CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function.

CTCF and the associated cohesin complex play a central role in insulator function and higher-order chromatin organization of mammalian genomes. Recent studies identified a correlation between the orientation of CTCF-binding sites (CBSs) and chromatin loops. To test the functional significance of this observation, we combined CRISPR/Cas9-based genomic-DNA-fragment editing with chromosome-conformation-capture experiments to show that the location and relative orientations of CBSs determine the specificity of long-range chromatin looping in mammalian genomes, using protocadherin (Pcdh) and ß-globin as model genes. Inversion of CBS elements within the Pcdh enhancer reconfigures the topology of chromatin loops between the distal enhancer and target promoters and alters gene-expression patterns. Thus, although enhancers can function in an orientation-independent manner in reporter assays, in the native chromosome context, the orientation of at least some enhancers carrying CBSs can determine both the architecture of topological chromatin domains and enhancer/promoter specificity. These findings reveal how 3D chromosome architecture can be encoded by linear genome sequences.

Predicting high-risk pre-capillary pulmonary hypertension: an echocardiographic multiparameter scoring index.

BACKGROUND: The risk stratification of pulmonary arterial hypertension proposed by the European Society of Cardiology /European Respiratory Society guidelines in 2015 and 2022 included two to three echocardiographic indicators. However, the specific value of echocardiography in risk stratification of pre-capillary pulmonary hypertension (pcPH) has not been efficiently demonstrated. Given the complex geometry of the right ventricular (RV) and influencing factors of echocardiographic parameter, there is no single echocardiographic parameter that reliably informs about PH status. We hypothesize that a multi-parameter comprehensive index can more accurately evaluate the severity of the pcPH. The purpose of this study was to develop and validate an echocardiographic risk score model to better assist clinical identifying high risk of pcPH during initial diagnosis and follow-up. METHODS: We studied 197 consecutive patients with pcPH. A multivariable echocardiographic model was constructed to predict the high risk of pcPH in the training set. Points were assigned to significant risk factors in the final model based on ß-coefficients. We validated the model internally and externally. RESULTS: The echocardiographic score was constructed by multivariable logistic regression, which showed that pericardial effusion, right atrial (RA) area, RV outflow tract proximal diameter (RVOT-Prox), the velocity time integral of the right ventricular outflow tract (TVIRVOT) and S' were predictors of high risk of pcPH. The area under curve (AUC) of the training set of the scoring model was 0.882 (95%CI: 0.809-0.956, p < 0.0001). External validation was tested in a test dataset of 77 patients. The AUC of the external validation set was 0.852. A 10-point score risk score was generated, with scores ranging from 0 to 10 in the training cohort. The estimate risk of high risk of pcPH ranged from 25.1 to 94.6%. CONCLUSIONS: The echocardiographic risk score using five echocardiographic parameters could be comprehensive and useful to predict the high risk of pcPH for initial assessment and follow-up.

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.

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.

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.

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.

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.

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.

Identification of the gene cluster for bistropolone-humulene meroterpenoid biosynthesis in Phoma sp.

Eupenifeldin, a bistropolone meroterpenoid, was first discovered as an antitumor agent from the fungus Eupenicillium brefeldianum. We also isolated this compound and a new congener from a strain of Phoma sp. (CGMCC 10481), and evaluated their antitumor effects. Eupenifeldin showed potent in vitro anti-glioma activity. This tropolone-humulene-tropolone meroterpenoid could be originated from two units of tropolone orthoquinone methides and a 10-hydroxyhumulene moiety via hetero-Diels-Alder reactions. To explore the biosynthesis of this class of tropolonic sesquiterpenes, the genome of a eupenifeldin-producing Phoma sp. was sequenced and analyzed. The biosynthetic gene cluster of eupenifeldin (eup) was identified and partially validated by genomic analysis, gene disruption, and product analysis. A nonreducing polyketide synthase EupA, a FAD-dependent monooxygenase EupB, and a non-heme Fe (II)-dependent dioxygenase EupC, were identified as the enzymes responsible for tropolone formation. While the terpene cyclase EupE of an unknown family was characterized to catalyze humulene formation, and a cytochrome P450 enzyme EupD was responsible for hydroxylation of humulene. This study sheds light on the biosynthesis of eupenifeldin, and paves the way to further decipher its biosynthetic pathway.

Characterization of a cluster of CTCF-binding sites in a protocadherin regulatory region.

