A Study on Near-Infrared Non-Invasive Blood Glucose Concentration Regression Prediction Based on PSO-MKL-SVR

To improve the accuracy of predicting non-invasive blood glucose concentration in the near-infrared spectrum, we utilized the Particle Swarm Optimization (PSO) algorithm to optimize hyperparameters for the Multi-Kernel Learning Support Vector Machine (MKL-SVR). With these optimized hyperparameters, we established a non-invasive blood glucose regression model, referred to as the PSO-MKL-SVR model. Subsequently, we conducted a comparative analysis between the PSO-MKL-SVR model and the PSO-SVR model. In a dataset comprising ten volunteers, the PSO-MKL-SVR model exhibited significant precision improvements, including a 16.03% reduction in Mean Square Error and a 0.29% increase in the Squared Correlation Coefficient. Moreover, there was a 0.14% higher probability of the Clark’s Error Grid Analysis falling within Zone A. Additionally, the PSO-MKL-SVR model demonstrated a faster operational speed compared to the PSO-SVR model.

Non-Invasive Approach to Early Diagnosis of the Formation of Oncological Neoplasms

The currently developed instrumental approaches for detecting pathological changes in the body have a number of disadvantages. The most important of them is that the equipment is sensitive to the detection of diseases only from a certain threshold level of destructive changes in the body. The present article discusses the possibility of using the new instrumental complex “Bioscope” for early and non-invasive diagnosis of the beginning of the formation of ontological neoplasm’s in the body.

Evaluation of Non-Invasive Markers of Liver Fibrosis in Chronic Hepatitis B Patients in a Sub-Saharan African Setting: Transient Elastography versus APRI, FIB4, GTT/Platelet Scores

Background: Non-invasive markers which use routine laboratory tests are less expensive and highly needed to assess and stage liver fibrosis in chronic hepatitis B patients in Sub-Saharan Africa. We aimed at evaluating liver fibrosis, using the Aspartate aminotransferase to Platelet Ratio Index (APRI), Fibrosis Index Based on 4 factors (FIB4), and Gamma-glutamyl transpeptidase to Platelet Ratio (GPR) in chronic hepatitis B patients with transient elastography as the reference so as to choose an alternative to transient elastography. Method: We carried out a cross-sectional study using the records of patients who attended the Douala General Hospital and Marie O Polyclinic Douala from 2012 to 2017. Non-invasive tests were compared with Transient Elastography. The Spearman coefficient was used to determine correlation. The sensitivity, specificity, positive predictive values and negative predictive values were used to get the optimal cut-off values. The diagnostic accuracy was estimated by calculating the area under the Receiver Operating Characteristic Curve (ROC). P Results: Of the 243 patient records studied, the median age or interquartile range (IQR) was 35 (29 - 42) years with a male predominance of 73.7%. More than 60% of the study population had normal transaminases. Significant fibrosis was found in 88 (36.2%) patients and 32 (13.7%) patients had cirrhosis. APRI had the best cut-off values and highest area under the ROC Curve, for significant fibrosis and cirrhosis with 0.55 (0.823 95% CI [0.769 - 0.869], P Conclusion: APRI, had the best diagnostic properties to detect liver fibrosis and cirrhosis in patients with Chronic Hepatitis B in Douala. The cut-off values are 0.55 and 0.65 for significant fibrosis and cirrhosis respectively.

A Non-Invasive Skin Treatment Combining LED with Pharmacologic and Ultrasonic Technologies for Facial Rejuvenation

