Discovery and Validation of Serum MicroRNAs as Early Diagnostic Biomarkers for Prostate Cancer in Chinese Population

Prostate cancer (PCa) incidence has been rising in Chinese population. Current PSA-based biopsy has limited positive rate. Our research focused on development of serum markers for the diagnosis of PCa in patients with elevated PSA. miRNAs are found to be aberrantly expressed in many types of cancer. They are readily detectable in plasma and serum. Currently, miRNAs are being evaluated as potential prognostic and diagnostic tools for many types of cancer. We first profiled global serum miRNAs in a pilot set of PCa and benign prostatic hyperplasia (BPH) cases undergoing TRUS-guided prostate biopsy due to elevated PSA levels. A total of 20 differentially expressed miRNAs were discovered by high throughput microarray for further testing using qRT-PCR. In the training phase with 78 PCa and 77 BPH cases, miR-365a-3p, miR-4286, miR-424-5p, miR-27a-3p, and miR-29b-3p were found to have potential diagnostic value. The Logistics regression equation was established by 5 parameters including PSA, prostate volume, miR-4286, miR-27a-3p, and miR-29b-3p and ROC analysis of this model was made with AUC up to 0.892 (95% CI: 0.832-0.937, sensitivity 78.95%, and specificity 92.21%). The panel had excellent diagnostic performance and its significance was confirmed in 100 serum samples in the validation cohort. Overall, we found a panel of serum microRNAs that have considerable clinical significance in detecting early-stage prostate cancer. When combined with PSA and prostate volume, these microRNAs exhibit favorable diagnostic potency.

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Diagnostic value of research methods in diagnostics of chronic pancreatitis

Kazan medical journal ◽

10.17816/kmj2021-528 ◽

2021 ◽

Vol 102 (4) ◽

pp. 528-536

Author(s):

G R Aliyeva

Keyword(s):

Chronic Pancreatitis ◽

Early Stage ◽

Imaging Modality ◽

Magnetic Resonance Cholangiopancreatography ◽

Clinical History ◽

Diagnostic Value ◽

Diagnostic Tools ◽

Invasive Approach ◽

Pancreas Function ◽

Function Testing

Chronic pancreatitis remains an unsolved problem for clinicians. One of the biggest dilemmas is to establish a clear diagnosis. Diagnosis can be particularly elusive in patients with early chronic pancreatitis. Many studies have been undertaken to improve diagnostics in chronic pancreatitis, but this has been significantly limited by the lack of a gold standard. The evaluation of patients with suspected chronic pancreatitis should follow a progressively non-invasive to more invasive approach. Computed tomography is the best primary imaging modality to obtain as it has good sensitivity for severe chronic pancreatitis and may exclude the need for other diagnostic tests. When ambiguous results are obtained, a magnetic resonance cholangiopancreatography may require for a more detailed evaluation of both the pancreatic parenchyma and ducts. If the diagnosis remains in doubt, endoscopic ultrasound with or without pancreas function testing becomes the preferred method. Endoscopic retrograde cholangiopancreatography remains a last line diagnostic test and generally should be used only for diagnostic purposes. Future researches in the field of diagnosis of early-stage chronic pancreatitis should purpose optimizing current diagnostic tools. A definitive diagnosis of chronic pancreatitis may not be made simply by clinical history, imaging or function testing alone, but rather by the data gathered by a combination of these diagnostic tools.

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Diagnostic value of macrophage inhibitory cytokine 1 as a novel prognostic biomarkers for early gastric cancer screening

10.21203/rs.3.rs-17962/v1 ◽

2020 ◽

Author(s):

Xin Ge ◽

Xiaolei Zhang ◽

Yanling Ma ◽

Shaohua Chen ◽

Zhaowu Chen ◽

...

