Individualized prognosis stratification in muscle invasive bladder cancer: A pairwise TP53-derived transcriptome signature.

TP53 is the most frequently mutated gene in muscle invasive bladder cancer (MIBC) and there are two gene signatures regarding TP53 developed for MIBC prognosis. However, they are limited to immune genes only and unable to be used individually across platforms due to their quantitative manners. We used 827 gene expression profiles from seven MIBC cohorts with varied platforms to build a pairwise TP53-derived transcriptome signature, 13 gene pairs (13-GPs). Since the 13-GPs model is a single sample prognostic predictor, it can be applied individually in practice and is applicable to any gene-expression platforms without specific normalization requirements. Survival difference between high-risk and low-risk patients stratified by the 13-GPs test was statistically significant (HR range: 2.26-2.76, all P < .0001). Discovery and validation sets showed that the 13-GPs was an independent prognostic factor after adjusting other clinical features (HR range: 2.21-2.82, all P < .05). Moreover, it was a potential supplement to the consensus molecular classification of MIBC to further stratify the LumP subtype (patients with better prognoses). High- and low-risk patients by the 13-GPs model presented distinct immune microenvironment and DDR mutation rates, suggesting that it might have the potential for immunotherapy. Being a general approach to other cancer types, this study demonstrated how we integrated gene variants with pairwise gene panels to build a single sample prognostic test in translational oncology.

Can we infer tumor presence of single cell transcriptomes and their tumor of origin from bulk transcriptomes by machine learning?

There is a growing need to build a model that uses single cell RNA-seq (scRNA-seq) to separate malignant cells from nonmalignant cells and to identify tumor of origin of single cells and/or circulating tumor cells (CTCs). Currently, it is infeasible to build a tumor of origin model learnt from scRNA-seq by machine learning (ML). We then wondered if an ML model learnt from bulk transcriptomes is applicable to scRNA-seq to infer single cells' tumor presence and further indicate their tumor of origin. We used k-nearest neighbors, one-versus-all support vector machine, one-versus-one support vector machine, random forest and introduced scTumorTrace to conduct a pioneering experiment containing leukocytes and seven major cancer types where bulk RNA-seq and scRNA-seq data were available. 13 ML models learnt from bulk RNA-seq were all reliable to use (F-score > 96%) shown by a validation set of bulk transcriptomes, but none of them was applicable to scRNA-seq except scTumorTrace. Making inferences from bulk RNA-seq to scRNA-seq was impaired by feature selection and improved by log2-transformed TPM units. scTumorTrace with transcriptome-wide 2-tuples showed F-score beyond 98.74 and 94.29% in inferring tumor presence and tumor of origin at single-cell resolution and correctly identified 45 single candidate prostate CTCs but lineage-confirmed non-CTCs as leukocytes. We concluded that modern ML techniques are quantitative and could hardly address the raised questions. scTumorTrace with transcriptome-wide 2-tuples is qualitative, standardization-free and not subject to log2-transformed quantities, enabling us to infer tumor presence of single cell transcriptomes and their tumor of origin from bulk transcriptomes.

Extended endocrine therapy in breast cancer: A basket of length-constraint feature selection metaheuristics to balance Type I against Type II errors.

Extended endocrine therapy beyond 5 years is of major concern to ER + breast cancer survivors. However, it might be unsuitable to apply routinely used genomic tests designed for early recurrence risks to distant recurrence within 10 years in extended treatment context. These tests initially aim at high sensitivities with Type I errors much higher than Type II. Having lower positive predictive values (PPVs), these tests can bring many false positives who might not need further treatment options to avoid adversely affecting quality of life. Alternatively, we proposed a top-down approach to the raised issues. We built 149 targeted genes from four genomic tests upon 381 ER-positive node-negative patients with either metastasis free beyond 10 years (n = 202) or metastasis within 10 years (n = 179). By a basket of SVM-wrapped length-constraint feature selection (LCFS), we discovered four genomic SVMs that traded off Type I against Type II errors. Two independent cohorts were used to validate disease outcome predictions. A 36-gene SVM balanced sensitivities with PPVs at good levels: 74% vs 76% on 10-fold cross validation (n = 347) and 75% vs 71% on a test set (n = 34). Neither Oncotype DX RS (cutoff = 18, 31, 60.97) nor PAM50 ROR-S (cutoff = 29, 53, 61.18) could. Independent cohorts showed the 36-gene SVM predicted disease free survival (n = 136, HR = 2.59; 95% CI, 1.4-4.8) and disease specific survival (n = 127, HR = 4.06; 95% CI, 1.63-10.11) better than RS (DFS, HR = 2.15; DSS, HR = 3.86) and ROR-S (DFS, HR = 2.29; DSS, HR = 2.76). The case study demonstrated how we identified a genomic test to balance Type I against Type II errors for risk stratification. The top-down approach centered around the LCFS-metaheuristics basket is a generic methodology for clinical decision-making and quality of life using targeted profiling data where the number of dimensions (p) is smaller than the number of samples (n).