Background: Non-invasive facial treatments have the ability to rejuvenate the facial profile when specific pharmacologic agents and modalities are prescribed and used in combination taking into consideration each patient’s unique skin type and condition. RATIONALE Epinova is a non-invasive skin treatment that combines the correct concentrations and combinations of topicals and modalities to elicit facial rejuvenation with no down-time or side effects. Purpose: This paper focuses on facial rejuvenation improvements combining the RATIONALE Essential Six skincare system (RATIONALE, Victoria, Australia) to protect and repair the skin with the RATIONALE Epinova facial treatment every 4-6 weeks—which uses non-invasive technologies and professional strength active ingredients to deliver visible changes to skin tone and texture. Methods: Subjects underwent a RATIONALE consultation, including taking a skin history and skin imaging, followed by a data analysis and diagnosis of skin condition and prescription of a customized RATIONALE treatement (Epinova), including appropriate pharmacologic agents and treatment with personalized photo/sono therapeutic devices. Results: Subjects reported increased skin hydration, tactile improvements, skin firmness and visible radiance following the RATIONALE Epinova treatment. Further investigations will be initiated to explore the potential for longer term improvements, including connenctive tissue deposition, reduction of erythema etc. Treatments should be performed every 4-6 weeks for patients under 40 and every 3-4 weeks for patients over 40, to support cell differentiation, migration and desquamation to achieve non-invasive facial rejuvenation. Conclusion: This study demonstrated that the synergy of pharmacologic, LED light therapy and ultrasonic technologies when prescribed and administered by a trained skin therapist, can lead to a visible improvement in the signs of facial ageing and photodamage, restoring the appearance of healthy, radiant skin. .

Diagnosis and therapies for gastric non-invasive neoplasia

There has been a great discrepancy of pathological diagnosis for gastric non-invasive neoplasia/dysplasia between Japanese and western pathologists. In Japan, lesions that most western pathologists diagnose as dysplasia are often considered adenocarcinoma based on nuclear and structural atypia regardless of the presence of invasion. In the Vienna classification, gastric non-invasive intraepithelial neoplasia(NIN) weredivided into low grade and high grade(including intramucosal cancer of Japanese criteria). The diagnosis by both endoscopy and pathology of biopsy specimen is difficult. Recent advances of diagnostic modality such as magnified endoscopy and imaged enhanced endoscopy is expected to improve the diagnostic yield for NIN. There are two treatment strategies for NIN, observation and diagnostic therapy by endoscopic resection(ER). ER is acceptable because of its less invasiveness and high local control rate, on the other hand, cancer-developing rate of low-grade NIN is reported to be low. Therefore there is controversy for the treatment of gastric NIN. Prospective study based on unified pathological definition is required in the future.

Characteristics of Emission Non-nulling Pulsars Through Simulation

We investigate the population and several properties of radio pulsars whose emission does not null(non-nulling)through simulation of a large pulsar sample.Emission from a pulsar is identified as non-nulling if(i)the emission does not cease across the whole pulse profile,and(ii)the emission is detectable.For(i),we adopt a model for switching in the plasma charge density,and emission persists if the charge density is non-zero.For(ii),we assume that detectable emission originates from source points where it is emitted tangentially to the magnetic field-line and parallel to the line-of-sight.We find that pulsars exhibiting non-nulling emission possess obliquity angles with an average of 42°.5,and almost half the samples maintain a duty cycle between 0.05 and 0.2.Furthermore,the pulsar population is not fixed but dependent on the obliquity angle,with the population peaking at 20°.In addition,three evolutionary phases are identified in the pulsar population as the obliquity angle evolves,with the majority of samples having an obliquity angle between 20°and 65°.Our results also suggest that emission from a pulsar may evolve between nulling and non-nulling during its lifetime.

Non-invasive diagnosis of liver fibrosis and cirrhosis

The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this "gold-standard" is imperfect; even according to its proponents, it is only "the best" among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future.

Effects of rh BNP after PCI on non-invasive hemodynamic in acute myocardial infarction patients with left heart failure

Objective: To investigate the effects of exogenous recombinant human brain natriuretic peptide(rh BNP) after primary percutaneous coronary intervention(PCI) on non-invasive hemodynamic in acute myocardial infarction patients with left ventricular failure. Methods: A number of 96 acute myocardial infarction patients accompanied with heart failure after PCI hospitalized in the People's Hospital of Sanya during February 2012 to October 2015 were selected. They were randomly divided into the therapy group(n = 50) and control group(n = 46). On the basis of routine treatment, patients in the therapy group were treated with intravenous rh BNP(1.5 μg/kg was intravenous injection with uniform speed of 3 min, followed by continuous infusion 0.007 5 μg/kg·min for 72 h), while the control group received conventional treatment. Bio Z-2011 non-invasive hemodynamic real-time monitoring system was used to monitor the hemodynamic parameters changes and the leves of plasma pro-BNP, serum creatinine, serum potassium, serum sodium and urine volume of each group before and after treating for 30 min, 1 h, 3 h, 6 h, 12 h, 24 h, 48 h, 72 h. Results: Patients in the therapy group showed no effect on heart rate, while after 30 min of intravenous injection of rh BNP, CO, CI, SV, and SI increased significantly and LVET and TFC reduced at the same time, which had certain effect on blood pressure(SBP/DBP). Compared with the control group, the therapy group showed a faster and more effective improvement on haemodynamics. Conclusions: Acute myocardial infarction patients complicated with left heart failure after primary PCI can significantly improve hemodynamics by treating with rh BNP.