Keyword(s):

Gastric Cancer ◽

Early Gastric Cancer ◽

Cancer Diagnosis ◽

Early Stage ◽

Precancerous Lesions ◽

Diagnostic Value ◽

Low Grade ◽

Serum Samples ◽

Early Screening ◽

Roc Curve Analysis

Abstract BACKGROUND Early diagnosis is very important to improve the survival rate of patients with gastric cancer, especially in asymptomatic participants. However, low sensitivity of common biomarkers has caused difficulties in early screening of gastric cancer. In this study, we explored whether MIC-1 can improve the detection rate of early gastric cancer.METHODS We screened 8,257 participants based on risk factors such as age, gender, and family history for physical examination including gastroscopy. Participant blood samples were taken for measure MIC-1, CA-199, CA72-4 and PG1/PG2 levels. The diagnostic performance of MIC-1 was assessed and compared with CA-199, CA72-4 and PG1/PG2, and its role in early gastric cancer diagnosis and the assessment of the risk of precancerous lesions have also been studied.RESULTS Based on endoscopic and histopathological findings, 55 participants had gastric cancer, 566 participants had low-grade neoplasia, 2605 participants had chronic gastritis. MIC-1 levels were significantly elevated in gastric cancer serum samples as compared to controls (p<0.001). The sensitivity of serum MIC-1 for gastric cancer diagnosis was much higher than that of CA-199 (49.1% vs. 20.0%) with similar specificities. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MIC-1 had a better performance compared with CA-199, CA72-4 and PG1/PG2 in distinguishing early-stage gastric cancer (AUC: 72.9% vs. 69.5%, 67.5%, 44.0% respectively).CONCLUSIONS Serum MIC-1 is significantly elevated in most patients with early gastric cancer. MIC-1 can serve as a novel diagnostic marker of early gastric cancer and value the risk of gastric cancer.

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Complement component C9 as a new biomarker for esophageal adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.19 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 19-19 ◽

Cited By ~ 1

Author(s):

Virendra Joshi ◽

Alok Shah ◽

Ian Brown ◽

Clay Winterford ◽

Michelle Hill

Keyword(s):

Esophageal Adenocarcinoma ◽

Early Stage ◽

Multiple Reaction Monitoring ◽

Diagnostic Value ◽

Complement Component ◽

Endoscopic Surveillance ◽

Disease Stage ◽

Receiver Operating Curve ◽

Diagnostic Tools ◽

Serum Glycoprotein

19 Background: Esophageal adenocarcinoma (EAC) continues an upward trend. Mortality rate and treatment costs for EAC are very high overall and significantly increase with disease stage. Diagnosis at early stage (T1) compared to advanced stage (T3) improves 5 year survival from 20% to 80-90%. Endoscopic surveillance has been ineffective in reducing EAC. Therefore the need for better diagnostic tools for early detection.Previously we reported validation of a list of serum glycoprotein biomarker candidates for EAC in an Australian cohort (Shah et al. 2015 Mol Cell Proteomics. 14:3023-39.). Here we further evaluate the serum and tissue expression of top candidate C9 in an independent cohort from the USA. Methods: Serum samples (n=38) and FFPE tissue sections (n=34) were collected from participants with IRB approved protocol, from the Ochsner Clinic undergoing endoscopic surveillance for Barrett’s and esophageal cancer. Serum glycoprotein candidates were measured using lectin magnetic bead array-coupled multiple reaction monitoring assay (Shah et al. 2015 Mol Cell Proteomics. 14:3023-39.). Immunohistochemistry was optimised for complement component C9 antibody. Initial evaluation of 2 different antibodies gave similar results, thereafter, a polyclonal antibody from Sigma Aldrich was used. Staining was assessed by a gastrointestinal pathologist. Results: Specific glycosylated forms of 3 candidate serum biomarkers were confirmed to be significantly different between EAC and benign groups (p<0.05, Kruskal-Wallis). The diagnostic value for the 3 individual markers, complement component C9, gelsolin and alpha-1-antichymotrypsin (Serpin A3) was 0.71 to 0.82 area under the receiver operating curve (AUROC). A multivariate panel consisting of 8 glycoprotein biomarkers achieved AUROC of 0.96, indicative of high diagnostic value. Immunohistochemistry of tissues detected high levels of C9 in BE and EAC compared to normal squamous epithelium. Infiltrated lymphocytes showed variable staining. Conclusions: We propose a novel candidate biomarker complement component C9 which could add to current endoscopic surveillance strategy for early detection of adenocarcinoma.

