circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC).

BACKGROUND: Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC. METHODS: Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis. RESULTS: The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance. CONCLUSIONS: Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance.

Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

Computed tomography-determined skeletal muscle density predicts 3-year mortality in initial-dialysis patients in China.

BACKGROUND: Skeletal muscle mass and quality assessed by computed tomography (CT) images of the third lumbar vertebra (L3) level have been established as risk factors for poor clinical outcomes in several illnesses, but the relevance for dialysis patients is unclear. A few studies have suggested a correlation between CT-determined skeletal muscle mass and quality at the first lumbar vertebra (L1) level and adverse outcomes. Generally, chest CT does not reach beyond L1. We aimed to determine whether opportunistic CT scan (chest CT)-determined skeletal muscle mass and quality at L1 are associated with mortality in initial-dialysis patients. METHODS: This 3-year multicentric retrospective study included initial-dialysis patients from four centres between 2014 and 2017 in China. Unenhanced CT images of the L1 and L3 levels were obtained to assess skeletal muscle mass [by skeletal muscle index, (SMI), cm2 /m2 ] and quality [by skeletal muscle density (SMD), HU]. Skeletal muscle measures at L1 were compared with those at L3. The sex-specific optimal cutoff values of L1 SMI and L1 SMD were determined in relation to all-cause mortality. The outcomes were all-cause death and cardiac death. Cox regression models were applied to investigate the risk factors for death. RESULTS: A total of 485 patients were enrolled, of whom 257 had both L1 and L3 images. Pearson's correlation coefficient between L1 and L3 SMI was 0.84 (P < 0.001), and that between L1 and L3 SMD was 0.90 (P < 0.001). No significant association between L1 SMI and mortality was observed (P > 0.05). Low L1 SMD (n = 280, 57.73%) was diagnosed based on the optimal cutoff value (<39.56 HU for males and <33.06 HU for females). Multivariate regression analysis revealed that the low L1 SMD group had higher risks of all-cause death (hazard ratio 1.80; 95% confidence interval 1.05-3.11, P = 0.034) and cardiac death (hazard ratio 3.74; 95% confidence interval 1.43-9.79, P = 0.007). CONCLUSIONS: In initial-dialysis patients, there is high agreement between the L1 and L3 measures for SMI and SMD. Low SMD measured at L1, but not low SMI, is an independent predictor of both all-cause death and cardiac death.

Fat quantification: Imaging methods and clinical applications in cancer.

Recently, the study of the relationship between lipid metabolism and cancer has evolved. The characteristics of intratumoral and peritumoral fat are distinct and changeable during cancer development. Subcutaneous and visceral adipose tissue are also associated with cancer prognosis. In non-invasive imaging, fat quantification parameters such as controlled attenuation parameter, fat volume fraction, and proton density fat fraction from different imaging methods complement conventional images by providing concrete fat information. Therefore, measuring the changes of fat content for further understanding of cancer characteristics has been applied in both research and clinical settings. In this review, the authors summarize imaging advances in fat quantification and highlight their clinical applications in cancer precaution, auxiliary diagnosis and classification, therapy response monitoring, and prognosis.

circ_rac GTPase-Activating Protein 1 Facilitates Stemness and Metastasis of Non-Small Cell Lung Cancer via Polypyrimidine Tract-Binding Protein 1 Recruitment to Promote Sirtuin-3-Mediated Replication Timing Regulatory Factor 1 Deacetylation.

