Systematic review of risk factors,prognosis,and management of colorectal signet-ring cell carcinoma

BACKGROUND Colorectal signet-ring cell carcinoma(CSRCC)is a rare clinical entity which accounts for approximately 1%of all colorectal cancers.Although multiple studies concerning this specific topic have been published in the past decades,the pathogenesis,associated risk factors,and potential implications on treatment are still poorly understood.Besides the low incidence,historically confusing histological criteria have resulted in confusing data.Nevertheless,the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis,highlight the actual interest to synthesize the known literature regarding CSRCC.AIM To provide an updated overview of risk factors,prognosis,and management of CSRCC.METHODS A literature search in the MEDLINE/PubMed database was conducted with the following search terms used:‘Signet ring cell carcinoma’and‘colorectal’.Studies in English language,published after January 1980,were included.Studies included in the qualitative synthesis were evaluated for content concerning epidemiology,risk factors,and clinical,diagnostic,histological,and molecular features,as well as metastatic pattern and therapeutic management.If possible,presented data was extracted in order to present a more detailed overview of the literature.RESULTS In total,67 articles were included for qualitative analysis,of which 54 were eligible for detailed data extraction.CSRCC has a reported incidence between 0.1%-2.4%and frequently presents with advanced disease stage at the time of diagnosis.CSRCC is associated with an impaired overall survival(5-year OS:0%-46%)and a worse stagecorrected outcome compared to mucinous and not otherwise specified adenocarcinoma.The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised.Surgery is the mainstay of treatment,although the rates of curative resection in CSRCC(21%-82%)are lower compared to those in other histological types.In case of peritoneal metastasis,cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should only be proposed in selected patients.CONCLUSION CSRCC is a rare clinical entity most often characterized by young age and advanced disease at presentation.As such,diagnostic modalities and therapeutic approach should be tailored accordingly.

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.

Identifying the Hydrochemical Characteristics,Genetic Mechanisms and Potential Human Health Risks of Fluoride and Nitrate Enriched Groundwater in the Tongzhou District,Beijing,North China

Fluoride and nitrate enriched groundwater are potential threats to the safety of the groundwater supply that may cause significant effects on human health and public safety,especially in aggregated population areas and economic hubs.This study focuses on the high F^(−)and NO_(3)^(−)concentration groundwater in Tongzhou District,Beijing,North China.A total of 36 groundwater samples were collected to analyze the hydrochemical characteristics,elucidate genetic mechanisms and evaluate the potential human health risks.The results of the analysis indicate:Firstly,most of the groundwater samples are characterized by Mg-HCO_(3) and Na-HCO_(3) with the pH ranging from 7.19 to 8.28 and TDS with a large variation across the range 471-2337 mg/L.The NO_(3)^(−)concentration in 38.89%groundwater samples and the F^(−)concentration in 66.67%groundwater samples exceed the permissible limited value.Secondly,F^(−)in groundwater originates predominantly from water-rock interactions and the fluorite dissolution,which is also regulated by cation exchange,competitive adsorption of HCO_(3)−and an alkaline environment.Thirdly,the effect of sewage disposal and agricultural activities have a significant effect on high NO3-concentration,while the high F^(−)concentration is less influenced by anthropogenic activity.The alkaline environment favors nitrification,thus being conducive to the production of NO_(3)^(−).Finally,the health risk assessment is evaluated for different population groups.The results indicate that high NO_(3)^(−)and F^(−)concentration in groundwater would have the largest threat to children’s health.The findings of this study could contribute to the provision of a scientific basis for groundwater supply policy formulation relating to public health in Tongzhou District.

