Role of Additional MRI-Based Morphologic Measurements on the Performance of VI-RADS for Muscle-Invasive Bladder Cancer.

BACKGROUND: Vesical Imaging-Reporting and Data System (VI-RADS) is a pathway for the standardized imaging and reporting of bladder cancer staging using multiparametric (mp) MRI. PURPOSE: To investigate additional role of morphological (MOR) measurements to VI-RADS for the detection of muscle-invasive bladder cancer (MIBC) with mpMRI. STUDY TYPE: Retrospective. POPULATION: A total of 198 patients (72 MIBC and 126 NMIBC) underwent bladder mpMRI was included. FIELD STRENGTH/SEQUENCE: 3.0 T/T2-weighted imaging with fast-spin-echo sequence, spin-echo-planar diffusion-weighted imaging and dynamic contrast-enhanced imaging with fast 3D gradient-echo sequence. ASSESSMENT: VI-RADS score and MOR measurement including tumor location, number, stalk, cauliflower-like surface, type of tumor growth, tumor-muscle contact margin (TCM), tumor-longitudinal length (TLL), and tumor cellularity index (TCI) were analyzed by three uroradiologists (3-year, 8-year, and 15-year experience of bladder MRI, respectively) who were blinded to histopathology. STATISTICAL TESTS: Significant MOR measurements associated with MIBC were tested by univariable and multivariable logistic regression (LR) analysis with odds ratio (OR). Area under receiver operating characteristic curve (AUC) with DeLong's test and decision curve analysis (DCA) were used to compared the performance of unadjusted vs. adjusted VI-RADS. A P-value <0.05 was considered statistically significant. RESULTS: TCM (OR 9.98; 95% confidence interval [CI] 4.77-20.8), TCI (OR 5.72; 95% CI 2.37-13.8), and TLL (OR 3.35; 95% CI 1.40-8.03) were independently associated with MIBC at multivariable LR analysis. VI-RADS adjusted by three MORs achieved significantly higher AUC (reader 1 0.908 vs. 0.798; reader 2 0.906 vs. 0.855; reader 3 0.907 vs. 0.831) and better clinical benefits than unadjusted VI-RADS at DCA. Specially in VI-RADS-defined equivocal lesions, MOR-based adjustment resulted in 55.5% (25/45), 70.4% (38/54), and 46.4% (26/56) improvement in accuracy for discriminating MIBC in three readers, respectively. DATA CONCLUSION: MOR measurements improved the performance of VI-RADS in detecting MIBC with mpMRI, especially for equivocal lesions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Trigred motif 36 regulates neuroendocrine differentiation of prostate cancer via HK2 ubiquitination and GPx4 deficiency.

Neuroendocrine prostate cancer (NEPC), the most lethal subtype of castration-resistant prostate cancer (PCa), may evolve from the neuroendocrine differentiation (NED) of PCa cells. However, the molecular mechanism that triggers NED is unknown. Trigred motif 36 (TRIM36), a member of the TRIM protein family, exhibits oncogenic or anti-oncogenic roles in various cancers. We have previously reported that TRIM36 is highly expressed to inhibit the invasion and proliferation of PCa. In the present study, we first found that TRIM36 was lowly expressed in NEPC and its overexpression suppressed the NED of PCa. Next, based on proteomic analysis, we found that TRIM36 inhibited the glycolysis pathway through suppressing hexokinase 2 (HK2), a crucial glycolytic enzyme catalyzing the conversion of glucose to glucose-6-phosphate. TRIM36 specifically bound to HK2 through lysine 48 (lys48)-mediated ubiquitination of HK2. Moreover, TRIM36-mediated ubiquitination degradation of HK2 downregulated the level of glutathione peroxidase 4 (GPx4), a process that contributed to ferroptosis. In conclusion, TRIM36 can inhibit glycolysis via lys48-mediated HK2 ubiquitination to reduce GPX4 expression and activate ferroptosis, thereby inhibiting the NED in PCa. Targeting TRIM36 might be a promising approach to retard NED and treat NEPC.

Biopsy-free AI-aided precision MRI assessment in prediction of prostate cancer biochemical recurrence.