Evolving strategies for liver fibrosis staging: Non-invasive assessment

Transient elastography and the acoustic radiation force impulse techniques may play a pivotal role in the study of liver fibrosis. Some studies have shown that elastography can detect both the progression and regression of fibrosis. Similarly, research results have been analysed and direct and indirect serum markers of hepatic fibrosis have shown high diagnostic accuracy for advanced fibrosis/cirrhosis. The prognosis of different stages of cirrhosis is well established and various staging systems have been proposed, largely based on clinical data. However, it is still unknown if either noninvasive markers of liver fibrosis or elastography may contribute to a more accurate staging of liver cirrhosis, in terms of prognosis and fibrosis regression after effective therapy. In fact, not enough studies have shown both the fibrosis regression in different cirrhosis stages and the point beyond which the prognosis does not change- even in the event of fibrosis regression. Therefore, future studies are needed to validate noninvasive methods in predicting the different phases of liver cirrhosis.

Non-invasive prediction of non-alcoholic steatohepatitis in Japanese patients with morbid obesity by artificial intelligence using rule extraction technology

AIM To construct a non-invasive prediction algorithm for predicting non-alcoholic steatohepatitis(NASH), we investigated Japanese morbidly obese patients using artificial intelligence with rule extraction technology.METHODS Consecutive patients who required bariatric surgery underwent a liver biopsy during the operation. Standard clinical, anthropometric, biochemical measurements were used as parameters to predict NASH and were analyzed using rule extraction technology. One hundred and two patients, including 79 NASH and 23 non-NASH patients were analyzed in order to create the predictionmodel, another cohort with 77 patients including 65 NASH and 12 non-NASH patients were analyzed to validate the algorithm.RESULTS Alanine aminotransferase, C-reactive protein, homeostasis model assessment insulin resistance, albumin were extracted as predictors of NASH using a recursive-rule extraction algorithm. When we adopted the extracted rules for the validation cohort using a highly accurate rule extraction algorithm, the predictive accuracy was 79.2%. The positive predictive value, negative predictive value,sensitivity and specificity were 88.9%, 35.7%, 86.2% and 41.7%, respectively.CONCLUSION We successfully generated a useful model for predicting NASH in Japanese morbidly obese patients based on their biochemical profile using a rule extraction algorithm.

Progress in non-invasive detection of liver fibrosis

Liver fibrosis is an important pathological precondition for hepatocellular carcinoma.The degree of hepatic fibrosis is positively correlated with liver cancer.Liver fibrosis is a series of pathological and physiological process related to liver cell necrosis and degeneration after chronic liver injury,which finally leads to extracellular matrix and collagen deposition.The early detection and precise staging of fibrosis and cirrhosis are very important for early diagnosis and timely initiation of appropriate therapeutic regimens.The risk of severe liver fibrosis finally progressing to liver carcinoma is>50%.It is known that biopsy is the gold standard for the diagnosis and staging of liver fibrosis.However,this method has some limitations,such as the potential for pain,sampling variability,and low patient acceptance.Furthermore,the necessity of obtaining a tissue diagnosis of liver fibrosis still remains controversial.An increasing number of reliable non-invasive approaches are now available that are widely applied in clinical practice,mostly in cases of viral hepatitis,resulting in a significantly decreased need for liver biopsy.In fact,the noninvasive detection and evaluation of liver cirrhosis now has good accuracy due to current serum markers,ultrasound imaging,and magnetic resonance imaging quantification techniques.A prominent advantage of the non-invasive detection and assessment of liver fibrosis is that liver fibrosis can be monitored repeatedly and easily in the same patient.Serum biomarkers have the advantages of high applicability(>95%)and good reproducibility.However,their results can be influenced by different patient conditions because none of these markers are liver-specific.The most promising techniques appear to be transient elastography and magnetic resonance elastography because they provide reliable results for the detection of fibrosis in the advanced stages,and future developments promise to increase the reliability and accuracy of the staging of hepatic fibrosis.This article aims to describe the recent progress in the development of non-invasive assessment methods for the staging of liver fibrosis,with a special emphasize on computer-aided quantitative and deep learning methods.

