Background: Acute respiratory viral infections can result in cardiovascular involvement, with such patients having a significantly higher mortality rate than those without cardiovascular involvement. Due to the ongoing coronavirus disease 2019 (COVID-19) pandemic, it is important to determine whether cardiovascular risk factors are associated with the severity of COVID-19.Methods: These nationwide data were provided by the Korea Disease Control and Prevention Agency. We defined a patient as having a “critical illness” if they required more than invasive mechanical ventilation and “fatal illness” if they died.Results: Among the total 5,307 patients, 2,136 (40.8%) were male. The critical illness rate was 5.1%  and the fatality rate was 4.54%. The multivariable analysis showed that age ≥60 years, male sex, diabetes mellitus, hypertension, heart failure, chronic kidney disease, cancer, and dementia were independent risk factors for critical illness. The risk scoring model showed the significance of multiple risk factors. Patients with four risk factors; old age (≥60 years), male sex, hypertension, and diabetes mellitus had a more than a 100 times higher risk for severe COVID-19 than those without these risk factors .Conclusions: This study demonstrated that cardiovascular risk factors are also significant risk factors for severe COVID-19. In particular, patients who have multiple cardiovascular risk factors are more likely to progress to severe COVID-19. Therefore, early and appropriate treatment of these patients is crucial. The risk of myocardial infarction is known to be proportional to the severity of an acute respiratory infection . Acute vSince the end of 2019, coronavirus disease 2019 (COVID-19) caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread to more than 200 countries around the world. It has displayed high transmission power, severity, and mortality. The clinical manifestation of COVID-19 is broad, ranging from no symptoms to fever, acute respiratory distress syndrome, multiple organ failure, and death . Many coExcess mortality was reported in the United States during the influenza pandemic. Although the association with secondary infections was not identified, cardiovascular event may have been a contributing factor , 6. A reHence, in this study, we focused and analyzed the clinical implications of cardiovascular risk factors and the presence or absence of cardiovascular disease on the outcome and severity of COVID-19. Research on cardiovascular risk factors, including hypertension and diabetes mellitus, which are prevalent in the entire population, and the effect of sex and age on the severity of COVID-19 are not only important to cardiologists, but are significant public health topics. Further, this study can provide important prognostic information for patients.The previous studies are mostly conducted early on in the pandemic and have limited study populations. The Republic of Korea reduced the spread of COVID-19 by proactively and systematically identifying patients with COVID-19 based on the national health insurance system, which is a single-payer, compulsory subscription system. Accordingly, we have a good basis for analyzing the characteristics of the clinical features of COVID-19 using data from across Korea. Here, we analyzed whether cardiovascular disease and/or the associated risk factors affect the severity of COVID-19 using data provided by the Korea Disease Control and Prevention Agency (KDCA).http://ncov.mohw.go.kr/en/) and through the media. The KDCA developed a registry of confirmed COVID-19 cases and provided the anonymized data to select researchers. The data includes only COVID-19 patients that had been released from isolation or died until 30 April 2020. We analyzed the data received from the KDCA via encrypted, remote access.This is a retrospective cohort study, using nationwide data from the Republic of Korea. Study candidates are the patients with COVID-19 who had been hospitalized, among the patients released from isolation or died as of April 30, 2020. Since the first confirmed case of COVID-19 in Korea on January 19, 2020, the KDCA has actively tracked almost all patients and their contacts in an attempt to control the spread of COVID-19. Further, cumulative statistics are released daily on a public web site  test with respiratory specimens: upper respiratory specimens , with or without a lower respiratory specimen (sputum), regardless of their clinical manifestations .Disease severity was defined according to the KDCA and World Health Organization guidelines , 12 as fInformation on comorbidities was reviewed to determine whether patients had previously been diagnosed with specific comorbidities. Body temperature and body mass index were the initial findings on hospital admission.U, or Wilcoxon rank-sum tests were performed for body temperature. Univariate and multivariable logistic regression models were applied to evaluate the risk factors of critical and fatal illness. Age was given as a categorical variable in units of 10 years. There were no critical or death cases reported in the 20–29-year age (20s) group. So, age group was categorized as <40 (20s + 30s) years, 40s, 50s, 60s, 70s, and ≥80 years for logistic regression, and the 60s used as the reference.The baseline characteristics of the subjects were described as a frequency and proportion for categorical data. The chi-square test was used to compare the categorical variables. The values of continuous variables were expressed as the median and interquartile range . The Mann-Whitney Multivariable logistic regression was used to analyze the independent risk of critical and fatal illness after adjusting for several comorbid diseases: diabetes mellitus, hypertension, heart failure, chronic heart disease (other than hypertension and heart failure), bronchial asthma, chronic obstructive lung disease (COPD), chronic kidney disease (CKD), chronic liver disease, rheumatic disease, cancer (excluding cured cases), and dementia.Utilizing the cardiovascular risk factors, a model for criticality and fatality prediction was made with age ≥60, male sex, medical history of diabetes mellitus, and hypertension as one point each. Theses ranged from a minimum of zero to a maximum of four points.Next, the criticality and fatality prediction models were analyzed by logistic regression model, odds ratios (ORs) and c-statistics were obtained. The c-statistics were equivalent to the area under the receiver operating characteristic (ROC) curve, based on the predicted probability of the outcomes  in the logistic regression models with the risk score as independent variable. In this model, each score was treated as binary category of 0 or 1.For risk score validation, we performed internal validation using bootstrap resampling. To evaluate the performance of compensating overfitting of logistic regression and the risk score model, a total of 1,000 random bootstrap samples were generated for replacement of the original data, and each bootstrap sample size was the same scale as the original data. Then the means and 95% confidence intervals of bootstrap samples were calculated. The c-statistic difference between original data and bootstrap samples was defined as optimism. Optimism-corrected c-statistic can be obtained by subtracting the estimated mean of the optimism estimate value from the c-index in the original sample.P-value of < 0.05 was considered statistically significance. The statistical analysis was performed using the SAS software .A This study was deemed exempt from ethical review and the requirement for informed consent was waived by the Ewha Womans University Mokdong hospital Institutional Review Board (EUMC2020-07-002) because all of the data were fully anonymized and did not include personally identifiable information.P < 0.001), and the fatality of the study group was 4.54%. Number of cases is highest in the 20s and 50s, but no critical illness or fatal illness was in the 20s. Meanwhile, critical illness started to rise steeply from the age of 50s, reaching 43.5% in the 80s.The baseline demographic and clinical characteristics are presented in 2 also showed a higher in the critical illness than in the non-critical illness patients.Clinical symptoms including cough, sputum, sore throat and diarrhea did not differ according to severity, but shortness of breath was more frequently reported in the critical illness than in the non-critical illness (20.4 vs. 2.9%) patients. Patients with systolic blood pressures of <120 or ≥140 mmHg were more likely to be critically ill than those with a systolic blood pressure between 120 and 140 mmHg. Underweight patients with a body mass index of <18.5 kg/mPatients with chronic diseases , cardiovascular diseases , respiratory disorder , cancer, and/or dementia presented higher rate of critical illness than those without. No significant difference in severity was seen between patients with chronic liver disease or rheumatic disorder and those without. Among the 271 critically ill patients, 19 survived with invasive ventilation and 11 ECMO, whereas the remaining 241 did not survived.Logistic analyses were performed to evaluate the risk factors for critical and fatal illness . In the In addition, we performed multivariable analyses with four major cardiovascular risk factors (model 2). The results showed similar ORs with model 1 in Model 1 and model 2 showed good performance for prediction of critical illness  and fatal illness . Interestingly, model 2 showed excellent performance similar to model 1. Furthermore, all the values of model 2; bootstrap, original, and corrected, c-statistics showed ≥0.9 for critical and fatal illness.According to the result of model 2, we calculated risk score with simplified four variables: age ≥60 years, male sex, diabetes mellitus, and hypertension, which are also known to be cardiovascular risk factors. Each one risk factor was calculated as one point. This study demonstrated that cardiovascular risk factors are also significant risk factors for severe COVID-19. In particular, age ≥60 years was shown to be a strong risk factor; the risk of severe COVID-19 significantly increased by 10 times in those aged ≥80 years compared to those in their 60s. Similar to heart disease, male had a higher risk, and more than twice the odds ratio for critical COVID-19 than female. Hypertension was a risk factor for critical illness rather than fatal illness which was same to heart failure. Additionally, dementia and cancer were found to be poor prognostic factors. Respiratory diseases, such as asthma and COPD were not found to be significant risk factors. Regarding the risk score model, the risk of critical or fatal illness increased sharply according to every increase in score compared to those without risk factors (risk score zero). Therefore, the more risk factors a patient has, the greater their likelihood of progressing to severe COVID-19.Cardiovascular risk factors are known as smoking, hypertension, diabetes, obesity, physical inactivity, age, male sex , 14. HowPrevious studies have shown an association between the Middle East respiratory syndrome (MERS) and SARS with acute myocarditis, myocardial infarction, and heart failure as well as a relationship of COVID-19 and myocardial injury , 3, 15. Potential mechanisms for the association between acute viral infection and increased myocardial damage are as follows: 1) type 1 myocardial infarction, which is caused by atherosclerotic plaque rupture or coronary thrombosis related acute inflammation; (2) type 2 myocardial infarction, which is related to the mismatch of oxygen demand and supply, and (3) direct effect of the virus and inflammation on the cardiac cells  type 1 m, 20. A cPrevious studies have shown that elevated cardiac troponin and pro-brain natriuretic peptide are each independently associated with poor outcomes in patients with COVID-19 patients , 21. HowThis study showed that CKD, cancer, and dementia are also risk factors. Dementia is a disease that is more prevalent in older individuals. However, it was still found to be a significant risk factor even after adjusting for age and other comorbid conditions. Several studies have found that CKD is related to an increased risk of mortality from COVID-19 , 12. In In general, patients with an underlying respiratory disease appear to have a poor prognosis for respiratory infections . PreviouThe current study has some limitations. First, since no cardiac biomarkers were available, such as cardiac troponin or pro-brain natriuretic peptide, that can reflect myocardial damage or heart failure, it is unclear as to whether the disease severity associated with cardiovascular risk factors is directly related to actual heart damage. Second, specific disease condition was not available in this study. For example, we could not know whether the result related to chronic heart disease is due to which of ischemic heart disease, valvular heart disease, and cardiomyopathy. In addition, our data did not include information on atrial fibrillation, which was known to be one of the poor prognostic