group had higher N-terminal pro-B-type natriuretic peptide (p < 0.001), right atrial pressure (RAP) (p = 0.018), right ventricular basal diameter (RVD)/left ventricular basal diameter (LVD) ratio (p < 0.001), larger right ventricle (RV) (p < 0.001) and lower tricuspid annular plane systolic excursion (p = 0.006) compared with Trace and Mild group. TR-sPAPECHO in Moderate TR group had the greatest correlation coefficient with mPAPRHC (0.742, p < 0.001) followed by Mild (0.635, p < 0.001) and severe group (0.592, p = 0.033), while there was no correlation in Trace TR group (0.308, p = 0.076). Multivariate logistic regression showed three significant independent echocardiography predictors of high-risk precapillary PH: RVD/LVD ratio (OR = 5.734; 95%CI1.502-21.889, p = 0.011), RA area (OR 1.054; 95% CI 1.004-1.107, p = 0.035) and systolic annular tissue velocity of the lateral tricuspid annulus (S') (OR 0.735, 95% CI 0.569-0.949, p = 0.018). CONCLUSIONS: Precapillary PH was not necessarily accompanied by significant TR. None or Trace TRaccounted for 26% in our population and TR-sPAPECHO was not applicable to estimate PAP in these patients. RVD/LVD ratio, RA area and S' can independently predict the high-risk patients with precapillary PH. TR may play an indirect role in risk stratification by affecting these indicators.

Proteomic characteristics of plasma and blood cells in natural aging rhesus monkeys.

Aging has become a serious social issue that places a heavy burden on society. However, the underlying mechanisms of aging remain unclear. This study sought to understand the aging process as it may be affected by proteins in the blood, the most important functional system for material transportation in the body. We analyzed and compared the protein expression spectrums in the blood of old and young rhesus monkeys and found 257 proteins expressed differentially in plasma and 1183 proteins expressed differentially in blood cells. Through bioinformatics analysis, we found that the differentially-expressed proteins in plasma were involved in signal pathways related to complement and coagulation cascades, pertussis, malaria, phagosome, and cholesterol metabolism, while the differentially-expressed proteins in blood cells were involved in endocytosis, proteasome, ribosome, protein processing in the endoplasmic reticulum, and Parkinson's disease. We confirmed that the protein levels of complement C2 in plasma and actin-related protein 2/3 complex subunit 2 (ARPC2) in blood cells obviously decreased, whereas the complement C3 and complement component 4 binding protein beta (C4BPB) significantly increased in plasma of old rhesus monkeys and C57BL/6 mice. Our results suggest that C2, C3, C4BPB, and ARPC2 can be used as target proteins for anti-aging research.

Longitudinal single-cell transcriptomics reveals distinct patterns of recurrence in acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous and aggressive blood cancer that results from diverse genetic aberrations in the hematopoietic stem or progenitor cells (HSPCs) leading to the expansion of blasts in the hematopoietic system. The heterogeneity and evolution of cancer blasts can render therapeutic interventions ineffective in a yet poorly understood patient-specific manner. In this study, we investigated the clonal heterogeneity of diagnosis (Dx) and relapse (Re) pairs at genetic and transcriptional levels, and unveiled the underlying pathways and genes contributing to recurrence. METHODS: Whole-exome sequencing was used to detect somatic mutations and large copy number variations (CNVs). Single cell RNA-seq was performed to investigate the clonal heterogeneity between Dx-Re pairs and amongst patients. RESULTS: scRNA-seq analysis revealed extensive expression differences between patients and Dx-Re pairs, even for those with the same -presumed- initiating events. Transcriptional differences between and within patients are associated with clonal composition and evolution, with the most striking differences in patients that gained large-scale copy number variations at relapse. These differences appear to have significant molecular implications, exemplified by a DNMT3A/FLT3-ITD patient where the leukemia switched from an AP-1 regulated clone at Dx to a mTOR signaling driven clone at Re. The two distinct AML1-ETO pairs share genes related to hematopoietic stem cell maintenance and cell migration suggesting that the Re leukemic stem cell-like (LSC-like) cells evolved from the Dx cells. CONCLUSIONS: In summary, the single cell RNA data underpinned the tumor heterogeneity not only amongst patient blasts with similar initiating mutations but also between each Dx-Re pair. Our results suggest alternatively and currently unappreciated and unexplored mechanisms leading to therapeutic resistance and AML recurrence.