BACKGROUND: To investigate the predictive ability of high-throughput MRI with deep survival networks for biochemical recurrence (BCR) of prostate cancer (PCa) after prostatectomy. METHODS: Clinical-MRI and histopathologic data of 579 (train/test, 463/116) PCa patients were retrospectively collected. The deep survival network (iBCR-Net) is based on stepwise processing operations, which first built an MRI radiomics signature (RadS) for BCR, and predicted the T3 stage and lymph node metastasis (LN+) of tumour using two predefined AI models. Subsequently, clinical, imaging and histopathological variables were integrated into iBCR-Net for BCR prediction. RESULTS: RadS, derived from 2554 MRI features, was identified as an independent predictor of BCR. Two predefined AI models achieved an accuracy of 82.6% and 78.4% in staging T3 and LN+. The iBCR-Net, when expressed as a presurgical model by integrating RadS, AI-diagnosed T3 stage and PSA, can match a state-of-the-art histopathological model (C-index, 0.81 to 0.83 vs 0.79 to 0.81, p > 0.05); and has maximally 5.16-fold, 12.8-fold, and 2.09-fold (p < 0.05) benefit to conventional D'Amico score, the Cancer of the Prostate Risk Assessment (CAPRA) score and the CAPRA Postsurgical score. CONCLUSIONS: AI-aided iBCR-Net using high-throughput MRI can predict PCa BCR accurately and thus may provide an alternative to the conventional method for PCa risk stratification.

Performance of Artificial Intelligence-Aided Diagnosis System for Clinically Significant Prostate Cancer with MRI: A Diagnostic Comparison Study.

BACKGROUND: The high level of expertise required for accurate interpretation of prostate MRI. PURPOSE: To develop and test an artificial intelligence (AI) system for diagnosis of clinically significant prostate cancer (CsPC) with MRI. STUDY TYPE: Retrospective. SUBJECTS: One thousand two hundred thirty patients from derivation cohort between Jan 2012 and Oct 2019, and 169 patients from a publicly available data (U-Net: 423 for training/validation and 49 for test and TrumpeNet: 820 for training/validation and 579 for test). FIELD STRENGTH/SEQUENCE: 3.0T/scanners, T2 -weighted imaging (T2 WI), diffusion-weighted imaging, and apparent diffusion coefficient map. ASSESSMENT: Close-loop AI system was trained with an Unet for prostate segmentation and a TrumpetNet for CsPC detection. Performance of AI was tested in 410 internal and 169 external sets against 24 radiologists categorizing into junior, general and subspecialist group. Gleason score >6 was identified as CsPC at pathology. STATISTICAL TESTS: Area under the receiver operating characteristic curve (AUC-ROC); Delong test; Meta-regression I2 analysis. RESULTS: In average, for internal test, AI had lower AUC-ROC than subspecialists (0.85 vs. 0.92, P < 0.05), and was comparable to junior (0.84, P = 0.76) and general group (0.86, P = 0.35). For external test, both AI (0.86) and subspecialist (0.86) had higher AUC than junior (0.80, P < 0.05) and general reader (0.83, P < 0.05). In individual, it revealed moderate diagnostic heterogeneity in 24 readers (Mantel-Haenszel I2  = 56.8%, P < 0.01), and AI outperformed 54.2% (13/24) of readers in summary ROC analysis. In multivariate test, Gleason score, zonal location, PI-RADS score and lesion size significantly impacted the accuracy of AI; while effect of data source, MR device and parameter settings on AI performance is insignificant (P > 0.05). DATA CONCLUSION: Our AI system can match and to some case exceed clinicians for the diagnosis of CsPC with prostate MRI. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Renal Lipoma-Like Angiomyolipoma of Tumour Thrombus Extending to the Confluence of Inferior Vena Cava with Right Atrium: A Rare Case Report and Literature Review.

Angiomyolipoma (AML) complicated with tumour thrombus extending to the confluence of inferior vena cava (IVC) with right atrium is rarely observed. We report a female AML patient admitted to our centre on January 21, 2020, with complication of tumour thrombus extending to the confluence of IVC with right atrium and had no sign of difficult breathing. She underwent whole-abdominal enhanced CT for abdominal pain and was diagnosed with a possible renal AML with tumour thrombus. Open radical nephrectomy and thrombectomy of vena cava were performed. Intraoperative transoesophageal echocardiography indicated that the tumour thrombus has reached the confluence of IVC with right atrium. The operation took 255 min with an intraoperative haemorrhage of 800mL. The patient was discharged 7 days after surgery. Pathology revealed lipoma-like AML. Immunohistochemistry showed vimentin (+), EMA (-), HMB45 (+), S-100 (-), SMA (+), TFE-3 (-), melan A (+). After 2 years of follow-up, we found that the patient showed full recovery and had no recurrence. Therefore, lipoma-like AML should also be followed closely for recurrence and metastasis. When AML involves IVC tumour thrombus, open thrombectomy and radical nephrectomy are safe and effective methods.