Planetary health risks in urban agriculture

Urban agriculture is gaining recognition for its potential contributions to environmental resilience and climate change adaptation,providing advantages such as urban greening,reduced heat island effects,and decreased air pollution.Moreover,it indirectly supports communities during weather events and natural disasters,ensuring food security and fostering community cohesion.However,concerns about planetary health risks persist in highly urbanized and climate-affected areas.Employing electronic databases such as Web of Science and PubMed and adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,we identified 55 relevant papers to comprehend the planetary health risks associated with urban agriculture,The literature review identified five distinct health risks related to urban agriculture:(1)trace metal risks in urban farms;(2)health risks associated with wastewater irrigation;(3)zoonotic risks;(4)other health risks;and(5)social and economic risks.The study highlights that urban agriculture,while emphasizing environmental benefits,particularly raises concerns about trace metal bioaccumulation in soil and vegetables,posing health risks for populations.Other well studied risks included wastewater irrigation and backyard livestock farming.The main limitations in the available literature were in studying infectious diseases and antibiotic resistance associated with urban agriculture.

Predicting Users’ Latent Suicidal Risk in Social Media: An Ensemble Model Based on Social Network Relationships

Suicide has become a critical concern,necessitating the development of effective preventative strategies.Social media platforms offer a valuable resource for identifying signs of suicidal ideation.Despite progress in detecting suicidal ideation on social media,accurately identifying individuals who express suicidal thoughts less openly or infrequently poses a significant challenge.To tackle this,we have developed a dataset focused on Chinese suicide narratives from Weibo’s Tree Hole feature and introduced an ensemble model named Text Convolutional Neural Network based on Social Network relationships(TCNN-SN).This model enhances predictive performance by leveraging social network relationship features and applying correction factors within a weighted linear fusion framework.It is specifically designed to identify key individuals who can help uncover hidden suicidal users and clusters.Our model,assessed using the bespoke dataset and benchmarked against alternative classification approaches,demonstrates superior accuracy,F1-score and AUC metrics,achieving 88.57%,88.75%and 94.25%,respectively,outperforming traditional TextCNN models by 12.18%,10.84%and 10.85%.We assert that our methodology offers a significant advancement in the predictive identification of individuals at risk,thereby contributing to the prevention and reduction of suicide incidences.

Fuzzy Risk Assessment Method for Airborne Network Security Based on AHP-TOPSIS

With the exponential increase in information security risks,ensuring the safety of aircraft heavily relies on the accurate performance of risk assessment.However,experts possess a limited understanding of fundamental security elements,such as assets,threats,and vulnerabilities,due to the confidentiality of airborne networks,resulting in cognitive uncertainty.Therefore,the Pythagorean fuzzy Analytic Hierarchy Process(AHP)Technique for Order Preference by Similarity to an Ideal Solution(TOPSIS)is proposed to address the expert cognitive uncertainty during information security risk assessment for airborne networks.First,Pythagorean fuzzy AHP is employed to construct an index system and quantify the pairwise comparison matrix for determining the index weights,which is used to solve the expert cognitive uncertainty in the process of evaluating the index system weight of airborne networks.Second,Pythagorean fuzzy the TOPSIS to an Ideal Solution is utilized to assess the risk prioritization of airborne networks using the Pythagorean fuzzy weighted distance measure,which is used to address the cognitive uncertainty in the evaluation process of various indicators in airborne network threat scenarios.Finally,a comparative analysis was conducted.The proposed method demonstrated the highest Kendall coordination coefficient of 0.952.This finding indicates superior consistency and confirms the efficacy of the method in addressing expert cognition during information security risk assessment for airborne networks.