factors associated with COVID-19 . There iThis study has a strong point as nation-wide cohort study which minimizing selection bias. The data is based on the unique single-payer, compulsory subscription system of the Republic of Korea and infectious disease control system integrated by the government through KDCA. Hence, the study could be good reference to explore the situation of a single country and elucidate interracial differences for future investigation. Another novelty of this study is the study population is younger and predominantly females compared to other large series on COVID-19. Since young patients and female patients were included in the analysis, it can be considered to apply to a wider range of populations.In conclusion, we have described the clinical characteristics and disease severity of hospitalized patients with confirmed COVID-19 in the Republic of Korea, using nationwide data from 5,307 patients. Our results showed that those over 60 years, of the male sex, or those with heart failure, cardiovascular risk factors; hypertension, diabetes mellitus, and CKD have an increased risk of severe COVID-19. Further, the risk scoring model showed the significance of multiple risk factors. Those with four risk factors, old age (≥60 years), male sex, hypertension, and diabetes mellitus, had odds ratio more than 100 of severe COVID-19 than those without these risk factors, although it should be taken into account that it can be statistically exaggerated due to relatively small numbers of patients. In addition, dementia and cancer were also found to be related to severe COVID-19.http://ncov.mohw.go.kr/en/) and through the media by KCDA. You may contact KDCA and/or the corresponding author for the detailed data in current study.Data cannot be shared publicly for protecting personal information by the Korea Disease Control and Prevention Agency (KDCA). Broad information regarding Korean COVID-19 statistics are released daily on a public web site (The studies involving human participants were reviewed and approved by Ewha Womans University Mokdong Hospital Institutional Review. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.KK and IK: conceptualization and data curation. KK: formal analysis. KK, SJ, MY, JP, and IK: investigation and validation. SJ and IK: methodology and writing—original draft. SJ: visualization. KK, SJ, and IK: writing—review and editing. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Sacroiliitis (SI), an inflammatory arthropathy, may accompany pediatric inflammatory bowel diseases (IBDs), present with non- specific back pain, hence might be unnoticed. The aims of this study were to assess the frequency of the SI in children with IBD and determine the characteristics of the association of SI with the clinical hallmarks of the IBD.In this prospective, cross sectional study, twenty-seven children with IBD, 7–18 years of age were evaluated. Patients with low back pain or stiffness, alternating buttock pain, or hip pain were examined for the presence of SI. The radiologic manifestations on X-ray suggesting sacroilitis were confirmed with Magnetic resonance imaging (MRI).Twenty-seven children , with mean age of 12.55±3.6 years, of which 52% had ulcerative colitis (UC), 41% had Crohn’s disease (CD), and two had indeterminate colitis (IC). The median time from IBD diagnosis was 6.0 (18.0) months for patients with SI and 12.0 (13.5) months for patients without SI. Low back pain or stiffness was observed in 13 patients (48%). SI was present in eight (30%) of the children with IBD. The patients with CD were more prone to SI (45% of CD vs. 21% of UC patients). All patients with SI were negative for HLA-B27 genotyping. The disease activity and gender were not associated with increased risk for SI. MRI was remarkable for bone marrow edema in all of the patient, followed by erosions in six of them (75%), synovial enhancement observed in five (63%), and erosion associated enthesitis of the pelvic region was observed in two (25%) of the patients.SI may remain obscured in children with IBD. Children with CD are more prone to SI than those with UC. Pediatric rheumatology-pediatric gastroenterology collaboration might augment screening in at-risk patients. Inflammatory bowel diseases (IBDs) are a group of chronic inflammatory disorders affecting mainly the gastrointestinal tract. However, approach as a systemic disease should be considered since associated extraintestinal manifestations (EIMs) involving the eyes, skin, hepatobiliary, and musculoskeletal systems may be observed [observed . Musculoobserved . Musculoobserved . It is wobserved , whereasobserved . Axial iobserved .Previous studies have suggested increased risk for peripheral arthritis and SI in subjects with Crohn’s disease (CD) than those with ulcerative colitis (UC), especially in CD with perianal and upper gastrointestinal involvement . The diaTwenty-seven children, 7–18 years of age, diagnosed with CD, UC, or indeterminate colitis (IC) followed in a pediatric gastroenterology clinic were included in the study. The patients were receiving 5 ASA and azathioprine treatment, with or without methylprednisolone. Height, weight, and body mass index were settled to age- and sex-adjusted Standard deviation scores (SD Z scores) using World Health Organization’s growth charts. The diagnosis of UC was done if the child with diarrhea and/or blood or mucus in the stools had evidence of continuous macroscopic inflammation on the colonoscopy, extending from the rectum to the proximal regions of the colon and histological features typical of UC, excluding CD of the small bowel through radiology, endoscopy, and histology. CD was diagnosed in the presence of typical clinical features such as weight loss, abdominal pain, and diarrhea with macroscopic inflammation such as skipped and patchy lesions, segmental inflammation, aphtoid ulcers, cobble-stoning or strictures and histological evidence of inflammatory infiltrate toward the lamina propria with or without epithelioid granuloma formation. The diagnosis of IC was done if there were no clear criteria for the diagnosis of CD or UC despite remarkable macroscopic and/or microscopic evidence for the presence of the IBD .•Sacroiliitis in pediatric IBD may be more frequent than expected.•Early detection and initiation of prompt therapy are essential for preventing permanent joint damage.•Pediatric rheumatology screening for at-risk patients is needed.Disease activity indexes for CD and UC were calculated using the Pediatric Cohn’s Disease Activity Index (PCDAI) and the Pediatric Ulcerative Colitis Activity Index (PUCAI) , 16. CliMusculoskeletal examination: All patients, who had musculoskeletal complaints suggestive of SI, were further evaluated by a single pediatric rheumatologist, who was blinded to the specific diagnosis and clinical history of the patient, including the disease subtype, musculoskeletal symptoms, and received therapy. Patients with low back pain or stiffness, alternating buttock pain, or hip pain were further evaluated for the presence of SI. Defined as the painful or asymptomatic inflammation of the sacroiliac joint, SI may present as back pain, usually persisting beyond 3 months, with or without associated morning stiffness which usually improves with physical activity . The senThe radiologic manifestations on X-ray suggesting sacroilitis were confirmed with MRI , 11. AllLocal Ethics Committee has approved the study .The data were analyzed by the Statistical Package for the Social Sciences (SPSS) version 11 for Windows . Shapiro-Wilks test was used to determine the distribution of the variables. Independent Samples t-test was used for comparison of normally distributed data; accordingly the results were shown as mean and SD. Mann Whitney U test was used for non-normally distributed variables and the results were reported as interquartile range. Pearson Correlation Test, Fisher’s exact test, and Chi-square test were used to compare the absence or presence of SI, and p<0.05 were accepted as significant.The trial involved 27 children , with a mean age of 12.55 ± 3.6 years, of which fourteen (52%) had UC, eleven (41%) had CD, and two (7%) had IC. The median time from the diagnosis of IBD was 6.0 (18.0) months in patients with SI and 12.0 (13.5) months in patients without SI. A total of 13 patients (48%) with symptomatic low back pain and/or morning stiffness were examined and SI was found in eight (30%) of them. Bilateral SI was observed in three of the patients, two with CD, one with UC, whereas five had only unilateral involvement . Disease phenotype and medications for IBH treatment were summarized in The association between SI and clinical variables, including age, gender, body mass index SDs, IBD activity index, and SI distribution among IBD type were detailed in All patients with SI were negative for HLA-B27genotyping and had no perinuclear anti-neutrophil cytoplasmic antibodies; however, two of them were positive for anti-nuclear antibodies . Erythema nodosum was previously diagnosed in three subjects (9%), two with UC and one with IC; however, none of these patients had SI. No dactilitis was observed, however, concomitant enthesial involvement was noted in six of the patients with SI.Ophthalmic examination revealed no uveitis. Differences between UC and CD according to SIJ involvement were detailed in On MRI, BME was detected in all patients with SI (100%) , followed by erosions in six patients (75%) , synovial enhancement in five (63%) and erosion-associated enthesitis of the pelvic region in two (25%) of the patients. No subchondral sclerosis or ancylosis was noted. Children, diagnosed with SI were further treated with sulphasalazine (three patients with UC) alone or azathioprine was switched to methotrexate (two patients with CD) and intravenous infusions of anti-TNF monoclonal antibody.IBD-associated SI was detected in eight out of 27 patients with IBD (30%). As far as we know, this is the first pediatric rheumatology-pediatric gastroenterology collaborated study, reporting SI in children with IBD, based upon the physical examination findings, confirmed by MRI. Recent studies showed a close relationship between IBD and SpAs. The common pathogenic pathway for both entities may explain this association . AS and Interestingly SI, diagnosed by symptoms or imaging was more common in females than males within the pediatric IBD group (46.15% vs. 20.0%) . AccordiThe EIMs of the IBD’s were more frequently observed in children with CD compared to UC or IC (22.5% vs. 10.3%) . AccordiThere is a controversy about the relationship of SI and the duration of IBD. In adults, there was no association between SI and disease duration , 19. AccOne of the interesting findings of the present study was that patients with SI had elevated erythrocyte sedimentation rate and C-reactive protein levels; however, PCDAI and PUCAI scores are similar with no differences in aspect of disease activity between the two groups. Queiro et al. found no relationship between SI and the type or severity of IBD, such as Kelly et al. who also had found no significant correlation with any measure of SI and the disease activity , 20. HowNo one of our patients with SI had HLA-B27 concurrence; however there exists a well-known association between the presence of HLA-B27 and SpAs , suggestAs noted in previous trials, as well as the present study, bone marrow edema and erosions were the most common findings of SI in children . StructuThe present study had a few limitations. The study was done with a limited number of patients; therefore it can be accepted as preliminary trial. Moreover, four of the patients with SI presented initially to the pediatric rheumatology unit, IBD diagnosis were received thereafter; hence the presence of the rheumatology unit may contribute to higher detection rates of the SI. In addition, many of the drugs used to control IBD, including salicylate derivatives , cytotoxic medications such as azathioprine (used by 85% of the patients) and oral steroids (used by 19%), are also effective in the treatment of SI. This may interfere with the musculoskeletal pain perception as well as with timed diagnosis of SI, therefore naïve patients with active intestinal disease and drug-free may have increased SI frequencies. Two or more SIJ examinations, first at the diagnosis and thereafter, at the time of remission, would give more extensive information about the IBD associated SI in children.In conclusion, this analysis of the children with IBD found a high prevalence of SI, especially in patients with CD which was consistent with previous adult and pediatric studies. Children with IBD need to be carefully screened for the presence of back pain as part of their routine follow-up. Of note, depending on the leading manifestations, patients are followed up by a gastroenterologist or a rheumatologist that might overlook the articular or bowel manifestations of the disease, respectively. Delayed diagnosis and inappropriate treatment such as immobilization can contribute significantly to morbidity such as irreversible joint damage.