MUC20 as a novel prognostic biomarker in ccRCC correlating with tumor immune microenvironment modulation.

Tumor microenvironment (TME) broadly participates in genesis development of clear cell renal cell carcinoma (ccRCC). To recognize the immune and stromal modulation in TME, we screened the differentially expressed TME-related genes generated by the ESTIMATE algorithm in ccRCC specimens. Following the construction of protein-protein interaction (PPI) network and univariate COX regression, mucin 20 (MUC20) was judged to be a predictive factor. Further analysis, including immunohistochemistry (IHC) showed that MUC20 was positively correlated with survival and negatively correlated with the clinicopathologic characteristics (grade, clinical and TNM stages) in ccRCC patients. Gene Set Enrichment Analysis suggested that the low-expression MUC20 group was primarily enriched in immune-related activities, inflammation and epithelial-mesenchymal transition. Based on the CIBERSORT analysis for tumor-infiltrating immune cells (TICs), MUC20 was positively correlated with CD8+ T cells and resting mast cells and negatively correlated with activated CD4+ memory T cells, Treg cells, and plasma cells, implying that MUC20 may contribute to immune component in TME. Additionally, the patients with low MUC20 expression had better response to immune checkpoint blockades (ICBs) and 17 potential anticancer drugs were screened regarding calculating IC50 value. Thus, MUC20 may contain a value of prognosis assessment for ccRCC patients and indicate the immune modulation status of TME, which provided a novel insight for comprehensive immunotherapy.

Near Miss Research in the Healthcare System: A Scoping Review.

OBJECTIVES: The aim of this study was to depict a comprehensive description of near miss research and clarify research gaps. BACKGROUND: Learning from near miss can provide early warnings and is critical for proactive and prospective risk management. Because of the lack of structured reviews, there is little knowledge about how near miss management has been managed in the past. METHODS: This review was conducted following the Arksey and O'Malley's methodology and reported by the PRISMA Extension for Scoping Reviews. RESULTS: Sixty-seven research articles were included. The results revealed that the most investigated fields include near miss reporting, near miss characteristics, and good catch project. Poor theoretical investigation, underreporting, and inconsistent outcome indicators are major problems. CONCLUSIONS: Solely understanding causes of near misses cannot guarantee effective learning; we also need to apply appropriate learning theories. Advanced technologies should be applied to solve long-standing underreporting issues. Accurate and consistent indicators should be applied in near miss research and management.

Cross-cultural adaptation and validation of the strategic learning assessment map for Chinese nursing organisation: A cross-sectional study.

AIM: To translate the Strategic Learning Assessment Map into Chinese and validate it in Chinese nursing organisations. BACKGROUND: Nursing is the largest occupational organisation in the health sector and its adaptation and innovation are important for the realisation of sustainable development goals. Organisational learning is critical in cultivating the adaptive and innovative abilities of organisations, but there is limited research on its measurement. Although the Strategic Learning Assessment Map is a widely acknowledged organisational measurement instrument, it has not yet been adapted and validated in China. DESIGN: A cross-sectional study design was used. METHODS: The Chinese version of the Strategic Learning Assessment Map was generated through forward-backward translation and was tested with a convenience sample of 2745 nurses from 7 administrative regions of mainland China. The internal consistency, content validity, structural validity and theoretical framework were examined. RESULTS: Results validated the theoretical framework and showed excellent content validity, convergent validity and fitness of the measurement model; only discriminant validity was not satisfactory. Cronbach's α values for the overall scale and its subscales ranged from 0.97 to 0.99. CONCLUSIONS: The Chinese version of the Strategic Learning Assessment Map is a reliable organisational learning instrument for Chinese nursing organisations.

