Data Flow Construction and Quality Evaluation of Electronic Source Data in Clinical Trials: Pilot Study Based on Hospital Electronic Medical Records in China.

Background: The traditional clinical trial data collection process requires a clinical research coordinator who is authorized by the investigators to read from the hospital's electronic medical record. Using electronic source data opens a new path to extract patients' data from electronic health records (EHRs) and transfer them directly to an electronic data capture (EDC) system; this method is often referred to as eSource. eSource technology in a clinical trial data flow can improve data quality without compromising timeliness. At the same time, improved data collection efficiency reduces clinical trial costs. Objective: This study aims to explore how to extract clinical trial-related data from hospital EHR systems, transform the data into a format required by the EDC system, and transfer it into sponsors' environments, and to evaluate the transferred data sets to validate the availability, completeness, and accuracy of building an eSource dataflow. Methods: A prospective clinical trial study registered on the Drug Clinical Trial Registration and Information Disclosure Platform was selected, and the following data modules were extracted from the structured data of 4 case report forms: demographics, vital signs, local laboratory data, and concomitant medications. The extracted data was mapped and transformed, deidentified, and transferred to the sponsor's environment. Data validation was performed based on availability, completeness, and accuracy. Results: In a secure and controlled data environment, clinical trial data was successfully transferred from a hospital EHR to the sponsor's environment with 100% transcriptional accuracy, but the availability and completeness of the data could be improved. Conclusions: Data availability was low due to some required fields in the EDC system not being available directly in the EHR. Some data is also still in an unstructured or paper-based format. The top-level design of the eSource technology and the construction of hospital electronic data standards should help lay a foundation for a full electronic data flow from EHRs to EDC systems in the future.

Application of 3D-PCASL combined with t-ASL and MRA in the diagnosis of patients with isolated vertigo induced by posterior circulation ischemia.

OBJECTIVES: Isolated vertigo induced by posterior circulation ischemia (PCIV) can further progress into posterior circulation infarction. This study aimed to explore the diagnostic values of three-dimensional pseudo-continuous arterial spin labeling (3D-PCASL) combined with territorial arterial spin labeling (t-ASL) and magnetic resonance angiography (MRA) in visualizing and evaluating PCIV, seeking improved diagnostic tools for clinical guidance. METHODS: 28 PCIVs (11 males, 17 females, aged from 55 to 83 years, mean age: 69.68 ± 9.01 years) and 28 healthy controls (HCs, 12 male, 16 female, aged from 56 to 87 years, mean age: 66.75 ± 9.86 years) underwent conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), MRA, 3D-PCASL, and t-ASL. We compared the incidence of anatomic variants of the posterior circle of Willis in MRA, cerebral blood flow (CBF) and anterior collateral blood flow on postprocessing maps obtained from 3D-PCASL and t-ASL sequence between PCIVs and HCs. Chi-square test and paired t-test were analyzed statistically with SPSS 24.0 software. RESULTS: 7 PCIVs (7/28, 25%) and 6 HCs (6/28, 21%) showed fetal posterior cerebral artery (FPCA) on MRA, including 1 HC, and 6 PCIVs with FPCA appeared hypoperfusion. 18 PCIVs (64%) and 2 HCs (7%) showed hypoperfusion in the posterior circulation (PC), including 1 HC and 7 PCIVs displayed anterior circulation collateral flow. Chi-square analyses demonstrated a difference in PC hypoperfusion between PCIVs and HCs, whether in the whole or FPCA-positive group assessment (P < 0.05). Paired t-test showed that the CBF values were significant difference for the bilateral PC asymmetrical perfusion in the PCIVs (P < 0.01). When compared to the bilateral PC symmetrical non-hypoperfusion area in the PCIVs and HCs, the CBF values were not significant (P > 0.05). The CBF values of the PC in PCIVs were lower than in HCs (P < 0.05). The reduction rate in the hypoperfusion side of the bilateral PC asymmetrical perfusion of the PCIVs ranged from 4% to 37%, while the HCs reduction rate was 7.7%. The average PC symmetrical perfusion average reduction rate of the PCIVs was 52.25%, while the HCs reduction rate was 42.75%. CONCLUSION: 3D-PCASL is a non-invasive and susceptible method for detecting hypoperfusion in PC, serving as a potential biomarker of PCIV. The suspected hypoperfusion in PC may be attributed to the emergence of FPCA and the manifestation of anterior collateral flow when combining t-ASL and MRA sequences. These findings demonstrated that 3D-PCASL combined with t-ASL and MRA sequences are the potential method to identify PCIV, leading to early diagnosis of PCIV and reducing the risk of progressing into infarction.