Non-invasive diagnosis of advanced fibrosis and cirrhosis

Liver cirrhosis is a common and growing public health problem globally.The diagnosis of cirrhosis portends an increased risk of morbidity and mortality.Liver biopsy is considered the gold standard for diagnosis of cirrhosis and staging of fibrosis.However,despite its universal use,liver biopsy is an invasive and inaccurate gold standard with numerous drawbacks.In order to overcome the limitations of liver biopsy,a number of non-invasive techniques have been investigated for the assessment of cirrhosis.This review will focus on currently available non-invasive markers of cirrhosis.The evidence behind the use of these markers will be highlighted,along with an assessment of diagnostic accuracy and performance characteristics of each test.Non-invasive markers of cirrhosis can be radiologic or serum-based.Radiologic techniques based on ultrasound,magnetic resonance imaging and elastography have been used to assess liver fibrosis.Serum-based biomarkers of cirrhosis have also been developed.These are broadly classified into indirect and direct markers.Indirect biomarkers reflect liver function,which may decline with the onset of cirrhosis.Direct biomarkers,reflect extracellular matrix turnover,and include molecules involved in hepatic fibrogenesis.On the whole,radiologic and serum markers of fibrosis correlate well with biopsy scores,especially when excluding cirrhosis or excluding fibrosis.This feature is certainly clinically useful,and avoids liver biopsy in many cases.

Hepatic steatosis and fibrosis: Non-invasive assessment

Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and noninvasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy.

Non-invasive ventilation improves hemorheology status in hypoxemic patients with acute myocardial infarction after PCI

血氧不足有时在经皮的冠的干预(一种总线标准) 以后与尖锐心肌的梗塞(AMI ) 在病人发生在紧急情况房间里，甚至在那些与常规高流动的氧吸入的管理。现在的学习是在与 AMI 和 hypoxemia.MethodsThis 在病人改进血氧内容和 hemorheology 评估非侵略的通风(NIV ) 的有效性的 of 未来的学习与 AMI 注册了 50 个连续合格病人(72.3 ??? 折？？

Non-invasive assessment of liver fibrosis in chronic hepatitis B

The goal of this review is to provide a comprehensive picture of the role,clinical applications and future perspectives of the most widely used non-invasive techniques for the evaluation of hepatitis B virus(HBV)infection.During the past decade many non-invasive methods have been developed to reduce the need for liver biopsy in staging fibrosis and to overcome whenever possible its limitations,mainly:invasiveness,costs,low reproducibility,poor acceptance by patients.Elastographic techniques conceived to assess liver stiffness,in particular transient elastography,and the most commonly used biological markers will be assessed against their respective role and limitations in staging hepatic fibrosis.Recent evidence highlights that both liver stiffness and some bio-chemical markers correlatewith survival and major clinical end-points such as liver decompensation,development of hepatocellular carcinoma and portal hypertension.Thus the non-invasive techniques here discussed can play a major role in the management of patients with chronic HBV-related hepatitis.Given their prognostic value,transient elastography and some bio-chemical markers can be used to better categorize patients with advanced fibrosis and cirrhosis and assign them to different classes of risk for clinically relevant outcomes.Very recent data indicates that the combined measurements of liver and spleen stiffness enable the reliable prediction of portal hypertension and esophageal varices development.

Sequential algorithms combining non-invasive markers and biopsy for the assessment of liver fibrosis in chronic hepatitis B