[Gonadoblastoma: Clinicopathological study and literature review of 3 cases].

OBJECTIVE: To investigate the clinical feature, pathological morphology, special histopathological subtype and immunohistochemical characteristic of gonadoblastoma. METHODS: Three patients of gonadoblastoma treated from 2014 to 2020 were enrolled, and the clinical characteristics, histological morphology and immunophenotype were analyzed, and the literatures were also reviewed. RESULT: Three phenotypical females were 14,17 and 27 years old. Case 1 was 46,XX with normal gonadal development. Case 2 was 46,XY and case 3 was chromosomal chimeric type (46, XY 90%/45,X 10%), both with dysgenetic gonads. Microscopically, the morphology of classic type was observed in all cases more or less, manifesting small nests of primitive germ cells and surrounding clustered sex cord-like cells, usually with Call-Exner like bodies and calcification. In additon, the morphology of special subtype can be seen in case 1,exhibiting cord-like tumor cells, which was segmentated by cellular fibrous stroma. Cases 2 and 3 were accompanied by dysgerminoma components. Immunohistochemically,all the primal germ cells were positive for OCT3/4, PLAP and CDll7 , and sexcord-like cells were positive for inhibin, SF-1, SOX9 and FOXL2 . Patients were followed up for 10 years, 6 years and 4 years respectively without recurrence. CONCLUSION: Gonadoblastoma is a rare germ cell-sex cord stromal tumor, which is usually accompanied by gonadal hypoplasia. As a special subtype, dissecting gonadoblastoma will be easily confused with dysgerminoma/seminoma, but the prognosis is better. So we should improve the understanding of this subtype and avoid overdiagnosis.

A comprehensive prostate biopsy standardization system according to quantitative multiparametric MRI and PSA value: P.R.O.S.T score.

BACKGROUND: Although most studies believe that systematic biopsy (SB) and targeted biopsy (TB) should be performed simultaneously in patients with suspected prostate cancer, we believe that patients with the Prostate Imaging-Reporting and Data System (PI-RADS) score of 4/5 may be able to perform TB only. METHODS: We retrospectively analyzed the pathological results of patients undergoing transperineal prostate biopsy with PI-RADS 4 and 5 in our center. We use the data from 2019 to 2020 as the training set to establish the prediction model and the data from 2021 as the verification set to test the effectiveness. Through stepwise logistics regression analysis, we integrate statistically significant clinical factors and establish a model to further predict whether the target area is tumor. RESULTS: The results showed that age (O), total number of lesions (T), histological region (R), PI-RADS score (S), and PSA density (P) were significantly correlated with the results of TB, and the formula was: p = 1/[1 + e^(- 11.387 + 0.058 × O + (- 0.736 × T) + 0.587 × R + 1.574 × S + 7.338 × P)]. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the prediction model was 0.840 (95% CI 0.802-0.877), with the optimal threshold of 0.762. And the corresponding specificity and sensitivity were 0.765 and 0.752. In the validation set, the AUC of the prediction model was 0.816 (95% CI 0.759-0.874), which means that it has good prediction efficiency. CONCLUSION: The P.R.O.S.T score can effectively screen PI-RADS 4/5 lesions, which may help physicians shunt patients who need prostate biopsy to reduce unnecessary systematic biopsies.

The application value of multi-parameter cystoscope in improving the accuracy of preoperative bladder cancer grading.