A successful surgical management for a thrombosed giant left coronary aneurysm with right ventricular fistula in a young patient.

Giant coronary aneurysm with ventricular fistula is rare. Due to the limited data from randomised clinical trials, therapeutic strategies for coronary aneurysms predominantly rely on on case series and anecdotal evidences. Reporting cases that provide practical experience in managing these aneurysms is therefore crucial. In this article, we report a rare case of a successful surgical management for a thrombosed giant left coronary aneurysm with right ventricular fistula, which is larger than any previously reported cases.

Optimized method for polarization-based image dehazing.

Image dehazing is desired under the foggy, rainy weather, or the underwater condition. Since the polarization-based image dehazing utilizes additional polarization information of light to de-scatter, image detail can be recovered well, but how to segment the polarization information of the background radiance and the object radiance becomes the key problem. For solving this problem, a method which combing polarization and contrast enhancement is demonstrated. This method contains two main steps, (a) by seeking the region of large mean intensity, low contrast and large mean degree of polarization, the no-object region can be found, and (b) through defining a weight function and judging whether the dehazed image can achieve high contrast and low information loss, the degree of polarization for object radiance can be estimated. Based on the estimated parameters, the scatter of light by the mediums can be diminished considerably. The theoretical derivation shows that this method can achieve advantages complementation, such as being able to obtain more details like the polarization-based method and high image contrast like the contrast enhancement based method. Besides, it is physically sound and can achieve good dehazing performance under different conditions, which has been verified by different hazing polarization images.

Attitude Correlated Frames Based Calibration Method for Star Sensors.

Star sensors undergo laboratory calibration before they leave the factory. In addition, recalibration is necessary after they experience vibration, deformation, etc. Using the analysis of attitude-dependent and attitude-independent interstar angular invariance calibration methods (IAICMs) as a reference, an attitude-correlated frame-based calibration method (ACFCM) is proposed in this work, which combines the advantages of both methods. Using outdoor star observations, the ACFCM correlates star image frames obtained at different times via a strapdown gyro unit. As a result, the number of efficient star images for calibration increases rapidly and the distribution of star images becomes much more uniform, thus improving the calibration accuracy of the star sensor. A simulation and experimental tests were designed and carried out. Both the simulation and experimental results verify the feasibility of the proposed ACFCM method. Furthermore, by comparing our method with the IAICMs, the repeatability and reliability of the principal point obtained from the calibration with the ACFCM method proposed in this work were significantly improved.

Molecular Characteristics of T Cell-Mediated Tumor Killing in Hepatocellular Carcinoma.