This single-center retrospective observational study aimed to verify whether a diagnosis of bandemia could be a predictive marker for bacteremia. We assessed 970 consecutive patients  who underwent two or more sets of blood cultures between April 2015 and March 2016 in both inpatient and outpatient settings. We assessed the value of bandemia (band count > 10%) and the percentage band count for predicting bacteremia using logistic regression models. Bandemia was detected in 151 cases (15.6%) and bacteremia was detected in 188 cases (19.4%). The incidence of bacteremia was significantly higher in cases with bandemia  = 7.15; 95% confidence interval (CI) 4.91–10.5). The sensitivity and specificity of bandemia for predicting bacteremia were 0.42 and 0.91, respectively. The bandemia was retained as an independent predictive factor for the multivariable logistic regression model . Bandemia is useful for establishing the risk of bacteremia, regardless of the care setting (inpatient or outpatient), with a demonstrable relationship between increased risk and bacteremia. A bandemia-based electronic alert for blood-culture collection may contribute to the improved diagnosis of bacteremia. Bacteremia is a form of severe infection associated with a high probability of mortality and substantial financial healthcare costs .Bacteremia is a poor prognostic factor for infectious diseases and is one of the leading causes of death in developed countries ,3. SpeciThe clinical decision support system (CDSS) has been demonstrated to improve the quality of medical care in various medical settings; however, its usefulness in diagnosing acute illnesses has not yet been verified . Most ofBandemia is a condition in which 10% or more counts of band cells (a type of immature neutrophil) are observed in peripheral blood smears, being a potentially useful objective predicting factor for bacteremia . Indeed,Previous CDSS studies on bandemia are unavailable. We hypothesized that a system to generate blood-culture alerts, triggered by new onset bandemia, could contribute to the early diagnosis of bacteremia if incorporated into the electronic medical records; additionally, we tested the association between the presence of bandemia and bacteremia using retrospective data.This was a single-center retrospective observational study. We included consecutive outpatients and inpatients who underwent two or more sets of blood cultures and a complete blood count, with a differential white blood cell (WBC) test. Tests were taken 24 h from the time of the patients’ presentation in an outpatient facility and the onset of fever in the inpatient facility at Dokkyo Medical University Hospital between 1 April 2015, and 31 March 2016. The exclusion criteria were developed to exclude factors that can affect WBC differentials or blood culture results and were as follows: age ≤ 14 years, antibiotic usage the day prior to blood sampling, use of granulocytecolony stimulating factors within 1 week, use of steroids and immunosuppressants within 1 week, chemotherapy for cancer within 4 weeks, history of hematological malignancy or bone metastasis of a solid tumor, irradiation therapy for a malignant tumor, pregnancy, systemic lupus erythematosus, post-resuscitation, human immunodeficiency virus infection, or contamination cases. This study was approved by the Ethics Committee of Dokkyo Medical University Hospital and conducted in accordance with the Declaration of Helsinki. The requirement for written informed consent was waived due to the retrospective study design. Blood culture and WBC differential tests were performed at the discretion of the examining doctors and subsequently performed by an automated analyzer. The sample of the blood cell count were collected by drawing blood into a tube containing an ethylenediaminetetraacetic acid dipotassium. The measurements of the blood cell count, including band count, were analyzed using the Sysmex XN-2000 automatic blood cell analyzer.3 [We extracted data regarding age, sex, body temperature, WBC count, eosinophil count, percentage band count in the differential WBC test, and blood culture results from the electronic medical records. The primary outcome measurement was bacteremia, which was defined as a positive blood culture 1 week after the samples were collected . We defi3 .p-values for statistical tests were two-tailed, and a p-value < 0.05 was considered statistically significant. All statistical analyses were performed using R version 3.6.1 .Continuous variables are presented as medians, with 25th and 75th percentiles, and categorical variables as counts (percentage). Continuous variables were compared using the Wilcoxon rank-sum test. Categorical variables were compared by using chi-square test. Univariate and multivariate logistic regression models were used to assess the predictive values of bandemia. We created two multivariate logistic regression models as follows: the first included age (over 65 or not), sex, body temperature (between 36.0 and 38.0 or not), WBC count , and eosinopenia as variables (baseline model); the second added bandemia as a variable to the baseline model (with band model). Furthermore, we calculated the area under the receiver-operating characteristic curve (AUROC) of each model with a 95% confidence interval (CI). We compared the AUROCs of the above-mentioned two models, calculated the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) to assess the improvement of the predictive value after including the percentage band count into a baseline model. The 3; median eosinophil count was 20  cells/mm3; and the median percentage band count was 0%  (p = 0.004), while there was no significant differences of the incidence of bacteremia between inpatients and outpatients .In total, 4879 cases during the study period were considered eligible and 970 cases  were included in the final analysis. The median age was 73  years; 629 (64.8%) were men; median body temperature was 38.1  °C; median white blood cell (WBC) count was 10,600  cells/mme, 0–2%) . Overalle, 0–2%) . The incp < 0.001). The sensitivity and specificity of bandemia for predicting bacteremia were 0.42  and 0.91 , respectively. This was consistent in outpatients  and inpatients . The bandemia was retained as an independent predictive factor in a multivariable logistic regression model  and IDI  were statistically significant.Furthermore, the AUROC of the prediction model for bacteremia was statistically improved from 0.71 (95% CI 0.67–0.75) to 0.77 (95% CI 0.73–0.80) in the band-count model compared to the baseline model . SimilarThis study presents three main findings. First, in patients considered as having indicators for blood cultures by a physician, the prevalence of bacteremia was significantly higher among patient with than without bandemia. Second, bandemia revealed a high specificity and OR for predicting bacteremia. Third, the band-count percentage as a continuous variable, was an independent predictor for bacteremia, and the AUROC was improved by adding the band-count percentage as a continuous variable to the baseline predictive model including age, sex, body temperature, WBC count, and eosinophil count. Our findings support the value of bandemia for predicting bacteremia among patients with a suspected bacterial or fungal infection. Consistent data from recent studies indicate bandemia (band count > 5% or 10%) as an independent predictor of bacteremia in patients who presented to the emergency department ,28 and wThe strengths of this study include its demonstration of bandemia as a risk factor for bacteremia in both inpatient and outpatient settings and the use of machine-determined bandemia techniques, leading to an easy and objective determination of results. The advantage of bandemia is that the presence or absence of findings can be determined inexpensively, using labor-saving and labor-free machine counts. In recent years, new techniques such as an antibody microarray coupled to a Surface Plasmon Resonance imager (SPRi), PCR methods and Fluorescent in situ hybridization (FISH), were developed ,33,34,35There are several limitations to this study which should be acknowledged in the interpretation of the results for practice. Th most important limitations are the retrospective study design, the lack of specific criteria indicating the collection of blood cultures , and the non-inclusion of other objective variables in the analysis, such as vital signs, owing to the lack of data. Second, the conditions under which CBCs were collected may not be constant. Whether the patient is fasting or not, the time of collection, and the location of the blood collection were not included in this analysis. Third, this is not a prospective study of CDSS, although we have shown that bandemia is a useful trigger for noticing bacteremia in both in- and out-patients. Fourth, this study excluded children and, therefore, may not be applicable to pediatric populations. Lastly, our data were derived from a single tertiary academic hospital. As such, the study population tended to present serious medical conditions which, arguably, could be the reason for the high incidence of bacteremia. Additionally, several patients were omitted based on the exclusion criteria. Therefore, the study results should be applied with caution in patients who present with at least one of the exclusion criteria. The next step is to validate our results in a prospective CDSS study that incorporates the exclusion criteria.In conclusion, this study demonstrated that bandemia is a useful predictor for bac-teremia, regardless of the care setting, and that there is a correlation between bandemia and an increased risk of bacteremia in adults. Therefore, the inclusion of bandemia-based electronic alerts or CDSS for blood-culture collection may improve the diagnosis of bacteremia in both outpatient and inpatient settings in adults.