A simpler noninvasive method of predicting markedly elevated pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension.

Several echocardiographic methods to estimate pulmonary vascular resistance (PVR) have been proposed. So far, most studies have focused on relatively low PVR in patients with a nonspecific type of pulmonary hypertension. We aimed to clarify the clinical usefulness of a new echocardiographic index for evaluating markedly elevated PVR in chronic thromboembolic pulmonary hypertension (CTEPH). We studied 127 CTEPH patients. We estimated the systolic and mean pulmonary artery pressure using echocardiography (sPAPEcho, mPAPEcho) and measured the left ventricular internal diameter at end diastole (LVIDd). sPAPEcho/LVIDd and mPAPEcho/LVIDd were then correlated with invasive PVR. Using receiver operating characteristic curve analysis, a cutoff value for the index was generated to identify patients with PVR > 1000 dyn·s·cm-5. We analyzed pre- and postoperative hemodynamics and echocardiographic data in 49 patients who underwent pulmonary endarterectomy (PEA). In this study, mPAPEcho/LVIDd moderately correlated with PVR (r = 0.51, p < 0.0001). There was a better correlation between PVR and sPAPEcho/LVIDd (r = 0.61, p < 0.0001). sPAPEcho/LVIDd ≥ 1.94 had an 77.1% sensitivity and 75.4% specificity to determine PVR > 1000 dyn·s·cm-5 (area under curve = 0.804, p < 0.0001, 95% confidence interval [CI], 0.66-0.90). DeLong's method showed there was a statistically significant difference between sPAPEcho/LVIDd with tricuspid regurgitation velocity2/velocity-time integral of the right ventricular outflow tract (difference between areas 0.14, 95% CI, 0.00-0.27). The sPAPEcho/LVIDd and mPAPEcho/LVIDd significantly decreased after PEA (both p < 0.0001). The sPAPEcho/LVIDd and mPAPEcho/LVIDd reduction rate (ΔsPAPEcho/LVIDd and ΔmPAPEcho/LVIDd) was significantly correlated with PVR reduction rate (ΔPVR), respectively (r = 0.58, p < 0.01; r = 0.69, p < 0.05). In conclusion, the index of sPAPEcho/LVIDd could be a simpler and reliable method in estimating CTEPH with markedly elevated PVR and also be a convenient method of estimating PVR both before and after PEA.

The accuracy and influencing factors of Doppler echocardiography in estimating pulmonary artery systolic pressure: comparison with right heart catheterization: a retrospective cross-sectional study.

BACKGROUND: Noninvasive assessment of pulmonary artery systolic pressure by Doppler echocardiography (sPAPECHO) has been widely adopted to screen for pulmonary hypertension (PH), but there is still a high proportion of overestimation or underestimation of sPAPECHO. We therefore aimed to explore the accuracy and influencing factors of sPAPECHO with right heart catheterization (RHC) as a reference. METHODS: A total of 218 highly suspected PH patients who underwent RHC and echocardiography within 7 days were included. The correlation and consistency between tricuspid regurgitation (TR)-related methods and RHC results were tested by Pearson and Bland-Altman methods. TR-related methods included peak velocity of TR (TR Vmax), TR pressure gradient (TR-PG), TR mean pressure gradient (TR-mPG), estimated mean pulmonary artery pressure (mPAPECHO), and sPAPECHO. With mPAP ≥ 25 mm Hg measured by RHC as the standard diagnostic criterion of PH, the ROC curve was used to compare the diagnostic efficacy of sPAPECHO with other TR-derived parameters. The ratio (sPAPECHO-sPAPRHC)/sPAPRHC was calculated and divided into three groups as follows: patients with an estimation error between - 10% and + 10% were defined as the accurate group; patients with an estimated difference greater than + 10% were classified as the overestimated group; and patients with an estimation error greater than - 10% were classified as the underestimated group. The influencing factors of sPAPECHO were analyzed by ordinal regression analysis. RESULTS: sPAPECHO had the highest correlation coefficient (r = 0.781, P < 0.001), best diagnostic efficiency (AUC = 0.98), and lowest bias (mean bias = 0.07 mm Hg; 95% limits of agreement, - 32.08 to + 32.22 mm Hg) compared with other TR-related methods. Ordinal regression analysis showed that TR signal quality, sPAPRHC level, and pulmonary artery wedge pressure (PAWP) affected the accuracy of sPAPECHO (P < 0.05). Relative to the good signal quality, the OR values of medium and poor signal quality were 0.26 (95% CI: 0.14, 0.48) and 0.23 (95% CI: 0.07, 0.73), respectively. Compared with high sPAPRHC level, the OR values of low and medium sPAPRHC levels were 21.56 (95% CI: 9.57, 48.55) and 5.13 (95% CI: 2.55, 10.32), respectively. The OR value of PAWP was 0.94 (95% CI: 0.89, 0.99). TR severity and right ventricular systolic function had no significant effect on the accuracy of sPAPECHO. CONCLUSIONS: In this study, we found that all TR-related methods, including sPAPECHO, had comparable and good efficiency in PH screening. To make the assessment of sPAPECHO more accurate, attention should be paid to TR signal quality, sPAPRHC level, and PAWP.