Background: Although checkpoint blockade is a promising approach for the treatment of hepatocellular carcinoma (HCC), subsets of patients expected to show a response have not been established. As T cell-mediated tumor killing (TTK) is the fundamental principle of immune checkpoint inhibitor therapy, we established subtypes based on genes related to the sensitivity to TKK and evaluated their prognostic value for HCC immunotherapies. Methods: Genes regulating the sensitivity of tumor cells to T cell-mediated killing (referred to as GSTTKs) showing differential expression in HCC and correlations with prognosis were identified by high-throughput screening assays. Unsupervised clustering was applied to classify patients with HCC into subtypes based on the GSTTKs. The tumor microenvironment, metabolic properties, and genetic variation were compared among the subgroups. A scoring algorithm based on the prognostic GSTTKs, referred to as the TCscore, was developed, and its clinical and predictive value for the response to immunotherapy were evaluated. Results: In total, 18 out of 641 GSTTKs simultaneously showed differential expression in HCC and were correlated with prognosis. Based on the 18 GSTTKs, patients were clustered into two subgroups, which reflected distinct TTK patterns in HCC. Tumor-infiltrating immune cells, immune-related gene expression, glycolipid metabolism, somatic mutations, and signaling pathways differed between the two subgroups. The TCscore effectively distinguished between populations with different responses to chemotherapeutics or immunotherapy and overall survival. Conclusions: TTK patterns played a nonnegligible role in formation of TME diversity and metabolic complexity. Evaluating the TTK patterns of individual tumor will contribute to enhancing our cognition of TME characterization, reflects differences in the functionality of T cells in HCC and guiding more effective therapy strategies.

18F-labeled Dimer-Sansalvamide A Cyclodecapeptide: A Novel Diagnostic Probe to Discriminate Pancreatic Cancer from Inflammation in a Nude Mice Model.

Early detection of pancreatic cancer has been a long-standing challenge. Inflammatory mass is the main source of false-positive findings in 18F-labeled fluorodeoxyglucose (18F-FDG) positron emission tomography / computed tomography (PET/CT). Heat shock protein 90 (Hsp90) is an established biomarker overexpressed in pancreatic cancer. We modified a Dimer-Sansalvamide A cyclodecapeptide by conjugating it with the bifunctional chelator NOTA (1,4,7-triazacyclononane-1,4,7-trisacetic acid), yielding 18F-NOTA-Dimer-Sansalvamide A cyclodecapeptide (18F-NOTA-Dimer-San A). The binding specificity of the probe was confirmed by in vitro cell uptake assays in Hsp90-positive PL45 pancreatic cancer cells. Hsp90 expression was imaged via MicroPET in pancreatic cancer xenografts and inflammation in mice. All of the mice received an intravenous injection of 18F-NOTA-Dimer-San A, and images were acquired at 1 and 2 hour time points. The novel probe demonstrated prominent tumor uptake in the pancreatic cancer xenografts (4.00 ± 0.88 %ID/g, 5.80 ± 0.94 %ID/g), and the inflammatory thigh showed minimal uptake (0.85 ± 0.01 %ID/g, 1.50 ± 0.20 %ID/g) at 1 and 2 hours after injection, respectively. The activity accumulation between the two groups was significantly different (P < 0.05), and the biodistribution data was consistent with the images. Moreover, immunohistochemistry (IHC) confirmed that the expression of Hsp90 was positive in PL45 pancreatic cancer but negative in the muscles next to the tumor and inflammatory muscles. We concluded that 18F-NOTA-Dimer-San A PET might allow non-invasive imaging for Hsp90 expression in tumors and has the potential to discriminate pancreatic cancer from inflammatory mass.

Quantitative assessment of articular cartilage degeneration using 3D ultrashort echo time cones adiabatic T1ρ (3D UTE-Cones-AdiabT1ρ) imaging.