Ochotona curzoniae) was used to investigate such effects at three alpine meadow sites on the Eastern Tibetan Plateau, where pairs of disturbed vs. undisturbed plots were randomly selected and sampled. We also explored the relationships between soil properties and BGB/AGB across the plots in the presence and absence of plateau pikas, respectively. We found that BGB and BGB/AGB were 11.40 and 8.20% lower in the presence of plateau pikas than in their absence, respectively. We also found that the BGB/AGB was positively related to soil moisture and soil total nitrogen (STN) in the absence of plateau pikas. In contrast, BGB/AGB was positively related to STN, soil organic carbon (SOC), soil carbon/nitrogen (C/N), and soil total phosphorus in the presence of plateau pikas. These factors indicated plateau pika disturbance increased AGB allocation. The relationship between AGB and BGB of alpine meadow plants to soil variables was also different between sites with and without plateau pika disturbance. In conclusion, small semi-fossorial herbivore disturbance is likely to alter grassland carbon stock and should be well controlled for sustainable conservation and management of alpine meadows on the Tibetan Plateau.Small semi-fossorial herbivores can affect plant aboveground biomass (AGB) in grasslands and possibly alter the allocation of AGB and belowground biomass (BGB). In this study, plateau pika ( The allocation of aboveground biomass (AGB) and belowground biomass (BGB) is widely used to characterize the carbon pool dynamics of grassland ecosystems , which iHerbivores are important biotic factors that can affect the allocation of AGB and BGB in grasslands . Large gSmall semi-fossorial herbivores can affect soil properties by burrowing tunnels , excretiOchotona curzoniae) is a small semi-fossorial herbivore that is philopatric , Gangcha County , and Luqu County . The elevations of the three sites were 3,750, 3,265, and 3,505 m; the average annual precipitation was 400, 572.3, and 644 mm; and the average annual temperature was 4.1, 0.89, and 3.16°C, respectively. According to the Chinese Soil Classification System , the soi2; Field surveys at each site were conducted in the cold grazing areas of the alpine meadows. A random stratified and paired design was used to establish plots at each site. The plot size was 35 m × 35 m, which was close to the size of the average home range of plateau pikas  was used to collect soil samples for the measurement of SBD. The plant shoots, soil cores, and soil samples were stored at 4°C.The field survey was conducted during early August 2017, as this coincides with the peak in the plateau pika population  and thus4+-N) and ammonium nitrogen (NO3–-N) were extracted with potassium chloride , and their concentrations were measured using the flow injection method . STN was measured using the Kjeldahl method . STP and SAP were analyzed using inductively coupled plasma spectrometers . SAN was the sum of the NH4+-N and NO3–-N concentrations.In the laboratory, plant shoots were dried at 80°C in an oven to a constant weight and weighed to calculate the AGB. Soil cores were placed into 0.45-mm mesh filter gauze bags to collect the BGB by washing. For each soil core, fresh roots were divided into live roots and dead roots by color, consistency, and presence of attached fine roots , and theThe AGB, BGB, BGB/AGB, SM, soil pH, SBD, SOC, STN, SAN, STP, and SAP data for each plot were generated by pooling the values of these variables for each of the five subplots. Soil carbon/nitrogen (C:N) for each plot was the average SOC/STN of the five subplots.t-test was used to evaluate the effects of plateau pika disturbance on the AGB, BGB, and BGB/AGB at each site.We first checked the data for normality using the Shapiro-Wilk test. A linear mixed model (LMM) from “lmer” in the lme4 package of R version 4.1.1  was then used to analyze the effects of plateau pika disturbance on the AGB, BGB, and BGB/AGB at each site. In the LMM, AGB, BGB, and BGB/AGB were response variables, the presence/absence of plateau pika disturbance (Dist.) and the three sites (site) were fixed effects, and paired plots within site was a random effect. When site effects were significant, a non-parametric paired p < 0.05); soil variables not showing significant relationships to BGB/AGB were common explanatory variables. Subordinate explanatory variables were common explanatory variables that were significantly related to each of the main explanatory variables (p < 0.05).Pearson’s rank correlations were used to select the explanatory variables and subordinate explanatory variables by testing for the significance of relationships of BGB/AGB with soil physical properties  and soil chemical properties . The main explanatory variables were soil variables that were significantly related to BGB/AGB  and Akaike information criterion (AIC) (δAICc < 2).Generalized additive models (GAMs) in the “mgcv” package in R were used to analyze the effect of each main explanatory variable on the BGB/AGB in the presence and absence of plateau pika . Sites d2) statistic, whole model p-value, goodness-of-fit index (GFI), and root-mean-square error of approximation (RMSEA) were used to optimize the base SEM and improve model fit. This improved model had low χ2-values, low RMSEA values (< 0.08), high GFI values (> 0.96), and low p-values (> 0.05), and the differences between this model and observed values were the lowest.To quantify the integrated effect of the main explanatory variables and subordinate explanatory variables on BGB/AGB, a structural equation model (SEM) in the “lavaan” package in R was used to identify the pathway and direct or indirect effect of each main and subordinate explanatory variable. As soil properties are mutual interaction between AGB and BGB, BGB/AGB was used to construct an SEM. A hypothesis-oriented pathway was used to construct a base SEM . The thrWhen the data from the three sites were analyzed together, the plant BGB and BGB/AGB were 11.40 and 8.20% lower in the presence of plateau pikas than in their absence, respectively; plant AGB did not significantly differ among plots with and without plateau pikas . When daR2 = 0.63, p < 0.05), SOC , soil C:N , and STP  in the presence of plateau pikas and with SM  and STN  in the absence of plateau pikas ; no other soil property variables were significantly related to each of the main explanatory variables in the absence of plateau pikas. These results indicated that SBD was a subordinate explanatory variable.Soil organic carbon was the only main explanatory variable significantly correlated with SBD in the presence of plateau pikas  of the variance in BGB/AGB in the presence and absence of plateau pikas, respectively. The SEM analysis showed that BGB/AGB at each site was affected through different pathways in the presence and absence of plateau pikas (The results of the SEM analysis explained 53 and 58% (au pikas .Large grazing herbivores have been found to affect the allocation of AGB and BGB in shrub-steppes , semiariThe results of our study revealed that disturbance by plateau pikas had no impact on AGB, but it decreased BGB and BGB/AGB, which indicates that plateau pikas can affect the allocation of AGB and BGB. This is consistent with the result of some previous studies  but incovia the aforementioned three consequences of plateau pika disturbance are offset by the decrease in AGB associated with plant consumption.Although the consumption of plants by plateau pikas can decrease AGB , there aPlateau pika disturbance contributes to a decrease in BGB in three ways. First, plateau pika disturbance increases the heterogeneity of the soil , and thiThe main soil factors affecting BGB/AGB differed in the presence and absence of plateau pikas. The presence of plateau pikas increased the net effect of soil chemical properties on BGB/AGB but decreased the net effect of soil physical properties on BGB/AGB. BGB/AGB is closely related to SM and STN in the absence of plateau pikas; however, in the presence of plateau pikas, BGB/AGB is closely related to STN, SOC, soil C:N, and STP, suggesting that disturbance by plateau pikas can alter the main soil physical and chemical factors that control BGB/AGB. There are three likely causes for the differences in the soil properties most closely related to BGB/AGB in the presence and absence of plateau pikas. First, compared with alpine meadow microhabitats with small semi-fossorial herbivores, alpine meadow microhabitats without small semi-fossorial herbivores are relatively stable , and theThe effects of plateau pikas on the allocation of AGB and BGB were examined across three sites ranging in elevation from 3,265 to 3,750 m and ranging in average annual precipitation from 250 to 633 mm. BGB and BGB/AGB were lower in the presence of plateau pikas than in their absence, and AGB did not vary in the presence and absence of plateau pikas. The main factors affecting the allocation of AGB and BGB might shift from SM and STN in the absence of plateau pikas to SOC, STN, soil C:N, and STP in the presence of plateau pikas. These results reveal the general effects of small semi-fossorial herbivores on the allocation of AGB and BGB and provide new insight into the relationships between small semi-fossorial herbivores and the carbon stock in grassland ecosystems.The original contributions presented in the study are included in the article/QW and ZG designed the experiments, analyzed the data, and wrote the manuscript. QW and XP performed the experiments. All authors read and approved the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