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Aspartyl (Asparaginyl) ß hydroxylase (AABH) as a serum bio-marker for prostate cancer to identify prostate cancer, regardless of PSA level.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.10 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 10-10

Author(s):

Mahmood Moshiri ◽

Kiarash Moshiri ◽

Arsha Moshiri ◽

Hassan Monhemi ◽

Mohammad Hadi Sekhavati

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Early Stage ◽

Sandwich Elisa ◽

Specific Antigen ◽

High Serum ◽

Cancer Tissue ◽

Serum Samples ◽

Psa Testing ◽

Detect Prostate Cancer

10 Background: Background: Prostate Specific Antigen (PSA) is a molecular marker of prostate cancer (PC). I most countries, standard of care suggests annual PSA testing in all men over 50 years of age; and for men at high risk, the test is recommended from 40 years of age. Due to low Specificity and low sensitivity of the PSA test, a large number of unnecessary biopsies occur every year. This low specificity can be due to the fact that PSA is found in both benign and malignant lesions of Prostate tissue. To date measurement of the percentage of free PSA, have resulted an small improvements in specificity of PSA testing. Thus, the development of a simple blood test to detect prostate cancer that exhibits higher specificity compared to PSA could have the potential of reducing biopsies performed due to false positive screening results and improve the quality of medical care. Methods: We have investigated the utility of aspartyl (asparaginyl) β-hydroxylase (AABH) as a prostate cancer biomarker. AABH has been detected by immunohistochemical staining (IHC) in a broad range of cancers including Prostate Adenocarcinoma through out the world. AABH have been detected by IHC in more than 97% of tumor specimens tested (n > 200) while absent in normal and non cancer tissue. We have developed a sandwich ELISA test for the detection of AABH in serum samples. Preliminary results showed an accuracy of 91- 94% for detecting cancer patients from non-cancer patients in different types of Cancer. Here we have utilized this assay to detect AABH levels in the sera of patients diagnosed with Prostate cancer (biopsy proven, pre-treatment samples), compared to non-cancer individuals. Results: AABH was detected above a threshold level of 1.2 ng/mL in 91% of the sera of PC patients (n = 60), in all different stages and grades of Prostate Cancer. All non-cancer individuals (n = 30) had AABH values below the threshold. Further study of direct comparison of AABH to PSA levels (n = 4,000) is underway. Conclusions: Our data suggest that measurement of serum AABH levels may help to detect Prostate Cancer in early stage and potentially reduce the number of prostate biopsies performed due to increased high serum PSA.

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Multicenter Evaluation of an Artificial Neural Network to Increase the Prostate Cancer Detection Rate and Reduce Unnecessary Biopsies

Clinical Chemistry ◽

10.1093/clinchem/48.8.1279 ◽

2002 ◽

Vol 48 (8) ◽

pp. 1279-1287 ◽

Cited By ~ 100

Author(s):

Carsten Stephan ◽

Henning Cammann ◽

Axel Semjonow ◽

Eleftherios P Diamandis ◽

Leon FA Wymenga ◽

...

Keyword(s):

Neural Network ◽

Prostate Cancer ◽

Artificial Neural Network ◽

Prostate Volume ◽

Specific Antigen ◽

Digital Rectal Examination ◽

Clinical Information ◽

Diagnostic Value ◽

Increased Risk ◽

Artificial Neural

Abstract Background: The percentage of free prostate-specific antigen (%fPSA) has been shown to improve specificity for the diagnosis of prostate cancer (PCa) over total PSA (tPSA). A multicenter study was performed to evaluate the diagnostic value of a %fPSA-based artificial neural network (ANN) in men with tPSA concentrations between 2 and 20 μg/L for detecting patients with increased risk of a positive prostate biopsy for cancer. Methods: We enrolled 1188 men from six different hospitals with PCa or benign prostates between 1996 and 2001. We used a newly developed ANN with input data of tPSA, %fPSA, patient age, prostate volume, and digital rectal examination (DRE) status to calculate the risk for the presence of PCa within different tPSA ranges (2–4, 4.1–10, 2–10, 10.1–20, and 2–20 μg/L) at the 90% and 95% specificity or sensitivity cutoffs, depending on the tPSA concentration. ROC analysis and cutoff calculations were used to estimate the diagnostic improvement of the ANN compared with %fPSA alone. Results: In the low tPSA range (2–4 μg/L), the ANN detected 72% and 65% of cancers at specificities of 90% or 95%, respectively. At 4–10 μg/L tPSA, the ANN detected 90% and 95% of cancers with specificities of 62% and 41%, respectively. Use of the ANN with 2–10 μg/L tPSA enhanced the specificity of %fPSA by 20–22%, thus reducing the number of unnecessary biopsies. Conclusions: Enhanced accuracy of PCa detection over that obtained using %fPSA alone can be achieved with a %fPSA-based ANN that also includes clinical information from DRE and prostate volume measurements.