Single-Cell Profiling Reveals Heterogeneity of Primary and Lymph Node Metastatic Tumors and Immune Cell Populations and Discovers Important Prognostic Significance of CCDC43 in Oral Squamous Cell Carcinoma.

Although substantial progress has been made in biological research and clinical treatment in recent years, the clinical prognosis of oral squamous cell carcinoma (OSCC) is still not satisfactory. Tumor immune microenvironment (TIME) is a potential target, which plays an essential role in the response of anti-tumor immunity and immunotherapy. In this study, we used scRNA-seq data, revealing the heterogeneity of TIME between metastatic and primary site. We found that in the metastatic site, the content of cytotoxic T cells and classical activated macrophages (M1 macrophages) increases significantly, while alternately activated macrophages (M2 macrophages) and inflammatory cancer-associated fibroblasts (iCAFs) decrease, which may be due to the increased immunogenicity of OSCC cells in the metastatic site and the changes in some signal pathways. We also found that iCAFs may recruit alternately activated macrophages (M2 macrophages) by secreting CXCL12. Then, we described a regulatory network for communication between various TIME cells centered on OSCC cells, which can help to clarify the possible mechanism of lymph node metastasis in OSCC cells. By performing pseudotime trajectory analysis, we found that the expression CCDC43 is upregulated in more advanced OSCC cells and is an independent prognostic factor for poor living conditions. Other than this, the high expression of CCDC43 may impair the antitumor immunity of the human body and promote the metastasis of OSCC cells. Our research provides a profound insight into the immunological study of OSCC and an essential resource for future drug discovery.

New Bioactive Sesquiterpeniods From the Plant Endophytic Fungus Pestalotiopsis theae.

Three new secondary metabolites pestalothenins A-C (1-3), including two new humulane-derived sesquiterpeniods (1 and 2) and one new caryophyllene-derived sesquiterpeniod (3), together with five known compounds (4-8) were isolated from the crude extract of the plant endophytic fungus Pestalotiopsis theae (N635). Their structures were elucidated by the extensive analyses of HRESIMS and NMR spectroscopic data. The absolute configurations of 1-3 were determined by comparison of experimental and calculated electronic circular dichroism (ECD) spectra. The cytotoxic effects of these compounds were evaluated in vitro. Compound 6 showed moderate cytotoxicity against T24 and MCF7 cell lines. In addition, compounds 1-8 were also evaluated for antibacterial activity.

Diagnostic role of 18F-FDG PET/MRI in the TNM staging of breast cancer: a systematic review and meta-analysis.