Magnetic resonance imaging-based radiomics model for preoperative assessment of risk stratification in endometrial cancer

BACKGROUND Preoperative risk stratification is significant for the management of endometrial cancer(EC)patients.Radiomics based on magnetic resonance imaging(MRI)in combination with clinical features may be useful to predict the risk grade of EC.AIM To construct machine learning models to predict preoperative risk stratification of patients with EC based on radiomics features extracted from MRI.METHODS The study comprised 112 EC patients.The participants were randomly separated into training and validation groups with a 7:3 ratio.Logistic regression analysis was applied to uncover independent clinical predictors.These predictors were then used to create a clinical nomogram.Extracted radiomics features from the T2-weighted imaging and diffusion weighted imaging sequences of MRI images,the Mann-Whitney U test,Pearson test,and least absolute shrinkage and selection operator analysis were employed to evaluate the relevant radiomic features,which were subsequently utilized to generate a radiomic signature.Seven machine learning strategies were used to construct radiomic models that relied on the screening features.The logistic regression method was used to construct a composite nomogram that incorporated both the radiomic signature and clinical independent risk indicators.RESULTS Having an accuracy of 0.82 along with an area under the curve(AUC)of 0.915[95%confidence interval(CI):0.806-0.986],the random forest method trained on radiomics characteristics performed better than expected.The predictive accuracy of radiomics prediction models surpassed that of both the clinical nomogram(AUC:0.75,95%CI:0.611-0.899)and the combined nomogram(AUC:0.869,95%CI:0.702-0.986)that integrated clinical parameters and radiomic signature.CONCLUSION The MRI-based radiomics model may be an effective tool for preoperative risk grade prediction in EC patients.

Penetration Study of Key Technologies for Cybersecurity Risk Assessment

In recent years,with the frequent occurrence of cyber security incidents,people have paid more attention to it.Information security risk assessment is a very important research topic.This paper gives a brief overview of the theory of cybersecurity risk assessment,focuses on the description of the current mainstream cybersecurity risk assessment methods,classifies and compares the existing methods according to the nature of the methods,and analyses the advantages,disadvantages,and application scope of each method.Finally,the main factors affecting the evaluation results are summarized and refined,and future research hotspots in this field are proposed.Through the empirical analysis of the three factors,the influence of the correlation of the three factors,the uncertainty of the evaluation indexes,and the timeliness of the evaluation on the evaluation results are concluded,which provides a reference for future research on evaluation methods.

Systematic Risk Analysis of Listed Financial Institutions from the Perspective of Complex Network

Based on the complex network theory,this paper studies the systemic financial risks in China’s financial market.According to the industry classification of the China Securities Regulatory Commission in 2012,the daily closing prices of 45 listed financial institutions are collected and the daily return rates of each financial institution are measured according to the logarithmic return rate calculation formula.In this paper,the risk spillover value ΔCoVaR is used to measure the contribution degree of each financial institution to systemic risk.Finally,the relationship between the risk spillover valueΔCoVaR and the node topology index of the risk transmission network is investigated by using a regression model,and some policy suggestions are put forward based on the regression results.

Research on Risk Prevention and Resolution Strategies of College Network Ideology in the Context of the Internet

With the rapid development of the Internet,the network ideology of colleges and universities is facing severe challenges.This paper deeply analyzes the root of the risk of network ideology and makes a specific investigation of the status quo of network public opinion in colleges and universities.On this basis,the study explores and puts forward a series of targeted risk prevention and resolution strategies,aiming at providing a systematic solution for the network ideology security of colleges and universities.In this paper,with the combination of theory and practice as the path,we verify the effectiveness and applicability of the proposed strategy through the analysis of the implementation effect of the strategy.This study also provides theoretical support and practical guidance for the prevention and control of ideological risks and public opinion guidance in universities under the network environment,which has important practical significance.With the continuous progress of network technology,the threats to the network ideology of colleges and universities are increasing.For example,the spread of false information has become a serious problem affecting the security of college network ideology.

Safety Risk Assessment Analysis of Bridge Construction Using Backpropagation Neural Network

The evaluation of construction safety risks has become a crucial task with the increasing development of bridge construction.This paper aims to provide an overview of the application of backpropagation neural networks in assessing safety risks during bridge construction.It introduces the situation,principles,methods,and advantages,as well as the current status and future development directions of backpropagation-related research.

