Exploring non-invasive diagnostics for metabolic dysfunctionassociated fatty liver disease

The population with metabolic dysfunction-associated fatty liver disease(MAFLD)is increasingly common worldwide.Identification of people at risk of progression to advanced stages is necessary to timely offer interventions and appropriate care.Liver biopsy is currently considered the gold standard for the diagnosis and staging of MAFLD,but it has associated risks and limitations.This has spurred the exploration of non-invasive diagnostics for MAFLD,especially for steatohepatitis and fibrosis.These non-invasive approaches mostly include biomarkers and algorithms derived from anthropometric measurements,serum tests,imaging or stool metagenome profiling.However,they still need rigorous and widespread clinical validation for the diagnostic performance.

Research Progress of Noninvasive Diagnostic Methods for Nonalcoholic Steatohepatitis

Distinguishing between nonalcoholic steatohepatitis(NASH) and advanced liver fibrosis is the key for clinical diagnosis of non-alcoholic fatty liver disease(NAFLD). Liver biopsy, which is widely used for diagnosis of liver diseases at present, has many drawbacks, such as being invasive, expensive and unstable. This article compares and summarizes the commonly used non-invasive diagnostic methods, including their diagnostic parameters, advantages and disadvantages, in order to provide a useful reference for the diagnosis of NASH.

FibroScan-aspartate transaminase:A superior non-invasive model for diagnosing high-risk metabolic dysfunction-associated steatohepatitis

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)with hepatic histological NAFLD activity score≥4 and fibrosis stage F≥2 is regarded as“at risk”non-alcoholic steatohepatitis(NASH).Based on an international consensus,NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH),respectively;hence,we introduced the term“high-risk MASH”.Diagnostic values of seven non-invasive models,including FibroScan-aspartate transaminase(FAST),fibrosis-4(FIB-4),aspartate transaminase to platelet ratio index(APRI),etc.for high-risk MASH have rarely been studied and compared in MASLD.AIM To assess the clinical value of seven non-invasive models as alternatives to liver biopsy for diagnosing high-risk MASH.METHODS A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via liver biopsy at Beijing Ditan Hospital,between January 2012 and December 2020.After screening for MASLD and the exclusion criteria,279 patients wereincluded and categorized into high-risk and non-high-risk MASH groups.Utilizing threshold values of each model,sensitivity,specificity,positive predictive value(PPV),and negative predictive values(NPV),were calculated.Receiver operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve(AUROC).RESULTS MASLD diagnostic criteria were met by 99.4%patients with NAFLD.The MASLD population was analyzed in two cohorts:Overall population(279 patients)and the subgroup(117 patients)who underwent liver transient elastography(FibroScan).In the overall population,FIB-4 showed better diagnostic efficacy and higher PPV,with sensitivity,specificity,PPV,NPV,and AUROC of 26.9%,95.2%,73.5%,72.2%,and 0.75.APRI,Forns index,and aspartate transaminase to alanine transaminase ratio(ARR)showed moderate diagnostic efficacy,whereas S index and gamma-glutamyl transpeptidase to platelet ratio(GPR)were relatively weaker.In the subgroup,FAST had the highest diagnostic efficacy,its sensitivity,specificity,PPV,NPV,and AUROC were 44.2%,92.3%,82.1%,67.4%,and 0.82.The FIB-4 AUROC was 0.76.S index and GPR exhibited almost no diagnostic value for high-risk MASH.CONCLUSION FAST and FIB-4 could replace liver biopsy as more effectively diagnostic methods for high-risk MASH compared to APRI,Forns index,ARR,S index,and GPR;FAST is superior to FIB-4.