Circular RNAs have been identified as diagnostic and therapeutic targets for various tumors. The expression of circ_rac GTPase-activating protein 1 (circRACGAP1) is reported to drive the development of non-small cell lung cancer (NSCLC). This study further explored the potential mechanism of circRACGAP1-mediated development of NSCLC. The circRACGAP1 level was detected by quantitative RT-PCR. Sphere formation, CD133-positive cell percentage, and expression of octamer-binding transcription factor 4, Sox2, Nanog, and CD133 were detected to evaluate stemness of NSCLC. Migration and invasion were determined using wound healing and transwell assays. Protein expression was measured using Western blotting. The molecular mechanism was evaluated using RNA pull-down, RNA immunoprecipitation, and coimmunoprecipitation assays. In vivo tumor growth and metastasis were determined in nude mice. circRACGAP1 was highly expressed in NSCLC and was associated with stemness marker Sox2 expression. The stemness, metastasis, and epithelial mesenchymal transformation were repressed in circRACGAP1-depleted NSCLC cells. Mechanistically, circRACGAP1 recruited RNA-binding protein polypyrimidine tract-binding protein 1 to enhance the stability and expression of sirtuin-3 (SIRT3), which subsequently led to replication timing regulatory factor 1 (RIF1) deacetylation and activation of the Wnt/ß-catenin pathway. circRACGAP1 overexpression counteracted SIRT3 or RIF1 knockdown-mediated inhibition in stemness and metastasis of NSCLC cells. The in vivo tumor growth and metastasis were repressed by circRACGAP1 depletion. Patients with NSCLC with a higher serum exosomal circRACGAP1 level had a lower overall survival rate. In conclusion, circRACGAP1 facilitated stemness and metastasis of NSCLC cells through the recruitment of polypyrimidine tract-binding protein 1 to promote SIRT3-mediated RIF1 deacetylation. Our results uncover a novel regulatory mechanism of circRACGAP1 in NSCLC and identify circRACGAP1 as a promising therapeutic target.

High-throughput precision MRI assessment with integrated stack-ensemble deep learning can enhance the preoperative prediction of prostate cancer Gleason grade.

BACKGROUND: To develop and test a Prostate Imaging Stratification Risk (PRISK) tool for precisely assessing the International Society of Urological Pathology Gleason grade (ISUP-GG) of prostate cancer (PCa). METHODS: This study included 1442 patients with prostate biopsy from two centres (training, n = 672; internal test, n = 231 and external test, n = 539). PRISK is designed to classify ISUP-GG 0 (benign), ISUP-GG 1, ISUP-GG 2, ISUP-GG 3 and ISUP GG 4/5. Clinical indicators and high-throughput MRI features of PCa were integrated and modelled with hybrid stacked-ensemble learning algorithms. RESULTS: PRISK achieved a macro area-under-curve of 0.783, 0.798 and 0.762 for the classification of ISUP-GGs in training, internal and external test data. Permitting error ±1 in grading ISUP-GGs, the overall accuracy of PRISK is nearly comparable to invasive biopsy (train: 85.1% vs 88.7%; internal test: 85.1% vs 90.4%; external test: 90.4% vs 94.2%). PSA ≥ 20 ng/ml (odds ratio [OR], 1.58; p = 0.001) and PRISK ≥ GG 3 (OR, 1.45; p = 0.005) were two independent predictors of biochemical recurrence (BCR)-free survival, with a C-index of 0.76 (95% CI, 0.73-0.79) for BCR-free survival prediction. CONCLUSIONS: PRISK might offer a potential alternative to non-invasively assess ISUP-GG of PCa.

PI-RADSAI: introducing a new human-in-the-loop AI model for prostate cancer diagnosis based on MRI.

BACKGROUND: This study aims to develop and validate an artificial intelligence (AI)-aided Prostate Imaging Reporting and Data System (PI-RADSAI) for prostate cancer (PCa) diagnosis based on MRI. METHODS: The deidentified MRI data of 1540 biopsy-naïve patients were collected from four centres. PI-RADSAI is a two-stage, human-in-the-loop AI capable of emulating the diagnostic acumen of subspecialists for PCa on MRI. The first stage uses a UNet-Seg model to detect and segment biopsy-candidate prostate lesions, whereas the second stage leverages UNet-Seg segmentation is trained specifically with subspecialist' knowledge-guided 3D-Resnet to achieve an automatic AI-aided diagnosis for PCa. RESULTS: In the independent test set, UNet-Seg identified 87.2% (628/720) of target lesions, with a Dice score of 44.9% (range, 22.8-60.2%) in segmenting lesion contours. In the ablation experiment, the model trained with the data from three centres was superior (kappa coefficient, 0.716 vs. 0.531) to that trained with single-centre data. In the internal and external tests, the triple-centre PI-RADSAI model achieved an overall agreement of 58.4% (188/322) and 60.1% (92/153) with a referential subspecialist in scoring target lesions; when one-point margin of error was permissible, the agreement rose to 91.3% (294/322) and 97.3% (149/153), respectively. In the paired test, PI-RADSAI outperformed 5/11 (45.5%) and matched the performance of 3/11 (27.3%) general radiologists in achieving a clinically significant PCa diagnosis (area under the curve, internal test, 0.801 vs. 0.770, p < 0.01; external test, 0.833 vs. 0.867, p = 0.309). CONCLUSIONS: Our closed-loop PI-RADSAI outperforms or matches the performance of more than 70% of general readers in the MRI assessment of PCa. This system might provide an alternative to radiologists and offer diagnostic benefits to clinical practice, especially where subspecialist expertise is unavailable.