OBJECTIVES: To evaluate articular cartilage degeneration using quantitative three-dimensional ultrashort-echo-time cones adiabatic-T1ρ (3D UTE-Cones-AdiabT1ρ) imaging. METHODS: Sixty-six human subjects were recruited for this study. Kellgren-Lawrence (KL) grade and Whole-Organ Magnetic-Resonance-Imaging Score (WORMS) were evaluated by two musculoskeletal radiologists. The human subjects were categorized into three groups, namely normal controls (KL0), doubtful-minimal osteoarthritis (OA) (KL1-2), and moderate-severe OA (KL3-4). WORMS were regrouped to encompass the extent of lesions and the depth of lesions. The UTE-Cones-AdiabT1ρ values were obtained using 3D UTE-Cones data acquisitions preceded by seven paired adiabatic full passage pulses that corresponded to seven spin-locking times (TSLs) of 0, 12, 24, 36, 48, 72, and 96 ms. The performance of the UTE-Cones-AdiabT1ρ technique in evaluating the degeneration of knee cartilage was assessed via the ANOVA comparisons with subregional analysis and Spearman's correlation coefficient as well as the receiver-operating-characteristic (ROC) curve. RESULTS: UTE-Cones-AdiabT1ρ showed significant positive correlations with KL grade (r = 0.15, p < 0.05) and WORMS (r = 0.57, p < 0.05). Higher UTE-Cones-AdiabT1ρ values were observed in both larger and deeper lesions in the cartilage. The differences in UTE-Cones-AdiabT1ρ values among different extent and depth groups of cartilage lesions were all statistically significant (p < 0.05). Subregional analyses showed that the correlations between UTE-Cones-AdiabT1ρ and WORMS varied with the location of cartilage. The AUC value of UTE-Cones-AdiabT1ρ for mild cartilage degeneration (WORMS=1) was 0.8. The diagnostic threshold value of UTE-Cones-AdiabT1ρ for mild cartilage degeneration was 39.4 ms with 80.8% sensitivity. CONCLUSIONS: The 3D UTE-Cones-AdiabT1ρ sequence can be useful in quantitative evaluation of articular cartilage degeneration. KEY POINTS: • The 3D UTE-Cones-AdiabT1ρ sequence can distinguish mild cartilage degeneration from normal cartilage with a diagnostic threshold value of 39.4 ms for mild cartilage degeneration with 80.8% sensitivity. • Higher UTE-Cones-AdiabT1ρ values were observed in both larger and deeper lesions in the articular cartilage. • UTE-Cones-AdiabT1ρ is a promising biomarker for quantitative evaluation of early cartilage degeneration.

Modelled Economic Analysis for Dacomitinib-A Cost Effectiveness Analysis in Treating Patients With EGFR-Mutation-Positive Non-Small Cell Lung Cancer in China.

OBJECTIVES: To establish the cost-effectiveness of dacomitinib compared to gefitinib from the Chinese healthcare system perspective. PATIENTS: Advanced non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations. METHODS: Partitioned survival analysis was undertaken to examine the cost-effectiveness of dacomitinib utilising individual patient data (IPD) from the pivotal randomised controlled trial (RCT) (ARCHER 1050). The three health states modelled were progression-free, post-progression, and death. Parametric survival distributions were fitted to IPD against the Kaplan-Meier survival curves corresponding to progression-free survival (PFS) and overall survival (OS) outcomes by randomised groups. Costs included drug acquisition and administration, outpatient management (outpatient consultation and examinations), and best supportive care costs. Utility weights were sourced from the pivotal trial and other published literature. The incremental cost-effectiveness ratio (ICER) was calculated with costs and quality-adjusted life years (QALYs) discounted at an annual rate of 5%. Both deterministic and probabilistic sensitivity analyses were undertaken. RESULTS: In the base case, dacomitinib (CNY 265,512 and 1.95 QALY) was associated with higher costs and QALY gains compared to gefitinib (CNY 247,048 and 1.61 QALYs), resulting in an ICER of CNY 58,947/QALY. Using the empirical WTP/QALY threshold, dacomitinib is a cost-effective treatment strategy for patients with EGFR-mutation-positive advanced NSCLC. The probabilistic sensitivity analysis suggested that dacomitinib had a 97% probability of being cost-effective. CONCLUSIONS: Dacomitinib is a cost-effective treatment strategy in treating patients with EGFR-mutation-positive NSCLC from the Chinese healthcare system perspective. The uncertainty around the cost-effectiveness of dacomitinib could be reduced if long-term survival data become available. CLINICAL TRIAL REGISTRATION: NCT01024413.

