Guidelines for application of high-content screening in traditional Chinese medicine:concept,equipment,and troubleshooting

High-content screening(HCS)technology combines automated high-speed imaging hardware and single-cell quantitative analysis.It can greatly accelerate data acquisition in cellular fluorescence imaging and is a powerful research technique in traditional Chinese medicine(TCM).An increasing number of laboratories and platforms,including TCM laboratories,have begun utilizing HCS systems.However,this technology is still in its infancy in TCM research and there is a lack of sufficient experience with the associated concepts,instrument configurations,and analysis methods.To improve the understanding of HCS among researchers in the field of TCM,this paper summarizes the concept of HCS,software and hardware configuration,the overall research process,as well as common problems and related solutions of HCS in TCM research based on our team’s previous research experience,providing several research examples and an outlook on future perspectives,aiming to provide a technical guide for HCS in TCM research.

Identification of fangchinoline as a broad-spectrum enterovirus inhibitor through reporter virus based high-content screening

Hand,foot,and mouth disease(HFMD)is a common pediatric illness mainly caused by enteroviruses,which are important human pathogens.Currently,there are no available antiviral agents for the therapy of enterovirus infection.In this study,an excellent high-content antiviral screening system utilizing the EV-A71-eGFP reporter virus was developed.Using this screening system,we screened a drug library containing 1042 natural compounds to identify potential EV-A71 inhibitors.Fangchinoline(FAN),a bis-benzylisoquinoline alkaloid,exhibits potential inhibitory effects against various enteroviruses that cause HFMD,such as EV-A71,CV-A10,CV-B3 and CV-A16.Further investigations revealed that FAN targets the early stage of the enterovirus life cycle.Through the selection of FAN-resistant EV-A71 viruses,we demonstrated that the VP1 protein could be a potential target of FAN,as two mutations in VP1(E145G and V258I)resulted in viral resistance to FAN.Our research suggests that FAN is an efficient inhibitor of EV-A71 and has the potential to be a broad-spectrum antiviral drug against human enteroviruses.

Development of a high-content screening method to evaluate the cellular population-based biological activity of new siRNA delivering reagent

Normally, cellular responses to modified siRNAs or new siRNA delivery systems have been studied in group cell behavior by PCR, western blotting and fluorescence microscopy. In this study, we present a novel high-content screening （HCS） strategy to evaluate a novel delivery system （named CLD） of siRNA therapeutics, with which both the content of intracellular siRNAs and changes in protein expressing levels have been quantified in group cells and cellular population. We also observed that with the better cell uptake, CLD provided siRNA therapeutics （siBraf） better antitumor capability. This novel strategy was proved to be with efficiency, accuracy and high competency to adherent cell lines, thus making siRNA research more simplified.

Colorectal cancer screening:A review of current knowledge and progress in research

Colorectal cancer(CRC)is one of the most prevalent malignancies worldwide,being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally.Despite the progress in screening,early diagnosis,and treatment,approximately 20%-25%of CRC patients still present with metastatic disease at the time of their initial diagnosis.Furthermore,the burden of disease is still expected to increase,especially in individuals younger than 50 years old,among whom early-onset CRC incidence has been increasing.Screening and early detection are pivotal to improve CRC-related outcomes.It is well established that CRC screening not only reduces incidence,but also decreases deaths from CRC.Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality,though variations in efficacy have been reported across the literature.However,uncertainties persist regarding the optimal screening method,age intervals and periodicity.Moreover,adherence to CRC screening remains globally low.In recent years,emerging technologies,notably artificial intelligence,and non-invasive biomarkers,have been developed to overcome these barriers.However,controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice.In this review,we aim to cover the current evidence surrounding CRC screening.We will further critically assess novel approaches under investigation,in an effort to differentiate promising inno-vations from mere novelties.

Esophageal cancer screening,early detection and treatment:Current insights and future directions

Esophageal cancer ranks among the most prevalent malignant tumors globally,primarily due to its highly aggressive nature and poor survival rates.According to the 2020 global cancer statistics,there were approximately 604000 new cases of esophageal cancer,resulting in 544000 deaths.The 5-year survival rate hovers around a mere 15%-25%.Notably,distinct variations exist in the risk factors associated with the two primary histological types,influencing their worldwide incidence and distribution.Squamous cell carcinoma displays a high incidence in specific regions,such as certain areas in China,where it meets the cost-effect-iveness criteria for widespread endoscopy-based early diagnosis within the local population.Conversely,adenocarcinoma(EAC)represents the most common histological subtype of esophageal cancer in Europe and the United States.The role of early diagnosis in cases of EAC originating from Barrett's esophagus(BE)remains a subject of controversy.The effectiveness of early detection for EAC,particularly those arising from BE,continues to be a debated topic.The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses.In areas with higher incidences,such as China and Japan,early diagnosis is more common,which has led to the advancement of endoscopic methods as definitive treatments.These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality.Early screening,prompt diagnosis,and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.