Rapid diagnostic method for transplutonium isotope production in high flux reactors

Transplutonium isotopes are scarce and need to be produced by irradiation in high flux reactors.However,their production is inefficient,and optimization studies are necessary.This study analyzes the physical nature of transplutonium isotope produc-tion using ^(252)Cf,^(244)Cm,^(242)Cm,and ^(238)Pu as examples.Traditional methods based on the Monte Carlo burnup calculation have the limitations of many calculations and cannot analyze the individual energy intervals in detail;thus,they cannot sup-port the refined evaluation,screening,and optimization of the irradiation schemes.After understanding the physical nature and simplifying the complexity of the production process,we propose a rapid diagnostic method for evaluating radiation schemes based on the concepts“single energy interval value(SEIV)”and“energy spectrum total value(ESTV)”.The rapid diagnostic method not only avoids tedious burnup calculations,but also provides a direction for optimization.The optimal irradiation schemes for producing ^(252)Cf,^(244)Cm,^(242)Cm,and ^(238)Pu are determined based on a rapid diagnostic method.Optimal irradiation schemes can significantly improve production efficiency.Compared with the initial scheme,the optimal scheme improved the production efficiency of ^(238)Pu by 7.41 times;^(242)Cm,11.98 times;^(244)Cm,65.20 times;and ^(252)Cf,15.08 times.Thus,a refined analysis of transplutonium isotope production is conducted and provides a theoretical basis for improving production efficiency.

Study of Failure Diagnostic Methods and Intelligent Diagnostic System for Reciprocating Compressors

Three categories of failure diagnostic methods for reciprocating compressors are classified according to the signals adopted by the diagnosis. They are parameter method, vibration method, and oil analysis method. In this paper, the applicable range and operational difficulties of these methods are discussed on the basis of analysis and induction upon normal failure. It is proposed that a compressor's normal failure can be divided into thermodynamical property failure and mechanical function failure. As to the former, the parameter method that takes a cylinder pressure signal as the main diagnostic signal may be applied; and as to the latter, the vibration signal frequency spectrum can be used to diagnose. At the same time, the structure of an intelligent diagnostic system based on neural networks is introduced, and its schematic is given.

Advances in Laboratory Diagnostic Methods for Duck Circovirus Infection

Duck circovirus infection is an immunosuppressive disease that is characterized by growth retardant and odd deaths. Its infection is usually combined with other pathogens, making the clinical diagnosis more difficult. With the rapid development of molecular biological and immunological technologies, the laboratory diagnostic methods for duck circovirus infection also advance greatly. The paper summarizes the research advances in various laboratory detection methods for duck cireovirus infection including PCR, nested PCR, multiple PCR, fluorescence quantitative PCR, LAMP, nucleic acid probe and ELISA, as well as their ad- vantages and shortages, aiming at providing reference for finding novel detection methods and for the diagnosis and comprehensive prevention and control.

Triple non-invasive diagnostic test for exclusion of common bile ducts stones before laparoscopic cholecystectomy

AIM: To evaluate the impact of a preoperative "triple non-invasive diagnostic test" for diagnosis and/or exclusion of common bile duct stones. METHODS: All patients with symptomatic gallstone disease, operated on by laparoscopic cholecystectomy from March 2004 to March 2006 were studied retrospectively. Two hundred patients were included and reviewed by using a triple diagnostic test including: patient's medical history, routine liver function tests and routine ultrasonography. All patients were followed up 2-24 mo after surgery to evaluate the impact of triple diagnostic test. RESULTS: Twenty-five patients were identified to have common bile duct stones. Lack of history of stones, negative laboratory tests and normal ultrasonography alone was proven to exclude common bile duct stones in some patients. However, a combination of these three components (triple diagnostic), was proven to be the most statistically significant test to exclude common bile duct stones in patients with gallstone disease. CONCLUSION: Using a combination of routinely used diagnostic components as triple diagnostic modality would increase the diagnostic accuracy of common bile duct stones preoperatively. This triple non-invasive test is recommended for excluding common bile duct stones and to identify patients in need for other investigations.

Emerging role of non-invasive and liquid biopsy biomarkers in pancreatic cancer

A global increase in the incidence of pancreatic cancer(PanCa)presents a major concern and health burden.The traditional tissue-based diagnostic techniques provided a major way forward for molecular diagnostics;however,they face limitations based on diagnosis-associated difficulties and concerns surrounding tissue availability in the clinical setting.Late disease development with asymptomatic behavior is a drawback in the case of existing diagnostic procedures.The capability of cell free markers in discriminating PanCa from autoimmune pancreatitis and chronic pancreatitis along with other precancerous lesions can be a boon to clinicians.Early-stage diagnosis of PanCa can be achieved only if these biomarkers specifically discriminate the non-carcinogenic disease stage from malignancy with respect to tumor stages.In this review,we comprehensively described the non-invasive disease detection approaches and why these approaches are gaining popularity for their early-stage diagnostic capability and associated clinical feasibility.