BACKGROUND: To investigate the value of 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) in diagnosing local tumor invasion (T stage), evaluating regional lymph node involvement (N stage), and detecting distant metastasis (M stage) in breast cancer patients. METHODS: A comprehensive computer search and manual search were performed to select any potentially eligible studies that evaluated the diagnostic efficacy of 18F-FDG PET/MRI in the tumor-node-metastasis (TNM) staging of breast cancer. Data from the included studies were extracted to calculate the pooled sensitivity, specificity, and area under the curve (AUC) to evaluate the value of 18F-FDG PET/MRI in TNM staging. Quality and publication bias were also assessed in this meta-analysis. RESULTS: Based on seven studies, the pooled sensitivity, specificity and AUC for the diagnosis of T stage were 91% (95% CI: 84-96%), 91% (95% CI: 81-96%), and 0.96 (95% CI: 0.94-0.98), respectively. For N stage evaluation, four studies were included, with values of 94% (95% CI: 83-98%), 90% (95% CI: 81-95%), and 0.96 (95% CI: 0.94-0.97). For M stage detection, five studies were evaluated, with values of 98% (95% CI: 96-99%), 96% (95% CI: 83-99%), and 0.99 (95% CI: 0.98-1.00). CONCLUSIONS: 18F-FDG PET/MRI demonstrates higher diagnostic value in the TNM staging of breast cancer and can serve as an effective and promising imaging biomarker for future evaluation of TNM stage in breast cancer patients.

Chest CT findings in patients with coronavirus disease 2019 (COVID-19): a comprehensive review.

The objective of this review was to summarize the most pertinent CT imaging findings in patients with coronavirus disease 2019 (COVID-19). A literature search retrieved eligible studies in PubMed, EMBASE, Cochrane Library and Web of Science up to June 1, 2020. A comprehensive review of publications of the Chinese Medical Association about COVID-19 was also performed. A total of 84 articles with more than 5340 participants were included and reviewed. Chest CT comprised 92.61% of abnormal CT findings overall. Compared with real-time polymerase chain reaction result, CT findings has a sensitivity of 96.14% but a low specificity of 40.48% in diagnosing COVID-19. Ground glass opacity (GGO), pure (57.31%) or mixed with consolidation (41.51%) were the most common CT features with a majority of bilateral (80.32%) and peripheral (66.21%) lung involvement. The opacity might associate with other imaging features, including air bronchogram (41.07%), vascular enlargement (54.33%), bronchial wall thickening (19.12%), crazy-paving pattern (27.55%), interlobular septal thickening (42.48%), halo sign (25.48%), reverse halo sign (12.29%), bronchiectasis (32.44%), and pulmonary fibrosis (26.22%). Other accompanying signs including pleural effusion, lymphadenopathy and pericardial effusion were rare, but pleural thickening was common. The younger or early stage patients tended to have more GGOs, while extensive/multilobar involvement with consolidation was prevalent in the older or severe population. Children with COVID-19 showed significantly lower incidences of some ancillary findings than those of adults and showed a better performance on CT during follow up. Follow-up CT showed GGO lesions gradually decreased, and the consolidation lesions first increased and then remained relatively stable at 6-13 days, and then absorbed and fibrosis increased after 14 days. Chest CT imaging is an important component in the diagnosis, staging, disease progression and follow-up of patients with COVID-19.

STARR-seq identifies active, chromatin-masked, and dormant enhancers in pluripotent mouse embryonic stem cells.

BACKGROUND: Enhancers are distal regulators of gene expression that shape cell identity and control cell fate transitions. In mouse embryonic stem cells (mESCs), the pluripotency network is maintained by the function of a complex network of enhancers, that are drastically altered upon differentiation. Genome-wide chromatin accessibility and histone modification assays are commonly used as a proxy for identifying putative enhancers and for describing their activity levels and dynamics. RESULTS: Here, we applied STARR-seq, a genome-wide plasmid-based assay, as a read-out for the enhancer landscape in "ground-state" (2i+LIF; 2iL) and "metastable" (serum+LIF; SL) mESCs. This analysis reveals that active STARR-seq loci show modest overlap with enhancer locations derived from peak calling of ChIP-seq libraries for common enhancer marks. We unveil ZIC3-bound loci with significant STARR-seq activity in SL-ESCs. Knock-out of Zic3 removes STARR-seq activity only in SL-ESCs and increases their propensity to differentiate towards the endodermal fate. STARR-seq also reveals enhancers that are not accessible, masked by a repressive chromatin signature. We describe a class of dormant, p53 bound enhancers that gain H3K27ac under specific conditions, such as after treatment with Nocodazol, or transiently during reprogramming from fibroblasts to pluripotency. CONCLUSIONS: In conclusion, loci identified as active by STARR-seq often overlap with those identified by chromatin accessibility and active epigenetic marking, yet a significant fraction is epigenetically repressed or display condition-specific enhancer activity.