Visible-Light Photoredox-Catalyzed Decarboxylation of α-Oxo Carboxylic Acids to C1-Deuterated Aldehydes and Aldehydes.

The synthesis of high-value-added C1-deuterated aldehydes would improve the availability of deuterated lead compounds for deuterium-labeled drug discovery. Herein, we develop a metal-free synthesis of C1-deuterated aldehydes with D2O from α-oxo carboxylic acids at ambient temperature. Via visible-light photoredox-catalyzed decarboxylation, stoichiometric reductants and oxidants were avoided. Various functional groups were tolerated and resulted in C1-deuterium aldehydes in up to 92% yield and 91-97% D incorporation under mild conditions. This method is also applied to the synthesis of various aldehydes. Primary mechanistic studies indicate that the catalytic pathway occurs via a reductive quenching pathway followed by hydrogen atom transfer.

Insight into microvascular adaptive alterations in the Glisson system of biliary atresia after Kasai portoenterostomy using X-ray phase-contrast CT.

OBJECTIVES: To investigate microvascular alterations in the Glisson system of biliary atresia (BA) patients after Kasai portoenterostomy (KP) using three-dimensional (3D) virtual histopathology based on X-ray phase-contrast CT (PCCT). METHODS: Liver explants from BA patients were imaged using PCCT, and 32 subjects were included and divided into two groups: KP (n = 16) and non-KP (n = 16). Combined with histological analysis and 3D visualization technology, 3D virtual histopathological assessment of the biliary, arterial, and portal venous systems was performed. According to loop volume ratio, 3D spatial density, relative surface area, tortuosity, and other parameters, pathological changes of microvasculature in the Glisson system were investigated. RESULTS: In the non-KP group, bile ducts mostly manifested as radial multifurcated hyperplasia and twisted into loops. In the KP group, the bile duct hyperplasia was less, and the loop volume ratio of bile ducts decreased by 13.89%. Simultaneously, the arterial and portal venous systems presented adaptive alterations in response to degrees of bile duct hyperplasia. Compared with the non-KP group, the 3D spatial density of arteries in the KP group decreased by 3.53%, and the relative surface area decreased from 0.088 ± 0.035 to 0.039 ± 0.015 (p < .01). Deformed portal branches gradually recovered after KP, with a 2.93% increase in 3D spatial density and a decrease in tortuosity from 1.17 ± 0.06 to 1.14 ± 0.04 (p < .01) compared to the non-KP group. CONCLUSION: 3D virtual histopathology via PCCT clearly reveals the microvascular structures in the Glisson system of BA patients and provides key insights into the morphological mechanism of microvascular adaptation induced by biliary tract dredging after KP in BA disease. KEY POINTS: • 3D virtual histopathology via X-ray phase-contrast computed tomography clearly presented the morphological structures and pathological changes of microvasculature in the Glisson system of biliary atresia patients. • The morphological alterations of microvasculature in the Glisson system followed the competitive occupancy mechanism in the process of biliary atresia.

Preoperative Diagnosis of Dual-Phenotype Hepatocellular Carcinoma Using Enhanced MRI Radiomics Models.