Development and validation of a prediction model for early screening of people at high risk for colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a serious threat worldwide.Although early screening is suggested to be the most effective method to prevent and control CRC,the current situation of early screening for CRC is still not optimistic.In China,the incidence of CRC in the Yangtze River Delta region is increasing dramatically,but few studies have been conducted.Therefore,it is necessary to develop a simple and efficient early screening model for CRC.AIM To develop and validate an early-screening nomogram model to identify individuals at high risk of CRC.METHODS Data of 64448 participants obtained from Ningbo Hospital,China between 2014 and 2017 were retrospectively analyzed.The cohort comprised 64448 individuals,of which,530 were excluded due to missing or incorrect data.Of 63918,7607(11.9%)individuals were considered to be high risk for CRC,and 56311(88.1%)were not.The participants were randomly allocated to a training set(44743)or validation set(19175).The discriminatory ability,predictive accuracy,and clinical utility of the model were evaluated by constructing and analyzing receiver operating characteristic(ROC)curves and calibration curves and by decision curve analysis.Finally,the model was validated internally using a bootstrap resampling technique.RESULTS Seven variables,including demographic,lifestyle,and family history information,were examined.Multifactorial logistic regression analysis revealed that age[odds ratio(OR):1.03,95%confidence interval(CI):1.02-1.03,P<0.001],body mass index(BMI)(OR:1.07,95%CI:1.06-1.08,P<0.001),waist circumference(WC)(OR:1.03,95%CI:1.02-1.03 P<0.001),lifestyle(OR:0.45,95%CI:0.42-0.48,P<0.001),and family history(OR:4.28,95%CI:4.04-4.54,P<0.001)were the most significant predictors of high-risk CRC.Healthy lifestyle was a protective factor,whereas family history was the most significant risk factor.The area under the curve was 0.734(95%CI:0.723-0.745)for the final validation set ROC curve and 0.735(95%CI:0.728-0.742)for the training set ROC curve.The calibration curve demonstrated a high correlation between the CRC high-risk population predicted by the nomogram model and the actual CRC high-risk population.CONCLUSION The early-screening nomogram model for CRC prediction in high-risk populations developed in this study based on age,BMI,WC,lifestyle,and family history exhibited high accuracy.

Non-participation of asymptomatic candidates in screening protocols reduces early diagnosis and worsens prognosis of colorectal cancer

The Agatsuma et al’s study shows that despite the evidence of the benefits of an early colorectal cancer(CRC)diagnosis,through screening in asymptomatic subjects,up to 50%of candidates reject this option and many of those affected are diagnosed later,in advanced stages.The efficacy of screening programs has been well-established for several years,which reduces the risk of CRC morbidity and mortality,without taking into account the test used for screening,or other tools.Nevertheless,a significant proportion of patients remain unscreened,so understanding the factors involved,as well as the barriers of the population to adherence is the first step to possibly modify the participation rate.These barriers could include a full range of social and political aspects,especially the type of financial provision of each health service.In Japan,health services are universal,and this advantageous situation makes it easier for citizens to access to these services,contributing to the detection of various diseases,including CRC.Interestingly,the symptomatic CRC group had a lower early-stage diagnosis rate than the patients detected during follow-up for other comorbidities,and symptomatic and cancer screening groups showed similar early-stage diagnosis.

Genetic screening of liver cancer:State of the art

Liver cancer,primarily hepatocellular carcinoma,remains a global health challenge with rising incidence and limited therapeutic options.Genetic factors play a pivotal role in the development and progression of liver cancer.This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer.We discuss the genetic underpinnings of liver cancer,emphasizing the critical role of risk-associated genetic variants,somatic mutations,and epigenetic alterations.We also explore the intricate interplay between environmental factors and genetics,highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy,and advancements in high-throughput sequencing technologies.By synthesizing the latest research findings,we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer,shedding light on their potential to revolutionize early detection,risk assessment,and targeted therapies in the fight against this devastating disease.