Regional right ventricular longitudinal systolic strain for detection of severely impaired right ventricular performance in pulmonary hypertension.

OBJECTIVES: Right ventricular (RV) function is identified as a key determinant of the outcome in patients with pulmonary hypertension (PH). Several studies have assessed the role of peak global longitudinal RV strain in PH patients; however, less emphasis was given to the RV regional longitudinal strain. The aim of this study was to evaluate the regional RV systolic strain in PH patients and investigate the relationship of these parameters with the severity of PH. METHODS: RV regional longitudinal peak systolic strain (LPSS) and strain rate (LPSSR) were measured using speckle tracking echocardiography on 100 patients with PH who underwent right heart catheterization, and 29 control subjects. Severe PH was identified by a decreased cardiac index (CI) (<2.0 L/min/m2 ). RESULTS: LPSS and LPSSR of the RV free wall were significantly lower in PH patients than control subjects, especially when comparing the basal and mid regions (P < .001). When comparing severe PH and nonsevere PH, basal and mid LPSS and LPSSR were significantly lower (P < .001). RV free wall mid LPSSR correlated with CI (r = -.703, P < .001). In the multiple logistic regression analysis, mid LPSSR was identified as an independent predictor of severe PH (odds ratio 1.82; 95% confidential interval 1.39-2.40; P < .001). In the receiver operating characteristics curve analysis, a cutoff value of mid LPSSR of -0.92 s-1 predicted severe PH, with a sensitivity and specificity of 75.0% and 93.7%, respectively (AUC = 0.889, P < .001). CONCLUSIONS: RV free wall mid longitudinal peak systolic strain rate may be useful for the detection of severely impaired RV performance in PH.

Whole-Liver Apparent Diffusion Coefficient Histogram Analysis for the Diagnosis and Staging of Liver Fibrosis.

BACKGROUND: Conventional diffusion-weighted imaging is limited in the quantitative evaluation of liver fibrosis, and whole-liver apparent diffusion coefficient (ADC) histogram analysis might contribute to the diagnosis and staging of liver fibrosis. PURPOSE: To explore the value of whole-liver ADC histogram parameters in the diagnosis and staging of liver fibrosis. STUDY TYPE: Retrospective. POPULATION: Twenty individuals with no liver disease and 86 patients with liver fibrosis, including 30 with chronic viral hepatitis, 29 with autoimmune hepatitis, and 27 with unexplained liver fibrosis patients. FIELD STRENGTH/SEQUENCE: 3.0T/T1 -weighted, T2 -weighted, and diffusion-weighted images. ASSESSMENT: A region of interest (ROI) was drawn in each slice of the diffusion-weighted images. Whole-liver histogram parameters were obtained with dedicated software by accumulating all ROIs. The effectiveness of the parameters in differentiating stage 1 or greater (≥F1), stage 2 or greater (≥F2), and stage 3 or greater (≥F3) liver fibrosis was assessed. STATISTICAL TESTS: Mann-Whitney U-test and receiver operating characteristic curve analysis. RESULTS: Kurtosis, entropy, skewness, mode, and 90th and 75th percentiles exhibited significant differences among the pathological fibrosis stages (P < 0.05). Kurtosis was found to be the most meaningful parameter in differentiating fibrosis stages of the viral hepatitis, autoimmune hepatitis, and unexplained liver fibrosis group (area under the curve) (AUC = 0.793, 0.771, 0.798, respectively). In the combined liver fibrosis group, kurtosis achieved the highest AUC (0.801; 95% confidence interval [CI]: 0.702-0.900; sensitivity: 0.750; specificity: 0.850; positive likelihood ratio: 4.953; negative likelihood ratio: 0.302; positive predictive value: 0.946; negative predictive value: 0.486), with a cutoff value of 1.817, in differentiating fibrosis stage ≥F1. DATA CONCLUSION: Kurtosis, entropy, skewness, mode, and 90th and 75th percentiles may contribute to the diagnosis and staging of liver fibrosis, especially kurtosis. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1745-1754.