The mammalian clustered protocadherin (Pcdh) locus contains more than 50 highly-similar genes arrayed in tandem. These Pcdh genes are organized into three closely-linked clusters (Pcdhα, Pcdhß, and Pcdhγ). The encoded PCDH proteins play critical roles in neuronal diversity, single cell identity, and synaptic connectivity. Recent studies revealed that directional CTCF (CCCTC-binding factor) binding to CBS (CTCF-binding site) determines the specific interaction between enhancers and promoters, and the three Pcdhßγ clusters form two CCDs (CTCF/cohesin- mediated chromatin domain) which is important for gene regulation. Here, we characterized a regulatory region, which contains several HSs (DNase I hypersensitive sites), downstream of the Pcdhß clusters. Specifically, CTCF ChIP-Seq (Chromatin immunoprecipitation-sequencing) experiments revealed several peaks in the Pcdhßγ regulatory regions. In addition, we performed comprehensive EMSA (Electrophoresis mobility shift assay) experiments and identified exact 42-bp CBS sites for each CTCF peak. Interestingly, we found that single CTCF peaks can contain two CBS sites. Finally, genome-wide computational analyses revealed many CBS sites close to chromatin marks of regulatory elements, such as enhancers and promoters. We propose that CTCF may mediate specific interactions between enhancers and promoters to form active transcription hub for gene expression.

Arabidopsis thaliana defense response to the ochratoxin A-producing strain (Aspergillus ochraceus 3.4412).

KEY MESSAGE: OTA-producing strain Aspergillus ochraceus induced necrotic lesions, ROS accumulation and defense responses in Arabidopsis . Primary metabolic and defense-related proteins changed in proteomics. Ascorbate-glutathione cycle and voltage-dependent anion-selective channel proteins fluctuated. Mycotoxigenic fungi, as widespread contaminants by synthesizing mycotoxins in pre-/post-harvest infected plants and even stored commercial cereals, could usually induce plant-fungi defense responses. Notably, ochratoxin A (OTA) is a nephrotoxic, hepatotoxic, teratogenic, immunotoxic and phytotoxic mycotoxin. Herein, defense responses of model system Arabidopsis thaliana detached leaves to infection of Aspergillus ochraceus 3.4412, an OTA high-producing strain, were studied from physiological, proteomic and transcriptional perspectives. During the first 72 h after inoculation (hai), the newly formed hypersensitive responses-like lesions, decreased chlorophyll content, accumulated reactive oxygen species and upregulated defense genes expressions indicated the defense response was induced in the leaves with the possible earlier motivated jasmonic acid/ethylene signaling pathways and the later salicylic acid-related pathway. Moreover, proteomics using two-dimensional gel electrophoresis 72 hai showed 16 spots with significantly changed abundance and 13 spots corresponding to 12 unique proteins were successfully identified by MALDI-TOF/TOF MS/MS. Of these, six proteins were involved in basic metabolism and four in defense-related processes, which included glutathione-S-transferase F7, voltage-dependent anion-selective channel protein 3 (VDAC-3), osmotin-like protein OSM34 and blue copper-binding protein. Verified from proteomic and/or transcriptional perspectives, it is concluded that the primary metabolic pathways were suppressed with the ascorbate-glutathione cycle fluctuated in response to A. ochraceus and the modulation of VDACs suggested the possibility of structural damage and dysfunction of mitochondria in the process. Taken together, these findings exhibited a dynamic overview of the defense responses of A. thaliana to A. ochraceus and provided a better insight into the pathogen-resistance mechanisms in plants.

Incidences of aortic and mitral valve strands in patients with migraine with aura.

OBJECTIVE: To analyze the potential association between valvular strands and migraine with aura. METHODS: During a 1-year period,transesophageal echocardiography was performed in 51 consecutive patients with migraine with aura and 75 control subjects who underwent transesophageal echocardiography for other purposes and had no history of migraine. The presence of aortic and mitral valve strands was evaluated. RESULTS: The incidence of valvular strands was 21.5% (11/51) in migraine patients and 28.0% (21/75) in control subjects (Χ²=0.663, P=0.416). The incidence of patent foramen ovale was significantly higher in patients with migraine with aura than in control subjects (50.9% vs.29.3%) (Χ²=6.302, P=0.012). The incidence of aortic valve strands was significantly higher than that of mitral valve strands in migraine patients (Χ²=4.320,P=0.038). CONCLUSION: Valvular strands are not associated with migraine with aura and show little clinical significance.