PURPOSE: To develop and validate a preoperative cystoscopic-based predictive model for predicting postoperative high-grade bladder cancer (BCa), which could be used to guide the surgical selection and postoperative treatment strategies. MATERIALS AND METHODS: We retrospectively recruited 366 patients with cystoscopy biopsy for pathology and morphology evaluation between October 2010 and January 2021. A binary logistic regression model was used to assess the risk factors for postoperative high-grade BCa. Diagnostic performance was analyzed by plotting receiver operating characteristic curve and calculating area under the curve (AUC), sensitivity, specificity. From January 2021 to July 2021, we collected 105 BCa prospectively to validate the model's accuracy. RESULTS: A total of 366 individuals who underwent transurethral resection of bladder tumor (TURBT) or radical cystectomy following cystoscopy biopsy were included for analysis. 261 (71.3%) had a biopsy pathology grade that was consistent with postoperative pathology grade. We discovered five cystoscopic parameters, including tumor diameter, site, non-pedicled, high-grade biopsy pathology, morphology, were associated with high-grade BCa. The established multi-parameter logistic regression model ("JSPH" model) revealed AUC was 0.917 (P < 0.001). Sensitivity and specificity were 86.2% and 84.0%, respectively. And the consistency of pre- and post-operative high-grade pathology was improved from biopsy-based 70.5% to JSPH model-based 85.2%. In a 105-patients prospective validation cohort, the consistency of pre- and post-operative high-grade pathology was increased from 63.1 to 84.2% after incorporation into JSPH model for prediction. CONCLUSION: The cystoscopic parameters based "JSPH model" is accurate at predicting postoperative pathological high-grade tumors prior to operations.

Protective effect of rosuvastatin against the formation of benign esophageal stricture.

BACKGROUND: Benign esophageal strictures result from caustic or radiation injury or surgical procedures. Statins have anti-inflammatory and anti-fibrotic activities. We examined the role of rosuvastatin in preventing benign esophageal fibrosis and stricture formation in a rabbit model. METHODS: Twenty-six rabbits were assigned to control and rosuvastatin groups. The rabbits in the rosuvastatin group were administered rosuvastatin 5 mg/day, 2 weeks prior to the esophageal stricture phase. Esophageal strictures were established by applying 4% sodium hydroxide solution to the middle esophagus. Esophagography was performed to evaluate the degree of esophageal stenosis, and histopathologic assessment of esophageal tissue damage was performed with hematoxylin-eosin and Masson staining. The expressions of transforming growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) were examined by immunohistochemistry. RESULTS: The incidence of strictures was significantly lower in the rosuvastatin group. Esophagography demonstrated mild stenosis in the narrowest inner esophageal diameter in the rosuvastatin group than in the control group, and Masson staining demonstrated significantly less collagen deposition in the rosuvastatin group. In addition, immunohistochemistry results showed that the expressions of TGF-ß1, CTGF, and α-SMA significantly reduced in the rosuvastatin group. CONCLUSIONS: The present study demonstrated that rosuvastatin prevents benign esophageal stricture formation. This effect may be exerted through the anti-fibrotic activity of rosuvastatin, which may be exerted by the inhibition of CTGF and α-SMA production induced by TGF-ß1.

Artificial intelligence is a promising prospect for the detection of prostate cancer extracapsular extension with mpMRI: a two-center comparative study.

PURPOSE: A balance between preserving urinary continence as well as sexual potency and achieving negative surgical margins is of clinical relevance while implementary difficulty. Accurate detection of extracapsular extension (ECE) of prostate cancer (PCa) is thus crucial for determining appropriate treatment options. We aimed to develop and validate an artificial intelligence (AI)-based tool for detecting ECE of PCa using multiparametric magnetic resonance imaging (mpMRI). METHODS: Eight hundred and forty nine consecutive PCa patients who underwent mpMRI and prostatectomy without previous radio- or hormonal therapy from two medical centers were retrospectively included. The AI tool was built on a ResNeXt network embedded with a spatial attention map of experts' prior knowledge (PAGNet) from 596 training patients. Model validation was performed in 150 internal and 103 external patients. Performance comparison was made between AI, two experts using a criteria-based ECE grading system, and expert-AI interaction. RESULTS: An index PAGNet model using a single-slice image yielded the highest areas under the receiver operating characteristic curve (AUC) of 0.857 (95% confidence interval [CI], 0.827-0.884), 0.807 (95% CI, 0.735-0.867), and 0.728 (95% CI, 0.631-0.811) in training, internal, and external validation data, respectively. The performance of two experts (AUC, 0.632 to 0.741 vs 0.715 to 0.857) was lower (paired comparison, all p values < 0.05) than that of AI assessment. When experts' interpretations were adjusted by AI assessments, the performance of two experts was improved. CONCLUSION: Our AI tool, showing improved accuracy, offers a promising alternative to human experts for ECE staging using mpMRI.