BACKGROUND: Dual-phenotype hepatocellular carcinoma (DPHCC) is highly aggressive and difficult to distinguish from hepatocellular carcinoma (HCC). PURPOSE: To develop and validate clinical and radiomics models based on contrast-enhanced MRI for the preoperative diagnosis of DPHCC. STUDY TYPE: Retrospective. POPULATION: A total of 87 patients with DPHCC and 92 patients with non-DPHCC randomly divided into a training cohort (n = 125: 64 non-DPHCC; 61 DPHCC) and a validation cohort (n = 54: 28 non-DPHCC; 26 DPHCC). FIELD STRENGTH/SEQUENCE: A 3.0 T; dynamic contrast-enhanced MRI with time-resolved T1-weighted imaging sequence. ASSESSMENT: In the clinical model, the maximum tumor diameter and hepatitis B virus (HBV) were independent risk factors of DPHCC. In the radiomics model, a total of 1781 radiomics features were extracted from tumor volumes of interest (VOIs) in the arterial phase (AP) and portal venous phase (PP) images. For feature reduction and selection, Pearson correlation coefficient (PCC) and recursive feature elimination (RFE) were used. Clinical, AP, PP, and combined radiomics models were established using machine learning algorithms (support vector machine [SVM], logistic regression [LR], and logistic regression-least absolute shrinkage and selection operator [LR-LASSO]) and their discriminatory efficacy assessed and compared. STATISTICAL TESTS: The independent sample t test, Mann-Whitney U test, Chi-square test, regression analysis, receiver operating characteristic curve (ROC) analysis, Pearson correlation analysis, the Delong test. A P value < 0.05 was considered statistically significant. RESULTS: In the validation cohort, the combined radiomics model (area under the curve [AUC] = 0.908, 95% confidence interval [CI]: 0.831-0.985) showed the highest diagnostic performance. The AUCs of the PP (AUC = 0.879, 95% CI: 0.779-0.979) and combined radiomics models were significantly higher than that of clinical model (AUC = 0.685, 95% CI: 0.526-0.844). There were no significant differences in AUC between AP or PP radiomics model and combined radiomics model (P = 0.286, 0.180 and 0.543). CONCLUSION: MRI radiomics models may be useful for discriminating DPHCC from non-DPHCC before surgery. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

[The Role of Whole Body DWI in the Evaluation of Bone Disease in Multiple Myeloma].

OBJECTIVE: To explore the characteristics of ADC value changes in DWI of newly diagnosed symptomatic MM patients and its correlation with R-ISS stage. METHODS: The data of 148 newly diagnosed symptomatic MM patients treated by whole-body DWI scan at The First Affiliated Hospital of Soochow University from June 2016 to June 2019 were selected and retrospectively analyzed and 30 cases of age-matched healthy people were selected as controls. The differences of ADC values between the patients in normal control group, DWI- group and DWI+ group were compared, and the relationship between ADC values and R-ISS stage in MM patients was compared. RESULTS: The plasma cell percentage of the patients in DWI+ group was higher than those in DWI- group. ADC values of vertebra, sternum, rib, pectoral girdle, pelvic girdle of the patients in DWI+ group were significantly higher than those in DWI- group and normal control group. The ADC values of each part of the patients in DWI- group were higher than those in normal control group. ADC values of sternum, rib and pectoral girdle in the patients at R-ISS stage III were higher than those at R-ISS stage I and II, while, there was no statistical difference between R-ISS stage I and II groups. And there was no significant difference in ADC values of other bone parts such as vertebra and pelvic girdle in patients at R-ISS stage Ⅰ-Ⅲ. CONCLUSION: DWI+ in MM patients is related to higher tumor invasion. The ADC values of the DWI+ group are higher than those of the DWI- group; the bone ADC values of the DWI- patients are still higher than the normal ones. And there is a certain relationship between ADC value and R-ISS stage.

Hyperprogressive Disease After Immunotherapy: A Case Report of Pulmonary Enteric Adenocarcinoma.

Primary pulmonary enteric adenocarcinoma (PEAC) is a rare invasive adenocarcinoma clinically similar to metastatic colorectal adenocarcinoma (MCRC). Although many studies have addressed the differential diagnosis of PEAC, few have described the treatment of PEAC, especially using immunotherapy. This report describes a 61-year-old man who presented initially with pain in the ribs. Pathological analysis of biopsy samples shows malignant tumors of the right pleura, and next-generation sequencing of 26 genes showed a KRAS gene mutation. Positron emission tomography-computed tomography (PET-CT) found no evidence of gastrointestinal malignancy. Due to multiple metastases, the patient could not undergo radical surgery. The patient was treated with a combination chemotherapy regimen of paclitaxel plus carboplatin, along with sindilizumab immunotherapy, but, after one cycle of treatment, the tumor showed a hyperprogressive state. The patient is still being monitored regularly. These findings indicate that chemotherapy combined with immunotherapy may be ineffective in the treatment of primary PEAC with positive driver genes.

Evaluation of right-to-left shunt on contrast-enhanced transcranial Doppler in patent foramen ovale-related cryptogenic stroke: Research based on imaging.

