CT-based identification of pediatric non-Wilms tumors using convolutional neural networks at a single center.

BACKGROUND: Deep learning (DL) is more and more widely used in children's medical treatment. In this study, we have developed a computed tomography (CT)-based DL model for identifying undiagnosed non-Wilms tumors (nWTs) from pediatric renal tumors. METHODS: This study collected and analyzed the preoperative clinical data and CT images of pediatric renal tumor patients diagnosed by our center from 2008 to 2020, and established a DL model to identify nWTs noninvasively. RESULTS: A total of 364 children who had been confirmed by histopathology with renal tumors from our center were enrolled, including 269 Wilms tumors (WTs) and 95 nWTs. For DL model development, all cases were randomly allocated to training set (218 cases), validation set (73 cases), and test set (73 cases). In the test set, the DL model achieved area under the curve of 0.831 (95% CI: 0.712-0.951) in discriminating WTs from nWTs, with the accuracy, sensitivity, and specificity of 0.781, 0.563, and 0.842, respectively. The sensitivity of our model was higher than a radiologist with 15 years of experience. CONCLUSIONS: We presented a DL model for identifying undiagnosed nWTs from pediatric renal tumors, with the potential to improve the image-based diagnosis. IMPACT: Deep learning model was used for the first time to identify pediatric renal tumors in this study. Deep learning model can identify non-Wilms tumors from pediatric renal tumors. Deep learning model based on computed tomography images can improve tumor diagnosis rate.

Imaging features and differences among the three primary malignant non-Wilms tumors in children.

BACKGROUND: The pathology, treatment and prognosis of malignant non-Wilms tumors (NWTs) are different, so it is necessary to differentiate these types of tumors. The purpose of this study was to review the clinical and imaging features of malignant NWTs and features of tumor metastasis. METHODS: We retrospectively analyzed the CT images of 65 pediatric patients with NWTs from March 2008 to July 2020, mainly including clear cell sarcoma of the kidney (CCSK), malignant rhabdomyoma tumor of the kidney (MRTK) and renal cell carcinoma (RCC). Available pretreatment contrast-enhanced abdominal CT examinations were reviewed. The clinical features of the patients, imaging findings of the primary mass, and locoregional metastasis patterns were evaluated in correlation with pathological and surgical findings. RESULTS: The study included CCSK (22 cases), MRTK (27 cases) and RCC (16 cases). There were no significant differences observed among the sex ratios of CCSK, MRTK and RCC (all P > 0.05). Among the three tumors, the onset age of MRTK patients was the smallest, while that of RCC patients was the largest (all P < 0.05). The tumor diameter of CCSK was larger than that of MRTK and RCC (all P < 0.001). For hemorrhage and necrosis, the proportion of MRTK patients was larger than that of the other two tumors (P = 0.017). For calcification in tumors, the proportion of calcification in RCC was highest (P = 0.009). Only MRTK showed subcapsular fluid (P < 0.001). In the arterial phase, the proportion of slight enhancement in RCC was lower than that in the other two tumors (P = 0.007), and the proportion of marked enhancement was the highest (P = 0.002). In the venous phase, the proportion of slight enhancement in RCC was lower than that in the other two tumors (P < 0.001). Only CCSK had bone metastasis. There was no liver and lung metastasis in RCC. CONCLUSIONS: NWTs have their own imaging and clinical manifestations. CCSK can cause vertebral metastasis, MRTK can cause subcapsular effusion, and RCC tumor density is usually high and calcification. These diagnostic points can play a role in clinical diagnosis.

LINC00667 promotes Wilms' tumor metastasis and stemness by sponging miR-200b/c/429 family to regulate IKK-ß.