Immune-Related lncRNA to Construct Novel Signature and Predict the Immune Landscape of Human Hepatocellular Carcinoma.

The signature composed of immune-related long noncoding ribonucleic acids (irlncRNAs) with no requirement of specific expression level seems to be valuable in predicting the survival of patients with hepatocellular carcinoma (HCC). Here, we retrieved raw transcriptome data from The Cancer Genome Atlas (TCGA), identified irlncRNAs by co-expression analysis, and recognized differently expressed irlncRNA (DEirlncRNA) pairs using univariate analysis. In addition, we modified Lasso penalized regression. Then, we compared the areas under curve, counted the Akaike information criterion (AIC) values of 5-year receiver operating characteristic curve, and identified the cut-off point to set up an optimal model for distinguishing the high- or low-disease-risk groups among patients with HCC. We then reevaluated them from the viewpoints of survival, clinic-pathological characteristics, tumor-infiltrating immune cells, chemotherapeutics efficacy, and immunosuppressed biomarkers. 36 DEirlncRNA pairs were identified, 12 of which were included in a Cox regression model. After regrouping the patients by the cut-off point, we could more effectively differentiate between them based on unfavorable survival outcome, aggressive clinic-pathological characteristics, specific tumor immune infiltration status, low chemotherapeutics sensitivity, and highly expressed immunosuppressed biomarkers. The signature established by paring irlncRNA regardless of expression levels showed a promising clinical prediction value.

Molecular gene mutation profiles, TMB and the impact of prognosis in Caucasians and east Asian patients with lung adenocarcinoma.

BACKGROUND: The difference in molecular gene mutation profile, tumor mutational burden (TMB) and their prognostic effects in lung adenocarcinoma between different ethnic groups are still unknown. A retrospective analysis was used to investigate the differences in lung adenocarcinoma driver gene mutations, TMB, and their impact on prognosis across different ethnic groups. METHODS: The incidence of epidermal growth factor receptor (EGFR) mutations and follow-up data of 647 Chinese lung adenocarcinoma patients were compared with the data from 522 Caucasian patients in The Cancer Genome Atlas (TCGA) database. Moreover, a comprehensive analysis was performed to compare the differences in gene mutation frequency, signaling pathway variation, and TMB using the whole-exome sequencing (WES) data of Chinese patients with that of Caucasian patients. RESULTS: A comparison of tumor signaling pathways and gene mutation profiles between Caucasians and Chinese revealed ethnic variations in the incidence of mutations in TGF-ß and RTK-RAS signaling pathways, with P values of 0.012 and 0.016, respectively. In the Caucasian population, the mutations in 5 signaling pathways and 18 genes were all significantly correlated with TMB, whereas in the Chinese population, only mutations in the Notch pathway and 6 genes were found to be associated with TMB-high. EGFR mutations showed a better prognosis in Chinese patients with lung adenocarcinoma, while the opposite was found in Caucasians patients. CONCLUSIONS: Variations in the incidence of mutations in signaling pathways involved in lung adenocarcinoma and the correlation of the signaling pathways with TMB may exist across different ethnic groups.

Intervertebral disc degeneration associated with vertebral marrow fat, assessed using quantitative magnetic resonance imaging.

OBJECTIVE: To investigate the potential clinical application of quantitative MRI in assessing the correlation between lumbar vertebrae bone marrow fat deposition and intervertebral disc degeneration. MATERIALS AND METHODS: A total of 104 chronic lower-back pain volunteers underwent 3.0-T MRI with T2-weighted imaging, T2 mapping, and iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL-IQ) between August 2018 and June 2019. Each disc was assessed with T2 value by T2 mapping, and the L1-S1 vertebral bone marrow fat fraction was assessed by IDEAL-IQ. The differences and relationship between T2 value and the adjacent vertebral bone marrow fat fraction values within the five Pfirrmann groups, five age groups, and five lumbar levels were statistically analyzed. RESULTS: The vertebral bone marrow fat fraction had a significant negative correlation with T2 values of nucleus pulposus' T2 values (p < 0.001). However, the significant negative correlation was only found between T2 values of nucleus pulposus and adjacent vertebral bone marrow fat in Pfirrmann II-III, L1/2-L5/S1 level, and 40-49 years' age groups. Pfirrmann grades of the intervertebral disc were positively correlated with adjacent vertebrae bone marrow fat fraction (p < 0.05). CONCLUSION: Lumbar bone marrow fat deposition significantly increases during the early stages of intervertebral disc degeneration. Quantitative measurements of bone marrow fat deposition and water content of intervertebral discs have a predictive value and are an important supplement to the qualitative traditional classification strategies for the early stages of intervertebral disc degeneration.