BACKGROUND: Cardiogenic embolism caused by patent foramen ovale (PFO) is a common etiology of cryptogenic stroke (CS), particularly in young and middle-aged patients. Studies about right-to-left shunt (RLS) detection using contrast-enhanced transcranial Doppler (c-TCD) are numerous. According to the time phase and number of microbubbles detected on c-TCD, RLS can be classified and graded. We hypothesized that the characteristics of an infarction lesion on diffusion-weighted imaging differs when combining the type and grade of RLS on c-TCD in patients with PFO-related CS. AIM: To explore the characteristics of infarction lesions on diffusion-weighted imaging when combining the RLS type and grade determined by c-TCD. METHODS: We retrospectively evaluated CS patients from August 2015 to December 2019 at a tertiary hospital. In total, 111 PFO-related CS patients were divided according to whether RLS was permanent (microbubbles detected both at resting state and after the Valsalva maneuver) or latent (microbubbles detected only after the Valsalva maneuver) on c-TCD. Each group was subdivided into small, mild and large RLS according to the grade of shunt on c-TCD. A normal control group was composed of 33 patients who suffered from simple dizziness. Intragroup and intergroup differences were analyzed in terms of clinical, laboratory and diffusion-weighted imaging lesion characteristics. The correlation between RLS grade evaluated by c-TCD and size of PFO determined by transesophageal echocardiography were also analyzed. RESULTS: In 111 patients with PFO-related CS, 68 had permanent RLS and 43 had latent RLS. Clinical characteristics and laboratory tests were not significantly different among the permanent RLS, latent RLS and normal control groups. The proportion of patients with multiple territory lesions in the permanent RLS group (50%) was larger than that in the latent RLS group (27.91%; P = 0.021). Posterior circulation was more likely to be affected in the latent RLS group than in the permanent RLS group (30.23% vs 8.82%, P = 0.004). Permanent-large and latent-large RLS were both more likely to be related to multiple (P trend = 0.017 and 0.009, respectively), small (P trend = 0.035 and 0.006, respectively) and cortical (P trend = 0.031 and 0.033, respectively) lesions. The grade of RLS evaluated by c-TCD was correlated to the size of PFO determined by transesophageal echocardiography (r = 0.758, P < 0.001). CONCLUSION: Distribution of the infarct suggested the possible type of RLS. Multiple, small and cortical infarcts suggest large RLS induced by a large PFO.

Distribution Characteristics of Colorectal Peritoneal Carcinomatosis Based on the Positron Emission Tomography/Peritoneal Cancer Index.

Background: Colorectal peritoneal carcinomatosis (CRPC) is a primary cause of death in colorectal cancer (CRC) patients. In the past, computed tomography (CT) has been the primary method used to evaluate the distribution of CRPC. This study uses 18F-FDG positron emission tomography/computed tomography (PET/CT) to investigate the distribution characteristics of CRPC. Materials and Methods: The distribution characteristics of 46 patients with CRC who were treated in the authors' hospital were retrospectively analyzed using the peritoneal cancer index (PCI). Results: The 46 patients in the study showed CRPC involvement in 203 of the 598 abdominal and pelvic regions studied (33.9%, 203/598). The regional proportions of CRPC involvement, from high to low, were as follows: region 6 (13.8%), region 0 (10.3%), region 1 (9.9%), region 5 (8.9%), region 7 (8.4%), region 3 (8.4%), region 2 (7.4%), region 4 (7.4%), region 11 (6.9%), region 8 (6.4%), region 12 (5.4%), region 9 (3.4%), and region 10 (3.4%). Thirty-three patients had a PCI of <20, and 13 patients had a PCI of ≥20. Those 13 were among the 17 (37% 17/46) who had CRPC involvement in all three regions. According to the location of the primary CRC focus, the 46 patients were divided into three groups: right hemicolon, left hemicolon, and rectum. The frequency of CRPC was greater in the rectum group than in the left hemicolon group, and the SUVmax of CRPC was greater in the right hemicolon group than in the left hemicolon group; these differences were statistically significant (p < 0.05). Conclusions: The distribution of CRPC has certain characteristics in the abdominal and pelvic cavities. The PET-PCI scores can provide a basis for the diagnosis and clinical treatment strategies in patients with CRC.

Identification of CDPKs involved in TaNOX7 mediated ROS production in wheat.