Longitudinal Multiparametric MRI Assessment of Irradiated Salivary Gland in a Rat Model: Correlated With Histological Findings.

BACKGROUND: Several magnetic resonance imaging (MRI) sequences have been applied to assess injured glands but without histological validation. PURPOSE: To evaluate longitudinal changes in multiparametric MRI (mp-MRI) of irradiated salivary glands in a rat model and investigate correlations between mp-MRI and histological findings. STUDY TYPE: Prospective. ANIMAL MODEL: Submandibular glands of 36 rats were radiated using a single dose of 15 Gy X-ray (irradiation [IR] group), and 6 other rats were enrolled into sham-IR group. mp-MRI were scanned 1 day after sham-IR (n = 6), or 1, 2, 4, 8, 12, 24 weeks after IR (n = 36, 6 per subgroup). FIELD STRENGTH/SEQUENCE: A 3.0-T/Diffusion-weighted imaging (DWI), readout-segmented echo-planar imaging (EPI) sequence; intravoxel incoherent motion DWI, single-shot EPI sequence; T1 mapping, dual-flip-angle gradient-echo sequence with volumetric interpolated breath-hold examination; T2 mapping, turbo spin-echo sequence. ASSESSMENT: Parameters including apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D* ), perfusion fraction (f), T1 and T2 value were obtained. Histological examinations, including hematoxylin and eosin staining (for acinar cell fraction [AC%] detection), Masson's trichrome staining (for degree of fibrosis [F%] determination) and CD34-immunohistochemical staining (for microvessel density [MVD] calculation), were performed at corresponding time points. STATISTICAL TESTS: One-way analysis of variance was used to compare the mp-MRI and histological parameters among different groups. Spearman correlation analysis was applied to determine the correlation between mp-MRI and histological parameters. Two-sided P ≤ 0.05 was considered statistically significant. RESULTS: Changes of mp-MRI parameters (ADC, D, D* , f, T1, T2) and histological results (AC%, F%, MVD) among the seven groups were all significant. ADC, D, and T2 values negatively correlated with AC% (ADC, r = -0.728; D, r = -0.773; T2, r = -0.600), f positively correlated with MVD (r = 0.496), and T1 values positively correlated with F% (r = 0.714). DATA CONCLUSION: mp-MRI might be able to noninvasively and quantitatively evaluate the dynamic pathological changes within the irradiated salivary glands. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Job preferences of medical and nursing students seeking employment in rural China: a discrete choice experiment.

BACKGROUND: China has a shortage of health workers in rural areas, but little research exists on policies that attract qualified medical and nursing students to rural locations. We conducted a discrete choice experiment to determine how specific incentives would be valued by final-year students in a medical university in Guizhou Province, China. METHODS: Attributes of potential jobs were developed through the literature review, semi-structured interviews, and a pilot survey. Forty choice sets were developed using a fractional factorial design. A mixed logit model was used to estimate the relative strength of the attributes. Willingness to pay and uptake rates for a defined job were also calculated based on the mixed logit estimates. RESULTS: The final sample comprised 787 medical and nursing students. The statistically significant results indicated "Bianzhi" (the number of personnel allocated to each employer by the government) and physical conflicts between doctors and patients were two of the most important non-monetary job characteristics that incentivized both medical and nursing students. Policy simulation suggested that respondents were most sensitive to a salary increase, and the effect of incentive packages was stronger for students with a rural family background. CONCLUSIONS: Strategies for patient-doctor relationships, Bianzhi and salary should be considered to attract final-year medical and nursing students to work in rural China. In addition, specific recruitment policy designs tailored for students with different majors and backgrounds should be taken into account.

ALDH1A3 serves as a predictor for castration resistance in prostate cancer patients.