Development and refinement of diagnostic and therapeutic strategies for managing patients with cardiogenic stroke:An arduous journey

Cardioembolic stroke,referred to as cardiogenic stroke,is a clinical syndrome in which emboli from the heart pass through the circulatory system and cause cerebral artery embolism and corresponding brain dysfunction.Compared to other subtypes of ischemic stroke,cardiogenic stroke presents with more etiologies,greater severity,worse prognosis,and a higher recurrence rate.In this minireview,we provide new insights into the etiological classification,diagnostic methods,and interventions of cardiogenic stroke.

Current Problems of the Diagnostics and Treatment of Sepsis and Burn Injuries: The Modified Pathogenetic Concept

Background: The deep understanding of pathogenesis is a key moment in the formation of the modern strategy of modern medicine. We conducted the thorough analysis of the microscopic processes occurring in the bodies of patients with purulent-septic complications. The modified pathogenetic concept of the diagnostic and treatment model of diseases with septic complications is presented. The obtained information about the mechanisms of origin and development of these diseases is fundamentally important for finding the modern effective methods of treating patients. The aim of the research is to modify treatment tactics for patients with sepsis and burn injuries based on the modified pathogenetic concept using modern diagnostics, i.e. the method of fluorescence spectroscopy (MFS) and biomarkers. Materials and Methods: The proposed modified pathogenetic concept of the diagnostic and treatment model of diseases with purulent-septic complications along with standard methods was used successfully for effective treatment of 15 patients with sepsis and 25 with burn injuries. Results: 3 main scenarios of behaviour of spectral-fluorescence characteristics of patients with sepsis are illustrated. Spectral-fluorescence markers of sepsis were studied, which are informative 24 to 48 hours before the appearance of obvious clinical and laboratory signs of significant changes in the general somatic status of patients. Conclusions: The proposed diagnostic and therapeutic approach is new and fundamentally important for diagnostics and monitoring of the process of treatment of patients with purulent-septic diseases and burn injuries. An in-depth understanding of the dynamics of septic complications and the corresponding changes of the main markers of these diseases during treatment is especially relevant. The use of infusion therapy with solutions of donor albumin as an effective pathogenetic treatment is scientifically justified.

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.

Non-invasive glucose measuring apparatus based on conservation of energy method

A new non-invasive blood glucose measuring apparatus (NBGMA) made up of MSP430F149 SCM (single chip micyoco) was developed,which can measure blood glucose level (BGL) frequently,conveniently and painlessly. The hardware and software of this apparatus were designed,and detecting algorithms based on conservation of energy method (COEM) were presented. According to the law of conservation of energy that the energy derived by human body equals energy consumed by metabolism,and the relationship between convection,evaporation,radiation and the BGL was established. The sensor module was designed. 20 healthy volunteers were involved in the clinical experiment. The BGL measured by an automatic biochemical analyzer (ABA) was set as the reference. Regression analysis was performed to compare the conservation of energy method with the biochemical method,using the 20 data points with blood glucose concentrations ranging from 680 to 1 100 mg/L. Reproducibility was measured for healthy fasting volunteers. The results show that the means of BGL detected by NBGMA and ANA are very close to each other,and the difference of standard deviation (SD) is 24.7 mg/L. The correlative coefficient is 0.807. The coefficient of variation (CV) is 4% at 921.6 mg/L. The resultant regression is evaluated by the Clarke error grid analysis (EGA) and all data points are included in the clinically acceptable regions (region A:100%,region B:0%). Accordingly,it is feasible to measure BGL with COEM.