Wilms' tumor, also known as nephroblastoma, is a kind of pediatric renal cancer. Previous studies have indicated that microRNAs (miRNAs) regulate various cancers progression. However, whether miR-200 family regulated Wilms' tumor progression remains to be elucidated. In our study, miR-200b/c/429 expression was downregulated in Wilms' tumor tissue samples from 25 patients. And data from three independent analyses of quantitative real-time polymerase chain reaction revealed that the expression of miR-200b/c/429 was downregulated in Wilms' tumor cell lines. Functionally, Cell counting kit-8 assay revealed that cell viability was reduced by overexpressing miR-200b/c/429. Transwell assay manifested that cell migration and invasion was hindered by miR-200b/c/429 overexpression. Sphere-forming and western blot assays demonstrated that miR-200b/c/429 overexpression suppressed the sphere formation ability. Mechanically, nuclear factor-κB (NF-κB) pathway was confirmed to be associated with Wilms' tumor progression; miR-200b/c/429 overexpression inactivated NF-κB pathway as miR-200b/c/429 was identified to target IκB kinase ß (IKK-ß), an NF-κB pathway-related gene. Moreover, miR-200b/c/429 was sponged by LINC00667 in Wilms' tumor cells. LINC00667 competitively bound with miR-200b/c/429 to regulate IKK-ß expression and then activated NF-κB pathway in Wilms' tumor. Subsequently, rescue assays illustrated that silencing of IKK-ß could reverse the effect of miR-200b/c/429 inhibition on the progression of sh-LINC00667-transfected Wilms' tumor cells. In summary, LINC00667 promoted Wilms' tumor progression by sponging miR-200b/c/429 family to regulate IKK-ß.

Quantifying interindividual variability and asymmetry of face-selective regions: a probabilistic functional atlas.

Face-selective regions (FSRs) are among the most widely studied functional regions in the human brain. However, individual variability of the FSRs has not been well quantified. Here we use functional magnetic resonance imaging (fMRI) to localize the FSRs and quantify their spatial and functional variabilities in 202 healthy adults. The occipital face area (OFA), posterior and anterior fusiform face areas (pFFA and aFFA), posterior continuation of the superior temporal sulcus (pcSTS), and posterior and anterior STS (pSTS and aSTS) were delineated for each individual with a semi-automated procedure. A probabilistic atlas was constructed to characterize their interindividual variability, revealing that the FSRs were highly variable in location and extent across subjects. The variability of FSRs was further quantified on both functional (i.e., face selectivity) and spatial (i.e., volume, location of peak activation, and anatomical location) features. Considerable interindividual variability and rightward asymmetry were found in all FSRs on these features. Taken together, our work presents the first effort to characterize comprehensively the variability of FSRs in a large sample of healthy subjects, and invites future work on the origin of the variability and its relation to individual differences in behavioral performance. Moreover, the probabilistic functional atlas will provide an adequate spatial reference for mapping the face network.

Nano-enhanced immunotherapy: Targeting the immunosuppressive tumor microenvironment.

The tumor microenvironment (TME), which is mostly composed of tumor cells, immune cells, signaling molecules, stromal tissue, and the vascular system, is an integrated system that is conducive to the formation of tumors. TME heterogeneity makes the response to immunotherapy different in different tumors, such as "immune-cold" and "immune-hot" tumors. Tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells are the major suppressive immune cells and their different phenotypes interact and influence cancer cells by secreting different signaling factors, thus playing a key role in the formation of the TME as well as in the initiation, growth, and metastasis of cancer cells. Nanotechnology development has facilitated overcoming the obstacles that limit the further development of conventional immunotherapy, such as toxic side effects and lack of targeting. In this review, we focus on the role of three major suppressive immune cells in the TME as well as in tumor development, clinical trials of different drugs targeting immune cells, and different attempts to combine drugs with nanomaterials. The aim is to reveal the relationship between immunotherapy, immunosuppressive TME and nanomedicine, thus laying the foundation for further development of immunotherapy.

A Web-Based Prognostic Model for Pediatric Genitourinary Rhabdomyosarcoma: Analysis of Population-Based Cohort With External Validation.