AIM: To assess the performance of several non- invasive markers and of our recently proposed stepwise combination algorithms to diagnose significant fibrosis (F ≥ 2 by METAVIR) and cirrhosis (F4 by METAVIR) in chronic hepatitis B (CHB). METHODS: One hundred and ten consecutive patients (80 males, 30 females, mean age: 42.6 ± 11.3) with CHB undergoing diagnostic liver biopsy were included. AST- to-Platelet ratio (APRI), Forns’ index, AST-to-ALT Ratio, Goteborg University Cirrhosis Index (GUCI), Hui’s model and Fibrotest were measured on the day of liver biopsy. The performance of these methods and of sequential algorithms combining Fibrotest, APRI and biopsy was defined by positive (PPV) and negative (NPV) predictive values, accuracy and area under the curve (AUC). RESULTS: PPV for significant fibrosis was excellent (100%) with Forns and high (> 92%) with APRI, GUCI, Fibrotest and Hui. However, significant fibrosis could not be excluded by any marker (NPV < 65%). Fibro- test had the best PPV and NPV for cirrhosis (87% and 90%, respectively). Fibrotest showed the best AUC for both significant fibrosis and cirrhosis (0.85 and 0.76, respectively). Stepwise combination algorithms of APRI, Fibrotest and biopsy showed excellent performance (0.96 AUC, 100% NPV) for significant fibrosis and 0.95 AUC, 98% NPV for cirrhosis, with 50%-80% reduced need for liver biopsy. CONCLUSION: In CHB sequential combination of APRI, Fibrotest and liver biopsy greatly improves the diagnostic performance of the single non-invasive markers. Need for liver biopsy is reduced by 50%-80% but cannot be completely avoided. Non-invasive markers and biopsy should be considered as agonists and not antagonists towards the common goal of estimating liver fibrosis.

Non-invasive prediction of forthcoming cirrhosis-related complications

In patients with chronic liver diseases,identification of significant liver fibrosis and cirrhosis is essential for determining treatment strategies,assessing therapeutic response,and stratifying long-term prognosis.Although liver biopsy remains the reference standard for evaluating the extent of liver fibrosis in patients with chronic liver diseases,several non-invasive methods have been developed as alternatives to liver biopsies.Some of these non-invasive methods have demonstrated clinical accuracy for diagnosing significant fibrosis or cirrhosis in many cross-sectional studies with the histological fibrosis stage as a reference standard.However,non-invasive methods cannot be fully validated through cross-sectional studies since liver biopsy is not a perfect surrogate endpoint marker.Accordingly,recent studies have focused on assessing the performance of non-invasive methods through longterm,longitudinal,follow-up studies with solid clinical endpoints related to advanced stages of liver fibrosis and cirrhosis.As a result,current view is that these alternative methods can independently predict future cirrhosis-related complications,such as hepatic decompensation,liver failure,hepatocellular carcinoma,or liver-related death.The clinical role of non-invasive models seems to be shifting from a simple tool for predicting the extent of fibrosis to a surveillance tool for predicting future liver-related events.In this article,we will summarize recent longitudinal studies of non-invasive methods for predicting forthcoming complications related to liver cirrhosis and discuss the clinical value of currently available non-invasive methods based on evidence from the literature.

Non-invasive diagnosis of gastric mucosal atrophy in an asymptomatic population with high prevalence of gastric cancer

AIM: To validate a non-invasive method to detect gastric mucosal atrophy in a Chilean population with high prevalence of gastric cancer and a poor survival rate. METHODS: We first determined the optimal cut-off level of serum pepsinogen (PG)-1, PG-1/PG-2 ratio and 17-gastrin in 31 voluntary symptomatic patients (mean age: 66.1 years), of them 61% had histologically confirmed gastric atrophy. Then, in a population-based sample of 536 healthy individuals (209 residents in counties with higher relative risk and 327 residents in counties with lower relative risk for gastric cancer), we measured serum anti-H pylori antibodies, PG and 17-gastrin and estimated their risk of gastric cancer. RESULTS: We found that serum PG-1 < 61.5 μg/L, PG-1/PG-2 ratio < 2.2 and 17-gastrin > 13.3 pmol/L had a high specificity (91%-100%) and a fair sensitivity (56%-78%) to detect corpus-predominant atrophy. Based on low serum PG-1 and PG-1/PG-2 ratio together as diagnostic criteria, 12.5% of the asymptomatic subjects had corpus-predominant atrophy (0% of those under 25 years and 20.2% over 65 years old). The frequency of gastric atrophy was similar (12% vs 13%) but H pylori infection rate was slightly higher (77% vs 71%) in the high-risk compared to the low-risk counties. Based on their estimated gastric cancer risk, individuals were classified as: low-risk group (no H pylori infection and no atrophy; n = 115; 21.4%); moderate-risk group(H pylori infection but no atrophy; n = 354, 66.0%); and high-risk group (gastric atrophy, with or without H pylori infection; n = 67, 12.5%). The high-risk group was significantly older (mean age: 61.9 ± 13.3 years), more frequently men and less educated as compared with the low-risk group. CONCLUSION: We propose to concentrate on an upper gastrointestinal endoscopy for detection of early gastric cancer in the high-risk group. This intervention model could improve the poor prognosis of gastric cancer in Chile.

