Evaluation of a short RNA within Prostate Cancer Gene 3 in the predictive role for future cancer using non-malignant prostate biopsies.

BACKGROUND: Prostate Cancer 3 (PCA3) is a long non-coding RNA (ncRNA) upregulated in prostate cancer (PCa). We recently identified a short ncRNA expressed from intron 1 of PCA3. Here we test the ability of this ncRNA to predict the presence of cancer in men with a biopsy without PCa. METHODS: We selected men whose initial biopsy did not identify PCa and selected matched cohorts whose subsequent biopsies revealed PCa or benign tissue. We extracted RNA from the initial biopsy and measured PCA3-shRNA2, PCA3 and PSA (qRT-PCR). RESULTS: We identified 116 men with and 94 men without an eventual diagnosis of PCa in 2-5 biopsies (mean 26 months), collected from 2002-2008. The cohorts were similar for age, PSA and surveillance period. We detected PSA and PCA3-shRNA2 RNA in all samples, and PCA3 RNA in 90% of biopsies. The expression of PCA3 and PCA3-shRNA2 were correlated (Pearson's r = 0.37, p<0.01). There was upregulation of PCA3 (2.1-fold, t-test p = 0.02) and PCA3-shRNA2 (1.5-fold) in men with PCa on subsequent biopsy, although this was not significant for the latter RNA (p = 0.2). PCA3 was associated with the future detection of PCa (C-index 0.61, p = 0.01). This was not the case for PCA3-shRNA2 (C-index 0.55, p = 0.2). CONCLUSIONS: PCA3 and PCA3-shRNA2 expression are detectable in historic biopsies and their expression is correlated suggesting co-expression. PCA3 expression was upregulated in men with PCa diagnosed at a future date, the same did not hold for PCA3-shRNA2. Futures studies should explore expression in urine and look at a time course between biopsy and PCa detection

Validation of Novel Biomarkers for Prostate Cancer Progression by the Combination of Bioinformatics, Clinical and Functional Studies

The identification and validation of biomarkers for clinical applications remains an important issue for improving diagnostics and therapy in many diseases, including prostate cancer. Gene expression profiles are routinely applied to identify diagnostic and predictive biomarkers or novel targets for cancer. However, only few predictive markers identified in silico have also been validated for clinical, functional or mechanistic relevance in disease progression. In this study, we have used a broad, bioinformatics-based approach to identify such biomarkers across a spectrum of progression stages, including normal and tumor-adjacent, premalignant, primary and late stage lesions. Bioinformatics data mining combined with clinical validation of biomarkers by sensitive, quantitative reverse-transcription PCR (qRT-PCR), followed by functional evaluation of candidate genes in disease-relevant processes, such as cancer cell proliferation, motility and invasion. From 300 initial candidates, eight genes were selected for validation by several layers of data mining and filtering. For clinical validation, differential mRNA expression of selected genes was measured by qRT-PCR in 197 clinical prostate tissue samples including normal prostate, compared against histologically benign and cancerous tissues. Based on the qRT-PCR results, significantly different mRNA expression was confirmed in normal prostate versus malignant PCa samples (for all eight genes), but also in cancer-adjacent tissues, even in the absence of detectable cancer cells, thus pointing to the possibility of pronounced field effects in prostate lesions. For the validation of the functional properties of these genes, and to demonstrate their putative relevance for disease-relevant processes, siRNA knock-down studies were performed in both 2D and 3D organotypic cell culture models. Silencing of three genes (DLX1, PLA2G7 and RHOU) in the prostate cancer cell lines PC3 and VCaP by siRNA resulted in marked growth arrest and cytotoxicity, particularly in 3D organotypic cell culture conditions. In addition, silencing of PLA2G7, RHOU, ACSM1, LAMB1 and CACNA1D also resulted in reduced tumor cell invasion in PC3 organoid cultures. For PLA2G7 and RHOU, the effects of siRNA silencing on proliferation and cell-motility could also be confirmed in 2D monolayer cultures. In conclusion, DLX1 and RHOU showed the strongest potential as useful clinical biomarkers for PCa diagnosis, further validated by their functional roles in PCa progression. These candidates may be useful for more reliable identification of relapses or therapy failures prior to the recurrence local or distant metastases

A Hybrid Fuzzy Multi-criteria Decision Making Model to Evaluate the Overall Performance of Public Emergency Departments: A Case Study