Reliable Method for Steady-State Concentrations and Current over the Diagnostic Biosensor Transducers

A mathematical modelling of diagnostic biosensors system at three basic types of enzyme kinetics is discussed in the presence of diffusion. Enzyme kinetics is adopted to be first order, Michaelis-Menten and ping-pong mechanism. In this paper, approximate analytical solutions are obtained for the non-linear equations under steady-state conditions by using the new Homotopy perturbation method. Simple and closed forms of analytical expressions for concentrations of substrate, product and co-substrate and corresponding current response have been derived for all possible values of parameters. Furthermore, the numerical simulation of the problem is also reported here by using Matlab program. Good agreement between analytical and numerical results is noted.

Diagnostic Validity of Cica Beta Test 1 for the Detection of Extended Spectrum Beta-Lactamase (ESBL) Producing Gram Negative Bacteria by Comparing with Phenotypic Method

Background: Detection of extended spectrum beta lactamase producing bacteria is an important issue in the clinical settings. Objective: The purpose of the present study was to validate the Cica Beta Test 1 for detection of extended spectrum beta-lactamase (ESBL) producing bacteria. Method: This analytical type of cross-sectional study was carried out in the Department of Microbiology and Immunology at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from January 2006 to December 2006 for a period of one (01) year. All the patients presented with the clinical features of urinary tract infection and surgical as well as burn wound infection at any age with both sexes were selected as study population. All bacteria were isolated and identified by their colony morphology, staining characters, pigment production, motility and other relevant biochemical tests. Phenotypic confirmation of ESBLs producing isolates were done by inhibitor potentiated disc diffusion test according to CLSI recommendation. The Cica Beta Test 1 was performed according to the manufacturer’s instructions. Result: A total number of 288 Gram negative bacteria were isolated. Among these isolates Cica Beta test 1 was positive in 97 strains and phenotypic confirmatory test was positive in 89 strains. The test sensitivity of Cica Beta Test 1 was 100% (95% CI 95.9% to 100.0%). Specificity of the test was 96.0% (95% CI 92.2% to 98.2%). The positive predictive value (PPV) and negative predictive value (NPV) were 92.7% (95% CI 84.5% to 95.7%) and 100.0% (95% CI 98.0% to 100.0%) respectively. The accuracy of the test was 97.2% (95% CI 95.1% to 99.1%). Area under ROC curve = 0.980 (95% CI 0.964 to 0.996);p value 0.0001. Conclusion: In conclusion, Cica Beta Test 1 is very high sensitivity and specificity for the detection of ESBL from Gram negative bacteria.

A Diagnostic Method for Fog Forecasting Using Numerical Weather Prediction(NWP)Model Outputs

An attempt has been made in the present study to forecast fog with a diagnostic method using the outputs of global NWP model.The diagnostic method is based on the combination of thresholds of meteorological variables involved in fog formation.The thresholds are computed using the observations during fog.These thresholds are applied to the output of a global NWP model for forecasting fog.The occurrence of fog is a common phenomenon during winter season over the northern plains of India.The diagnostic method is used to predict fog occurrences over three stations in north India.The proposed method is able to predict both occurrences and non-occurrences of fog at all the three stations.It is found that 94%of the fog events forecasted by the model using the diagnostic method have been actually observed at the selected stations.The performance of method in predicting fog is found best over Delhi with the highest accuracy(0.61)and probability of detection(0.60).The study signifies that diagnostic approach based on the output of a global model is a useful tool for predicting fog over a single location.

Non-invasive biomarkers for monitoring the fibrogenic process in liver:A short survey