Colorectal cancer screening: Modalities and adherence

In the last decade,several studies have explored various modalities and strategies for colorectal cancer(CRC)screening,taking into account epidemiological data,individual characteristics,and socioeconomic factors.In this editorial,we comment further on a retrospective study by Agatsuma et al published in the recent issue of the World Journal of Gastroenterology.Our focus is on screening trends,particularly in relation to efforts to improve the currently suboptimal uptake among the general population worldwide,aiming to enhance early diagnosis rates of CRC.There is a need to raise awareness through health edu-cation programs and to consider the use of readily available,non-invasive screening methods.These strategies are crucial for attracting screen-eligible populations to participate in first-line screening,especially those in high-or average-risk groups and in regions with limited resources.Liquid biopsies and biomarkers represent rapidly evolving trends in screening and diagnosis;however,their clinical relevance has yet to be standardized.

Reliability of a computerized system for strabismus screening

AIM:To evaluate the reliability of Photo-Hirschberg screening for global strabismus performed by non-specialized personnel.METHODS:Participants at three sites were enrolled.One person at each site was trained in visual acuity measurement and use of the computerized system.Visual acuity was measured,and strabismus testing was performed using two flash photographs.All data from the three primary observers were sent to an experienced assistant researcher,who was blinded to the primary results,for re-evaluation.The primary and re-evaluation results of the Photo-Hirschberg screenings using weighted kappa for agreement were compared.RESULTS:The study included 181 participants(88 males and 93 females)and the results for primary and re-evaluation screenings were corresponded.Ten participants with contrasting results presented with unclear corneal light reflex.Sensitivity and specificity were 100%[95%confidence interval(CI):29.0%-100%]and 99.4%(95%CI:96.6%-100%),respectively,based on the Agresti test of the primary evaluation,considering the re-evaluated classification as true.CONCLUSION:The computerized system can be used for primary strabismus screening by non-specialized personnel,with 98.8%agreement with specialists.However,it cannot be used as a substitute for professional examination.

Optimization of colorectal cancer screening strategies: New insights

In this editorial,we discuss the article by Agatsuma et al.We concentrate specifically on the current routinely used screening tests recommended by society guidelines and delve into the significance of early diagnosis of colorectal cancer(CRC)and its substantial impact on both incidence and mortality rates.Screening is highly recommended,and an early diagnosis stands out as the most crucial predictor of survival for CRC patients.Therefore,it is essential to identify and address the barriers hindering adherence to screening measures,as these barriers can vary among different populations.Furthermore,we focus on screening strategy optimization by selecting high-risk groups.Patients with comorbidities who regularly visit hospitals have been diagnosed at an early stage,showing no significant difference compared to patients undergoing regular screening.This finding highlights the importance of extending screening measures to include patients with comorbidities who do not routinely visit the hospital.

Screening, Treatment and Control of High Blood Pressure on Five Sites in Mali

Introduction: High blood pressure is defined as blood pressure greater than or equal to 140 mm Hg for systolic and or 90 mm Hg for diastolic. It constitutes a major public health problem, the leading chronic disease in the world. The objective was to determine the prevalence, treatment rate and control of hypertension. Methods: This was a cross-sectional and descriptive study which took place over a period of 6 months in a hospital environment and in the general population. Results: Of the 1000 participants, 637 had hypertension, giving a prevalence of 63.70% with a female predominance. Thirty-three percent (33%) were unaware of their high blood pressure. The age group 60 and more was the most represented (44%). A proportion of 33 and 23.20 were overweight and obese participants, respectively. Male subjects were more overweight than female, unlike obesity which was more common among female subjects. Sixty-two percent (62%) of hypertensives were treated, of whom 44% were non-compliant. The excessively high cost and consumption of medications as needed were the main factors in therapeutic non-compliance. Twenty-two percent (22%) of all hypertensive patients and 35% of treated hypertensive patients were controlled. Women were more treated but less observant and less controlled than men. Therapeutic coverage and combination therapy rates were lower in rural areas. Hypertensives who had a high level of education were better treated and controlled than those who had no level. Conclusion: High blood pressure remains a real public health problem in Mali. It is more common in people aged 60 and over and in females. One in three hypertensives were unaware of their hypertension. The majority received antihypertensive treatments, but only a minority of them had their hypertension controlled.