BACKGROUND: Aldehyde dehydrogenase 1A3 (ALDH1A3) has been implicated in the survival and proliferation of prostate cancer cells. METHODS: We retrospectively reviewed our patients with advanced disease on adjuvant hormonal therapy after prostatectomy. Time to castration resistance stage was documented. And Immunohistochemistry analysis for ALDH1A3 was performed for those patient samples on tissue microarray. Bioinformatics anslysis was used for RNA sequencing data of both primary prostate cancer and metastatic castration resistance prostate cancer (mCRPC) from online datasets. Crispr-Cas9 was used to knock out ALDH1A3 in prostate cancer luminal cells, and morphologic analysis as well as the Gene Set Enrichment Analysis (GSEA) were facilitated to discover the mechanisms of the resistance phenotype. RESULTS: We found that the patients with ALDH1A3 low expression had shorter time to progression to castration resistance compared with those of higher expression group on adjuvant hormonal therapy after radical prostatectomy. The ALDH1A3 knockout cells gradually acquired resistance to androgen deprivation therapy, a few cells have been found in knockout group showing as that the spindle-like luminal cells in charcoal stripped medium. Furthermore, PI3K pathway activation has been confirmed by Western blot. The PI3K pathway inhibitor BEZ235 has been demonstrated that the acquired ADT resistance by ALDH1A3 down regulation could be rescued by PI3K pathway inhibitor. CONCLUSION: These results suggested a novel function for ALDH1A3 in development of mCRPC, and indicated PI3K pathway inhibitor has the potential in the treatment of a subgroup of mCRPC patients.

[Clinical characteristics and treatment strategies of prostatic mucinous adenocarcinoma: A report of 10 cases and literature review].

OBJECTIVE: To investigate the clinical characteristics and treatment strategies of prostatic mucinous adenocarcinoma (PMAC). METHODS: We retrospectively analyzed the clinical data on 10 cases of PMAC treated in the First Affiliated Hospital of Nanjing Medical University from January 2014 to June 2018. The patients were aged 51－79 (65 ± 14) years, with a medium PSA level of 89 (14.63－128.05) µg/L and Gleason scores of 3 + 3 in 1 case, 3 + 4 in 2, 4 + 3 in 1 and 8 in 6 cases preoperatively, 1 treated by robot-assisted radical prostatectomy and the other 9 by laparoscopic radical prostatectomy. We conducted pelvic cavity lymph node dissection for all the patients and analyzed their prognosis and survival. RESULTS: Operations were successfully completed in all the cases. Pathological examination revealed 2 cases of mucinous adenocarcinoma with signet ring cell carcinoma in the 10 PMAC patients, 2 at stage ≤T2b, 5 at stage ≥T2c, 3 positive at pelvic lymph node dissection and 5 positive at the incision margin. The patients were followed up for 6－48 (median 26) months. Four of the patients were found with biochemical recurrence within 2 years after operation and treated by androgen-deprivation therapy, radiotherapy and chemotherapy, which reduced the PSA level to <1.0 µg/ml in all the 4 cases. CONCLUSIONS: PMAC has a good prognosis. Radical surgery is recommended for moderate and low-risk PMAC and the patients with postoperative biochemical recurrence can benefit from comprehensive treatment of total androgen blockade.

A machine learning-assisted decision-support model to better identify patients with prostate cancer requiring an extended pelvic lymph node dissection.

OBJECTIVES: To develop a machine learning (ML)-assisted model to identify candidates for extended pelvic lymph node dissection (ePLND) in prostate cancer by integrating clinical, biopsy, and precisely defined magnetic resonance imaging (MRI) findings. PATIENTS AND METHODS: In all, 248 patients treated with radical prostatectomy and ePLND or PLND were included. ML-assisted models were developed from 18 integrated features using logistic regression (LR), support vector machine (SVM), and random forests (RFs). The models were compared to the Memorial SloanKettering Cancer Center (MSKCC) nomogram using receiver operating characteristic-derived area under the curve (AUC) calibration plots and decision curve analysis (DCA). RESULTS: A total of 59/248 (23.8%) lymph node invasions (LNIs) were identified at surgery. The predictive accuracy of the ML-based models, with (+) or without (-) MRI-reported LNI, yielded similar AUCs (RFs+ /RFs- : 0.906/0.885; SVM+ /SVM- : 0.891/0.868; LR+ /LR- : 0.886/0.882) and were higher than the MSKCC nomogram (0.816; P < 0.001). The calibration of the MSKCC nomogram tended to underestimate LNI risk across the entire range of predicted probabilities compared to the ML-assisted models. The DCA showed that the ML-assisted models significantly improved risk prediction at a risk threshold of ≤80% compared to the MSKCC nomogram. If ePLNDs missed was controlled at <3%, both RFs+ and RFs- resulted in a higher positive predictive value (51.4%/49.6% vs 40.3%), similar negative predictive value (97.2%/97.8% vs 97.2%), and higher number of ePLNDs spared (56.9%/54.4% vs 43.9%) compared to the MSKCC nomogram. CONCLUSIONS: Our ML-based model, with a 5-15% cutoff, is superior to the MSKCC nomogram, sparing ≥50% of ePLNDs with a risk of missing <3% of LNIs.