To explore the feasibility of automatically detecting the degree of meniscus injury by radiomics fusion of dual-mode magnetic resonance imaging (MRI) features of sagittal and coronal planes of the knee joint.  This retrospective study included 164 arthroscopically confirmed meniscus injuries in 152 patients admitted to the Department of Orthopaedics of our hospital from July 2018 to March 2021. A total of 1316-dimensional radiomics signatures were extracted from single-mode sagittal and coronal plane images of menisci, respectively. Then, the sagittal and coronal plane features were fused to form a dual-mode joint feature group with a total of 2632-dimensional radiomics signatures. The minimum redundancy maximum relevance (mRMR) algorithm and the least absolute shrinkage and selection operator (LASSO) regression were used to select features and generate optimal radiomics signatures. The single-mode sagittal plane feature model (Model 1), single-mode coronal plane feature model (Model 2), and the combined sagittal and coronal plane feature model (Model 3) performance were tested by receiver operating characteristic (ROC) curves and Delong test. The calibration curve test was used to verify the reliability of radiomics signatures of the three models.  The average intra- and interobserver intraclass correlation coefficients (ICCs) of the most significant 8-dimensional radiomics signatures of Model 1 and Model 2 were 0.935 (range 0.832-0.998) and 0.928 (range 0.845-0.998), respectively. All the three models had good detection performance; Model 3 had the most significant performance (the areas under the curve (AUCs) of training, and validation sets were 0.947 and 0.923, respectively), which was superior to Model 1  and Model 2 . The detection probability of training and validation sets in the three models was highly consistent with the actual clinical probability.  It is feasible to establish a model for automatic detection of meniscus damage by means of radiomics. The detection performance of the dual-mode knee MRI model is better than that of any single-mode model, showing potent feature analysis ability and outstanding detection performance. Meniscus injury is the most common type of knee injury, which can be divided into meniscus tear and meniscus degeneration , 2. The At present, the medical image data shows an explosive growth with a lot of interference and useless information, which virtually brings a challenge to the professional ability of doctors and restricts the accuracy of judgment. Therefore, it is particularly important to carry out efficient, accurate, and effective information mining. Radiomics, an effective method for extracting key parameters from medical images, is also a powerful tool to guide diagnosis and treatment in modern medicine. In recent years, it has been applied in many fields such as the research on tumor diagnosis and treatment –9, mentaIn known studies, researchers used the deep approach of learning to extract features from MRI images of knee joints and detect injuries , 13 and Therefore, the novelty and motivation of the study is to distinguish meniscus degeneration from meniscus tear and automatically detect different degrees of meniscus injury by fusing the features of MRI images of sagittal and coronal planes of the knee joint, which is rarely reported both at home and abroad. It is hoped that a model for automatic detection of meniscus damage can be established by means of radiomics.The ethical approval of this retrospective study was provided by the Ethics Review Committee of our hospital, with the Ethics No. of [2021] No. 303 of the second Affiliated Hospital of Fujian Medical University. All patient information was kept strictly confidential. A total of 164 injured meniscals (per side) were collected from 152 patients admitted to the Department of Orthopaedics of the second Affiliated Hospital of Fujian Medical University from July 2018 to March 2021. All patients had arthroscopically confirmed meniscus injury and underwent MRI of the affected knee. Among the 152 patients, 97 were males and 55 were females, ranging in age from 9 to 76 years old, with an average of 52.4 ± 11.0 years. Meniscus injury was divided into meniscus tear and meniscus degeneration. Among the 164 meniscus injuries, 78 meniscus tears and 86 meniscus degeneration were found. The results of arthroscopy were obtained by orthopedic specialists with rich experience in arthroscopic surgery. MRI images of all menisci in enrolled patients were randomly divided into a training set and a validation set (7 : 3). The same proportion of meniscus degeneration and meniscus tear were maintained in the training and validation sets using stratified random sampling. The flow chart of the study is shown in Inclusion criteria were as follows: patients with arthroscopically confirmed meniscus injury and patients who underwent MRI scanning before treatment.Exclusion criteria were as follows: treatment before MRI scanning; unavailable or incomplete clinical or MRI information; poor MRI image quality with low signal-to-noise ratio (SNR); pregnant women and lactating patients; patients with metal implants; and patients with claustrophobia or other inability to cooperate with the examination.All patients were examined by the Philips 3.0 T MRI system , which was equipped with a dedicated 15-channel transmitting/receiving knee joint coil. Fixed with a sandbag on the lower leg, the patient was instructed to maintain the static orientation of the knee during the scan on the coronal and sagittal planes. The scanning center was horizontal to the articular space, the coronal scanning line was parallel to the tibial plateau, and the sagittal scanning line was perpendicular to the tibial plateau. The scanning parameters are as follows: T1WITR spin echo (SE) sequence = 450-500 ms, TE = 14 ms, average number of times = 2; gradient echo (MED) sequence T2 WI TR = 800-1000 ms, TE = 26 ms, matrix = 256 × 256, average number of times = 1, and flip angle = 30°. The layer spacing and thickness were 1 mm and 3 mm, respectively. Arthroscopy: The operating system of arthroscopy was digitalized by STRYKER, USA.All ROIs were completed independently by a radiologist  using ITK-SNAP 3.6.0, and meniscus images were manually segmented along each sagittal and coronal section of the ipsilateral meniscus . Referrihttp://pyradiomics. readthedocs.io).Using the radiomics module inserted in the AK software , 1316-dimensional radiomics signatures were extracted from the single-mode sagittal and coronal planes of menisci, respectively. Then, the sagittal and coronal plane features were fused to form a dual-mode joint feature group with a total of 2632-dimensional radiomics signatures. All the extracted features can be subdivided into the following categories: first-order statistics, shape-based, gray-level cooccurrence matrix (GLCM), gray-level size zone matrix (GLSZM), gray-level run-length matrix (GLRLM), first-order function (FIRSTORDER), and gray-level difference matrix (GLDM). A detailed description of the radiomics signatures can be found on the PyRadiomics Documentation website , the minimum redundancy maximum relevance (mRMR) algorithm  is helpfhttp://www.R-project.org/) for statistical analysis. Receiver operating characteristic (ROC) curves were drawn to determine the detection performance of the three models. Then, the area under the curve (AUC), as well as sensitivity, specificity, and accuracy were determined by the Youden index. The Delong test was performed for pairwise comparison of the detection performance among the three models. The detection probability of Model 3 was analyzed by Logistic regression. Calibration curves were used to determine the reliability of image features of the three models.This study used SPSS 24.0  software and R software (version 3.5.0; Among the 1316-dimensional radiomics signatures of the single-mode model, 981 with intraobserver and interobserver ICCs >0.80 were retained. The mRMR algorithm eliminated 981-dimensional radiomics signatures and retained 20-dimensional features . The optP < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001; This study examined the performance of the three models . In ModeP value of the ROC curve of Model 1 and Model 2 was 0.0447, suggesting that the detection performance of the sagittal model was significantly better than that of the coronal model; the P value of the ROC curve of Model 3 and Model 1 was 0.0216, which indicated that the performance of the dual-mode model was significantly better than that of the sagittal model; the P value of the ROC curve of Model 3 and Model 2 was 0.0309, suggesting that the performance of the dual-mode model was significantly better than that of the coronal model.Verification was performed on the training set and the validation set of the three models using the calibration curves, and the results showed that the detection probability of both sets in the three models was highly consistent with the actual clinical probability . PairwisMeniscus injury, a common type of knee joint injury, will easily lead to a series of clinical diseases such as knee joint pain and osteoarthritis without proper treatment , 22. CorRecently, the feasibility of artificial intelligence-based meniscus tear detection on MRI images has been confirmed , 23, 24.In this study, we used radiomics signatures based on MRI of the knee joint to distinguish meniscus degeneration from meniscus tear. ROC analysis revealed high performance of the radiomics model. The results showed that in the training set and validation set of Model 1, Model 2, and Model 3, the AUCs of the radiomics signatures were 0.889 and 0.876, 0.831 and 0.851, and 0.947 and 0.923, respectively, indicating that there were significant differences in heterogeneity between meniscus degeneration and meniscus tear. Hence, the selected radiomics signatures may be able to detect the difference between the two. In addition, the results showed that the detection models used to distinguish meniscus degeneration and meniscus tear had good performance, which was higher than the results of Bien et al.  in 2018,In clinical practice, we often have to face interference factors that affect the accurate judgment of meniscus injury. For example, in some cases, structures such as the ligaments of Humphry and Wrisberg are mistaken as the damaged part. Moreover, partial truncation artifact and magic angle effect can cause signals similar to mild tear at the edge of the meniscal body . All theIn this study, a dual-mode radiomics model was used to comprehensively analyze the MRI image feature differences between different degrees of meniscus injury, which is helpful for radiologists to deepen their understanding of the characteristics of meniscus injury, reduce the influence of some interference factors on the accurate diagnosis of different degrees of meniscus injury, and prevent unnecessary trauma caused by arthroscopic overexamination, especially when meniscus degeneration is suspected, so as to achieve the purpose of improving the detection efficiency of radiologists and orthopedic surgeons and saving medical resources.While the findings in this paper provide promising insights, there are some limitations. First of all, as a small-scale study, sample size is a problem. Second, all ROIs in this study were manually segmented, which is an intensive and time-consuming process without any automatic segmentation algorithm. Manual segmentation still has a long way to go to match the accuracy and reproducibility of automatic segmentation. Efficient segmentation algorithms for ROIs are needed to be studied. Finally, although the radiomics processing flow of this study has been relatively perfected, there are still some deficiencies, which need to be continuously improved and optimized in future research. Radiomics can be used as a complement to other omics such as proteomics and genomics. Therefore, it is worth expecting that the combination of multiple omics will be the best choice for the treatment of diseases. With the in-depth development of radiomics research, we will increase the number of research samples and optimize the operation process on the basis of this research to achieve further improvement.This study finds that it is feasible to establish an automatic detection model for different degrees of meniscus injury by means of radiomics. The detection performance of the dual-mode knee joint MRI radiomics model is better than that of any single-mode model, showing strong feature analysis ability and outstanding detection performance. It is hoped that in future research, the radiomics method can provide more rapid and effective help for radiologists and orthopedic surgeons.