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Diagnostic Value of Different Systematic Prostate Biopsy Methods in the Detection of Prostate Cancer with Ultrasonographic Hypoechoic Lesions - A Comparative Study

Urologia Internationalis ◽

10.1159/000381752 ◽

2015 ◽

Vol 95 (2) ◽

pp. 183-188 ◽

Cited By ~ 2

Author(s):

Guang Xu ◽

Minghua Yao ◽

Jian Wu ◽

Lehang Guo ◽

Lijing Feng ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Biopsy ◽

Detection Rate ◽

Prostate Volume ◽

Specific Antigen ◽

Diagnostic Value ◽

Lesion Core ◽

Biopsy Methods ◽

Hypoechoic Lesion ◽

A Prospective Study

Objective: To assess if a less extended biopsy in the transperineal approach is sufficient for detection of prostate cancer (PC) in patients with hypoechoic lesions. Methods: This was a prospective study of 167 consecutive patients with prostate hypoechoic lesion and who underwent transperineal ultrasound (TPUS)-guided 12-core and hypoechoic lesion core biopsy between January 2012 and February 2013. Results: PC was detected in 64.1% (107/167) of patients. The PC detection rate of the 12-core prostate biopsy scheme was the highest, but when including the hypoechoic lesion core, there was no difference between the 6- and 12-core schemes (all p > 0.05), irrespective of prostate volume or prostate-specific antigen levels (all p > 0.05). Conclusions: A more limited biopsy scheme could be sufficient for the detection of PC if the hypoechoic lesion is sampled.

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The diagnostic value of a new formula combining age and prostate volume in prostate cancer

10.31083/jomh.2021.080 ◽

2021 ◽

Keyword(s):

Prostate Cancer ◽

Linear Model ◽

Prostate Volume ◽

Specific Antigen ◽

Transrectal Ultrasound ◽

High Sensitivity ◽

Roc Curves ◽

Diagnostic Value ◽

Number Of Patients ◽

Log Linear

Background and objective: This study combined two clinical indicators (age and prostate volume (PV)) to generate age to PV (AVR) ratio, whose diagnostic value for prostate cancer (PCa) was examined based on prostate speciﬁc antigen (PSA) in the range of 4--20.0 ng/mL. Methods: The medical records of patients who underwent transrectal ultrasound-guided biopsy of the prostate in our hospital from June 2015 to June 2019 were examined retrospectively. According to the pathological results of the biopsy, the patients were divided into the PCa and benign prostatic hyperplasia (BPH) groups. Receiver operating characteristic (ROC) curves for TPSA, PSAD, PV, (F/T)PSA, AVR, and PSA-AV were plotted with SPSS 26.0 and GraphPad Prism 5.0, and areas under the ROC curves (AUROCs) were determined and compared by Delong test. A log-linear model was used to compare AVR and other parameters with similar high sensitivities, for speciﬁcity. Results: The AUROC for AVR was signiﬁcantly different from those of TPSA (p < 0.001), PV (p = 0.004),(F/T)PSA (p < 0.001), and PSA-AV (p = 0.006), and similar to that of PSAD (p = 0.064). With the same high sensitivity (90.0%), log-linear model analysis showed that the speciﬁcity of AVR was signiﬁcantly higher than those of TPSA and (F/T)PSA (p < 0.01), while there were no signiﬁcant differences among AVR and PSAD, PV and PSA-AV. Conclusion: With PSA in the range of 4--20.0 ng/mL, AVR may be useful in sparing an invasive intervention for a number of patients.