As the critical sensors and decoders of calcium signal, calcium-dependent protein kinase (CDPK) has become the focus of current research, especially in plants. However, few resources are available on the properties and functions of CDPK gene family in Triticum aestivum (TaCDPK). Here, a total of 79 CDPK genes were identified in the wheat genome. These TaCDPKs could be classified into four subgroups on phylogenesis, while they may be classified into two subgroups based on their tissue and organ-spatiotemporal expression profiles or three subgroups according to their induced expression patterns. The analysis on the signal network relationships and interactions of TaCDPKs and NADPH (reduced nicotinamide adenine dinucleotide phosphate oxidases, NOXs), the key producers for reactive oxygen species (ROS), showed that there are complicated cross-talks between these two family proteins. Further experiments demonstrate that, two members of TaCDPKs, TaCDPK2/4, can interact with TaNOX7, an important member of wheat NOXs, and enhanced the TaNOX7-mediated ROS production. All the results suggest that TaCDPKs are highly expressed in wheat with distinct tissue or organ-specificity and stress-inducible diversity, and play vital roles in plant development and response to biotic and abiotic stresses by directly interacting with TaNOXs for ROS production.

Integration of clinicopathologic identification and deep transferrable image feature representation improves predictions of lymph node metastasis in prostate cancer.

BACKGROUND: Accurate identification of pelvic lymph node metastasis (PLNM) in patients with prostate cancer (PCa) is crucial for determining appropriate treatment options. Here, we built a PLNM-Risk calculator to obtain a precisely informed decision about whether to perform extended pelvic lymph node dissection (ePLND). METHODS: The PLNM-Risk calculator was developed in 280 patients and verified internally in 71 patients and externally in 50 patients by integrating a set of radiologists' interpretations, clinicopathological factors and newly refined imaging indicators from MR images with radiomics machine learning and deep transfer learning algorithms. Its clinical applicability was compared with Briganti and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms. FINDINGS: The PLNM-Risk achieved good diagnostic discrimination with areas under the receiver operating characteristic curve (AUCs) of 0.93 (95% CI, 0.90-0.96), 0.92 (95% CI, 0.84-0.97) and 0.76 (95% CI, 0.62-0.87) in the training/validation, internal test and external test cohorts, respectively. If the number of ePLNDs missed was controlled at < 2%, PLNM-Risk provided both a higher number of ePLNDs spared (PLNM-Risk 59.6% vs MSKCC 44.9% vs Briganti 38.9%) and a lower number of false positives (PLNM-Risk 59.3% vs MSKCC 70.1% and Briganti 72.7%). In follow-up, patients stratified by the PLNM-Risk calculator showed significantly different biochemical recurrence rates after surgery. INTERPRETATION: The PLNM-Risk calculator offers a noninvasive clinical biomarker to predict PLNM for patients with PCa. It shows improved accuracy of diagnosis support and reduced overtreatment burdens for patients with findings suggestive of PCa. FUNDING: This work was supported by the Key Research and Development Program of Jiangsu Province (BE2017756) and the Suzhou Science and Technology Bureau-Science and Technology Demonstration Project (SS201808).

Myocardial extracellular volume fraction quantitation using cardiac dual-energy CT with late iodine enhancement in patients with heart failure without coronary artery disease: A single-center prospective study.

PURPOSE: To evaluate the relationship between myocardial extracellular volume (ECV) fraction measured using dual-energy computed tomography with late iodine enhancement (LIE-DECT) and risk of heart failure (HF) in patients without coronary artery disease (CAD), and to evaluate the relationship between ECV and left ventricular structure and function. MATERIALS AND METHODS: Sixty consecutive HF patients without CAD and 60 consecutive participants without heart disease who underwent coronary CT angiography (CCTA) following LIE-DECT were included. ECV of the left ventricle was calculated from the iodine maps and hematocrit levels using the American Heart Association (AHA) 16-segment model. Cardiac structural and functional parameters were collected including left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), left atrial volume (LAV), interventricular septal thickness (IVST), and N-terminal pro-brain natriuretic peptide (NT-pro-BNP). RESULTS: ECV in HF patients without CAD (31.3 ±â€¯4.0 %) was significantly higher than that in healthy subjects (27.1 ±â€¯3.7 %) (P < 0.001). Multivariate linear analysis revealed that ECV was associated with age (ß = 0.098, P = 0.010) and hypertension (ß = 2.093, P = 0.011) in all participants. Binary logistic regression analysis showed that after adjusting for age, sex, body mass index (BMI), smoking, and drinking, ECV was a risk factor affecting the occurrence of HF in those without CAD (OR = 1.356, 95 %CI：1.178-1.561, P < 0.001). A positive correlation was found between ECV and NT-pro-BNP, LVEDV, LVESV, and LAV (r = 0.629, 0.329, 0.346, and 0.338, respectively; all P < 0.001) in all participants. CONCLUSIONS: ECV could be measured using LIE-DECT iodine maps. ECV elevation was a risk factor for HF without CAD and correlated with cardiac structure and function.