Population genetics of marmosets in Asian primate research centers and loci associated with epileptic risk revealed by whole-genome sequencing

The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independently reported in two Asian primate research centers.Nevertheless,the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated.Here,we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing.We identified 14558184 single nucleotide polymorphisms(SNPs)from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples.Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers.In addition,SNP and copy number variation(CNV)analyses suggested that the WW domain-containing oxidoreductase(WWOX)and Tyrosine-protein phosphatase nonreceptor type 21(PTPN21)genes may be associated with epilepsy in marmosets.Notably,KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets.This study provides valuable population genomic resources for marmosets in two Asian primate centers.Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers,while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.

Significant risk factors for intensive care unit-acquired weakness:A processing strategy based on repeated machine learning

BACKGROUND Intensive care unit-acquired weakness(ICU-AW)is a common complication that significantly impacts the patient's recovery process,even leading to adverse outcomes.Currently,there is a lack of effective preventive measures.AIM To identify significant risk factors for ICU-AW through iterative machine learning techniques and offer recommendations for its prevention and treatment.METHODS Patients were categorized into ICU-AW and non-ICU-AW groups on the 14th day post-ICU admission.Relevant data from the initial 14 d of ICU stay,such as age,comorbidities,sedative dosage,vasopressor dosage,duration of mechanical ventilation,length of ICU stay,and rehabilitation therapy,were gathered.The relationships between these variables and ICU-AW were examined.Utilizing iterative machine learning techniques,a multilayer perceptron neural network model was developed,and its predictive performance for ICU-AW was assessed using the receiver operating characteristic curve.RESULTS Within the ICU-AW group,age,duration of mechanical ventilation,lorazepam dosage,adrenaline dosage,and length of ICU stay were significantly higher than in the non-ICU-AW group.Additionally,sepsis,multiple organ dysfunction syndrome,hypoalbuminemia,acute heart failure,respiratory failure,acute kidney injury,anemia,stress-related gastrointestinal bleeding,shock,hypertension,coronary artery disease,malignant tumors,and rehabilitation therapy ratios were significantly higher in the ICU-AW group,demonstrating statistical significance.The most influential factors contributing to ICU-AW were identified as the length of ICU stay(100.0%)and the duration of mechanical ventilation(54.9%).The neural network model predicted ICU-AW with an area under the curve of 0.941,sensitivity of 92.2%,and specificity of 82.7%.CONCLUSION The main factors influencing ICU-AW are the length of ICU stay and the duration of mechanical ventilation.A primary preventive strategy,when feasible,involves minimizing both ICU stay and mechanical ventilation duration.

Risk Assessment of Deep-Water Horizontal X-Tree Installation

Due to the high potential risk and many influencing factors of subsea horizontal X-tree installation,to guarantee the successful completion of sea trials of domestic subsea horizontal X-trees,this paper established a modular risk evaluation model based on a fuzzy fault tree.First,through the analysis of the main process oftree down and combining the Offshore&Onshore Reliability Data(OREDA)failure statistics and the operation procedure and the data provided by the job,the fault tree model of risk analysis of the tree down installation was established.Then,by introducing the natural language of expert comprehensive evaluation and combining fuzzy principles,quantitative analysis was carried out,and the fuzzy number was used to calculate the failure probability of a basic event and the occurrence probability of a top event.Finally,through a sensitivity analysis of basic events,the basic events of top events significantly affected were determined,and risk control and prevention measures for the corresponding high-risk factors were proposed for subsea horizontal X-tree down installation.