The clinical course ofchronic liver diseases is significantly dependent on the progression rate and the extent offibrosis, i.e. the non-structured replacement of necrotic parenchyma by extracellular matrix. Fibrogenesis, i.e. the development offibrosis can be regarded as an unlimited wound healing process, which is based on matrix (connective tissue) synthesis in activated hepatic stellate cells, fibroblasts (fibrocytes), hepatocytes and biliary epithelial cells, which are converted to matrix-producing (myo-)fibroblasts by a process defined as epithelial-mesenchymal transition. Blood (noninvasive) biomarkers offibrogenesis and fibrosis can be divided into class and class analytes. Class biomarkers are those single tests, which are based on the pathophysiology offibrosis, whereas class biomarkers aremostly multiparametric algorithms, which have been statistically evaluated with regard to the detection and activity ofongoing fibrosis. Currently available markers fulfil the criteria ofideal clinical-chemical tests only partially, but increased understanding ofthe complex pathogenesis offibrosis offers additional ways for pathophysiologically well based serum (plasma) biomarkers. They include TGF-β-driven marker proteins, bone marrow-derived cells (fibrocytes), and cytokines, which govern proand anti-fibrotic activities. Proteomic and glycomic approaches ofserum are under investigation to set up specific protein or carbohydrate profiles in patients with liver fibrosis. These and other novel parameters will supplement or eventually replaceliver biopsy/histology, high resolution imaging analysis, and elastography for the detection and monitoring of patients at risk ofdeveloping liver fibrosis.

Current and future molecular diagnostics in colorectal cancer and colorectal adenoma

Colorectal cancer(CRC)is one of the most prevalent cancers in developed countries.On the other hand,CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy.Since CRC develops slowly from precancerous lesions,early detection can reduce both the incidence and mortality of the disease.Fecal occult blood test is a widely used non-invasive screening tool for CRC.Although fecal occult blood test is simple and cost-effective in screening CRC,there is room for improvement in terms of the accuracy of the test.Genetic dysregulations have been found to play an important role in CRC development.With better understanding of the molecular basis of CRC,there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC.In this review,the molecular basis of CRC development,the characteristics and applications of different non-invasive molecular biomarkers,as well as the technologies available for the detection were discussed.This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state,colorectal adenoma.

Non-invasive assessment of liver fibrosis in chronic liver diseases:Implementation in clinical practice and decisional algorithms

Chronic hepatitis B and C together with alcoholic and non-alcoholic fatty liver diseases represent the major causes of progressive liver disease that can eventually evolve into cirrhosis and its end-stage complications,including decompensation,bleeding and liver cancer.Formation and accumulation of fibrosis in the liver is the common pathway that leads to an evolutive liver disease.Precise definition of liver fibrosis stage is essential for management of the patient in clinical practice since the presence of bridging fibrosis represents a strong indication for antiviral therapy for chronic viral hepatitis,while cirrhosis requires a specif ic follow-up including screening for esophageal varices and hepatocellular carcinoma.Liver biopsy has always represented the standard of reference for assessment of hepatic fibrosis but it has some limitations being invasive,costly and prone to sampling errors.Recently,blood markers and instrumental methods have been proposed for the non-invasive assessment of liver fibrosis.However,there are still some doubts as to their implementation in clinical practice and a real consensus on how and when to use them is not still available.This is due to an unsatisfactory accuracy for some of them,and to an incomplete validation for others.Some studies suggest that performance of non-invasive methods for liver fibrosis assessment may increase when they are combined.Combination algorithms of non-invasive methods for assessing liver fibrosis may represent a rational and reliable approach to implement non-invasive assessment of liver fibrosis in clinical practice and to reduce rather than abolish liver biopsies.

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.

Comparisons of Methods for Pregnancy Diagnosis in Female Poodles

In this study, five 2 -4 years old healthy female poodles were selected and mated after spontaneous estrus for pregnancy diagnosis with external observa- tion, human chorionic gonadotropin colloidal gold rapid test strips （human early pregnancy test strips）, ultrasonic diagnosis and blood routine examination. Accord- ing to the results, female dogs showed abdominal circumference increment and mammogenesis from a month post-mating to parturition and lactated before parturi- tion. At 5, 6, 7, 15, 25 and 35 d post-mating, pregnancy diagnosis with human chorionic gonadotropin colloidal gold rapid test strips showed negative results. Hu- man early pregnancy test strips can not be used for pregnancy diagnosis in female dogs. Currently, ultrasonic method is the most accurate method to diagnose preg- nancy in female dogs, and the optimal diagnosis time is the 30th d post-mating. External observation and blood routine examination can be used as auxiliary methods to diagnose pregnancy in female dogs.