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Exploration of Potential Diagnostic Value of Protein Content in Serum Small Extracellular Vesicles for Early-Stage Epithelial Ovarian Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.707658 ◽

2021 ◽

Vol 11 ◽

Author(s):

Pu Li ◽

Yuezong Bai ◽

Boer Shan ◽

Wei Zhang ◽

Zhanjie Liu ◽

...

Keyword(s):

Ovarian Carcinoma ◽

Extracellular Vesicles ◽

Roc Analysis ◽

Early Stage ◽

Diagnostic Value ◽

Population Based ◽

Serum Markers ◽

Epithelial Ovarian Carcinoma ◽

Protein Levels ◽

Set Up

Epithelial ovarian carcinoma (EOC) is one of the most common gynecologic malignancies with a high mortality rate. Serum biomarkers and imaging approaches are insufficient in identifying EOC patients at an early stage. This study is to set up a combination of proteins from serum small extracellular vesicles (sEVs) for the diagnosis of early-stage EOC and to determine its performance. A biomarker for early-stage ovarian cancer (BESOC) cohort was used as a Chinese multi-center population-based biomarker study and registered as a Chinese Clinical Trial ChiCTR2000040136. The sEV protein levels of CA125, HE4, and C5a were measured in 299 subjects. Logistic regression was exploited to calculate the odds ratio and to create the sEV protein model for the predicted probability and subsequently receiver-operating characteristic (ROC) analysis. The combined sEV marker panel of CA125, HE4, and C5a as a sEV model obtained an area under curve (AUC) of 0.912, which was greater than the serum model (0.809), by ROC analysis to identify EOC patients from the whole cohort. With the cutoff of 0.370, the sensitivity and specificity of the sEV model were 0.80 and 0.89, which were much better performance than the serum markers (sensitivity: 0.55~0.66; specificity: 0.59~0.68) and the risk of ovarian malignancy algorithm (ROMA) index approved by the U.S. Food and Drug Administration (sensitivity: 0.65; specificity: 0.61), to identify EOC patients from patients with benign ovarian diseases or other controls. The sEV levels of CA125 significantly differed among early-stage and late-stage EOC (p < 0.001). Moreover, the AUC of ROC to identify early-stage EOC patients was 0.888. Further investigation revealed that the sEV levels of these 3 proteins significantly decreased after cytoreductive surgery (CA125, p = 0.008; HE4, p = 0.025; C5a, p = 0.044). In summary, our study showed that CA125, HE4, and C5a levels in serum sEVs can identify EOC patients at the early stage, elucidating the possibility of using a sEV model for the diagnosis of early-stage EOC.

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Evaluation of the auxiliary diagnosis value of antibodies assays for the detection of novel coronavirus (SARS-Cov-2)

10.1101/2020.03.26.20042044 ◽

2020 ◽

Cited By ~ 7

Author(s):

Gao Yong ◽

Yuan Yi ◽

Li Tuantuan ◽

Wang Xiaowu ◽

Li Xiuyong ◽

...

Keyword(s):