Prostate cancer early diagnosis: circulating microRNA pairs potentially beyond single microRNAs upon 1231 serum samples.

The accuracy of prostate-specific antigen or clinical examination in prostate cancer (PCa) screening is in question, and circulating microRNAs (miRNAs) can be alternatives to PCa diagnosis. However, recent circulating miRNA biomarkers either are identified upon small sample sizes or cannot have robust diagnostic performance in every aspect of performance indicators. These may decrease applicability of potential biomarkers for the early detection of PCa. We reviewed recent studies on blood-derived miRNAs for prostate cancer diagnosis and carried out a large case study to understand whether circulating miRNA pairs, rather than single circulating miRNAs, could contribute to a more robust diagnostic model to significantly improve PCa diagnosis. We used 1231 high-throughput miRNA-profiled serum samples from two cohorts to design and verify a model based on class separability miRNA pairs (cs-miRPs). The pairwise model was composed of five circulating miRNAs coupled to miR-5100 and miR-1290 (i.e. five miRNA pairs, 5-cs-miRPs), reaching approximately 99% diagnostic performance in almost all indicators (sensitivity = 98.96%, specificity = 100%, accuracy = 99.17%, PPV = 100%, NPV = 96.15%) shown by a test set (n = 484: PCa = 384, negative prostate biopsies = 100). The nearly 99% diagnostic performance was also verified by an additional validation set (n = 140: PCa = 40, healthy controls = 100). Overall, the 5-cs-miRP model had 1 false positive and 7 false negatives among the 1231 serum samples and was superior to a recent 2-miRNA model (so far the best for PCa diagnosis) with 18 false positives and 80 false negatives. The present large case study demonstrated that circulating miRNA pairs could potentially bring more benefits to PCa early diagnosis for clinical practice.

Imaging findings of inflammatory pseudotumor-like follicular dendritic cell tumors of the liver: Two case reports and literature review.

BACKGROUND: Inflammatory pseudotumor-like follicular dendritic cell (IPT-like FDC) tumors of the liver is an uncommon tumor with extremely low incidence. To date, the radiologic findings of this tumor in multiphase computed tomography (CT) and magnetic resonance imaging (MRI) imaging have not been described. CASE SUMMARY: Patient 1 is a 31-year-old Chinese female, whose complaining incidentally coincided with the finding of multiple liver masses. In the local hospital, an abdominal enhanced CT found two hypo-dense solid lesions, with heterogeneous sustained hypoenhancement, in the upper segment of the liver's right posterior lobe. In our hospital, enhanced magnetic resonance imaging (MRI) with hepatocyte-specific contrast agents showed a similar enhanced pattern of lesions with patchy hyperintensity in the hepatobiliary phase (HBP). The patient underwent surgery and recovered well. The final pathology confirmed an IPT-like FDC tumor. No recurrence was found on the regular re-examination. Patient 2 is a 48-year-old Chinese male admitted to our hospital for a huge unexpected hepatic lesion. A dynamic enhanced abdominal CT revealed a huge heterogeneous enhanced solid tumor in the right lobe of the liver with a size of 100 mm × 80 mm, which showed a heterogeneous sustained hypoenhancement. In addition, enlarged lymph nodes were found in the hilum of the liver. This patient underwent a hepatic lobectomy and lymph node dissection. The final pathology confirmed an IPT-like FDC tumor. No recurrence was found upon regular re-examination. CONCLUSION: When a hepatic tumor shows heterogeneous sustained hypoenhancement with a patchy enhancement during HBP, an IPT-like FDC tumor should be considered in the differential diagnosis.

Hospital nursing, care quality, and patient satisfaction: cross-sectional surveys of nurses and patients in hospitals in China and Europe.