Using support vector machine analysis to assess PartinMR: A new prediction model for organ-confined prostate cancer.

BACKGROUND: Partin tables represent the most widely used predictive tool for prostate cancer stage at prostatectomy but with potential limitations. PURPOSE: To develop a new PartinMR model for organ-confined prostate cancer (OCPCA) by incorporating Partin table and mp-MRI with a support vector machine (SVM) analysis. STUDY TYPE: Retrospective. POPULATION: In all, 541 patients with biopsy-confirmed prostate cancer underwent mp-MRI. FIELD STRENGTH: T2 -weighted, diffusion-weighted imaging with a 3.0T MR scanner. ASSESSMENT: Candidate predictors included age, prostate-specific antigen, clinical stage, biopsy Gleason score (GS), and mp-MRI findings, ie, tumor location, Prostate Imaging and Reporting and Data System (PI-RADS) score, diameter (D-max), and 6-point MR stage. The PartinMR model with combination of a Partin table and mp-MRI findings was developed using SVM and 5-fold crossvalidation analysis. STATISTICAL TESTS: The predicted ability of the PartinMR model was compared with a standard Partin and a modified Partin table (mPartin) which used for mp-MRI staging. Statistical tests were made by area under receiver operating characteristic curve (AUC), adjusted proportional hazard ratio (HR), and a cost-effective benefit analysis. RESULTS: The rate of OCPCA at prostatectomy was 46.4% (251/541). Using MR staging, mPartin table (AUC, 0.814, 95% confidence interval [CI]: 0.779-0.846, P = 0.001) is appreciably better than the Partin table (AUC, 0.730, 95% CI: 0.690-0.767). Contrarily, adding all MR variables, the PartinMR model (AUC, 0.891, 95% CI: 0.884-0.899, P < 0.001) outperformed any other scheme, with 79.3% sensitivity, 75.7% specificity, 79% positive predictive value, and 76.0% negative predictive value for OCPCA. MR stage represented the most influential predictor of extracapsular extension (HR, 2.77, 95% CI: 1.54-3.33), followed by D-max (2.01, 95% CI: 1.31-2.68), biopsy GS (1.64, 95% CI: 1.35-2.12), and PI-RADS score (1.21, 95% CI: 1.01-1.98). DATA CONCLUSION: The new PartinMR model is superior to the conventional Partin table for OCPCA. Clinical implications of mp-MRI for prostate cancer stage must be confirmed in further trials. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2018;48:499-506.

Construction of a Preoperative Radiologic-Risk Signature for Predicting the Pathologic Status of Prostate Cancer at Radical Prostatectomy.

OBJECTIVE: We developed a radiologic-risk signature (RRS) that serves as a surrogate for the pathologic status of prostate cancer (PCA) and investigated its ability to predict disease-free survival. MATERIALS AND METHODS: This study included 631 patients with localized PCA who underwent prostatic multiparametric MRI before prostatectomy. Images from 426 training datasets were structurally interpreted and correlated to a postoperative Memorial Sloan Kettering Cancer Center (MSKCC) score by a stepwise partial least-squares regression analysis. The developed RRS, compared with a preoperative Kattan nomogram, was validated in a cohort of 205 patients with 3-year follow-up data after prostatectomy in terms of calibration, discrimination, and clinical usefulness. Statistical tests were performed by AUC analysis, Kaplan-Meier test, and decision curve analysis. RESULTS: The RRS, which consists of 12 preoperative variables, faithfully represented postoperative MSKCC score in 426 training (r = 0.75; p < 0.001) and 205 validation (r = 0.79; p < 0.001) datasets. For patients in the validation group, RRS showed better discriminative power (C-index, 0.859; 95% CI, 0.779-0.939; p = 0.013) than did the preoperative Kattan nomogram (C-index, 0.780; 95% CI, 0.701-0.859) for predicting 3-year biochemical recurrence and showed higher net benefits for a probability threshold of greater than 10%. CONCLUSION: Characteristics of RRS can faithfully represent the tumor pathologic status and predict accurately the disease postoperative outcome before prostatectomy.