Consensus on rapid screening for prodromal Alzheimer's disease in China

Alzheimer's disease(AD)is a common cause of dementia,characterised by cerebral amyloid-βdeposition,pathological tau and neurodegeneration.The prodromal stage of AD(pAD)refers to patients with mild cognitive impairment(MCl)and evidence of AD's pathology.At this stage,disease-modifying interventions should be used to prevent the progression to dementia.Given the inherent heterogeneity of MCl,more specific biomarkers are needed to elucidate the underlying AD's pathology.Although the uses of cerebrospinal fluid and positron emission tomography are widely accepted methods for detecting AD's pathology,their clinical applications are limited by their high costs and invasiveness,particularly in low-income areas in China.Therefore,to improve the early detection of Alzheimer's disease(AD)pathology through cost-effective screening methods,a panel of 45neurologists,psychiatrists andgerontologistswas invited to establish a formal consensus on the screening of pAD in China.The supportive evidence and grades of recommendations are based on a systematic literature review andfocus group discussion.National meetings were held to allow participants to review,vote and provide their expert opinions to reach a consensus.A majority(two-thirds)decision was used for questions for which consensus could not be reached.Recommended screening methods are presented in this publication,including neuropsychological assessment,peripheral biomarkers and brain imaging.In addition,a general workflow for Screening pAD in China is established,which will help clinicians identify individuals at high risk and determine therapeutic targets.

Colon cancer screening programs prevent cancer

In this article we comment on the article by Agatsuma et al.Our article focuses on the use of screening for colon cancer increases the likelihood of early diagnosis of colorectal cancer compared to those presenting after symptoms develop.Patients with symptoms were more likely to have left-sided lesions with resultant hematochezia and/or changes in bowel habits.In this study almost all patients in the screen group were first screened with immunochemical fecal occult blood testing.Colonoscopy was used either if it was thought to be the more appropriate initial screening modality or if the non-invasive test was positive.The exact timing when an initial screening colonoscopy should be performed is not totally clear from this study.However,early screening for colon cancer does reduce the risk of cancer diagnosis and more advanced cancer diagnoses.

Evidence for the Reliability and Validity of the Arabic Version of the Student Risk Screening Scale for Internalizing and Externalizing Behaviors (SRSS-IE)

School-based universal screening for behavioral/emotional risk is a necessary first step to providing services in an educational setting for students with emotional and behavioral disorders (EBDs). Psychometric properties are critical to making decisions about choosing a screening instrument. The purpose of the present study was to examine the psychometric properties of the student risk screening scale for internalizing and externalizing behaviors (SRSS-IE). Participants included 3145 students and their teachers. Item-level analyses of the current sample supported the retention of all items. The internal consistency of the SRSS items ranged from 0.83 to 0.85. Convergent validity between the SRSS-IE and a well-established screening tool, the strength and difficulties questionnaire (SDQ), was found for the total score (r = 0.70). Additionally, the results of this study demonstrate strong social validity, suggesting the SRSS-IE to be a useful and functional screening tool. We conclude that the SRSS-IE is a valid and reliable instrument for assessing the level of emotional and behavioral difficulties among elementary students.

Refining the targeted population and achieving better for colorectal cancer screening

This editorial comments on the article entitled“Stage at diagnosis of colorectal cancer through diagnostic route:Who should be screened?”by Agatsuma et al,who conducted a retrospective study aiming at clarifying the stage at colorectal cancer(CRC)diagnosis based on different diagnostic routes.We share our opinion about CRC screening programs.The current situation suggests the need for a more specific and targeted population for CRC screening.

From the perspective of experimental practice: High-throughput computational screening in photocatalysis

Photocatalysis,a critical strategy for harvesting sunlight to address energy demand and environmental concerns,is underpinned by the discovery of high-performance photocatalysts,thereby how to design photocatalysts is now generating widespread interest in boosting the conversion effi-ciency of solar energy.In the past decade,computational technologies and theoretical simulations have led to a major leap in the development of high-throughput computational screening strategies for novel high-efficiency photocatalysts.In this viewpoint,we started with introducing the challenges of photocatalysis from the view of experimental practice,especially the inefficiency of the traditional“trial and error”method.Sub-sequently,a cross-sectional comparison between experimental and high-throughput computational screening for photocatalysis is presented and discussed in detail.On the basis of the current experimental progress in photocatalysis,we also exemplified the various challenges associated with high-throughput computational screening strategies.Finally,we offered a preferred high-throughput computational screening procedure for pho-tocatalysts from an experimental practice perspective(model construction and screening,standardized experiments,assessment and revision),with the aim of a better correlation of high-throughput simulations and experimental practices,motivating to search for better descriptors.