Studies have shown the spatial specificity of cranial iron deposition in different regions in Parkinson's disease (PD). However, the time-specific patterns of iron deposition are not yet clear. The purpose of this study was to investigate the time pattern of iron variations and its clinical relevance in multiple gray matter nuclei in PD using quantitative susceptibility mapping (QSM). Thirty controls and 33 PD patients were enrolled, namely, 11 cases of early stage of PD (ESP) and 22 cases of advanced stage of PD (ASP) according to the Hoehn-Yahr stages. The iron content in the subcortical nuclei covering substantia nigra (SN), red nucleus (RN), head of the caudate nucleus (CN), globus pallidus (GP), and putamen (PT) was measured using QSM, and the clinical symptoms of PD were evaluated by various rating scales. The QSM values in SN, RN, GP, and PT significantly increased in PD patients compared with the controls. Further subgroup comparison with the controls indicated that the iron content in SN and GP  gradually elevated in the whole disease duration and was related to clinical features. While the iron content in RN and PT (neostriatum) only elevated significantly in ESP patients, further iron deposition was not obvious in ASP patients. Our study confirmed that QSM could be used as a disease biomarker and could be suitable for longitudinal monitoring. However, considering the temporal characteristics of iron deposition in neostriatum, iron deposition in the neostriatum should be paid more attention in the early stage of the disease, even in the preclinical stage, in future research. The progress of iron deposition in different brain regions is heterogeneous.- The QSM values could be used as a useful disease biomarker and be suitable for longitudinal monitoring in PD. QSM values in neostriatum should be paid more attention in the early stage of the disease, even in the preclinical stage.- These characteristics of iron deposition help us to understand the pathological changes of Parkinson's disease.Parkinson's disease (PD) is the second most common neurodegenerative disease and commonly manifested by typical motor symptoms such as bradykinesia, resting tremor, rigidity, postural instability, and an array of non-motor symptoms, which seriously affect the quality of life and exacerbate the disability of PD patients. The major pathology features of PD are characterized by the loss of dopaminergic neurons in the substantia nigra (SN), the accumulation of Lewy bodies and Lewy neurites , and excvia two routes , which has been validated to be the most accurate method so far for quantitatively detecting cranial iron content –15, to mPD patients: A total of 33 PD patients were consecutively recruited from Nanfang Hospital, The Third Affiliated Hospital of Sun Yat-sen University, and Guangdong 999 Brain Hospital. Diagnosis of PD was based on the MDS clinical diagnostic criteria for PD  evaluateSubjects in the control group: A total of 30 age- and gender-matched control patients were enrolled in this study. The subjects in the control group were from outpatient clinics in Nanfang Hospital who mostly complained of dizziness, headache, or other mild neurological diseases. The specific exclusion criteria are as follows: (1) severe neurological symptoms and positive signs; (2) known history of severe neurological disorders, such as cerebrovascular disease, encephalitis, brain tumor, meningitis, extrapyramidal disorder, and other intracranial lesions; (3) head trauma and history of surgery; and (4) mental illnesses or psychological diseases.The study was approved by the Ethics Committee of Nanfang Hospital, and all subjects enrolled in this study provided written informed consent before participation, and all experiments were performed in accordance with the relevant regulations.All patients with PD were assessed by a series of rating scales for evaluating the motor and non-motor symptoms. Severity of PD was assessed by H-Y stage , and thePD patients were subdivided into two subgroups according to H-Y stage. Eleven cases with H-Y stage <2.5 were classified as the early-stage PD (ESP) subgroup and 22 cases with H-Y stage ≥2.5 were the advanced-stage PD (ASP) subgroup. All PD patients were evaluated after withdrawing all antiparkinsonian medicine for at least 4 h.2, slice gap = 0.6 mm, slice thickness = 2 mm; flip angle = 10°. All subjects used a fixed foam pad to restrict the head movement during MRI scanning for a better image quality.All MR images were acquired using a 3.0-T MRI system  with an eight-channel head coil. Imaging parameters for the three-dimensional, multi-echo gradient echo sequence were as follows: TE of first echo = 5.9 ms, echo spacing = 7.0 ms, number of echoes = 5, TR = 38 ms; matrix = 183 × 156; field of view = 182 × 220 mmThe acquired 3D multi-echo GRE data were used for reconstructing QSM imaging by the STI Suite software  Duke Un. Due to In this study, ROIs of the following areas were obtained from both sides of the brain: SN, RN, CN, GP, and PT. These five ROIs were manually delineated on the QSM images by the ITK-SNAP software . First, p > 0.05. In this study, except for the HAMA and MMSE scores of PD group, all other variables were normally distributed.All data analyzed in this study used the standard statistical package SPSS V. 20.0 , and the graphical depictions were made using GraphPad Prism v. 6.07 . All the continuous variables, including age, disease duration, scores of clinical scales, and regional QSM values, were expressed as means ± standard deviations. The single-sample Kolmogorov–Smirnov test was performed on all continuous data, and normal distribution was confirmed if 2 test. For the continuous variables, if normally distributed, a two-tailed t-test was used for the comparison. If not normally distributed, variables were assessed by Mann-Whitney U test. One-way analysis of variance (ANOVA) was used to compare the differences in QSM values of different ROIs among the subgroups, and the least significance difference (LSD) method was used for post-hoc analysis, and the p-value was adjusted by Bonferroni correction. As the physiological iron accumulation may increase with age in the normal population, covariance analysis was used to investigate the differences of QSM values between control cases and each subgroup of PD cases, respectively. Pearson correlation analysis was conducted to explore the relationship between the iron deposition of each ROIs and the clinical symptoms of PD patients . Spearman correlation analysis was conducted to explore the relationship between the iron deposition of each ROIs and MMSE or HAMA. The receiver operative characteristic (ROC) analysis was performed to evaluate the diagnostic value of potential biomarkers in all PD.Discrete variables such as gender comparisons between control and PD groups were performed by Pearson χp-value < 0.05, which was indicated by *; if the p-value was < 0.01, data were indicated by **. The corrected p-value in multiple comparison was < 0.025.Statistical significance was defined by a The QSM values of five regions of two groups are summarized in Covariance analysis and one-way ANOVA was used for comparing regional QSM values among subgroups, respectively, and there is no significant difference between two methods. By comparing each subgroup with the control group concerning the regional iron deposition, r = 0.491, p = 0.001; r = 0.507, p = 0.001; r = 0.462, p = 0.008, respectively). Similarly, QSM values of GP also had a notable correlation with Hoehn-Yahr stage and UPDRS-III scores  in patients with PD. No correlation was found between the QSM values of RN and PT with clinical assessments of PD.Further correlation between regional QSM values and clinical measurements of PD cases is summarized in p < 0.001). Also, a cutoff QSM value in PT of 0.0377 with a sensitivity of 54.50%, a specificity of 90.00%, and an area under the curve of 0.789 (95% CI: 0.680–0.899) was determined for diagnosis of PD (p < 0.001)  in order to discriminate PD from control cases (< 0.001) .p < 0.001) (95% CI: 0.673–0.904). Youden's index was maximal with a sensitivity of 72.70% and a specificity of 83.30% when the QSM value in RN was 0.0666. The AUC of QSM values in PT was 0.789 (p < 0.001) (95% CI: 0.680–0.899). Youden's index was maximal with a sensitivity of 54.50% and a specificity of 90.00% when the QSM value in PT was 0.0377. ROC = receiver operator characteristic.The area under the curve (AUC) of QSM values in RN was 0.788   . Currentng (SWI) –14. A seng (SWI) , 30. At echnique , which aWe noted that the QSM values in SN and GP in ESP were elevated compared with that of control, although this tendency did not reach statistical significance, while in the ASP patients, the QSM values in SN and GP were significantly higher than that of the control group and ESP patients. In the early stage of PD, the increase in iron content within SN and GP may not be obvious, while in the advanced stage of PD, iron accumulation significantly increased with the progression of PD severity. This conclusion of excessive and progressive iron deposition in SN and GP was consistent with several previous investigations –35. PrevTime-specific characteristics of iron deposition in RN and PT were also confirmed in this study. Although with the emergence of QSM technology, the qualitative analysis of iron content is more and more accurate, many studies have not reached a consensus on the changes in iron content in RN and PT, and many studies have found that the iron content of PT has not increased , 35. OurThe time-specific difference of iron deposition in different brain regions is related to many factors: (1) There are obvious physical boundaries between different anatomic circuits, which make it difficult to influence each other. The RN–PT network can be dissociated from a nigro-centered striatal network despite the anatomic proximity between the RN and SN . (2) TheClinical data from PD cases analyzed by Pearson correlation analysis showed the QSM values in SN and GP to be significantly correlated with H-Y stage, UPDRS-III scores, and HAMD scores. The more iron accumulated in SN, the more advanced condition and the more severe the motor symptoms of PD, which was consistent with most previous reports , 34, 41.Our results demonstrated that the depression in PD might be closely relevant to the excessive iron content in SN, and no other correlation was found between regional QSM values with non-motor symptoms. Liu et al.  detectedThere are several limitations in the present study. First, we evaluated the QSM values in the SN or GP as a whole without subdividing these regions , which might lead to ambiguous and inaccurate conclusions. Second, the QSM values may be interrupted by other factors such as calcium, copper, or lipid, and the QSM technique is incapable of determining the exact iron content directly. Third, all cases in the PD group are not longitudinal assessment and lack of pathological evidence of PD diagnosis. Therefore, longitudinal cohort studies should also be performed to observe the iron deposition of more precise subregions in the brain. Finally, we did not use voxel-wise analysis of QSM to analyze whole brain iron deposition.In this study, we reported the time-specific patterns of regional iron deposition in PD. The increased iron deposition of the RN and PT (neostriatum) is mainly accumulated at the early stage of PD, while in the late stage of PD, the iron deposition in these two regions does not seem to continue to increase. The progressive pattern of iron deposition in the SN and GP  might be throughout the whole course of PD, particularly occurring in the late stage of PD, which is in line with PD progression and the severity of motor symptoms. Moreover, there may be a potential relevance between iron content in the SN and GP with some of non-motor symptoms such as depression. This study provides the evidence of time-specific iron deposition in different regions in PD.