BACKGROUND: This study provides a comprehensive evaluation of nurse resources in Chinese hospitals and the link between nurse resources and nurse and patient outcomes. METHODS: Survey data were used from 9688 nurses and 5786 patients in 181 Chinese hospitals to estimate associations between nurse workforce characteristics and nurse and patient outcomes in China. Nurse and patient assessments in China were compared with a similar study in Europe. RESULTS: Thirty-eight percent of nurses in China had high burnout and 45% were dissatisfied with their jobs. Substantial percentages of nurses described their work environment and the quality of care on their unit as poor or fair (61% and 29%, respectively) and graded their hospital low on patient safety (36%). These outcomes tend to be somewhat poorer in China than in Europe, though fewer nurses in China gave their hospitals poor safety grades. Nurses in Chinese hospitals with better work environments and higher nurse-assessed safety grades had lower odds of high burnout and job dissatisfaction (ORs ranged from 0.56 to 0.75) and of reporting poor or fair quality patient care (ORs ranged from 0.54 to 0.74), and patients in such hospitals were more likely to rate their hospital highly, to be satisfied with nursing communications, and to recommend their hospitals (significant ORs ranged from 1.24 to 1.40). Higher patient-to-nurse ratios were associated with poorer nurse outcomes (each additional patient per nurse increases both burnout and dissatisfaction by a factor of 1.04) and higher likelihoods of nurses reporting poor or fair quality of care (OR=1.05), but were unrelated to patient outcomes. Higher percentages of baccalaureate nurses were strongly related to better patient outcomes, with each 10% increase in the percent of baccalaureate nurses increasing patient satisfaction, high ratings, and willingness to recommend their hospital by factors ranging from 1.11 to 1.13. INTERPRETATION: Nursing is important in quality and safety of hospital care and in patients' perceptions of their care. Improving quality of hospital work environments and expanding the number of baccalaureate-prepared nurses hold promise for improving hospital outcomes in China.

[A comparative Raman study of carbon nanotubes allays].

A series of comparative Raman study of carbon nanotubes arrays prepared by thermal chemical vapor deposition are reported. The results suggest that the G mode and D mode of carbon nanotubes (CNTs) arrays are all downshifted as compared to that of polycrystalline graphite, and the shifted number in well-aligned CNTs arrays is more than that in misaligned CNTs arrays. Moreover, the intensity ratio ID/IG indicates the ordering in CNTs arrays. A lower ID/IG means a higher graphitization and less amorphous carbon in CNTs arrays.

[Establishment of a new low-density cDNA macroarray and the application in the activity of IFN against HBV].

OBJECTIVE: To investigate the expression profile of genes which are involved in IFN antiviral activity and IFN signal transduction pathway in Hep G2 and HepG2.2.15 cells. METHODS: Genes of interest were selected from the UniGene database (http://www.ncbi.nlm.gov/UniGene/Hs.Home.html). The 5'IMAGE clones with 0.5-0.8 kb length were chosen and ordered from RZPD company. The cDNA inserts were amplified by PCR and then were spotted onto the Hybond-N+ membranes. The membranes were denatured and neutralized for Macroarray analysis. HepG2.2.15 and Hep G2 cells were treated without or with IFN-alpha for 6 h, and the total cellular RNA was isolated using Trizol Reagent. Radio-labelled cDNA was generated from 20 microgram of RNA by reverse transcription using 360 units of reverse transcriptase in the presence of 30 microCi of alpha-32P dCTP. Hybridization was performed between 32P-labelled cDNA and membrane arrays. The membranes were then scanned, and the intensity of autoradiographic spots was quantitated by Cyclone Storage Phosphor System. The images were subsequently analysed by the OptiQuant Imager Analysis Software and converted into digital data. RESULTS: The authors found that just partially IFN-inducible genes were expressed in Hep G2 and HepG2.2.15 cells, and the majority of IFN-inducible genes was lowly responsive or non-responsive to IFN-a treatment. Some interferon-stimulated genes (ISGs) were inhibited or blocked, especially in HepG2.2.15 cells. Interestingly, the authors found that the IFN signal transduction pathway (Jak-STAT) was intact and unimpaired in HepG2.2.15 cells. CONCLUSION: Differential gene expression profiles in response to IFN were found between Hep G2 and HepG2.2.15 cells.