Effectiveness of colorectal cancer screening integrating non-genetic and genetic risk: a prospective study based on UK Biobank data

Objective: Few studies have evaluated the benefits of colorectal cancer(CRC) screening integrating both non-genetic and genetic risk factors. Here, we aimed to integrate an existing non-genetic risk model(QCancer-10) and a 139-variant polygenic risk score to evaluate the effectiveness of screening on CRC incidence and mortality.Methods: We applied the integrated model to calculate 10-year CRC risk for 430,908 participants in the UK Biobank, and divided the participants into low-, intermediate-, and high-risk groups. We calculated the screening-associated hazard ratios(HRs) and absolute risk reductions(ARRs) for CRC incidence and mortality according to risk stratification.Results: During a median follow-up of 11.03 years and 12.60 years, we observed 5,158 CRC cases and 1,487 CRC deaths, respectively. CRC incidence and mortality were significantly lower among screened than non-screened participants in both the intermediateand high-risk groups [incidence: HR: 0.87, 95% confidence interval(CI): 0.81±0.94;0.81, 0.73±0.90;mortality: 0.75, 0.64±0.87;0.70, 0.58±0.85], which composed approximately 60% of the study population. The ARRs(95% CI) were 0.17(0.11±0.24) and 0.43(0.24±0.61), respectively, for CRC incidence, and 0.08(0.05±0.11) and 0.24(0.15±0.33), respectively, for mortality. Screening did not significantly reduce the relative or absolute risk of CRC incidence and mortality in the low-risk group. Further analysis revealed that screening was most effective for men and individuals with distal CRC among the intermediate to high-risk groups.Conclusions: After integrating both genetic and non-genetic factors, our findings provided priority evidence of risk-stratified CRC screening and valuable insights for the rational allocation of health resources.

Diabetes Screening and Cardiovascular Risk in Tuberculosis Patients in Conakry and Surrounding Towns

Objective: To determine the prevalence of diabetes and the level of cardiovascular risk in tuberculosis patients treated in Conakry and surrounding towns. Method: This was a cross-sectional study carried out at tuberculosis treatment centers in Conakry and surrounding towns (Coyah and Dubréka) on World TB Day, November 14, 2022, among 350 tuberculosis patients. We determined the proportion of TB patients with diabetes and high hyperglycemia. We determined the Chi-square to identify the factors associated with the occurrence of diabetes in tuberculosis patients, and a significance threshold with p Results: The average age of participants was 33.5 ± 14.5 years, and they were predominantly male (59.7%). The majority of participants lived in Conakry (96.3%). 5.7% were known diabetics and 4.6% were known hypertensives. We found a prevalence of diabetes of 9.4%. Among diabetics, 39% were diabetes discoveries. 30% were hypertensive or had high blood pressure. Of these hypertensive patients, 26.4% were unrecognized hypertensives. Age and hypertension were statistically significantly associated with the onset of diabetes in tuberculosis patients. Medium, high and very high levels of cardiovascular risk were present in 23.4%, 8.9% and 3.4% respectively. Conclusion: Diabetes is common in tuberculosis patients. Cardiovascular risk factors, notably hypertension and cardiovascular risk level, are frequently associated with tuberculosis. Tuberculosis patients with cardiovascular risk factors should be screened for diabetes.

Development and validation of a novel questionnaire regarding vision screening among preschool teachers in Malaysia

AIM:To develop and evaluate the validity and reliability of a knowledge,attitude,and practice questionnaire related to vision screening(KAP-VST)among preschool teachers in Malaysia.METHODS:The questionnaire was developed through a literature review and discussions with experts.Content and face validation were conducted by a panel of experts(n=10)and preschool teachers(n=10),respectively.A pilot study was conducted for construct validation(n=161)and test-retest reliability(n=60)of the newly developed questionnaire.RESULTS:Based on the content and face validation,71 items were generated,and 68 items were selected after exploratory factor analysis.The content validity index for items(I-CVI)score ranged from 0.8-1.0,and the content validity index for scale(S-CVI)/Ave was 0.99.Internal consistency was KR^(2)0=0.93 for knowledge,Cronbach’s alpha=0.758 for attitude,and Cronbach’s alpha=0.856 for practice.CONCLUSION:The KAP-VST is a valid and reliable instrument for assessing knowledge,attitude,and practice in relation to vision screening among preschool teachers in Malaysia.