Background: We conduct an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) database, intending to identify prognostic factors of pediatric genitourinary rhabdomyosarcoma (PGU-RMS). Prognostic nomogram and web-based calculator were developed for potential clinical use. Methods: Data of PGU-RMS patients were extracted from the SEER database as training and internal validation cohort, patients diagnosed as PGU-RMS from 2001 to 2015 in Beijing Children's Hospital were collected as an external validation cohort. We used log-rank tests to seek risk factors on the overall survival (OS) in the overall SEER cohort, tumor site subgroups, radiation subgroups, and metastasis subgroups. The univariable and multivariate Cox regression analyses were applied to establish the prognosis model. Results: A total of 372 PGU-RMS patients in SEER and 84 patients from our center were included. 1-, 3-, and 5-year OS of the overall SEER cohort were 95.8, 82.1, and 78.8%. Subgroup analysis indicated that tumors located in the prostate/bladder were associated with a worse prognosis than the paratesticular, female genital system, and other sites (P < 0.001). Tumors of the T1/T2 stage, without regional lymph node, involvement or metastasis, can benefit from radiotherapy (P < 0.05). For patients without metastasis, younger age, T1/T2 stage, and undergoing radiation were associated with better prognosis (P < 0.05). The prognosis nomogram was well-calibrated, the concordance index (C-index) for the OS prediction was 0.823, 0.803, and 0.768 in training, internal and external validation cohort, the area under the receiver operating characteristic curve for 3-, and 5-year OS were 0.84, 0.84 in the training cohort, 0.90, 0.84 in internal validation cohort and 0.75, 0.80 in the external validation cohort. Decision curve analysis showed good clinical utility. The predictive performance of the nomogram was higher than the Intergroup Rhabdomyosarcoma Study Group (IRSG) pretreatment stage system based on the comparison of overtime C-index, net reclassification index, and integrated discriminatory index (P < 0.001). Conclusion: A comprehensive analysis of OS for PGU-RMS patients was conducted based on population cohort. The established prognosis nomogram has been fully validated and evaluated, exhibits better performance than the IRSG pretreatment stage system. Furthermore, a web-based risk calculator was developed to optimize clinical decisions.

A nomogram for prediction of distant metastasis in children with wilms tumor: A study based on SEER database.

INTRODUCTION: Accurate diagnosis of distant metastasis especially uncommon site of metastasis (UCM) in patients with Wilms tumor (WTs) is a demanding prerequisite for administration of appropriate therapy and achieving better survival outcome. OBJECTIVE: To develop and validate a nomogram to predict probability of distant metastasis, and identify population demanded for rigorous imaging evaluations in children with WTs. MATERIAL AND METHODS: Data of patients diagnosed with unilateral WTs and aged under 18 years old, were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The included patients were randomly allocated to the training and the validation cohort. Logistic regression analyses were performed to identify the independent risk factors and develop a predicting model of distant metastasis in WTs. The model-based nomogram was created and internally validated. Cut-off value of nomogram points was derived by using the receiver operating characteristics (ROC) curve analysis. Performance of the nomogram was evaluated in terms of discrimination, calibration and clinical usefulness. RESULTS: A total 717 WTs patients were included in the study. Age at diagnosis (OR 1.173, 95%CI: 1.079-1.279), LND (OR 8.260, 95%CI: 2.837-24.814) and tumor size (OR 2.141, 95%CI: 1.378-3.329) were identified as the independent risk factors of distant metastasis in WTs. These three factors were incorporated to develop a model and a nomogram. The nomogram presented with good discriminative ability in the training cohort (C-statistics, 0.703) and validation cohort (C-statistics, 0.764), respectively. The calibration curves demonstrated adequate agreement between predicted probability and observed probability of distant metastasis. The nomogram also revealed its clinical usefulness by application of decision curve analysis (DCA). Cut-off value of nomogram points was 58 and its corresponding probability of distant metastasis was 0.22. The value was applied in risk stratification dividing the general cohort into high-risk and low-risk group. DISCUSSION: Our study for the first time developed and validated a model and a visualized nomogram for individualized prediction of distant metastasis in WTs. C-statistics, calibration curves and DCA demonstrated good performance and clinical usefulness of the nomogram. Patients stratified as high-risk group were demanded for rigorous imaging evaluations to accurately identify UCM. CONCLUSION: The nomogram, developed by incorporation of three independent risk factors, which are age at diagnosis, LND and tumor size, is used to facilitate individualized prediction of distant metastasis in WTs. Rigorous imaging evaluations are recommended for patients in high-risk group to identify UCM.