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by the Ethics Committee of Nanfang Hospital. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.YX, XF, and QW designed the experiments. XF, JX, XChi, and YJ carried out the experiments and collected the data. MP, WS, and XCui processed images. YX measured the experiment data and XF analyzed the data and experimental results. XF and YX wrote the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This register-based national cohort study of 206,900 individuals investigated whether prenatal exposure to small extra doses of vitamin D from fortified margarine prevented inflammatory bowel disease (IBD) later in life; whether the risk of IBD varied according to month or season of birth; and finally, whether there was an interaction between exposure to extra D vitamin and month or season of birth. Fortification of margarine with vitamin D was mandatory in Denmark from the mid-1930s until 1st June 1985, when it was abolished. Two entire birth cohorts, each including two years, were defined: one exposed and one unexposed to the fortification policy for the entire gestation. All individuals were followed for 30 years from the day of birth for an IBD diagnosis in Danish hospital registers. Logistic regression analyses were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Odds for IBD was lower among those exposed to extra D vitamin compared to those unexposed, OR = 0.87 . No association with month or season of birth was found. However, estimates suggested that particularly children born during autumn may have benefitted from the effect of small extra doses of vitamin D. This is, to our knowledge, the first study to explore if prenatal exposure to vitamin D from fortification influenced the risk of IBD. Our results suggest that prenatal exposure to small amounts of extra vitamin D from food fortification may protect against the development of IBD before 30 years of age. Inflammatory bowel disease (IBD) is a chronic immune-mediated disease that can affects the entire digestive tract ,2. The tThe aetiology of IBD is multifactorial and still not fully understood, although it is often described to involve interactions between genes, environment, and gut microbiome . One envA recent review of meta-analyses showed moderate evidence for the association between vitamin D deficiency and IBD risk . This coAccording to the theory of foetal programming , low preSeveral studies have investigated the association between month or season of birth and IBD development with inconsistent results ,38,39,40This study aimed to investigate if exposure to a small extra dose of vitamin D from fortified margarine during gestation and in early life would lower the risk of offspring IBD later in life. We also explored whether individuals born in summer and autumn would have a higher risk of IBD and if the extra vitamin D from fortification prenatally would benefit, in particular, individuals born in summer and autumn.This study is a societal experiment based on the mandatory Danish margarine fortification policy and its abolishment on 1st June 1985. The study is part of the D-tect project, which has been described in detail earlier .All individuals were selected from two full-year birth cohorts from the Danish Medical Birth Registry immediately before and after the fortification policy’s termination. Exposed individuals were born between 1st June 1983, and 31st May 1985; unexposed individuals were born between 1st September 1986, and 31st August 1988. Individuals were either all exposed or all unexposed to the vitamin D fortification policy for the entire nine months of gestation calculated backwards from the date of birth. Of the exposed individuals, some were also exposed to the vitamin D fortification policy during early life (up to 13 months of age)—for simplicity, we only refer to prenatal exposure.A 15 month washout period  was added to account for margarine used to prepare foods that could be stored beyond its shelf life. The 15 months consisted of 4 months of margarine shelf-life and an additional 2 months to use up the fortified margarine from households and 9 months of a normal pregnancy. The follow-up period was 30 years from the day of birth. The design of the study is depicted in By merging this data with the Danish National Patient Registry, we identified individuals diagnosed with IBD . Only individuals with two records of diagnoses were included in the primary analysis to ensure the cases’ validity.The following covariates were included to increase the precision of the analyses: sex of the offspring , season of birth, month of birth, and type of IBD . Season of birth was categorized as: winter: November, December, January; spring: February, March, April; summer: May, June, July; autumn: August, September, October, based on the fluctuating serum-vitamin D levels during the year . Month oType of IBD was based on the diagnosis from the second record: The ICD-codes for CD were ICD-8; 563.01, 563.02, 563.08, and 563.09 until the end of 1993 and, hereafter, ICD-10 code K50; the codes for UC were ICD-8; 563.19, and 569.04 until the end of 1993 and, hereafter, ICD-10 code K51. Individuals registered with both an ICD-code for CD and UC at the second record were categorized as unclassified IBD (U-IBD).According to Danish law, ethical approval is not required for register-based studies when data are used for statistical and research purposes only, in the interest of the public. Permission to access data was granted by The Danish Health Data Authority. The Danish Data Protection Agency provided permission to process data (VD-2019–237).There were no patient or public involvement in designing the study, formulating the research question, performing analyses, interpreting the results, or writing the manuscript.p-values are given. Data management and descriptive statistics were performed using Stata-13. For the sensitivity analyses, OR was estimated in relation to having at least one, rather than minimum of two, records of IBD. Secondly, crude analysis was performed for the two main diagnoses, CD and UC, to test whether associations differed according to IBD type. Finally, season interaction effect analysis using a season definition based on the calendar , rather than serum–vitamin D levels, was performed. The statistical analyses were performed using R version 3.3.3 . All analyses were prespecified in a statistical analysis plan, which was read and approved by all co-authors before analyses.Logistic regression analyses were performed for all modelling. To test the overall association of month and season of birth and the interaction effect, likelihood ratio tests were performed. For the logistic regression analyses, odds ratio (OR), confidence intervals (CI), and Of 217,249 individuals, 103,606 had been exposed to the fortification policy prenatally, and 113,643 had not. Among those exposed, 1811 died before the end of follow-up, and 2939 emigrated; among those unexposed, 1888 died, and 3711 emigrated. A total of 206,900 individuals remained for the analyses, whereby 875 among the exposed and 1102 among the unexposed developed IBD .At the end of the 30-year follow-up, 47.8% among those without IBD had been exposed to extra vitamin D from fortification, compared to 44.3% of those diagnosed with IBD . More wop = 0.05) for CD among the exposed, compared to the unexposed at the end of the 30-year follow-up. For UC, the crude OR was 0.87 .Results were essentially similar whether the outcome was defined based on one or at least two IBD records (data not shown). This was similar when the two types of IBD (CD and UC) were analysed separately. The crude OR was 0.87 , and the results were essentially similar before and after adjustment (data not shown). No overall association with month of birth was found (p ≥ 0.17). The estimates’ direction could indicate a protective effect for spring births, compared to winter, and a higher risk among autumn births, compared to winter. In the sensitivity analysis, where we used the calendar definition of seasons, no overall difference between months were seen . However, there was a tendency for a slightly higher odds ratio for those born in autumn (Sep–Nov), compared to winter (Dec–Feb) OR = 1.13   .p = 0.28). However, among the autumn-born, extra vitamin D from the fortification policy reduced the odds of developing IBD ) ) .This study found that individuals exposed prenatally to extra vitamin D from the Danish mandatory fortification policy had 13% lower odds of developing IBD before age 30. This study thereby suggests that even a small extra dose of vitamin D from fortified margarine prenatally seemed protective against incident IBD. Experimental data support the plausibility of this association ,44,45,46Contrary to our findings, a previous Danish study found no association between vitamin D levels at birth and the development of IBD before age 18 years . HoweverFor the time of birth analyses, no overall association with season or month of birth was found, somewhat in contrast to other ,37,39,40It is noteworthy that, in a population with an overall insufficient vitamin D intake , a smallA strength of this study is the large study population, which supports a broad generalization of the results. In addition, the design using all subjects born in adjacent birth cohorts makes it likely that any risk factors associated with IBD and/or vitamin D deficiency were equally distributed between the two cohorts, and, therefore, these did not need adjustment. This study’s design is also well suited for exploring new hypotheses, as it can be done relatively easy and at a low cost. An additional strength of this study is the definition of IBD cases. The use of the Danish National Patient Register limits diagnosis to patients with contact to a hospital. An older Danish study assessed the diagnoses of CD and UC (using the ICD-8 coding system) in one single county . They foA limitation to this study is that we only had information about the exposure at a population level. Unfortunately, we had no access to individual dietary data or measured vitamin D levels, which could have strengthened the results. However, it is reasonable to assume that people in the years following the abolishment would have had an overall lower intake of vitamin D than during fortification . If someIt could be argued that our results are a simple consequence of a secular increase in IBD incidence. To explore this further, we estimated the expected rise in incident IBD cases between the two cohorts, based on Danish IBD incidence rates from 1980 until 2013. The expected rise in incident IBD for the general population was 6.4% during the average period of three years between the two cohorts [To our knowledge, this is the first study to explore the association between prenatal and early life exposure to vitamin D from a dietary source and the risk of IBD later in life. The indication of a protective effect from a small extra amount of vitamin D prenatally supports official recommendations to Danish pregnant women to consume vitamin D supplements during pregnancy . FurtherThis finding also adds to the debate of whether mandatory fortification of food items with vitamin D should be resumed . More reIn conclusion, our study suggests that the Danish vitamin D fortification policy, providing a small extra dose of vitamin D during gestation, lowered the odds of developing IBD over the subsequent 30 years. It was indicated that an insufficient intake of vitamin D during gestation might contribute to IBD development. However, the result could be biased, due to the rising incidence of IDB. Future studies ought to test this association using a more robust study design that can determine causality. If causality can be determined, it is also warranted to investigate who will benefit most from vitamin D supplementation/fortification in which situations and the optimal doses.