Climate change drives flooding risk increases in the Yellow River Basin

The Yellow River Basin(YRB)has experienced severe floods and continuous riverbed elevation throughout history.Global climate change has been suggested to be driving a worldwide increase in flooding risk.However,owing to insufficient evidence,the quantitative correlation between flooding and climate change remains illdefined.We present a long time series of maximum flood discharge in the YRB dating back to 1843 compiled from historical documents and instrument measurements.Variations in yearly maximum flood discharge show distinct periods:a dramatic decreasing period from 1843 to 1950,and an oscillating gentle decreasing from 1950 to 2021,with the latter period also showing increasing more extreme floods.A Mann-Kendall test analysis suggests that the latter period can be further split into two distinct sub-periods:an oscillating gentle decreasing period from 1950 to 2000,and a clear recent increasing period from 2000 to 2021.We further predict that climate change will cause an ongoing remarkable increase in future flooding risk and an∼44.4 billion US dollars loss of floods in the YRB in 2100.

Prevalence and risk factors of diabetes mellitus among elderly patients in the Lugu community

BACKGROUND Age is a significant risk factor of diabetes mellitus(DM).With the develop of population aging,the incidence of DM remains increasing.Understanding the epidemiology of DM among elderly individuals in a certain area contributes to the DM interventions for the local elderly individuals with high risk of DM.AIM To explore the prevalence of DM among elderly individuals in the Lugu community and analyze the related risk factors to provide a valid scientific basis for the health management of elderly individuals.METHODS A total of 4816 elderly people who came to the community for physical examination were retrospectively analyzed.The prevalence of DM among the elderly was calculated.The individuals were divided into a DM group and a non-DM group according to the diagnosis of DM to compare the differences in diastolic blood pressure(DBP)and systolic blood pressure(SBP),fasting blood glucose,body mass index(BMI),waist-to-hip ratio(WHR)and incidence of hypertension(HT),coronary heart disease(CHD),and chronic kidney disease(CKD).RESULTS DM was diagnosed in 32.70%of the 4816 elderly people.The BMI of the DM group(25.16±3.35)was greater than that of the non-DM group(24.61±3.78).The WHR was 0.90±0.04 in the non-DM group and 0.90±0.03 in the DM group,with no significant difference.The left SBP and SBP in the DM group were 137.9 mmHg±11.92 mmHg and 69.95 mmHg±7.75 mmHg,respectively,while they were 126.6 mmHg±12.44 mmHg and 71.15 mmHg±12.55 mmHg,respectively,in the non-DM group.These findings indicate higher SBP and lower DBP in DM patients than in those without DM.In the DM group,1274 patients were diagnosed with HT,accounting for 80.89%.Among the 3241 non-DM patients,1743(53.78%)were hypertensive and 1498(46.22%)were nonhypertensive.The DM group had more cases of HT than did the non-DM group.There were more patients with CHD or CKD in the DM group than in the non-DM group.There were more patients who drank alcohol more frequently(≥3 times)in the DM group than in the non-DM group.CONCLUSION Older adults in the Lugu community are at a greater risk of DM.In elderly individuals,DM is closely related to high BMI and HT,CHD,and CKD.Physical examinations should be actively carried out for elderly people to determine their BMI,SBP,DBP,and other signs,and sufficient attention should be given to abnormalities in the above signs before further diagnosis.

Prediabetes: An overlooked risk factor for major adverse cardiac and cerebrovascular events in atrial fibrillation patients