Detection of monorchidism in boys with unilateral undescended testes: clinical benefits and limitations of contralateral testicular size.

INTRODUCTION: Contralateral testicular size was recommended as an effective measurement in prediction of monorchidism in some previous studies but a few argued it as invalid. Further investigation was demanded. OBJECTIVES: To investigate the effectiveness of contralateral testicular size in prediction of monorchidism in patients with unilateral non-palpable undescended testes (NPT) aged between 9 and 48 months. MATERIALS AND METHODS: Total of 707 patients aged between 9 and 48 months and diagnosed with unilateral undescended testes (UDT) between January 2016 and December 2018 at the study department were enrolled. In accordance with physical examinations and surgical findings, patients were divided into three groups: palpable UDT (group A, n = 609), non-palpable but viable testes (group B, n = 57) and monorchidism (group C, n = 41). Contralateral testicular length and volume were evaluated with ultrasonography. Comparison of contralateral testicular size between three groups and calculation of optimal cut-off value and diagnostic performance of it among NPT were performed. RESULTS: The length and volume of contralateral testes of group C were larger than of group A (P < 0.01) and group B (P < 0.01), whereas these differences between groups were small. Among patients with NPT, a receiver operating characteristic curve was used to determine the optimal cut-off value. It revealed that both a testicular length of 17.5 mm and a volume of 1.05 ml provided the highest Youden's index for prediction of monorchidism. The sensitivity and specificity for testicular length were 34.1% and 94.7%, and volume were 34.1% and 93%, respectively. The predictive accuracy for testicular length and volume were 69.4% and 65.7%, respectively. Even though the negative predictive value was merely 66.6% (54/81) and 66.2% (53/80), the positive predictive value (PPV) reaches to 82.3% (14/17) and 77.7% (14/18) for testicular length and volume. DISCUSSION: Several factors including choosing of measurement tools, age range, ethnicity, and selection bias of cohorts may be accounted for the huge differences among cut-off values and predictive accuracy. The diagnostic performance of contralateral testicular size in prediction of monorchidism in patients with NPT was poor. But the PPV was relatively promising. Contralateral testicular hypertrophy can provide information for surgical planning. CONCLUSION: The overall diagnostic performance of contralateral testicular size in prediction of monorchidism in poatients with UDT aged between 9 and 48 months was poor. But the efficiency of cut-off value predicting absence of viable testes was relatively higher. This value should be objectively applied but only as a reference which would not be a complete replacement of laparoscopy exploration.

Extrarenal Wilms tumor in children: A retrospective observational case series.