Direct Formation of C-C Triple-Bonded Structural Motifs by On-Surface Dehalogenative Homocouplings of Tribromomethyl-Substituted Arenes.

On-surface synthesis shows significant potential in constructing novel nanostructures/nanomaterials, which has been intensely studied in recent years. The formation of acetylenic scaffolds provides an important route to the fabrication of emerging carbon nanostructures, including carbyne, graphyne, and graphdiyne, which feature chemically vulnerable sp-hybridized carbon atoms. Herein, we designed and synthesized a tribromomethyl-substituted compound. By using a combination of high-resolution scanning tunneling microscopy, non-contact atomic force microscopy, and density functional theory calculations, we demonstrated that it is feasible to convert these compounds directly into C-C triple-bonded structural motifs by on-surface dehalogenative homocoupling reactions. Concurrently, sp3 -hybridized carbon atoms are converted into sp-hybridized ones, that is, an alkyl group is transformed into an alkynyl moiety. Moreover, we achieved the formation of dimer structures, one-dimensional molecular wires, and two-dimensional molecular networks on Au(111) surfaces, which should inspire further studies towards two-dimensional graphyne structures.

Ablation of the Sox11 Gene Results in Clefting of the Secondary Palate Resembling the Pierre Robin Sequence.

Mouse gene inactivation has shown that the transcription factor Sox11 is required for mouse palatogenesis. However, whether Sox11 is primarily involved in the regulation of palatogenesis still remains elusive. In this study, we explored the role ofSox11in palatogenesis by analyzing the developmental mechanism in cleft palate formation in mutants deficient in Sox11. Sox11 is expressed both in the developing palatal shelf and in the surrounding structures, including the mandible. We found that cleft palate occurs only in the mutant in which Sox11is directly deleted. As in the wild type, the palatal shelves in the Sox11 mutant undergo outgrowth in a downward direction and exhibit potential for fusion and elevation. However, mutant palatal shelves encounter clefting, which is associated with a malpositioned tongue that results in physical obstruction of palatal shelf elevation at embryonic day 14.5 (E14.5). We found that loss of Sox11led to reduced cell proliferation in the developing mandibular mesenchyme via Cyclin D1, leading to mandibular hypoplasia, which blocks tongue descent. Extensive analyses of gene expression inSox11 deficiency identified FGF9 as a potential candidate target of Sox11 in the modulation of cell proliferation both in the mandible and the palatal shelf between E12.5 and E13.5. Finally we show, using in vitro assays, that Sox11 directly regulates the expression of Fgf9 and that application of FGF9 protein to Sox11-deficient palatal shelves restores the rate of BrdU incorporation. Taken together, the palate defects presented in the Sox11 loss mutant mimic the clefting in the Pierre Robin sequence in humans.

Expression of lactate dehydrogenase C correlates with poor prognosis in renal cell carcinoma.

Lactate dehydrogenase C is an isoenzyme of lactate dehydrogenase and a member of the cancer-testis antigens family. In this study, we aimed to investigate the expression and functional role of lactate dehydrogenase C and its basic mechanisms in renal cell carcinoma. First, a total of 133 cases of renal cell carcinoma samples were analysed in a tissue microarray, and Kaplan-Meier survival curve analyses were performed to investigate the correlation between lactate dehydrogenase C expression and renal cell carcinoma progression. Lactate dehydrogenase C protein levels and messenger RNA levels were significantly upregulated in renal cell carcinoma tissues, and the patients with positive lactate dehydrogenase C expression had a shorter progression-free survival, indicating the oncogenic role of lactate dehydrogenase C in renal cell carcinoma. In addition, further cytological experiments demonstrated that lactate dehydrogenase C could prompt renal cell carcinoma cells to produce lactate, and increase metastatic and invasive potential of renal cell carcinoma cells. Furthermore, lactate dehydrogenase C could induce the epithelial-mesenchymal transition process and matrix metalloproteinase-9 expression. In summary, these findings showed lactate dehydrogenase C was associated with poor prognosis in renal cell carcinoma and played a pivotal role in the migration and invasion of renal cell carcinoma cells. Lactate dehydrogenase C may act as a novel biomarker for renal cell carcinoma progression and a potential therapeutic target for the treatment of renal cell carcinoma.