Non-invasive Prenatal Diagnosis of Trisomy 21 by Dosage Ratio of Fetal Chromosome-specific Epigenetic Markers in Maternal Plasma

This study examined the methylation difference in AIRE and RASSF1A between maternal and placental DNA, and the implication of this difference in the identification of free fetal DNA in maternal plasma and in prenatal diagnosis of trisomy 21. Maternal plasma samples were collected from 388 singleton pregnancies, and placental or chorionic villus tissues from 112 of them. Methylation-specific PCR （MSP） and methylation-sensitive restriction enzyme digestion followed by fluorescent quantitative PCR （MSRE ＋ PCR） were employed to detect the maternal-fetal methylation difference in AIRE and RASSF1A. Diagnosis of trisomy 21 was established according to the ratio of fetal-specific AIRE to RASSF1A in maternal plasma. Both methods confirmed that AIRE and RASSF1A were hypomethylated in maternal blood cells but hypermethylated in placental or chorionic villus tissues. Moreover, the differential methylation for each locus could be seen during the whole pregnant period. The positive rates of fetal AIRE and RASSF1A in maternal plasma were found to be 78.1% and 82.1% by MSP and 94.8% and 96.9% by MSRE ＋ PCR. MSRE ＋ PCR was superior to MSP in the identification of fetal-specific hypermethylated sequences （P〈0.05）. Based on the data from 266 euploidy pregnancies, the 95% reference interval of the fetal AIRE/RASSF1A ratio in maternal plasma was 0.33-1.77, which was taken as the reference value for determining the numbers of fetal chromosome 21 in 102 pregnancies. The accu-racy rate in 98 euploidy pregnancies was 96.9% （95/98）. Three of the four trisomy 21 pregnancies were confirmed with this method. It was concluded that hypermethylated AIRE and RASSF1A may serve as fetal-specific markers for the identification of fetal DNA in maternal plasma and may be used for noninvasive prenatal diagnosis of trisomy 21.

Biomarkers for detecting colorectal cancer non-invasively: DNA,RNA or proteins?

Colorectal cancer(CRC)is a global problem affecting millions of people worldwide.This disease is unique because of its slow progress that makes it preventable and often curable.CRC symptoms usually emerge only at advanced stages of the disease,consequently its early detection can be achieved only through active population screening,which markedly reduces mortality due to this cancer.CRC screening tests that employ non-invasively detectable biomarkers are currently being actively developed and,in most cases,samples of either stool or blood are used.However,alternative biological substances that can be collected non-invasively(colorectal mucus,urine,saliva,exhaled air)have now emerged as new sources of diagnostic biomarkers.The main categories of currently explored CRC biomarkers are:(1)Proteins(comprising widely used haemoglobin);(2)DNA(including mutations and methylation markers);(3)RNA(in particular microRNAs);(4)Low molecular weight metabolites(comprising volatile organic compounds)detectable by metabolomic techniques;and(5)Shifts in gut microbiome composition.Numerous tests for early CRC detection employing such non-invasive biomarkers have been proposed and clinically studied.While some of these studies generated promising early results,very few of the proposed tests have been transformed into clinically validated diagnostic/screening techniques.Such DNA-based tests as Food and Drug Administration-approved multitarget stool test(marketed as Cologuard®)or blood test for methylated septin 9(marketed as Epi proColon®2.0 CE)show good diagnostic performance but remain too expensive and technically complex to become effective CRC screening tools.It can be concluded that,despite its deficiencies,the protein(haemoglobin)detection-based faecal immunochemical test(FIT)today presents the most cost-effective option for non-invasive CRC screening.The combination of non-invasive FIT and confirmatory invasive colonoscopy is the current strategy of choice for CRC screening.However,continuing intense research in the area promises the emergence of new superior non-invasive CRC screening tests that will allow the development of improved disease prevention strategies.