There are rare prediction models for esophageal squamous cell carcinoma (ESCC) for rural Chinese population. We aimed to develop and validate a prediction model for ESCC based on a cohort study for the population.Data of 115,686 participants were collected from esophageal cancer (EC) early diagnosis and treatment of cancer program as derivation cohort while data of 54,750 participants were collected as validation cohort. Risk factors considered included age, sex, smoking status, alcohol drinking status, body mass index (BMI), tea drinking status, marital status, annual household income, source of drinking water, education level, and diet habit. Cox proportional hazards model was used to develop ESCC prediction model at 5 years. Calibration ability, discrimination ability, and decision curve analysis were analyzed in both derivation and validation cohort. A score model was developed based on prediction model.R2, D statistic, and Harrell’s C statistic of prediction model were 43.56%, 1.70, and 0.798 in derivation cohort and 45.19%, 1.62, and 0.787 in validation cohort. The calibration analysis showed good coherence between predicted probabilities and observed probabilities while decision curve analysis showed clinical usefulness. The score model was as follows: age , sex (5 for men), BMI (1 for ≤25), alcohol drinking status , tea drinking status (2 for tea drinkers), and fresh fruit (2 for never) and showed good discrimination ability with area under the curve and its 95% confidence interval of 0.792  in the deviation cohort and 0.773  in the validation cohort. The calibration analysis showed great coherence between predicted probabilities and observed probabilities.One hundred eighty-six cases were diagnosed during 556,949.40 person-years follow-up in the derivation cohort while 120 cases from 277,302.70 in the validation cohort. Prediction model included the following variables: age, sex, alcohol drinking status, BMI, tea drinking status, and fresh fruit. The model had good discrimination and calibration performance: We developed and validated an ESCC prediction model using cohort study with good discrimination and calibration capability which can be used for EC screening for rural Chinese population. Cancer is a particularly important health problem among noncommunicable diseases and is also the first or second cause of premature mortality in more than 90 countries across the world . EsophagEndoscopy examination is one of the main inspection modality for ESCC or precursor lesion and endoscopic screening programs have been performed for high-risk populations across the world , 9. SeveIn 2006, a national early diagnosis and treatment guideline for EC was introduced and stated that cancer screening was to be performed by endoscopy accompanied with iodine staining and indicative biopsy in high-risk population in China , 22. SinTo the best of our knowledge, there are few risk prediction models for ESCC. Previous prediction models were developed in China, Japan, Sweden, and Iran population based on case-control studies –31 and wThe aim of this paper was to develop a risk prediction model of ESCC for rural Chinese population and tested its performance in both derivation cohort and validation cohort.This study was based on EC cancer screening data based on early diagnosis and treatment program from centers of the cancer prevention and treatment in Shandong province. The derivation cohort came from cancer prevention and treatment centers except in Feicheng city in Shandong province, and the data were collected from 2012 to 2018. The validation cohort came from the centers in Feicheng city, and data were collected from 2012 to 2019.Inclusion criteria of the study were as follows: (a) participants enrolled in the early diagnosis and treatment of cancer programs from 2012 in Shandong province; (b) participants aged older than 39 and younger than 70 years; (c) participants did not have a history of cancer recorded by the cancer registry and were not diagnosed of cancer at baseline; (d) participants were not diagnosed with dysplasia or worse at baseline by pathologic diagnosis; (e) participants who had filled the baseline questionnaire survey correctly; and (f) participants who had signed informed consent.The data that included questionnaire information, endoscopic examination results, and pathologic diagnosis of participants were collected in the derivation cohort and validation cohort. The questionnaire information included age, sex, height, weight, marital status, education level, source of drinking water, smoking, drinking, diet habits, history of gastrointestinal diseases and age diagnosed, family history of cancer, etc. The results of endoscopic examination included location, size and shape of lesions, and endoscopic diagnosis. Biopsies were taken at the site of the lesion, and the pathological diagnosis was made by biopsy. Pathological diagnosis was recorded as each participant’s highest-level diagnosis. Endoscopy, specimen treatment, and pathologic diagnosis are referred to Chinese cancer screening, early diagnosis, and early treatment technology published by the People’s Health Publishing House.2) and 1 (≤25 kg/m2). Smoking status was divided into two categories: 0 (nonsmokers) and 1 (smokers). Alcohol drinking status was also divided into two categories: 0  and 1 . Tea drinking status was also divided into two categories: 0 (nontea drinkers) and 1 (tea drinkers). Annual household income was divided into four categories  according to the quantile. Marital status was divided into two categories: 0  and 1 (married participants). Education level was divided into two categories: 0 (junior high school or lower level) and 1 (senior high school or higher level). Source of drinking water was divided into two categories: 0  and 1 (treated water: running water or purified water). Diet habit of fresh fruit and high-temperature food was divided into two categories: 0  and 1 (never). Diet habit of pickled food and fried food was divided into two categories: 0 (less than twice a week on average) and 1 (two times or more per week on average).The risk factors to be studied were selected according to previous research results, review articles, etc. , 33–42. New ESCC were diagnosed according to the International Classification of Diseases, 10th version as well as histology (ICD-O morphology codes). The follow-up time of the derivation cohort and validation cohort was up to December 31, 2020. The outcome was confirmed by cancer registration data.The risk predictors in the prediction model were determined using three steps. The first step was fitting full model with all candidate variables using a multivariable Cox regression model. The variable was eliminated from the full model if its coefficient was greater than 0.90 and less than 1.10 and was not statistically significant at level 0.01 in the second step , 44. In R2 value, D statistic and its 95% confidence interval (95% CI), Harrell’s C statistic and its 95% CI, calibration curve and decision curve analysis were used to test the model performance . Package survival was used for Cox regression analysis. Package cmprsk and package ggDCA were used for decision curve analysis.The analyses were performed using R software version 4.0.4  of the highest quintile was 46.47 , the HR (95% CI) of the fourth quintile was 16.87 , the HR (95% CI) of the third quintile was 7.30  and the HR (95% CI) of the second quintile was 1.92 .R2 of 43.82%, D statistic of 1.69, and Harrell’s C of 0.799  in the derivation cohort and R2 of 35.38%, D statistic of 1.33, and Harrell’s C of 0.729  in the validation cohort. We developed and validated an individual 5-year risk prediction model of ESCC using cohort study for population aged 40 to 69 years and provided an efficient tool for rural Chinese in this study. The prediction model included six variables, such as, age, sex, BMI, alcohol drinking status, tea drinking status, and diet habit of fresh fruit and showed good discrimination and calibration ability in both the derivation cohort and validation cohort. Decision curve analysis showed that the prediction model had clinical usefulness. A score model was derived from the prediction model and also showed good discrimination and calibration ability in both the internal validation and external validation.Since 2006, as the first batch of pilot, Feicheng city, a high incidence area of ESCC which the validation cohort came from, began the EC cancer screen program, and evidence had shown that the screen is associated with a reduction of the incidence of ESCC . It was There were rare prediction models for ESCC based on the cohort study. Chen et al. used logistic regression model and developed an ESCC prediction model based on multicenter cohort study in rural China without validation . The modThis study focused attention on questionnaire-related risk factors other than genetic or other risk factors. Previous studies had shown that the risk of ESCC in men was several times higher than that in women, and the ratio varied greatly among different populations . In thisThis paper also has some limitations. (1) The data were collected from one province of China, which could not represent the 40- to 69-year population of China. On the other hand, Shandong is a big province in China and accounting for nearly one-tenth of the population of China. To some extent, it is also representative. (2) Although our cohort was large, the number of outcomes with esophageal cancer is small, which was likely to cause residual bias. This problem could be solved by longer follow-up. (3) There might have a recall bias for the risk factors. (4) We did not obtain the data of the following risk factors: PAH and trace element. We will add related questions to the questionnaire in the near future.In summary, this paper provides a prediction model for ESCC with good discrimination and calibration in internal verification and external verification. Our prediction model is discriminative as previous established models with AUC of 0.796 in the derivation cohort and higher discriminative with AUC of 0.779 in the validation cohort as shown in the In this study, we developed and validated an ESCC prediction model for rural Chinese population based on a multicenter cohort study. The prediction model included five risk factors: age, sex, BMI, alcohol drinking status, tea drinking status, and diet habit of fresh fruit. The prediction model showed good discrimination and calibration ability in both the derivation cohort and validation cohort. Decision curve analysis showed its clinical usefulness. We transferred the prediction model into a score model for clinical use, and the score model also showed good discrimination and calibration ability in the derivation cohort and validation cohort. We provided a simple and useful prediction tool for ESCC and may be used for ESCC cancer screen.Data used in this research and related data could be offered upon reasonable request for the corresponding author.The studies involving human participants were reviewed and approved by Ethics Committee of Public Health, Shandong University. The patients/participants provided their written informed consent to participate in this study.JH and FX designed the study. JH carried out the analysis and wrote the first version of the manuscript. LW provided help in the process of data analysis. HZ, SM, ZW, GZ, YL, DZ, and JW helped with data collection and collation. All the authors participated in the discussion and agreed to publish the model in its current format. All authors contributed to the article and approved the submitted version.This study is funded by the National Key R&D Program of China (2020YFC2003500) from the Ministry of Science and Technology of the People’s Republic of China.The authors all declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.