INTRODUCTION: Pediatric extrarenal Wilms tumor (ERWT) is rare. The diversity of clinical characteristics makes diagnosis, treatment and judging the prognosis difficult. Long-term follow-up outcomes and the possible prognostic factors of ERWT are still insufficient. OBJECTIVE: To identify the characteristics, therapeutic strategies and long-term results of pediatric ERWT. PATIENTS AND METHODS: All children with ERWT in our institution were retrospectively reviewed. The National Wilms Tumor Study (NWTS) system was used to evaluate tumor grade. RESULTS: Among the 876 patients with Wilms tumor in our institution between January 1986 and July 2018, 5 (0.57%) patients had ERWT. Of the 5 children with ERWT, the locations were the retroperitoneum in 3 patients (including 1 presacral) and the gubernaculum testis of an undescended testis and a duplicate sigmoid colon in 1 patient each. Two patients were stage II, and 3 patients were stage III. The three patients with larger tumor sizes had preoperative tumor rupture. In the long-term follow-up, ranging from 1.0 to 10.8 years, 3 patients had disease-free survival, and 2 patients with older age, a larger tumor size and preoperative tumor rupture had recurrence with metastasis, including 1 death. DISCUSSION: Wilms tumor extremely rarely originates outside the kidney. The current case series represents the first report of ERWT accompanied by a duplicate sigmoid colon. ERWT can coassociate with congenital gastrointestinal and genitourinary system anomalies, such as undescended testis and duplicate sigmoid colon, which provide clues to the preoperative diagnosis of ERWT. Deep and not easily palpated locations for the ERWT and older ages were associated with diagnosis delay, which can lead to enlargement of the tumor, an increased risk of preoperative tumor rupture and advancement of the tumor stage. Although only 3% of ERWT cases were metastatic according to previous reports, 2 of 5 patients (patients 1 and 4) with older age, larger tumor size and preoperative tumor rupture had recurrence and metastases in the current study. Thus, patients with poor prognoses often require aggressive combination treatments, and more attention is needed in terms of the recurrence, metastases and fatality of ERWT. CONCLUSION: ERWTs are rare tumors and can coassociate with congenital gastrointestinal and genitourinary system anomalies. The prognosis of ERWT is comparable to that of Wilms tumor located at normal anatomical sites.

13% efficiency hybrid organic/silicon-nanowire heterojunction solar cell via interface engineering.

Interface carrier recombination currently hinders the performance of hybrid organic-silicon heterojunction solar cells for high-efficiency low-cost photovoltaics. Here, we introduce an intermediate 1,1-bis[(di-4-tolylamino)phenyl]cyclohexane (TAPC) layer into hybrid heterojunction solar cells based on silicon nanowires (SiNWs) and conjugate polymer poly(3,4-ethylenedioxy-thiophene):poly(styrenesulfonate) (PEDOT:PSS). The highest power conversion efficiency reaches a record 13.01%, which is largely ascribed to the modified organic surface morphology and suppressed saturation current that boost the open-circuit voltage and fill factor. We show that the insertion of TAPC increases the minority carrier lifetime because of an energy offset at the heterojunction interface. Furthermore, X-ray photoemission spectroscopy reveals that TAPC can effectively block the strong oxidation reaction occurring between PEDOT:PSS and silicon, which improves the device characteristics and assurances for reliability. These learnings point toward future directions for versatile interface engineering techniques for the attainment of highly efficient hybrid photovoltaics.

Flexible silver nanowire meshes for high-efficiency microtextured organic-silicon hybrid photovoltaics.

Hybrid organic-silicon heterojunction solar cells promise a significant reduction on fabrication costs by avoiding energy-intensive processes. However, their scalability remains challenging without a low-cost transparent electrode. In this work, we present solution-processed silver-nanowire meshes that uniformly cover the microtextured surface of hybrid heterojunction solar cells to enable efficient carrier collection for large device area. We systematically compare the characteristics and device performance with long and short nanowires with an average length/diameter of 30 µm/115 nm and 15 µm/45 nm, respectively, to those with silver metal grids. A remarkable power conversion efficiency of 10.1% is achieved with a device area of 1 × 1 cm(2) under 100 mW/cm(2) of AM1.5G illumination for the hybrid solar cells employing long wires, which represents an enhancement factor of up to 36.5% compared to the metal grid counterpart. The high-quality nanowire network displays an excellent spatial uniformity of photocurrent generation via distributed nanowire meshes and low dependence on efficient charge transport under a high light-injection condition with increased device area. The capability of silver nanowires as flexible transparent electrodes presents a great opportunity to accelerate the mass deployment of high-efficiency hybrid silicon photovoltaics via simple and rapid soluble processes.