[EN] Performance evaluation is relevant for supporting managerial decisions related to the improvement of public emergency departments (EDs). As different criteria from ED context and several alternatives need to be considered, selecting a suitable Multicriteria Decision-Making (MCDM) approach has become a crucial step for ED performance evaluation. Although some methodologies have been proposed to address this challenge, a more complete approach is still lacking. This paper bridges this gap by integrating three potent MCDM methods. First, the Fuzzy Analytic Hierarchy Process (FAHP) is used to determine the criteria and sub-criteria weights under uncertainty, followed by the interdependence evaluation via fuzzy Decision-Making Trial and Evaluation Laboratory(FDEMATEL). The fuzzy logic is merged with AHP and DEMATEL to illustrate vague judgments. Finally, the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) is used for ranking EDs. This approach is validated in a real 3-ED cluster. The results revealed the critical role of Infrastructure (21.5%) in ED performance and the interactive nature of Patient safety (C+R =12.771). Furthermore, this paper evidences the weaknesses to be tackled for upgrading the performance of each ED.Ortiz-Barrios, M.; Alfaro Saiz, JJ. (2020). A Hybrid Fuzzy Multi-criteria Decision Making Model to Evaluate the Overall Performance of Public Emergency Departments: A Case Study. International Journal of Information Technology & Decision Making. 19(6):1485-1548. https://doi.org/10.1142/S0219622020500364S14851548196Lord, K., Parwani, V., Ulrich, A., Finn, E. B., Rothenberg, C., Emerson, B., … Venkatesh, A. K. (2018). Emergency department boarding and adverse hospitalization outcomes among patients admitted to a general medical service. The American Journal of Emergency Medicine, 36(7), 1246-1248. doi:10.1016/j.ajem.2018.03.043Sørup, C. M., Jacobsen, P., & Forberg, J. L. (2013). 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(2018). A Fuzzy AHP–TOPSIS-Based Group Decision-Making Approach to IT Personnel Selection. International Journal of Fuzzy Systems, 20(5), 1576-1591. doi:10.1007/s40815-018-0474-7CHEN, M.-F., TZENG, G.-H., & TANG, T.-I. (2005). FUZZY MCDM APPROACH FOR EVALUATION OF EXPATRIATE ASSIGNMENTS. International Journal of Information Technology & Decision Making, 04(02), 277-296. doi:10.1142/s0219622005001520Gul, M., Celik, E., Gumus, A. T., & Guneri, A. F. (2016). Emergency department performance evaluation by an integrated simulation and interval type-2 fuzzy MCDM-based scenario analysis. European J. of Industrial Engineering, 10(2), 196. doi:10.1504/ejie.2016.075846Jovčić, Průša, Dobrodolac, & Švadlenka. (2019). A Proposal for a Decision-Making Tool in Third-Party Logistics (3PL) Provider Selection Based on Multi-Criteria Analysis and the Fuzzy Approach. Sustainability, 11(15), 4236. doi:10.3390/su11154236Saaty, T. L., & Vargas, L. G. (2012). 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K., Govindan, K., Antucheviciene, J., & Turskis, Z. (2016). Hybrid multiple criteria decision-making methods: a review of applications for sustainability issues. Economic Research-Ekonomska Istraživanja, 29(1), 857-887. doi:10.1080/1331677x.2016.1237302Lolli, F., Balugani, E., Ishizaka, A., Gamberini, R., Butturi, M. A., Marinello, S., & Rimini, B. (2019). On the elicitation of criteria weights in PROMETHEE-based ranking methods for a mobile application. Expert Systems with Applications, 120, 217-227. doi:10.1016/j.eswa.2018.11.030De Almeida Filho, A. T., Clemente, T. R. N., Morais, D. C., & de Almeida, A. T. (2018). Preference modeling experiments with surrogate weighting procedures for the PROMETHEE method. European Journal of Operational Research, 264(2), 453-461. doi:10.1016/j.ejor.2017.08.006Sun, G., Guan, X., Yi, X., & Zhou, Z. (2018). An innovative TOPSIS approach based on hesitant fuzzy correlation coefficient and its applications. Applied Soft Computing, 68, 249-267. doi:10.1016/j.asoc.2018.04.004Frazão, T. D. C., Camilo, D. G. G., Cabral, E. L. S., & Souza, R. P. (2018). Multicriteria decision analysis (MCDA) in health care: a systematic review of the main characteristics and methodological steps. BMC Medical Informatics and Decision Making, 18(1). doi:10.1186/s12911-018-0663-1Ortiz-Barrios, M. A., Herrera-Fontalvo, Z., Rúa-Muñoz, J., Ojeda-Gutiérrez, S., De Felice, F., & Petrillo, A. (2018). An integrated approach to evaluate the risk of adverse events in hospital sector. Management Decision, 56(10), 2187-2224. doi:10.1108/md-09-2017-0917Al Salem, A. A., & Awasthi, A. (2018). Investigating rank reversal in reciprocal fuzzy preference relation based on additive consistency: Causes and solutions. Computers & Industrial Engineering, 115, 573-581. doi:10.1016/j.cie.2017.11.027Aires, R. F. de F., & Ferreira, L. (2019). A new approach to avoid rank reversal cases in the TOPSIS method. Computers & Industrial Engineering, 132, 84-97. doi:10.1016/j.cie.2019.04.023Emrouznejad, A., & Yang, G. (2018). A survey