Immune-related prognosis biomarkers associated with osteosarcoma microenvironment.

BACKGROUND: Osteosarcoma is a highly aggressive bone tumor that most commonly affects children and adolescents. Treatment and outcomes for osteosarcoma have remained unchanged over the past 30 years. The relationship between osteosarcoma and the immune microenvironment may represent a key to its undoing. METHODS: We calculated the immune and stromal scores of osteosarcoma cases from the Target database using the ESTIMATE algorithm. Then we used the CIBERSORT algorithm to explore the tumor microenvironment and analyze immune infiltration of osteosarcoma. Differentially expressed genes (DEGs) were identified based on immune scores and stromal scores. Search Tool for the Retrieval of Interacting Genes Database (STRING) was utilized to assess protein-protein interaction (PPI) information, and Molecular Complex Detection (MCODE) plugin was used to screen hub modules of PPI network in Cytoscape. The prognostic value of the gene signature was validated in an independent GSE39058 cohort. Gene set enrichment analysis (GSEA) was performed to study the hub genes in signaling pathways. RESULTS: From 83 samples of osteosarcoma obtained from the Target dataset, 137 DEGs were identified, including 134 upregulated genes and three downregulated genes. Functional enrichment analysis and PPI networks demonstrated that these genes were mainly involved in neutrophil degranulation and neutrophil activation involved in immune response, and participated in neuroactive ligand-receptor interaction and staphylococcus aureus infection. CONCLUSIONS: Our study established an immune-related gene signature to predict outcomes of osteosarcoma, which may be important targets for individual treatment.

Assessment of the expression of the immune checkpoint molecules PD-1, CTLA4, TIM-3 and LAG-3 across different cancers in relation to treatment response, tumor-infiltrating immune cells and survival.

Immune checkpoint molecules have been identified as crucial regulators of the immune response, which motivated the emergence of immune checkpoint-targeting therapeutic strategies. However, the prognostic significance of the immune checkpoint molecules PD-1, CTLA4, TIM-3 and LAG-3 remains controversial. The aim of our study was to conduct a systematic assessment of the expression of these immune checkpoint molecules across different cancers in relation to treatment response, tumor-infiltrating immune cells and survival. Oncomine and PrognoScan database analyses were used to investigate the expression levels and prognostic values of these immune checkpoint molecule genes across various cancers. Then, we used Kaplan-Meier plotter to validate the associations between the checkpoint molecules and cancer survival identified in the PrognoScan analysis. TIMER analysis was used to evaluate immune cell infiltration data from The Cancer Genome Atlas. Finally, we used Gene Expression Profiling Interactive Analysis to investigate the prognostic value of these four checkpoint molecules and assess the correlations between these four checkpoint molecules and genetic markers. These immune checkpoint molecules may potentially serve as prognostic factors and therapeutic targets in breast cancer, ovarian cancer and lung cancer. The prognostic roles of these checkpoint molecules varied greatly across cancers, which implied a noteworthy amount of heterogeneity among tumors, even within the same molecular subtype. In addition, the expression patterns of these checkpoint molecules were closely associated with treatment response and provided some useful direction when choosing chemotherapeutic drugs. These findings enhance our understanding of these checkpoints in cancer treatment and identify strategies to promote synergistic activities in the context of other immunotherapies.

Co-occurring genetic alterations and primary EGFR T790M mutations detected by NGS in pre-TKI-treated NSCLCs.

INTRODUCTION: Next-generation sequencing (NGS)-based assays to understand various mutations and co-occurrence of genomic alterations in non-small cell lung cancer (NSCLC) have enabled understanding of treatment impact on clinical outcomes. METHODS: This retrospective study was conducted in 1353 formalin-fixed paraffin-embedded (FFPE) tissues from surgically resected, pre-TKI-treated NSCLC patients with identified gene alterations. Genomic DNA and RNA extraction was followed by NGS library preparation and sequencing using the Ion Ampliseq Colon and Lung Cancer Gene Panel V2 and the AmpliSeq RNA Lung Cancer Research Fusion Panel. RESULTS: A total of 2328 alterations in 25 genes were detected from the 1293 patients. DNA mutations and RNA fusions co-occurred in 27 patients with TP53 being the most common co-occurring DNA mutation (43.8%) with concurrent ALK fusions. Analysis of the 975 patients with EGFR mutations revealed that the incidence of dual EGFR L858R/T790M mutations was higher compared to EGFR 19del/T790M, and the mean allele fraction (MAF) of T790M was lower compared to 19del in dual EGFR 19del/T790M patients. CONCLUSION: NSCLC patients represented genetically heterogeneous subgroup with a high frequency of co-occurring mutations in cancer-associated pathways. This diverse mutational profile may have key clinical and research implications for understanding the variability of treatment outcome in pre-TKI-treated NSCLC population. The differences in the MAF of EGFR T790M may determine different responses to TKI therapy in patients harboring dual mutations.

Genome-wide profiling of prognosis-related alternative splicing signatures in sarcoma.

BACKGROUND: Sarcomas (SARCs) are rare malignant tumors with poor prognosis. Increasing evidence has suggested that aberrant alternative splicing (AS) is strongly associated with tumor initiation and progression. We considered whether survival-related AS events might serve as prognosis predictors and underlying targeted molecules in SARC treatment. METHODS: RNA-Seq data of the SARC cohort were downloaded from The Cancer Genome Atlas (TCGA) database. Survival-related AS events were selected by univariate and multivariate Cox regression analyses. Metascape was used for constructing a gene interaction network and performing functional enrichment analysis. Then, prognosis predictors were established based on statistically significant survival-related AS events and evaluated by receiver operator characteristic (ROC) curve analysis. Finally, the potential regulatory network was analyzed via Pearson's correlation between survival-related AS events and splicing factors (SFs). RESULTS: A total of 3,610 AS events and 2,291 genes were found to be prognosis-related in 261 SARC samples. The focal adhesion pathway was identified as the most critical molecular mechanism corresponding to poor prognosis. Notably, several prognosis predictors based on survival-related AS events showed excellent performance in prognosis prediction. The area under the curve of the ROC of the risk score was 0.85 in the integrated predictor. The splicing network proved complicated regulation between prognosis-related SFs and AS events. Also, driver gene mutations were significantly associated with AS in SARC patients. CONCLUSIONS: Survival-related AS events may become ideal indictors for the prognosis prediction of SARCs. Corresponding splicing regulatory mechanisms are worth further exploration.

Genome-Wide Profiling of Prognostic Alternative Splicing Pattern in Pancreatic Cancer.