Nucleic Acid ◽

Early Stage ◽

Clinical Information ◽

Diagnostic Value ◽

Nucleic Acid Detection ◽

Course Of Illness ◽

Combined Use ◽

Hospitalization Period ◽

Positive Rate ◽

Novel Coronavirus

AbstractBackgroundThe spread of an novel coronavirus (SARS-CoV-2, previously named 2019-nCoV) has already taken on pandemic proportions, affecting over 100 countries in a matter of weeks. Elucidating the diagnostic value of different methods, especially the auxiliary diagnosis value of antibodies assays for SARS-CoV-2 infection is helpful for improving the sensitivities of pathogenic-diagnosis, providing timely treatment, and differentiating the infected cases from the healthy, thus preventing further epidemics.MethodsMedical records from 38 patients with confirmed SARS-CoV-2 infection in the Second People’s Hospital of Fuyang from January 22, 2020 to February 28, 2020 were collected and retrospectively analyzed. Specimens including throat swabs, sputum and serum were collected during the hospitalization period, viral RNAs and serum IgM-IgG antibodies to SARS-CoV-2 were measured respectively. The detectability of different methods as well as the auxiliary diagnosis value of antibodies test for SARS-CoV-2 infection were analyzed.ResultsAmong 38 patients, the total seropositive rate for IgM and IgG was 50.0% and 92.1%, respectively. Two patients remained seronegative throughout the course of illness. In the early phase of illness, the RNA test for sputum specimens possessed the highest detectability(92.3%), followed by the the RNA test for throat swabs (69.2%), and the antibodies assays presented lower positive rates(IgM, 23.0%, IgG, 53.8%). While, the sensitivity of antibodies assays overtook that of RNA test since day 8 after onset (IgM, 50.0%; IgG, 87.5%). Of note, the positive rate of throat swabs was only 13.0% for cases in later phase(≥15 d.a.o), and the sensitivities of IgM and IgG rose to 52.2% and 91.3%, respectively. Combined use of antibodies assay and qRT-PCR at the same time was able to improve the sensitivities of pathogenic-diagnosis, especially for the throat swabs group at the later stage of illness. Moreover, most of these cases with undetectable viral RNA in throat swabs specimens at the early stage of illness were able to be IgM/IgG seropositive after 7 days.ConclusionsThe antibodies detection against SARS-CoV-2 offers vital clinical information for physicians, and could be used as an effective supplementary indicator for suspected cases of negative viral nucleic acid detection or in conjunction with nucleic acid detection in the diagnosis of suspected cases.

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Serum SARS-COV-2 Nucleocapsid Protein: A Sensitivity and Specificity Early Diagnostic Marker for SARS-COV-2 Infection

10.1101/2020.05.24.20111849 ◽

2020 ◽

Cited By ~ 2

Author(s):

Tao Li ◽

Li Wang ◽

Huihui Wang ◽

Xuemei Li ◽

Shubing Zhang ◽

...

Keyword(s):

Confidence Interval ◽

Sensitivity And Specificity ◽

Early Stage ◽

Characteristic Curve ◽

Diagnostic Value ◽

Enzyme Linked Immunosorbent Assay ◽

Cutoff Value ◽

Protein Assay ◽

N Protein ◽

Positive Rate

AbstractObjectiveThis study aimed to explore the diagnostic value of serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid(N) protein assay in the early stage of SARS-COV-2 infection.MethodSerum N protein in SARS-COV-2 infected patients and non-SARS-COV-2 infected population was measured by enzyme-linked immunosorbent assay (ELISA) double antibody sandwich assay. Colloidal gold immunochromatography assay is used to detect serum N protein antibodies in the above population.Results50 cases of SARS-CoV-2 nucleic acid positive and SARS-CoV-2 antibody negative patients had a serum N protein positive rate of 76%, including 2% with a concentration of 10.00-49.99 pg / mL, 8% with a concentration of 50.00-99.99 pg / mL, 22% with a concentration of 100.00 - 299.99 pg/mL, and 44% with a concentration≥ 300.00 pg / mL. 37 samples of patients with serum SARS-CoV-2 antibody positive after infection had a serum SARS-CoV-2 N protein positive rate of 2.7%, of which 2.7% had the concentration of 10.00-49.99 pg / mL and 0% had the concentration of 50.00-99.99 pg / mL, 100.00 −299.99 pg / mL, and >300.00 pg / mL. Serum N protein test results of 633 non-SARS-COV-2 infected patients including pregnant women, other respiratory infections, and increased rheumatoid factor were all negative, having a serum N protein concentration less than 10.00 pg/mL, with a specificity of 100%. Using SPSS 19.0 to calculate the receiver operating characteristic curve, the area under the curve was 0.9756 (95% confidence interval 0.9485-1.000, p <0.0001), sensitivity and specificity were 92% (95% confidence interval 81.16% to 96.85%) and 96.84% (95% confidence interval 95.17% to 97.15%). The best CUTOFF value is 1.850 pg / mL.ConclusionThe measurement of SARS-COV-2 serum N protein has a high diagnostic value for the infected patients before the antibody appears, and shortens the window period of serological diagnosis. The laboratory needs to establish an individual CUTOFF value according to purpose of the application.

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