Insight into Bile Duct Reaction to Obstruction from a Three-dimensional Perspective Using ex Vivo Phase-Contrast CT.

Background Biliary obstruction leads to an increase in biliary pressure within the biliary system, which induces the morphologic adaptation of the biliary tree. Purpose To observe and to quantify the morphologic characteristics of the adaptation in a bile duct ligation rat model and verify it in patients with biliary atresia in a three-dimensional (3D) manner using x-ray phase-contrast CT. Materials and Methods A bile duct ligation model was induced in 40 male Sprague-Dawley rats, which were divided into five groups: the control group (no ligation) and groups 2, 4, 6, and 8 weeks after bile duct ligation (eight animals in each group). Liver tissue samples (approximately 1.8 cm in length and 1.3 cm in height) were imaged by using phase-contrast CT and compared with histologic analysis. With a combination of phase-contrast CT and 3D visualization technology, the entire biliary system and the intrahepatic vascular system were quantitatively analyzed according to downstream, midstream, and upstream domains based on bile duct volume, surface area, and other parameters. Additionally, liver explant tissues from 28 patients with biliary atresia were studied to determine the impact of biliary tract reconstruction. Results To offset the increased biliary pressure within the biliary system, the ductular reaction in the downstream, midstream, and upstream domains manifested as dilatation, spiderweb-like looping, and interconnected honeycomb-like patterns, respectively. The most severe ductular reaction occurred in the upstream domain, and the relative surface area (mean, 0.02 µm-1 ± 0.01, 0.04 µm-1 ± 0.01, 0.07 µm-1 ± 0.02, and 0.10 µm-1 ± 0.02 for the 2-8-week groups, respectively; P < .01 among the groups) and volume fraction of ductules (mean, 16.54% ± 4.62, 19.69% ± 6.41, 26.92% ± 5.82, and 38.34% ± 10.36 for the 2-8-week groups, respectively; P < .01 among the groups except between the 2- and 4-week groups [P = .062]) significantly increased over time. In patients with biliary atresia, it was observed that both fibrosis and proliferative ductules regressed after successful biliary tract reconstruction following Kasai portoenterostomy. Furthermore, ductular reaction was accompanied by a progressive increase in the arterial supply but a loss of portal blood supply. Conclusion X-ray phase-contrast CT with three-dimensional rendering of the biliary system in a bile duct ligation rat model provides key insights into ductular reaction or biliary self-adaptation triggered by increased biliary pressure. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Vannier and Wang in this issue.

High-resolution three-dimensional visualization of hepatic sinusoids in cirrhotic rats via serial histological sections.

AIM: As a specialized intraparenchymal vascular conduit, hepatic sinusoids play a key role in liver microcirculation. This study aimed to explore the three-dimensional (3D) morphological changes of cirrhotic sinusoids by serial histological sections. METHODS: Cirrhosis was induced by tail vein injection of albumin in Wistar rats with a positive antibody. A total of 356 serial histological sections were prepared from liver tissue blocks of normal and cirrhotic rats. The optical microscope images were registered and reconstructed, and 3D reconstructions of the fine structures of fibrous tissues and sinusoids were subsequently visualized. RESULTS: The fibrosis area of the cirrhotic sample was 6-16 times that of the normal sample (P<0.001). Cirrhosis led to obvious changes in the distribution and morphology of sinusoids, which were mainly manifested as dilation, increased quantity and disordered distribution. Compared with normal liver, cirrhotic liver has a significantly increased volume ratio, number and volume of sinusoids (1.63-, 0.53-, and 1.75-fold, respectively, P<0.001). Furthermore, the samples were further divided into three zones according to the oxygen supply, and there were significant differences in the morphology of the sinusoids in the normal and cirrhotic samples (P<0.05). In particular, morphological parameters of the cirrhotic sinusoids near the portal area were obviously greater than those in the normal liver (P<0.05). CONCLUSION: 3D morphological structures of hepatic sinusoids were reconstructed, and the adaptive microstructure changes of cirrhotic sinusoids were accurately measured, which has an important implications for the study of hepatic microcirculation and pathological changes of cirrhosis.