Alternative splicing (AS) has a critical role in tumor progression and prognosis. Our study aimed to investigate pancreatic cancer-specific AS events using RNA-seq data, gaining systematic insights into potential prognostic predictors. We downloaded 10,623 genes with 45,313 pancreatic cancer-specific AS events from the Cancer Genome Atlas (TCGA) and SpliceSeq database. Cox univariate analyses of overall survival suggested there was a remarkable association between 6,711 AS events and overall survival in pancreatic cancer patients (P < 0.05). The area under the curves (AUC) of the receiver operator characteristic curves (ROC) of risk score was 0.89 for final prognostic predictor. Results indicated that AS events of DAZAP1, RBM4, ESRP1, QKI, and SF1 were significantly associated with overall survival. The results of FunRich showed that transcription factors KLF7, GABPA, and SP1 were the most highly related to survival-associated AS genes. Furthermore, using DriverDBv2, we identified 13 driver genes associated with survival-associated AS events, including TP53 and CDC27. Thus, we concluded that the aberrant AS patterns in pancreatic cancer patients might serve as prognostic predictors.

Magnetic resonance enterography (MRE) and ultrasonography (US) in the study of the small bowel in Crohn's disease: state of the art and review of the literature.

Crohn's disease (CD) is a chronic idiopathic disease and its diagnosis is based on a combination of clinical symptoms, laboratory tests and imaging data. There isn't a diagnostic gold standard: the ileocolonoscopy with mucosal biopsies represents the standard for luminal disease, while cross-sectional imaging such as Ultrasound (US), Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) can show transmural alterations and extraintestinal manifestations. CD is usually diagnosed in the young age and after baseline diagnosis, the patients have to undergo to variable follow-up depending on remission or active disease. The aim of our review is to compare Magnetic Resonance Enterography (MRE) to Ultrasonography (US) in the follow-up of CD.

Application of diffusion tensor imaging (DTI) and MR-tractography in the evaluation of peripheral nerve tumours: state of the art and review of the literature.

Peripheral nerves can be affected by a variety of benign and malignant tumour and tumour-like lesions. Besides clinical evaluation and electrophysiologic studies, MRI is the imaging modality of choice for the assessment of these soft tissue tumours. Conventional MR sequences, however, can fail to assess the histologic features of the lesions. Moreover, the precise topographical relationship between the peripheral nerve and the tumor must be delineated preoperatively for complete tumour resection minimizing nerve damage. Using Diffusion tensor imaging (DTI) and tractography, it is possible to obtain functional information on tumour and nerve structures, allowing the assess anatomy, function and biological features. In this article, we review the technical aspects and clinical application of DTI for the evaluation of peripheral nerve tumours.

Prevalence of ROS1 fusion in Chinese patients with non-small cell lung cancer.

BACKGROUND: The study was conducted to investigate the clinicopathological features and prevalence of ROS1 gene fusion in Chinese patients with non-small cell lung cancer (NSCLC). METHODS: The presence of ROS1 fusion was assessed by quantitative real-time PCR. Associations between ROS1 fusion and clinical characteristics were analyzed. RESULTS: In total, 6066 patients with pathologically confirmed NSCLC and ROS1 fusion test results were enrolled. The average age was 60.89 ± 10.60 years and fusion was detected in 157 (2.59%) patients. Fusion frequency was significantly correlated with age, gender, smoking status (all P < 0.001), pathology type (P = 0.017), and lymph node metastasis stage (P = 0.027). ROS1 fusion-positive patients were significantly younger (55.68 ± 11.34 vs. negative 61.02 ± 10.44 years; P < 0.01). Fusion frequency was higher in women (3.71% vs. men 1.81%), never-smokers (3.33% vs. smokers 1.21%), and patients with adenocarcinoma (2.77% vs. squamous lung cancer 0.93%) and at advanced node stages (1.31%, 1.40%, 2.07%, and 3.23% for N0, N1, N2, and N3, respectively). No significant correlation between ROS1 fusion status and pathological stage was found in subgroups classified by pathological, tumor, or metastasis stage (P > 0.05). Age, smoking status, and lymph node stage were statistically significantly correlated with ROS1 fusion frequency (all P < 0.05); gender and pathology type were not significantly correlated with ROS1 fusion status after adjusting for smoking status. CONCLUSION: An overall ROS1 fusion frequency of 2.59% was confirmed in this study. ROS1 fusion was more prevalent among younger patients, never-smokers, and those at advanced node stages.