Which technique is better for detection of right-to-left shunt in patients with patent foramen ovale: comparing contrast transthoracic echocardiography with contrast transesophageal echocardiography.

BACKGROUND: At present there is no consensus on which technique is more suitable for the detection of right-to-left shunt (RLS) in patients with patent foramen ovale (PFO). The aim of study was to compare the efficacy of contrast transthoracic echocardiography (cTTE) and contrast transesophageal echocardiography (cTEE) in the detection of RLS. METHODS: A prospective study was undertaken in 29 patients with PFO. Both cTTE with harmonic imaging modality and cTEE with fundamental imaging modality were performed for all the patients. The severity of RLS were semiquantitatively assessed with a four-level grade system by scaling the numbers of microbubbles (MBs) in the left atrium after complete opacification of the right atrium within the first 3 cardiac cycles. Level 1 represents no MBs, indicating no RLS. Level 2, ≤10 MBs, indicating mild RLS. Level 3, 11-30 MBs, indicating moderate RLS and Level 4, >30 MBs, indicating severe RLS. RESULTS: Contrast TTE demonstrated significantly higher sensitivity for detection of RLS than cTEE (86% vs. 56%, P < 0.05). For cTTE, there were 4, 1, 5, and 19 cases determined at levels 1, 2, 3, and 4, respectively, whereas for the same group of patients 13, 2, 6, and 7 cases were identified by cTEE at levels 1, 2, 3, and 4, respectively. The severity of RLS detected by cTTE was significantly greater than that by cTEE (P < 0.01). CONCLUSIONS: Contrast TTE is more efficacious in the detection of RLS than cTEE. The former can be used as an alternative to the latter in clinical practice.

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.

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.

Dual time point 18FDG-PET/CT versus single time point 18FDG-PET/CT for the differential diagnosis of pulmonary nodules: a meta-analysis.

BACKGROUND: Lung cancer is one of the most common cancer types in the world. An accurate diagnosis of lung cancer is crucial for early treatment and management. PURPOSE: To perform a comprehensive meta-analysis to evaluate the diagnostic performance of dual time point 18F-fluorodexyglucose position emission tomography/computed tomography (FDG-PET/CT) and single time point 18FDG-PET/CT in the diagnosis of pulmonary nodules. MATERIAL AND METHODS: PubMed (1966-2011.11), EMBASE (1974-2011.11), Web of Science (1972-2011.11), Cochrane Library (-2011.11), and four Chinese databases - CBM (1978-2011.11), CNKI (1994-2011.11), VIP (1989-2011.11), and Wanfang Database (1994-2011.11) - were searched. Summary sensitivity, summary specificity, summary diagnostic odds ratios (DOR), and summary positive likelihood ratios (LR+) and negative likelihood ratios (LR-) were obtained using Meta-Disc software. Summary receiver-operating characteristic (SROC) curves were used to evaluate the diagnostic performance of dual time point 18FDG-PET/CT and single time point 18FDG-PET/CT. RESULTS: The inclusion criteria were fulfilled by eight articles, with a total of 415 patients and 430 pulmonary nodules. Compared with the gold standard (pathology or clinical follow-up), the summary sensitivity of dual time point 18FDG-PET/CT was 79% (95%CI, 74.0-84.0%), and its summary specificity was 73% (95%CI, 65.0-79.0%); the summary LR+ was 2.61 (95%CI, 1.96-3.47), and the summary LR- was 0.29 (95%CI, 0.21-0.41); the summary DOR was 10.25 (95%CI, 5.79-18.14), and the area under the SROC curve (AUC) was 0.8244. The summary sensitivity for single time point 18FDG-PET/CT was 77% (95%CI, 71.9-82.3%), and its summary specificity was 59% (95%CI, 50.6-66.2%); the summary LR+ was 1.97 (95%CI, 1.32-2.93), and the summary LR- was 0.37 (95%CI, 0.29-0.49); the summary DOR was 6.39 (95%CI, 3.39-12.05), and the AUC was 0.8220. CONCLUSION: The results indicate that dual time point 18FDG-PET/CT and single time point 18FDG-PET/CT have similar accuracy in the differential diagnosis of pulmonary nodules. Dual time point 18FDG-PET/CT appears to be more specific than single time point 18FDG-PET/CT.

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.

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.