BACKGROUND Prediabetes is a well-established risk factor for major adverse cardiac and cerebrovascular events(MACCE).However,the relationship between prediabetes and MACCE in atrial fibrillation(AF)patients has not been extensively studied.Therefore,this study aimed to establish a link between prediabetes and MACCE in AF patients.AIM To investigate a link between prediabetes and MACCE in AF patients.METHODS We used the National Inpatient Sample(2019)and relevant ICD-10 CM codes to identify hospitalizations with AF and categorized them into groups with and without prediabetes,excluding diabetics.The primary outcome was MACCE(all-cause inpatient mortality,cardiac arrest including ventricular fibrillation,and stroke)in AF-related hospitalizations.RESULTS Of the 2965875 AF-related hospitalizations for MACCE,47505(1.6%)were among patients with prediabetes.The prediabetes cohort was relatively younger(median 75 vs 78 years),and often consisted of males(56.3%vs 51.4%),blacks(9.8%vs 7.9%),Hispanics(7.3%vs 4.3%),and Asians(4.7%vs 1.6%)than the non-prediabetic cohort(P<0.001).The prediabetes group had significantly higher rates of hypertension,hyperlipidemia,smoking,obesity,drug abuse,prior myocardial infarction,peripheral vascular disease,and hyperthyroidism(all P<0.05).The prediabetes cohort was often discharged routinely(51.1%vs 41.1%),but more frequently required home health care(23.6%vs 21.0%)and had higher costs.After adjusting for baseline characteristics or comorbidities,the prediabetes cohort with AF admissions showed a higher rate and significantly higher odds of MACCE compared to the non-prediabetic cohort[18.6%vs 14.7%,odds ratio(OR)1.34,95%confidence interval 1.26-1.42,P<0.001].On subgroup analyses,males had a stronger association(aOR 1.43)compared to females(aOR 1.22),whereas on the race-wise comparison,Hispanics(aOR 1.43)and Asians(aOR 1.36)had a stronger association with MACCE with prediabetes vs whites(aOR 1.33)and blacks(aOR 1.21).CONCLUSION This population-based study found a significant association between prediabetes and MACCE in AF patients.Therefore,there is a need for further research to actively screen and manage prediabetes in AF to prevent MACCE.

Adolescent suicide risk factors and the integration of socialemotional skills in school-based prevention programs

Adolescents are considered one of the most vulnerable groups affected by suicide.Rapid changes in adolescents’physical and mental states,as well as in their lives,significantly and undeniably increase the risk of suicide.Psychological,social,family,individual,and environmental factors are important risk factors for suicidal behavior among teenagers and may contribute to suicide risk through various direct,indirect,or combined pathways.Social-emotional learning is considered a powerful intervention measure for addressing the crisis of adolescent suicide.When deliberately cultivated,fostered,and enhanced,selfawareness,self-management,social awareness,interpersonal skills,and responsible decision-making,as the five core competencies of social-emotional learning,can be used to effectively target various risk factors for adolescent suicide and provide necessary mental and interpersonal support.Among numerous suicide intervention methods,school-based interventions based on social-emotional competence have shown great potential in preventing and addressing suicide risk factors in adolescents.The characteristics of school-based interventions based on social-emotional competence,including their appropriateness,necessity,cost-effectiveness,comprehensiveness,and effectiveness,make these interventions an important means of addressing the crisis of adolescent suicide.To further determine the potential of school-based interventions based on social-emotional competence and better address the issue of adolescent suicide,additional financial support should be provided,the combination of socialemotional learning and other suicide prevention programs within schools should be fully leveraged,and cooperation between schools and families,society,and other environments should be maximized.These efforts should be considered future research directions.

Machine Learning-Based Decision-Making Mechanism for Risk Assessment of Cardiovascular Disease

Cardiovascular disease(CVD)has gradually become one of the main causes of harm to the life and health of residents.Exploring the influencing factors and risk assessment methods of CVD has become a general trend.In this paper,a machine learning-based decision-making mechanism for risk assessment of CVD is designed.In this mechanism,the logistics regression analysismethod and factor analysismodel are used to select age,obesity degree,blood pressure,blood fat,blood sugar,smoking status,drinking status,and exercise status as the main pathogenic factors of CVD,and an index systemof risk assessment for CVD is established.Then,a two-stage model combining K-means cluster analysis and random forest(RF)is proposed to evaluate and predict the risk of CVD,and the predicted results are compared with the methods of Bayesian discrimination,K-means cluster analysis and RF.The results show that thepredictioneffect of theproposedtwo-stagemodel is better than that of the comparedmethods.Moreover,several suggestions for the government,the medical industry and the public are provided based on the research results.

Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.