and analysis of the first 40 years of scholarly literature in DEA: 1978–2016. Socio-Economic Planning Sciences, 61, 4-8. doi:10.1016/j.seps.2017.01.008Arya, A., & Yadav, S. P. (2017). Development of FDEA Models to Measure the Performance Efficiencies of DMUs. International Journal of Fuzzy Systems, 20(1), 163-173. doi:10.1007/s40815-017-0325-yMufazzal, S., & Muzakkir, S. M. (2018). A new multi-criterion decision making (MCDM) method based on proximity indexed value for minimizing rank reversals. Computers & Industrial Engineering, 119, 427-438. doi:10.1016/j.cie.2018.03.045Kaliszewski, I., & Podkopaev, D. (2016). Simple additive weighting—A metamodel for multiple criteria decision analysis methods. Expert Systems with Applications, 54, 155-161. doi:10.1016/j.eswa.2016.01.042Mousavi-Nasab, S. H., & Sotoudeh-Anvari, A. (2018). A new multi-criteria decision making approach for sustainable material selection problem: A critical study on rank reversal problem. Journal of Cleaner Production, 182, 466-484. doi:10.1016/j.jclepro.2018.02.062Chen, Z., Ming, X., Zhang, X., Yin, D., & Sun, Z. (2019). A rough-fuzzy DEMATEL-ANP method for evaluating sustainable value requirement of product service system. Journal of Cleaner Production, 228, 485-508. doi:10.1016/j.jclepro.2019.04.145Jumaah, F. M., Zadain, A. A., Zaidan, B. B., Hamzah, A. K., & Bahbibi, R. (2018). Decision-making solution based multi-measurement design parameter for optimization of GPS receiver tracking channels in static and dynamic real-time positioning multipath environment. Measurement, 118, 83-95. doi:10.1016/j.measurement.2018.01.011Singh, A., & Prasher, A. (2017). Measuring healthcare service quality from patients’ perspective: using Fuzzy AHP application. 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Multi-criteria decision analysis for supporting the selection of medical devices under uncertainty. European Journal of Operational Research, 247(1), 216-228. doi:10.1016/j.ejor.2015.05.075Kovacs, E., Strobl, R., Phillips, A., Stephan, A.-J., Müller, M., Gensichen, J., & Grill, E. (2018). Systematic Review and Meta-analysis of the Effectiveness of Implementation Strategies for Non-communicable Disease Guidelines in Primary Health Care. Journal of General Internal Medicine, 33(7), 1142-1154. doi:10.1007/s11606-018-4435-5Morley, C., Unwin, M., Peterson, G. M., Stankovich, J., & Kinsman, L. (2018). Emergency department crowding: A systematic review of causes, consequences and solutions. PLOS ONE, 13(8), e0203316. doi:10.1371/journal.pone.0203316Hermann, R. M., Long, E., & Trotta, R. L. (2019). Improving Patients’ Experiences Communicating With Nurses and Providers in the Emergency Department. Journal of Emergency Nursing, 45(5), 523-530. doi:10.1016/j.jen.2018.12.001Hawley, K. L., Mazer-Amirshahi, M., Zocchi, M. S., Fox, E. R., & Pines, J. M. (2015). Longitudinal Trends in U.S. Drug Shortages for Medications Used in Emergency Departments (2001-2014). Academic Emergency Medicine, 23(1), 63-69. doi:10.1111/acem.12838Stang, A. S., Crotts, J., Johnson, D. W., Hartling, L., & Guttmann, A. (2015). Crowding Measures Associated With the Quality of Emergency Department Care: A Systematic Review. Academic Emergency Medicine, 22(6), 643-656. doi:10.1111/acem.12682Chanamool, N., & Naenna, T. (2016). Fuzzy FMEA application to improve decision-making process in an emergency department. Applied Soft Computing, 43, 441-453. doi:10.1016/j.asoc.2016.01.007Farup, P. G. (2015). Are measurements of patient safety culture and adverse events valid and reliable? Results from a cross sectional study. BMC Health Services Research, 15(1). doi:10.1186/s12913-015-0852-xCarter, E. J., Pouch, S. M., & Larson, E. L. (2013). The Relationship Between Emergency Department Crowding and Patient Outcomes: A Systematic Review. Journal of Nursing Scholarship, 46(2), 106-115. doi:10.1111/jnu.12055Ebben, R. H. A., Siqeca, F., Madsen, U. R., Vloet, L. C. M., & van Achterberg, T. (2018). Effectiveness of implementation strategies for the improvement of guideline and protocol adherence in emergency care: a systematic review. BMJ Open, 8(11), e017572. doi:10.1136/bmjopen-2017-017572Innes, G. D., Sivilotti, M. L. A., Ovens, H., McLelland, K., Dukelow, A., Kwok, E., … Chochinov, A. (2018). Emergency overcrowding and access block: A smaller problem than we think. CJEM, 21(2), 177-185. doi:10.1017/cem.2018.446Di Somma, S., Paladino, L., Vaughan, L., Lalle, I., Magrini, L., & Magnanti, M. (2014). Overcrowding in emergency department: an international issue. Internal and Emergency Medicine, 10(2), 171-175. doi:10.1007/s11739-014-1154-8Uthman, O. 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Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c

Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29–39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance

Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c

Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29–39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe