In China, improving mental health has been far behind its accomplishments for other diseases. With depression as one of the most prevalent mental disorders, the aim of this study was to evaluate temporal trends in the prevalence and treatment of those who screen positive for depression in China, by age, gender, and province.We used data from three nationally representative sample surveys: the China Health and Retirement Longitudinal Study (CHARLS), the China Family Panel Studies (CFPS), and the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Depression was judged by the Centre for Epidemiologic Studies Depression Scale. Access to treatment was judged by two items: if respondents received any treatment like anti-depressants, or if respondents received counselling from a mental health professional. Survey-specific weighted regressions were fitted to estimate the temporal trend and subgroup disparities, and then pooled by meta-analysis.In total 168,887 respondents were investigated. The overall prevalence of China populations who screen positive for depression was 25.7% (95% CI 25.2–26.2) during 2016–2018, decreased from 32.2% (95% CI 31.6–32.8) during 2011–2012. The gender gap increased with age and had no significant improvement from 2011–2012 to 2016–2018. The prevalence of depression in developed areas is more likely to show a lower value and decreasing trend, while the prevalence in underdeveloped areas is more likely to show a higher value and increasing trend, from 2011–2012 to 2016–2018. The overall proportion of those who received any needed treatment or counselling from a mental health professional slightly increased from 2011  to 2018 , and mainly occurred for older adults aged 75 and above.The prevalence of those who screen positive for depression decreased by about 6.5% from 2011–2012 to 2016–2018 in China, but only tiny improvements were made in accessibility to mental health care. Corresponding disparities were identified in age, gender, and province. In China, mental health has typically been left far behind its achievements in communicable and non-communicable diseases . Since tIn China, about 15.9–38.6% of the general population suffer from common mental health problems , 4–7, anDepression is one of the common types of mental disorder and a leading cause of disability . The aimWe used publicly available data from three nationally representative sample surveys: the China Health and Retirement Longitudinal Study (CHARLS) (wave 2011 and 2018), the China Family Panel Studies (CFPS) , and the Chinese Longitudinal Healthy Longevity Survey (CLHLS) (wave 2018). The CHARLS is a biennial social science and health household survey conducted among Chinese adults aged 45 and older in 28 provinces of China. The CFPS is a biennial survey focused on the economic, non-economic, and well-being of the Chinese population of all ages in 25 provinces of China. The CLHLS was conducted to shed light on the determinants of healthy human longevity and oldest-old mortality, and provides information on the health status and quality of life of older adults aged 65 and above in 22 provinces of China. All the above three surveys were widely used in the scientific community. Detailed descriptions of these data, sampling methods and quality-control procedures have been reported elsewhere –16.The data are publicly available. The use of secondary de-identified data made/has made this study exempt from the institutional review board. CHARLS was approved by the Ethical Review Committee of Peking University (IRB00001052-11015). CFPS was approved by the Ethical Review Committee of Peking University (IRB00001052-14010). CLHLS was approved by the Ethical Review Committee of Duke University and Peking University (IRB00001052–13074).Depression was judged by the Centre for Epidemiologic Studies Depression (CES-D) Scale. This scale was developed for use in studies of the epidemiology of depressive symptomatology in the general population . Its purAccess to treatment was judged by two items: asking respondents “if they received any treatment like anti-depressants” or “if they received counselling from a mental health professional.” Notingly, only CHARLS provided the information on access to treatment.We investigated socio-demographic characteristics including age (years), gender , marital status , education attained , minority ethnicity (yes or no), and average annual household income per person. We also investigated the following variables because of their identified influence on depression in China, including residence place , and self-rated health status  , 20, 21.Due to the difference in the purpose, subjects, and sampling methods of the three nationally representative surveys we explored, the data cannot be pooled at the individual level. Therefore, we combined the results through a meta-analysis, which not only avoids the problem of bias caused by different surveys, but also increases the accuracy of our estimates for specific age groups .p < 0.1), a random-effect meta-analysis was performed to pool the estimates  was 51.0 (21.3) years.The overall prevalence of China populations who screen positive for depression in the past week was 25.7% (95% CI 25.2–26.2) during 2016–2018, decreased from 32.2% (95% CI 31.6–32.8) during 2011–2012. The decrease in prevalence of depression was greater among younger people and older people, while it was relatively small among middle-aged adults aged 45–54 . This reThe prevalence of depression had a 7.6% gender gap  during 2016–2018, decreased from 10.9%  during 2011–2012. The decrease favoured adolescents and older adults, but the improvement was not significant . Pre-pooBoth the prevalence of depression and its temporal trends showed great geographic variances. The prevalence of depression in developed areas was the lowest and decreased, such as Beijing (decreased from 15.4% during 2011–2012 to 10.8% during 2016–2018) and Shanghai (decreased from 18.2% during 2011–2012 to 12.0% during 2016–2018); but the prevalence in underdeveloped areas was the highest and increased, such as Xinjiang (increased from 39.4% during 2011–2012 to 47.1% during 2016–2018) and Qinghai (increased from 55.8% during 2011–2012 to 62.5% during 2016–2018) . Pre-pooAmong those who screen positive for depression and aged 45 and above, the overall proportion of those who received any needed treatment or counselling from a mental health professional increased from 2011  to 2018 , but remained quite low. Corresponding results by province, by age, and by gender were presented in Here we evaluated the temporal trends in the prevalence and treatment of those who screen positive for depression in China, by age, gender, and province. The prevalence of those who screen positive for depression in China decreased from 32.2% during 2011–2012 to 26.7% during 2016–2018, with the decrease mainly occurring in younger people and older adults. Salient subgroup disparities of the above prevalence were detected for age, gender, and province. The gender gap increased with age and had no significant improvement from 2011–2012 to 2016–2018. The prevalence of depression in developed areas is more likely to show a lower value and decreasing trend, while the prevalence in underdeveloped areas is more likely to show a higher value and increasing trend, from 2011–2012 to 2016–2018. The accessibility of mental health care slightly improved from 2011–2012 to 2016–2018 and mainly occurred for older adults aged 75 and above, but remained quite low (around 1%) both overall and by subgroup.Our findings indicated that the decrease in the prevalence of depression mainly happened in younger people and older adults, while the decrease in middle-aged adults aged 45–54 was relatively low. Given that the access to mental health care in China was quite low as revealed by our study, the above age-related decrease may be due to improvements in areas beyond mental health care. For younger people, the above decrease might be because of the prevalence of the internet and games, along with a focus on physical activity in school, which can help young people release their pressures or emotions , 24. ForAn unexpected finding was that the distribution between age and prevalence of depression in China changed from a linear growth trend in 2011–2012 to an “inverted U-shaped” pattern in 2016–2018, found within females but not males. A similar “inverted U-shaped” distribution was also reported by another China-based study . The resThe finding of low accessibility of mental health care is consistent with previous studies conducted in China . In geneBoth the prevalence of depression and its temporal trend, as well as corresponding findings on access to mental health treatment, showed great geographic variances in China. These geographic variances may be caused by geography-related differences in health behaviour  , 29, avaTo our knowledge, this is the first study to assess the temporal trends in the prevalence and treatment of those who screen positive for depression in China, by age, gender, and province. The longitudinal representative data enabled the exploration of the progress made to improve mental health in China. The subgroup analysis allowed for a more nuanced and practical assessment of this improvement process, and would contribute to formulating policies and implementing concrete action plans in practice.Our study was limited by the use of self-reported data, which may be subject to recall bias. Third, the evidence on the cut-off point for probable depression primarily comes from the western population, whether the validated cut-off point for probable depression meets Asian especially Chinese conditions need more studies in the future. Fourth, people with depression may have been taking antidepressants but they had no residual symptoms to be identified by the survey instruments. Such people would have been missed by this study, resulting in underestimating the proportion of people with depression.The prevalence of those who screen positive for depression had decreased in China, but only a tiny improvement was made in access to mental health care. There were disparities in temporal trends in the prevalence and treatment of those who screen positive for depression in China, by age, gender, and province. The disparities in the prevalence of depression and the low proportion of receiving treatment suggested that China’s mental health system needs to be fully integrated into all aspects of its health-system reform.https://charls.pku.edu.cn/en/ for CHARLS, https://www.isss.pku.edu.cn/cfps/en/index.htm for CFPS, and https://cpha.duke.edu/research/chinese-longitudinal-healthy-longevity-survey-clhls for CLHLS.Publicly available datasets were analysed in this study. This data can be found here: The studies involving human participants were reviewed and approved by Ethical Review Committee of Duke University and Peking University . Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.SC: full access to all the data in the study, take responsibility for the integrity of the data and the accuracy of the data analysis, acquisition, analysis, or interpretation of data, statistical analysis, administrative, technical, or material support, and supervision. Both authors: concept and design, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and approved the submitted version.


Poor QoL was strongly associated with increased mortality  and MACE . A similar trend was noted for women and men, but did not reach significance in women due to the smaller number of female patients. Conclusion: poor HRQoL is associated with subsequent mortality and MACE in patients undergoing PCI. By not assessing quality of life as a standard of care, an opportunity is lost to identify high-risk patients who may benefit from targeted interventions to improve health outcomes.Background and aim: poor quality of life (QoL) has been identified as an independent risk factor for mortality and major cardiac events (MACE) in patients with cardiovascular disease (CVD). The aim of this study was to assess health-related quality of life (HRQoL) at baseline and its association with outcome in patients with coronary artery disease presenting for percutaneous coronary intervention (PCI). The outcome was measured by mortality and MACE at 1-year, and whether there was any difference for sex and different age groups. Methods and results: all patients prospectively enrolled into the GenesisCare Outcome Registry (GCOR) over a 11-year period were included in the study. The EQ-5D-5L and VAS patient survey were used for assessment of baseline HRQoL. Of the 15,198 patients, only 6591 (43.4%) completed the self-assessment. Women had significantly more impairment of all five dimensions of the EQ-5D-5L survey, and their self-reported QoL was significantly lower than men (68.3 in women vs. 71.9 in men,  Cardiovascular disease (CVD) is still worldwide the major cause of death and morbidity . With thThe EQ-5D-5L health status survey is an internationally recognised generic instrument, well validated for the assessment of patients’ health status in cardiovascular disease, and has the benefit of being brief and very easy to use . The aimData were obtained from the GenesisCare Outcome registry (GCOR) and included all patients prospectively enrolled to the database over a 11-year period from January 2009 to December 2019. Patients eligible for the study must have completed a 1-year follow-up period, with complete data available on baseline demographics and all clinical variables. An EQ-5D-5L patient survey was issued to every patient with the index PCI procedure, to be completed at discharge or to be posted back. Patients were supplied with a patient information sheet and an opt-out consent was utilised.The PCI Registry and its entirety have been approved by the Bellberry Human Research Ethics Committee (HREC).The EQ-5D is a generic health instrument developed by the EuroQol Group ,11 and hSocio-demographic parameters, medical history and management including in-hospital investigations and procedure details were routinely recorded. All in-hospital complications following PCI were recorded at the time of discharge. For the current study, follow-up information for one-year post-procedure was used. Follow-up assessments were performed by research coordinators at discharge, at 30-day, and at 1-year post-procedure. All cardiac events were documented following review of medical records including death, myocardial infarction (MI), target vessel revascularisation , and rehospitalisation. MACE was the composite of death, MI and/or TVR events. Secondary prevention medication included adherence to statins, angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), beta-blockers, and antiplatelet therapy (aspirin/clopidogrel/ticagrelor/prasugrel).p < 0.05 between good and poor QoL, including patient age, sex, body mass index (BMI), smoking status, PCI presentation  at baseline, diabetes, left ventricular ejection fraction (LVEF), previous myocardial infarction (MI), peripheral vascular disease (PVD), previous coronary artery bypass surgery (CABG), heart failure within prior 2 weeks, renal failure, and cardiogenic shock. All statistical analyses were performed using Stata version 15.2 for Windows .Patients in the PCI registry who completed the EQ-5L-5D questionnaire at baseline and had complete covariate information available were included for the current analysis. A descriptive analysis was used (frequency/sample proportions or mean with standard deviations) to summarise baseline characteristics , and risk factors of the patients by availability of data. Student t-test, ANOVA or chi-square tests were used to compare the distributions of baseline characteristics including risk factors by availability of data. Among those with data available, a comparison was made of the baseline characteristics by baseline/pre-procedure QoL status based on VAS . The distribution of clinical outcomes by presence of problem was explored among those with QoL information available. The distribution of outcomes by sex and age for different responses was also explored. Further, the association of clinical outcomes within one-year post-procedure was explored with pre-procedural QoL status using univariate and multivariate Cox proportional hazard regression models. Multivariate regression models were adjusted for all confounding variables with a significance of p = 0.19), with patients completing the QoL survey significantly older . Patients presenting for an elective procedure (stable angina with a positive stress test) had a higher rate of completing the survey , while a persistently lower completion rate was noted in patients when presenting with a STEMI or cardiogenic shock.Of the 15,198 patients enrolled in the GCOR PCI database, 6591 (43.4%) completed the EQ-5L-5D questionnaire. p < 0.001). In patients with a poor QoL a higher prevalence of diabetes  was noted, with BMI significantly higher , and left ventricular ejection fraction  significantly lower. Patients with a poor quality of life had a higher rate of established coronary artery disease, with a higher proportion having a history of previous myocardial infarction , and previous CABG . Involvement of other vascular territories were also more common in patients reporting poor QoL, with a significantly higher prevalence of peripheral vascular disease . A history of previous cerebro-vascular disease  was also more common in patients with poor QoL but did not reach significance. The diagnosis of heart failure was more frequent in patients with a poor quality of life, including both a previous history of heart failure  as well as newly diagnosed heart failure . The presence of renal failure  was also significantly higher in patients with poor quality of life. Patients with poor quality of life were more likely to present with STEMI  and NSTEMI , and had a lower probability of presenting with stable coronary artery disease . The percentage of patients presenting with multivessel disease were similar for both groups (p = 0.21).With the assessment of patients’ self-rated quality of life , 5223 pap < 0.001). The quality of life as assessed by the VAS score was also significantly lower in women compared to men .In patients who completed the survey, a significant difference was noted between women and men for both the five dimensions and VAS score . Women hp < 0.001). When testing for significance of trend, all three dimensions achieved statistical significance. When assessing for pain/discomfort, older patients had a higher level of impairment (p < 0.001) but significance for trend was not as strong as seen with the modalities of physical activity (p = 0.19 for pain/discomfort). Younger patients reported a higher level of anxiety/depression (p < 0.001 for anxiety/depression), with significance for trend (p = 0.01). When assessing the VAS score, younger patients (<55 years) perceived their quality of life as significantly worse compared to older patients (p < 0.001) but did not reach significance when testing for trend (p = 0.54).The effect of age on quality of life was assessed by dividing the patients into three age groups: <55 years, 55–74 years, and ≥75 years . A statip = 0.01), MACE, MI, and unplanned cardiac readmissions (p < 0.001). Impairment of personal care was not associated with outcome, although a trend towards significance was noted for increased risk of death (p = 0.06). A decrease in usual activity was significantly associated with an increase in MACE (p = 0.03), MI (p = 0.003), and unplanned cardiac readmissions (p < 0.001). The domain of pain/discomfort was associated with an increased risk of MACE (p = 0.01), MI (p = 0.01), and unplanned cardiac readmissions (p = 0.01). No association was noted between anxiety/depression and risk of events. Involvement of all five modalities were very strongly associated with an increased risk of death (p = 0.03), with no effect on the risk of MACE, MI, or unplanned cardiac readmissions.In the cohort of patients in whom complete data on QoL were available, the five modalities of the descriptive component of the EQ-5D-5L  were sigp < 0.001) as well as a higher rate of MACE  and MI . No association was noted between QoL and adherence to secondary prevention medication, attending cardiac rehabilitation or unplanned cardiac readmissions. When assessing for the association between poor quality of life and outcomes, no association was demonstrated in female patients, except for poorer attendance at cardiac rehabilitation in women . In men, poor QoL was significantly associated with an increased risk of death , but no association was demonstrated with MACE, MI, or unplanned cardiac readmission.Patients who assessed their QoL as poor  had a hip < 0.001) and MACE . Further, when multivariable Cox regression analyses was performed, adjusting for all confounding variables with a significance of p < 0.05 between good and poor QoL, the increased risk persisted. The adjusted risk of death (p = 0.001). When adjusted for clinical variables, poor quality of life was associated with a significantly increased risk of death in men . A similar trend of increased risk was noted in women  but did not reach clinical significance due to the smaller number of female patients. The adjusted risk of MACE (p = 0.04). Poor QoL in both men  and women  was associated with a trend towards increased risk of MACE but did not reach significance.The association of baseline HRQoL with death and MACE at 1-year were assessed by Kaplan-Meier curves and adjusted Cox regression models. All patients with missing information on covariates were excluded for both models. With univariable Cox regression analyses  poor QoLof death  in patie of MACE  in patieA very low completion rate of the EQ-5D-5L and VAS questionnaire was observed in this study. In patients on whom information was available, poor HRQoL was more common in women and in younger patients, and strongly correlated with increased mortality and MACE at 1-year. Furthermore, significant predictors of poor HRQoL at baseline were identified.There is growing recognition that pre-existing health status has the potential to impact clinical outcomes as measured by mortality, risk of myocardial infarctions, and unplanned readmissions ,14. ThisIt is clear from the literature that the use of patient-reported health status is underutilised ,14. In tThe baseline health status of a patient is not only affected by the presenting disease, but also by additional pre-existing status ,17. In tA history of previous myocardial infarction has been well established to have a lasting effect on HRQoL ,19 and iBoth diabetes and high BMI were very strongly associated with poor baseline quality of life in the GCOR registry. This was in line with multiple studies investigating the impact of diabetes on the health status of patients presenting with ACS and treated with PCI , confirmIn this study heart failure was significantly associated with poor quality of life at baseline and is in concordance with large studies demonstrating both heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) ,26 to haIn an analysis of the GCOR data base, the presence of peripheral vascular disease strongly correlated with worse quality of life at baseline. The presence of peripheral vascular disease is well established in the literature to be associated with a poor quality of life, affecting quality of life on all domains . The CADAnalysis of the GCOR registry identified that CKD was strongly associated with poor self-assessment of quality of life at baseline. This was in line with the literature establishing a very strong association between different stages of chronic kidney disease (CKD) and HRQoL, with end-stage renal disease having the biggest impact on poor HRQoL ,31. The In patients with a diagnosis of coronary artery disease and treated with percutaneous intervention, evidence suggests that baseline health status of patients as measured with the EQ-5D-5L instrument is significantly associated with mortality independent of the clinical variables and complexity of disease . The strUnplanned readmissions after percutaneous intervention (PCI) for coronary artery disease is a very important quality metric, given its impact on the patient and the cost of healthcare . Very poIn the GCOR study, quality of life did not demonstrate any significant association between either adherence to secondary prevention medication or attendance of cardiac rehabilitation. Very limited information and conflicting results are available in the literature on the possible association between HRQoL at baseline and adherence to secondary prevention medication in patients with cardiovascular disease and after PCI.p < 0.001). This occurred despite having a lower burden of coronary disease, suggesting that other factors unrelated to disease severity might be implicated. Baseline QoL was significantly associated with subsequent MACE and mortality in the whole cohort. This association was observed for men and women, however, was not statistically significant in women, likely due to a smaller number of women. In the literature a marked difference between men and women were noted for the determining factors related to poor HRQoL, with studies suggesting social and psychological factors to play a more significant role in women. Some studies allude to the fact that gender roles might have an even greater impact on the differences seen comparing women and men [In the literature, women persistently reported worse health related quality of life, independent from the method of assessment ,35. The  and men ,34,36. I and men ,38. The It is clear from this study, and comprehensively supported from the literature , that boWhen patients were assessed in the GCOR registry for an association between age and HRQoL, older patients experienced a significant impairment of mobility, personal care, and usual activity, while pain/discomfort was not significantly impaired compared to the younger group of patients and anxiety/depression was significantly less affected in the older patient cohort. Conversely with the VAS score, older patients perceived their general state of health significantly better than the younger patients. These findings from the GCOR database were in line with other studies, including the RITA-2 trial  where agPotential limitations were observed in this study. By including only patients undergoing PCI, the study was not representative of all patients with coronary artery disease. A further possible limitation to the study was that a generic instrument, and not a disease specific instrument was used to assess quality of life, and the specific impact of angina symptoms on quality of life could not be assessed. The EQ-5D instrument however is well established and validated in the assessment of quality of life in patients with coronary artery disease. Another possible limitation was that the study looked only at sex  differences and did not adjust for sex-gender interaction and its possible impact on quality of life.This study confirmed that HRQoL is associated with subsequent MACE and mortality in patients undergoing PCI. By not assessing quality of life as standard of care, we are missing an opportunity to identify high-risk patients who may benefit from targeted interventions to improve health outcomes. This could include reducing unplanned readmissions and henceforth healthcare costs. Furthermore, the significant differences noted between women and men in baseline quality of life were unexplained by measures of disease severity, and further research is needed to address the differences.


The Runzhou white-crested (RWC) duck is a unique breed with excellent ornamental and economic value. It has complex feather protrusions, collectively known as crest cushions, which mainly comprise prominent soft tissues covered by skin and feathers. In this study, the number of crest cushions and various serum biochemical parameters of RWC ducks were observed and measured. The results showed that the number of crest cushions could be used to directly reflect the size of the crest. As the number of crest cushions increased, the weight and mortality increased. In addition, the number of crest cushions had a positive effect on various serum parameters, such as various mineral elements as well as triglyceride and immunoglobulin levels. Therefore, it is preliminarily speculated that the number of crest cushions may indirectly affect the health and immune performance of RWC ducks.p < 0.05). The serum Ca, Mg, Fe, Cu, Zn, and Se contents in the multiple-crest-cushion group were significantly higher (p < 0.05), as were the levels of triglycerides, immunoglobulin A, immunoglobulin G, immunoglobulin M, and immunoglobulin D (p < 0.01). The opposite results were seen for glycosylated low-density lipoprotein (p < 0.01). Propionic acid and acetic acid contents differed significantly between the two groups (p < 0.05), as did butyric acid content (p < 0.01), being higher in the multiple-crest-cushion group. Thus, an increase in the number of crest cushions coincided with a change in various serum biochemical indicators. The number of crest cushions might be involved in regulating various mechanisms of RWC ducks and might have an immunoregulatory effect.We investigated the effects of crest cushions in Runzhou white-crested (RWC) ducks. A total of 322 duck eggs were collected for incubation; 286 eggs were fertilized, and 235 RCW ducks were hatched. All the RWC ducks were weighed after 100 days and counted, and the volume of the crest cushion was measured. The number of crest cushions was positively correlated with the body weight, volume of the crest cushion, and distance from the mouth ( The crested-cushion white duck is a unique breed with complex plumage protrusion traits collectively known as the crown. It has been documented in various historical books; however, this high-quality variety was gradually lost over time and did not reappear until 2005, when it was discovered by Yangzhou University and Zhenjiang Tiancheng Agricultural Technology Co., Ltd. After rescue collection and collation, it was successfully restored in 2013 as a Runzhou white-crested (RWC) duck population, which was consistent with the records of historical books examined by the China Livestock and Poultry Resources Committee as a unique local breed in Jiangsu Province. The breed is characterized by a cluster of clumped feathers protruding behind the head and shaped like a fluffy ball. There is no significant difference in appearance between males and females, both having moderate body size, symmetrical structure, and compact and narrow bodies. The feathers are white in color and tight.Avian breeding accounts for a large proportion of the total agricultural output value in the country and worldwide. Meat duck breeding has gradually occupied a major position in the waterfowl industry in China, and annual production continues to rise . High-quThe feather crest cushion of domestic ducks reflects a head integument that inserts into the subcutaneous thickened skin of the parietooccipital region ,3. In poVertebrate serum contains many enzymes, nutrients, ions, hormones, and waste products, which are biomaterials that are widely used to determine animal health status . Other sSo far, most studies have detected the effects of different feeding methods and different feed additions on serum biochemical parameters of animals, and there is still a great gap in the study of the effects of different traits ,18. The All experimental ducks were approved by the Yangzhou University Animal Protection Association . All experimental ducks were managed and handled according to the guidelines established and approved by the Animal Care and Use Committee of Yangzhou University. All possible efforts were made to reduce the suffering of animals.2. Stocking density gradually decreased with increasing age until 42 d of age, when they entered the finishing period and remained at 5 animals/m2. In the duck house, they had the same living environment, with 24 h of uninterrupted light  and equipped with automatic drinkers and feeders so each duck had free access to food and water. The ducks were reared on the same diet; feed nutritional value requirements are shown in The RWC ducks used in this experiment were obtained from TianCheng Agricultural Technology Co., Ltd. We collected 322 RWC duck eggs for hatching. All breeding male and female ducks were healthy individuals and the ducks we raised had been injected with the vaccine; in addition to avoiding excessive egg contact with external pathogens, we collected embryos at the first time after laying eggs in female ducks, comprehensively disinfected the incubation box before hatching, and at the same time, the incubation box also ensured normal work. In order to eliminate the pathogen from interfering with the embryo during the whole hatching process, we also strictly followed the production requirements for disinfection. The eggs were candled on the eighth day after collection and the unfertilized and dead eggs were removed. Ducklings successively hatched on approximately day 28 of incubation. The duck shed was fumigated with formalin and potassium permanganate 1 week before housing and ventilation was restored after 24 h of closure. Ducklings were kept at 35 °C in the incubator before entering the cage, humidity was controlled between 70% and 75%, and all ducks were housed on ground covered with dry rice husk bedding; room temperature was maintained at 33–35 °C for 1 week during the brood period, then decreased by 2–3 °C per week, and out of temperature control after 3 weeks, during which stocking density remained at 15 ducks/mAfter 100 days of feeding, the feed was removed in the evening, and the number of crested cushions from 235 hatched RWC ducks were counted. One crested cushion was recorded as a single-crest group, and two or three crested cushions were recorded as multiple-crest groups. All individuals were weighed and recorded for statistical analyses. 3). Crested-cushion length was measured as the distance between the anterior and posterior sagittal ends of the cushion tissue, cushion width was measured as the distance from the left to the right end of the coronal plane of the crested cushion tissue, and height was measured as the distance between the lower ends of the coronal plane of the crested-cushion tissue. The volume was recorded as the product of the transverse diameter, longitudinal diameter, and height. A tape measure was used to determine the distance from the top edge of the bill to the front edge of the bottom of the crested cushion as the distance from the mouth, and the distance was determined from the front edge of the bottom of the crested cushion to the left eye as the distance from the left eye. The distance from the right eye and the distance from the left and right ears were determined using the same measurement technique and tools. The eggs that did not successfully hatch were collected separately and broken, and the number of embryos inside and the number of crested cushions were counted. Unhatched embryos were divided into a single-crest group and multiple-crest groups. Based on this, ducks were weighed using a weighing scale. A Vernier caliper was used to measure the length (mm), width (mm), and height (mm) of each duck crested cushion and to calculate the volume  and triglyceride (TG) levels in serum were measured by a CHOD-PAP commercial kit. High-density lipoprotein (HDL), low-density lipoprotein (LDL), glycosylated low-density lipoprotein (G-LDL), and very-low-density lipoprotein (vLDL) were detected by the clearance method. Immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin D (IgD) were detected by immunoturbidimetric enzyme-linked immunosorbent assay kits. Potassium (K) and sodium (Na) were detected by enzyme colorimetry commercial kits. Chlorine (Cl) was detected by Chloride Test kit (Colorimetric). Phosphorus (P) was detected by a molybdenum blue colorimetric method Phosphorus Kit. The levels of zinc (Zn), selenium (Se), copper (Cu), and calcium (Ca) were determined by colorimetry. Magnesium (Mg) was detected by a Calmagit Magnesium Kit. Iron (Fe) was detected using the Fe Test Kit FerroZine Colorimetric. All kits were from Beijing Huaying Institute of Biotechnology, and the kit catalog numbers are as follows: TC (HY-N0029), TG (HY-N0030), HDL (HY-N0031), LDL (HY-N0032), vLDL (HY-N0033), G-LDL (HY-N0034), IgA (HY-N0048), IgM (HY-N0049), IgG (HY-N0050), IgD (HY-N0051), K (HY-21007), Na (HY-21006), Cl (HY-N0020), P (HY-21008), Zn (HY-21005), Se (HY-21009), Cu (HY-21004), Ca (HY-21001), Mg (HY-21002), and Fe (HY-21003). All indicators were measured using an automatic biochemical analyzer . For samples left over from separated serum, we measured the serum SCFA levels and selected propionic acid, isobutyric acid, acetic acid, butyric acid, isovaleric acid, valeric acid, and caproic acid for concentration determination. Samples were analyzed using a gas chromatograph  and a mass spectrometer , and the results were handed over to Suzhou Panomix Bio-pharmaceutical Technology Co., Ltd., Suzhou, Jiangsu, China. All the measurements were performed in triplicate.For serum studies, after measuring the position of the crested cushion and body weight of the two groups, approximately 5 mL of blood was collected from the brachial vein of the ducks from two groups via venipuncture. The blood samples were shaken evenly in coagulation-promoting tubes using a refrigerated centrifuge at 3000× p < 0.05. Statistical analysis was performed using SPSS  for experimental data, and one-way analysis of variance was used to analyze the differences between samples. Duncan’s multiple comparison test was used to evaluate the significance of differences between the two groups. All results are expressed as the mean ± standard deviation (SD). The correlation between serum biochemical indices and the number of crested cushions in ducks was examined using the Pearson’s two-sided test. Pearson’s correlation coefficient is denoted by “r”, where r > 0 and r < 0 represent positive and negative correlation, respectively. Further, 0 ≤ |r| < 0.2, 0.2 ≤ |r| < 0.4, 0.4 ≤ |r| < 0.6, 0.6 ≤ |r| < 0.8, and 0.8 ≤ |r| ≤ 1.0 indicate no correlation, weak correlation, moderate correlation, strong correlation, and extremely strong correlation, respectively. Data were considered statistically significant when To determine whether there are significant differences in various indicators between groups with different numbers of crested cushions and whether the number of crested cushions is associated with various indicators, we measured the size and location of the crested cushion of the ducks, and a serum sample was taken to assess biochemical parameters, including the determination of some immune parameters.Egg hatching is an important process in poultry production. Therefore, embryo mortality during incubation can directly affect the economic benefits of duck farms. There were two peaks of mortality during egg incubation. The first death peak occurs from day 2 to 4 of the egg incubation process, which mainly depends on the fertilization and health status of the egg and appropriate environmental conditions, individual embryos are weak or presence of dead eggs from laying; improper egg storage also decreases embryo viability. The second death peak occurs from day 19 to 21 . The morOf the 322 duck eggs collected, 36 unfertilized eggs were removed after candling, and 235 ducks were finally hatched, including 141 ducks  with a single crested cushion and 94 ducks  with multiple crested cushions. There were 51 unhatched duck eggs, including 26 ducks with one crested cushion and 21 ducks with multiple crested cushions, which could not be identified because of accidental death. The results are presented in p < 0.01). The differences between the size of the crested cushions and the location are shown in p < 0.01). There was also a significant difference in the distance between the crested cushion and mouth (p < 0.05), and the greater the number of crested cushions, the closer was the distance to the mouth. There was no significant difference in the distance between the crested cushion and the left or right eye and between the crested cushion and the left or right ear (p > 0.05). After 100 days, the weights of all hatched ducklings and the crested cushions were measured. The results are presented in p < 0.05). It has been shown that Se and Zn are essential nutrients that play an important role in oxidative stress and immunity in addition to having anti-apoptotic activity, thereby enhancing immunity in poultry [p < 0.01), and there were no significant differences in Na, Cl, and P content between the two groups of ducks (p > 0.05) (p < 0.05) and highly significantly positively correlated with Fe and Cu content (p < 0.01).  . Fe is i< 0.01). . p < 0.05); moreover, there was no significant difference in TC (p > 0.05). As shown in p > 0.05), but the contents in multiple-crested-cushion groups were slightly higher than those in single-crested-cushion groups; results of the difference analysis showed that G-LDL content was significantly higher in the serum of single-crested-cushion ducks than in that of multiple-crested-cushion ducks (p < 0.01). In the background of the above results, we continued to correlate the data shown in p < 0.05) and significantly negatively correlated with G-LDL (p < 0.01). The results of basic serum biochemical parameters showed that the contents of TC and TG in multiple-crested-cushion ducks were higher than those in single-crested-cushion ducks, but only the TG content was significantly different between the two groups (p < 0.01). A correlation analysis was subsequently performed, and the results were the same as those of previous results (p < 0.01). The higher the number of crested cushions, the higher is the immunoglobulin content in the serum. In addition, lymphocytes in the innate immune system of birds can produce a variety of antibodies, such as IgM, IgG, and IgA, as the first line of defense against inflammation [To determine immune function and resistance to infection, we measured levels of serum immune markers, including immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin D (IgD). The effect of the number of crested cushions on the serum immune parameters is shown in  results . Thus, Iammation . p < 0.05), and the butyric acid content was significantly higher than that in the single-crested-cushion group (p < 0.01), and there was no significant difference in isobutyric acid content between the two groups (p > 0.05). Current studies on SCFAs in poultry have focused on gut flora and gut health, which directly affect the growth of poultry. The aim of this study is to screen out RWC ducks which are better in all aspects, so the content of SCFAs in duck serum is also an important criterion for evaluating duck health ,36. NextAnus platyrhynchos f. doni.) had encephalocele, disability, or loss of the upper beak, resulting in an inability to successfully incubate, with high mortality and central nervous system defects. Therefore, we speculate that the number of crest cushions may have an effect on the duck egg mortality rate, and individuals with a large number of crest cushions are more likely to die during the embryonic period. This result is likely due to cranial vault defects caused by the compression of brain tissue during embryonic growth, which subsequently blocks brain development. The crested cushion is a visible trait that is present in many birds and is characterized by a cluster of villous projections on the head of birds, forming a hair bulb; some birds have parenchymal tissue in the cluster of villous projections ,38,39. Ap > 0.05). These results preliminarily confirmed that the number of crested cushions had a negative impact on the hatching and survival rate of ducks. However, duck with multiple crest cushions are more advantageous during growth. To explore this effect, we measured serum biochemical parameters in ducks with different numbers of crested cushions. Studies by Puvača and Stana. [When measurements of the crest cushion, with respect to number, size, and position, were correlated with morphological traits, we found that ducks with multiple crest cushions had an extremely significantly higher body weight. Another highly significant difference was the distance of the crest cushions from the mouth, which was closer in ducks with multiple crested cushions. Bartels et al.  found thd Stana.  have shod Stana.  found thd Stana. ,44. Our d Stana.  found thd Stana.  found thNipponia nippon), an endangered bird worldwide, has a very high embryonic and nestling mortality rate, and comparing living and dead samples using high-throughput sequencing revealed that genes for glycan biosynthesis and metabolism (HYAL1 and HYAL4), as well as the immune system (JAM2), are associated with embryonic and nestling development. Serum immunoglobulins, especially IgA, IgG, and IgM produced by B cells, are important parameters reflecting the humoral immune status of animals and are associated with their important role in immune function and resistance to infection [The crested cushion is a tumor-like tissue. Schilling et al.  found thnfection ,50. Immlnfection  found thnfection . Elevatenfection . The resnfection . This wanfection ,56,57. Tnfection ,58. Studnfection ,60. Studnfection . The conBased on our previous work and the aforementioned results in the present study, we considered that a greater number of crests leads to brain exposure, which causes the body’s protective mechanism to compensate for the purpose of protecting the brain from viruses or bacteria, and leads to the increase in some key minerals and immune indicators related to the immune status through adaptive evolution. Another idea is that whenever the RWC duck grows a crested cushion, it stimulates the body’s immune process again. Therefore, the number of crested cushions can have an impact on mineral metabolism and immune status in RWC ducks.Our results show that the number of crested cushions could be used to directly reflect the size of the crested cushions. With an increase in the number of crested cushions, there is increased compression of the skull and brain by the crested cushion during the embryonic period, leading to a higher mortality. However, ducklings with multiple crested cushions gained weight more quickly after hatching. In addition, the number of crested cushions had a positive effect on various serum parameters, such as various mineral elements, as well as triglyceride and immunoglobulin levels. Therefore, it is preliminarily speculated that the number of crested cushions may indirectly affect the health of Runzhou crested white ducks and the advantages and disadvantages of their immune performance. This study lays a foundation to further improve the quality of RWC duck breeding. In the future, we may focus on breeding and expanding the population of RWC ducks according to the number of crested cushions to breed RWC ducks with better performance in all aspects.


The current study aimed to use network analysis to investigate medical and health students’ readiness for online learning during the coronavirus disease 2019 (COVID-19) pandemic at the University of Medicine and Pharmacy, Hue University.A questionnaire survey on the students’ readiness for online learning was performed using a Google Form from May 13 to June 22, 2021. In total, 1,377 completed responses were eligible for analysis out of 1,411 participants. The network structure was estimated for readiness scales with 6 factors: computer skills, internet skills, online communication, motivation, self-control, and self-learning. Data were fitted using a Gaussian graphical model with the extended Bayesian information criterion.In 1,377 students, a network structure was identified with 6 nodes and no isolated nodes. The top 3 partial correlations were similar in networks for the overall sample and subgroups of gender and grade levels. The self-control node was the strongest for the connection to others, with the highest nodal strength. The change of nodal strength was greatest in online communication for both gender and grade levels. The correlation stability coefficient for nodal strength was achieved for all networks.These findings indicated that self-control was the most important factor in students’ readiness network structures for online learning. Therefore, self-control needs to be encouraged during online learning to improve the effectiveness of achieving online learning outcomes for students. The current study was implemented during the fourth wave  of coronavirus disease 2019 (COVID-19) in Vietnam, which had the highest number of infected cases and most complicated situations compared to the previous waves [The literature shows that learners’ readiness is an essential issue in contributing to the success of online learning outcomes in higher education . StudentNetwork analysis has been applied to various psychological sciences such as depression, social anxiety disorder, and personality disorder . In receThis study aimed to investigate the important factors in students’ readiness for online learning at a medical university in Vietnam using a network analysis of survey data.The proposed research and instruments were approved by the Ethics Committee for Biomedical Researches of the University of Medicine and Pharmacy, Hue University . Informed consent was obtained from the participants during the online survey.This study is a network analysis of data obtained through an online survey.Hue University of Medicine and Pharmacy provides 10 regular training undergraduate programs for medicine and health sciences, including medicine, pharmacy, odonto-stomatology, preventive medicine, nursing, midwifery, traditional medicine, public health, medical laboratory technology, and radiological technology. The annual enrollment number is about 7,000 per academic year. The survey questionnaire was distributed to a total of 2,000 students from May 13 to June 22, 2021.The initial student’ responses were 1,411 out of 2,000 target students, and we excluded 34 cases with incomplete information before data analysis. The students confirmed their participation on the first page before filling out the questionnaire. They received an electronic link via Google Forms by email, comprising a consent form and a study information sheet. The participating students were from 8 majors .The variables for participants’ characteristics were age, sex, academic year, residence, monthly support, and their academic major. The variables of OLRS were computer skills, internet skills, online communication, self-learning, self-control, and online motivation.Raw response data from participants are available from The structured questionnaire was created using a Google Form, including general characteristics and the University Students’ Readiness for E-Learning scale . The meaThe OLRS mentions a variety of aspects, including 6 domains with 33 items, comprising computer skills (5 items), internet skills (4 items), online communication (5 items), self-learning (8 items), self-control (4 items), and online motivation (7 items). A 5-point Likert scale is used to score each item, ranging from 1  to 5 . A higher score indicates better preparation for online learning during the COVID-19 pandemic.There was no bias in selecting target students. Only data from actual responses were used for the analysis.For network analysis, the study size could not be estimated because all responses were included.https://www.rdocumentation.org/packages/huge/versions/1.3.5) transformation to normalize the readiness scales before estimating the networks. The network structure of the readiness scale was fitted using a Gaussian graphical model which wasregularized using the graphical lasso algorithm with the extended Bayesian information criterion (tuning=0.5) [https://www.rdocumentation.org/packages/qgraph/versions/1.9.2). The network accuracy and stability were examined under bootstrapped 95% confidence intervals (CI) of edge-weights by the bootnet R package ver. 1.5 . A correlation stability coefficient of at least 0.25 indicates the stability of the node centrality indices [The general characteristics of students were presented using numbers and percentages for categorical data and mean with standard deviation (SD) for continuous data. We tested the significance of differences between categorical variables (such as gender or grade levels) using the chi-square test or the Fisher exact test. All scores of total and 6 readiness domains had a skewed distribution according to the Shapiro-Wilk normality test. Then, we used nonparanormal  . The netThe overall characteristics were illustrated according to the total sample, gender and grade levels in In the overall sample of 1,377 students, a network structure comprised 6 nodes without any isolated nodes. A total of 12 edges were created, and 5 edge weights had a pc of over 0.3 for the total sample network . The strThe network structures for gender and grade levels are drawn in For the centrality indices, nodal strength, betweenness, and closeness were calculated and plotted in the supplemental materials –D. The hThe accuracy and central stability of networks were evaluated using the bootstrapped CIs of edge weights –N. OveraThe current study analyzed a total of 1,377 students from 8 majors of medicine and health sciences to investigate the network structure of OLRS. We found that the overall score of OLRS had a statistically significant difference between male and female students. Regarding the sub-dimensions, computer skills, internet skills, and online communication were stronger in male students than in female students. The NCT results indicated a significant difference between male and female students . By contIn this study, we used network analysis as a new perspective on exploring how network structures differ and which dimensions are more strongly connected or more important than others . A literRegarding the local network characteristics, centrality measures are the most common way to measure local network characteristics.Our findings indicated that the self-control node was the strongest for the connection to others, with the highest nodal strength for all the networks. Some previous studies reported that self-control is an important component of online learning readiness among students. Horzum et al.  suggesteThe readiness scale was evaluated for different aspects of students, and it focused on the individual self-efficacy for online learning. The current study may contain several limitations that need to be considered and mentioned. Firstly, even though the OLRS instrument was tested and thoroughly reviewed for use, the validated process in the new situation may have affected the results. Secondly, the behavior and attitude of students in enrollment also influenced their answers, and unbalanced responses, particularly regarding the grade levels of participants, may have contributed to noise in these findings. Thirdly, we only included the OLRS scores of students, without relevant factors that may directly influence online learning, such as the teaching or the infrastructure of the online learning process. Although lecture-based teaching is easily transitioned to an online format, interactive small group sessions and clinical exposure are not as easily replicated in the COVID-19 pandemic. Despite these gaps, our study is one of the first works to investigate the OLRS using the network structure in a difficult situation.These findings differed slightly from the study of Hung et al. , which iGrade level is directly related to competencies and influences online learning readiness outcomes. The current results are consistent with the previous studies in that the higher-grade students were more likely to have a higher score in all dimensions . MoreoveHung et al.  suggesteAlthough the sampling was not randomized, the participation of 19.7% of all students in the University of Medicine and Pharmacy, Hue University may provide enough power to represent the status of students in this university.The results of this study may be generalizable to medical and health students in Vietnam.The present study illustrates that the top 3 pairwise correlations were self-control and self-learning, self-control and study motivation, and computer skills and internet skills for all network structures. These findings indicate that self-control was the most important factor in the network structures of students' readiness for online learning. Online communication had the largest difference in node strength between subgroups of gender and grade levels. We highly recommend encouraging self-control during online learning to increase the effectiveness of achieving online learning outcomes for students.


Occult blood in stool is the screening modality of choice for colorectal cancer in most countries. Only a small percentage of patients with positive results of this test will have colorectal cancer. In the present study, we wanted to determine risk factors for having colorectal cancer among patients with positive fecal testing. We found that age, anemia, family history of colorectal cancer, and previous colorectal cancer are factors for having colorectal cancer among those with positive fecal testing. The practical implication of the findings of the present study is that people who have positive fecal testing and one of the found risk factors should be prioritized for colonoscopy scheduling.p < 0.001), and had significantly higher rates of hypertension , iron-deficiency anemia , family history of CRC , and previous CRC . Lower levels of hemoglobin, iron, and ferritin were found in the CRC group. Age, family history of CRC, and previous CRC were found to be significant risk factors for diagnosis of CRC after positive FOBT with OR of 1.057, 1.4, and 15.9, respectively. (4) Conclusions: Iron-deficiency anemia, family history of CRC, previous colorectal cancer, and low hemoglobin, iron, and ferritin levels should direct physicians to give high priority to colonoscopy scheduling.(1) Background: Fecal occult blood test (FOBT) is the modality of choice in most countries for colorectal cancer (CRC) screening. We aimed to investigate the risk factors for CRC among patients with a positive FOBT in real life. (2) Methods: This was a retrospective study that included patients who tested positive for FOBT. Data regarding the comorbidities and laboratories were collected and compared between CRC and non-CRC groups. (3) Results: Positive FOBT was found among 45,500 (5.36%) subjects and CRC was found in 1502 (3.3%). CRC patients were older, age 62.7 ± 7.15 years compared with 59.33 ± 7.3 years ( Colorectal cancer (CRC) is a common cancer, ranked as the third-most-common cancer worldwide, but as the second cancer in terms of mortality . Wide geA fecal occult blood test (FOBT) is the stool-based screening modality of choice for colorectal cancer (CRC) in most countries. The goal of CRC screening is the early detection of colon neoplasia in terms of advanced adenoma or carcinoma. As a result of CRC screening, early detection, removal of adenomas, and a reduction in mortality can reached ,6. Both In the present study, we enrolled subjects who performed fecal testing as a part of the CRC screening program between the ages 50 and 74 years and have positive FOBT tests during the study period, between the dates 1 January 2010 and 30 December 2020. An outreach-based annual fecal occult blood test screening program operated by Israel’s Health Maintenance Organizations (HMOs) was conducted. Since June 2016 FIT stool testing has been used for CRC screening while guaiac-based testing was used before. The study population was divided into two groups: the CRC group—subjects with positive FOBT and diagnosed with CRC—and the Non-CRC group—those with positive FOBT, but not diagnosed with CRC. CRC was considered to be related to the same FOBT test until two years after a positive test; patients diagnosed with CRC more than two years after the FOBT were excluded. CRC diagnosis was measured until two years following the performance of FOBT. In cases of positive FOBT without CRC, a follow-up was continued during the study period, while patients diagnosed with CRC were not followed after the CRC diagnosis.The data were collected from the organized CRC screening program for both study groups. Demographic  clinical and laboratory data were retrospectively collected, using data and results closest to performing the FOBT test. The number of entire performed tests, positive tests, and CRC diagnoses was collected. In addition, laboratory data including complete blood count (CBC), biochemistry, and Carcinoembryonic antigen (CEA) were also collected. The laboratory values were collected nearest to the fecal occult blood testing. Comorbidities  of the enrolled patients were reviewed and compared between the two groups. No data were available regarding adenoma or advanced adenoma found in the colonoscopy.https://www.mdclone.com, accessed on 11 May 2022). The MDclone platform includes synthetic data of patients of the HMO to protect the patient’s privacy. The platform includes data of every patient including diagnosis, events such as hospitalization, emergency department visits, surgeries, and laboratory results. Any new diagnosis, hospitalizations, or medical updates considered as new events for the specific patients can be extracted in relation to the lifespan of the patient. CHS is the largest of the four health maintenance organizations in Israel, with about 4.7 million insured, accounting for 53% of the Israeli population, and considered as one of the large HMOs worldwide.The data were extracted from Clalit Health Services (CHS) using Clalit’s Data sharing platform powered by MDclone  statistic. Variables, which could impact or be considered as risk factors such as age, gender, diabetes mellitus, iron-deficiency anemia, smoking, family history of CRC, or previous CRC were included in the model. The variables found to be significant in the univariate analysis were introduced into the multivariate model one after the other and non-significant variables in the univariate model were not included in the multivariate analysis. The order in which the variables entered the model was determined by the size of the univariate Odds Ratio. A logistic regression model was used for the prediction of risk factors for CRC diagnosis, age, gender, diabetes mellitus, iron-deficiency anemia, smoking, family history of CRC, and previous CRC were included in the model. The study was carried out in accordance with the principles of the Helsinki Declaration, approval number 0093-21-SOR of the local Helsinki committee in Soroka University Medical Center. The study was waived from informed consent due to the retrospective nature of the study.Data are presented as a mean ±SD for continuous variables and as a percentage (%) of the total for categorical variables. Univariate analyses were performed by the Mann–Whitney test (for continuous variables) and Fisher’s exact and chi-squared tests . All statistical analyses were performed using IBM SPSS version 26 . p < 0.001). In addition, patients diagnosed with CRC were more often found to have hypertension , a family history of CRC , and iron-deficiency anemia  as comorbidities. No significant differences were found regarding other comorbidities . Patients diagnosed in the past with CRC along with a positive FOBT had significantly higher CRC recurrence than those with a negative FOBT . No significant difference regarding gender was found . In addition, there was no significant difference regarding body mass index (BMI) but a lower rate of smoking in the CRC groups, 30% vs. 33.5%, p = 0.007.During the study period, 847,550 FOBTs were performed and 45,500 (5.36%) of the tests were positive. All patients are in the age group of CRC screening, between 50 and 74 years. During the long study period, two types of FOBTs were used in Israel, guaiac and fecal immunochemical (FIT) tests. Starting in 2016, the FIT test is used, while before 2016, the guaiac was the test used for screening. In our study, there were 25,372 guaiac-based tests (55.8%) and 20,128 (44.2%) FIT-based tests. Among those with positive tests, 1502 (3.3%) patients were diagnosed with colorectal cancer after the FOBT. The basic characteristics, demographics, and comorbidities of the two study groups (CRC and non-CRC groups) are summarized in p < 0.001), albumin , iron , and ferritin levels . In addition, a higher count of platelets, 275 ± 90 vs. 250 ± 74, p < 0.001) and a higher CEA level  were also observed among the CRC group. No significant differences were found regarding most other laboratory values .The laboratory values nearest to the time of FOBT of both groups were collected and are presented in p < 0.001, family history of CRC OR 1.4, p = 0.001, and previous CRC OR 15.9, p < 0.001 were found to be significant risk factors for CRC diagnosis among patients with positive FOBT. In the univariable model, the age , iron-deficiency anemia , family history of CRC  were found to be risk factors for CRC. Diabetes mellitus and gender were not found to be significant risk factors. In the multivariate analysis model, we observed an OR of 1.057 for age (p < 0.01), OR of 1.131 (p < 0.072) for iron-deficiency anemia, OR of 1.0404 for family history of CRC (p < 0.001), and OR of 15.935 (p < 0.001) for previous CRC.Uni- and multivariable analysis models for CRC diagnosis after positive FOBT were calculated and the results of the model for CRC diagnosis are presented in In this study, we evaluated the rate of CRC among patients with positive FOBT within an organized population-based CRC screening program and factors associated with increased risk for CRC. Overall, we report that about 3.3% of all patients with positive FOBT were diagnosed eventually with CRC. The main findings of our study are that subjects with a previous history of CRC, family history of CRC, iron-deficiency anemia, or lab values of anemia  were at significantly increased risk for harboring cancer. This finding is novel and has not been reported before in the context of real-life data until now and with a such large number of patients. Interestingly, subjects with either previous CRC or a family history of CRC or anemia should have been referred for colonoscopy and not FOBT. A significant proportion of the total subjects with positive FOBT have one of these indications, making up about 35% of all subjects with positive FOBT in our study. However, our data showed that in real life, practically, not all people who have a clear indication for colonoscopy will undergo it; instead, they perform stool testing. There are several reasons behind not completing a colonoscopy; however, only scant data has been published, focused on adherence to post-CRC surveillance colonoscopy. Metastasis and refusal of the patients for post-CRC surveillance were found to be reasons for nonadherence to colonoscopy among this specific group . In factIt is important to mention that iron-deficiency anemia is found at a higher rate among those diagnosed with CRC. In the present study, we found a higher rate of iron-deficiency anemia, appearing as “iron-deficiency anemia” in the list of diagnoses. Additionally, the levels of hemoglobin, iron, and ferritin were significantly lower among CRC patients. Of note, the diagnosis of iron-deficiency anemia was found to be a significant risk factor for CRC diagnosis in the univariate model analysis, while only a trend of statistical significance in the multivariate model analysis. Out of this, any patient with a positive FOBT combined with iron-deficiency anemia should be seriously encouraged to undergo a colonoscopy. Previous studies reported a higher rate of CRC among patients with a combination of a positive FOBT and iron-deficiency anemia. CRC was detected in 2.7% of patients with positive FOBT and iron-deficiency anemia compared to 0.4% for patients with a positive FOBT without iron-deficiency anemia ,33.An interesting finding is that patients with previous colon cancer have the highest risk for CRC diagnosis after a positive FOBT. Actually, patients with previous colon cancer should not perform FOBT but should perform a follow-up colonoscopy due to their high risk for recurrence disease and additional adenoma of carcinoma. Patients with previous CRC should be scheduled for post-CRC surveillance colonoscopy, according to the known guidelines. However, in real life, as we found in our study, a small selection of the performed FOBTs were conducted among patients with a previous diagnosis of CRC and, as found in our results, these people were found to be at the highest risk for CRC recurrence. Performing FOBT among part of the patients after CRC in our cohort could be related to patients’ preferences or to the fact that the FOBT test is sent automatically annually for patients in the target age group. Additional studies are needed in other countries to understand if it is common in other regions and local studies are needed in order to attain a deep understanding of this point. Despite this finding, we still suggest colonoscopy as a follow-up modality of choice in patients treated for CRC and continued surveillance, but the cases of patients not completing colonoscopy and having positive FOBT should be scheduled as priority for colonoscopy due to their high risk.The importance of analyzing possible risk factors is to identify high-risk subjects and to encourage them to undergo a colonoscopy. Singling out those with higher risk is of particular importance due to the low adherence to colonoscopy after a positive FOBT with the known diversity between the populations. The colonoscopy completion rate after positive FOBT varies between 30 and 80% ,34. IdenIn general, in the era of aging populations, increasing awareness regarding screening for cancer is a priority and colonoscopy is an important part, beginning at the level of healthcare organizations and providers using information technology. The risk for CRC for every patient with positive FOBT should be calculated. The calculation model should include the age, comorbidities, including diagnosis of iron-deficiency anemia, family history of CRC, and previous CRC, and laboratory values, including hemoglobin, iron, ferritin, and CEA. Patients at high risk should be prioritized for colonoscopy. The CRC risk evaluation can be made by general practitioners using a simple evaluation of the medical file, including the diagnosis list of the patients and evaluating the laboratory values and case of a conclusion that the patients are at high risk for CRC. The next step should be explaining the findings to the patients and their high-risk status in order to increase adherence to colonoscopy and to avoid postponing the colonoscopy. This is crucial as postponement of colonoscopy is associated with more advanced disease and higher mortality due to CRC among patients who performed their colonoscopies more than 12 months after the initial positive fecal occult blood test, as reported before .In summary, in this large study conducted within the Clalit, one of the largest HMOs worldwide, we report that a significant proportion of the subjects with positive FOBT eventually having CRC had iron-deficiency anemia, family history of CRC, or previous CRC. Although these patients should have been referred for colonoscopy primarily, once they have a positive FOBT, they should be prioritized for colonoscopy. Taken in the context of the post-COVID-19 era, with a huge impact on the screening program and a decrease in the endoscopy procedures performed in 2020, the disruption of screening programs in most countries resulted in a decrease in CRC incidence in 2020 compared to 2019 . MoreoveThe strengths of our study are the national-based design, with a large number of enrolled subjects, and access to the computerized medical file, including diagnosis and laboratories. To the best of our knowledge, there is no previous study that investigated this important issue with such a large number of patients and in a real-life setting.Despite these strengths, there are several limitations to mention. Firstly, the retrospective design, secondly, the long study period included using both the guaiac-based and FIT-based testing in the study, thirdly, no data were available regarding symptoms before colonoscopy or polyp/adenoma detection or localization of the neoplasm, and, lastly, in the platform, there are no accurate data regarding smoking because they are coded within the electronic medical records as different conditions. Smoking could be listed as: current smoker, a current smoker and wants to stop, or past smoker, so it is a weakness of the platform to obtain accurate data for this metric; lastly, not all patients may have complete laboratory data.Patients with positive FOBT and iron-deficiency anemia, previous colorectal cancer, family history of CRC, low hemoglobin, iron, and ferritin are at higher risk to be diagnosed with CRC. Finding one of these factors should direct physicians to give high priority to colonoscopy scheduling. These patients should be prioritized other average-risk patients. In addition, high-risk patients with a strong indication for colonoscopy should be referred for colonoscopy and not for fecal occult blood stool testing.


Serum uric acid (UA) within appropriate levels is reported to be beneficial in patients with idiopathic short stature (ISS). This study aimed to evaluate the association between serum UA levels and height standard deviation scores (SDS) in patients with ISS during growth hormone (GH) therapy.A longitudinal study (LG Growth Study) of 182 children (mean age: 7.29±2.60 years) with ISS was performed. All participants were in the prepubertal stage and treated with GH, and the data within a treatment period of 30 months were analyzed. In the adjusted Pearson’s correlation, UA was significantly correlated with height SDS after controlling for sex, age, and body mass index (BMI) SDS . In the adjusted multiple regression analyses, the height SDS was significantly associated with UA after controlling for sex, age, and BMI SDS . Within the 30-month treatment period, the UA levels significantly increased as the height SDS increased, and the mean UA levels at baseline and 30 months after treatment were 3.90±0.64 mg/dL and 4.71±0.77 mg/dL, respectively (p=0.007). In conclusion, UA is related to height SDS, and GH treatment leads to a significant increase in UA without hyperuricemia. Elevated UA is considered a favorable outcome of GH therapy, and further studies are needed to determine its role as a monitoring tool.  The number of studies on the association of uric acid (UA) on growth is extremely limited compared with that on the association between UA and metabolic problems. The general UA level in children gradually increases from birth to adolescence and that the fastest increase in UA occurs during puberty , 2. SexuWe used data from a registry study  designed to investigate the efficacy and long-term safety of GH treatment in short Korean children and adolescents with ISS, growth hormone deficiency (GHD), Turner syndrome, small for gestational age (SGA) without catch-up growth, or chronic renal failure. LGS was registered at ClinicalTrials.gov (identifier: NCT01604395). LGS is a multicenter, non-interventional study, and detailed descriptions of its background have been provided in previous publications introducing cohort characteristics and study protocols . WrittenA total of 367 patients with ISS were registered in the LGS between November 2011 and March 2017. The inclusion criteria were:1) height <3rd percentile for sex and age according to the data from the 2017 Korean National Growth Charts for children and adolescents (2). The SDSs for height, weight, and BMI were calculated based on the 2007 Korean National Growth Charts using the LMS method  , creatinine, UA, total protein, albumin, aspartate aminotransferase, alanine aminotransferase, total cholesterol (T-C), triglyceride, IGF-1, and IGF-binding protein 3(IGF-BP3) were performed prior to test drug administration in the GH stimulation test. The pediatric endocrinologists at each center performed the physical examinations to determine the Tanner stage and GH stimulation tests by selecting two of the commonly used methods in clinical practice, such as insulin-induced hypoglycemia, L-dopa, clonidine, and glucagon tests. In all research institutions, height was measured to the nearest 0.1 cm using a Harpenden stadiometer , while body weight was measured to the nearest 0.1 kg using a digital scale. BMI was calculated by dividing the weight by height in meters squared (kg/mriation) . The IGFriation) . Anthrophttps://www.r-project.org). To compare the statistical significance between groups, Fisher’s exact test or chi-square test was used for categorical variables, while the t-test or Mann-Whitney U test was used for continuous variables. Pearson’s correlation tests were performed at baseline to examine the correlation between UA and other anthropometric and biochemical variables, while partial correlation was used after adjusting for sex, age, and BMI SDS. Multiple linear regression analysis was conducted to investigate the independent association between UA and height SDS, after adjusting for sex, age, and BMI SDS at baseline. The clinical variables were expressed as mean ± standard deviation. Statistical significance was set at p<0.05.Statistical analyses were performed using SAS version 9.4  and the R statistical software  and adjusted  correlation analyses. Other variables, including weight, SDS, BUN, total protein, albumin, and T-C, were significantly positively correlated with UA levels in the adjusted correlation analysis (p<0.05).Pearson’s correlation analysis was performed to analyze the relationship between UA levels and anthropometric and biochemical variables. As shown in p=0.023). Height SDS also had a significantly positive association with UA levels in the adjusted multiple linear regression analysis after controlling for sex, age, and BMI SDS . The other variable associated with height SDS in the unadjusted and adjusted multiple linear regression analyses was the weight SDS.Results of the unadjusted and adjusted multiple linear regression analyses of the association between UA and the anthropometric and biochemical variables are shown in p<0.001). The UA levels increased significantly during the treatment period, in line with the increasing trend of these factors (p<0.001). The BMI also steadily increased significantly during the period of GH treatment (p<0.05), but the BMI SDS did not show a statistically significant change.The different variables monitored within the 30-month GH treatment period are listed in Our findings identified an independent correlation between height SDS and serum UA levels in children with ISS, as confirmed by multiple regression analysis after adjusting for age, sex, and BMI SDS. More importantly, the serum UA levels significantly increased with elevation in height SDS during the 30-month GH treatment. No hyperuricemia was observed in the GH-treated patients.The reference range for UA levels in healthy children and adolescents has been reported to have a specific distribution. According to a study of UA reference values for Brazilian children and adolescents, UA slowly increases with age throughout childhood and remains the same in both sexes, and sexual differences in distribution begin at puberty . The resGH treatment results in improvements in body composition and long-term beneficial effects on muscle and adipose tissues , 16. MatHowever, little is known regarding the association of GH therapy with UA metabolism. Dixit et al. reported an increase in UA levels after GH treatment in children with short stature aged 4–17 years . The serThis study, as well as the study by Wang et al. , suggestA major limitation of this study was that data such as dual-energy X-ray absorptiometry related to body composition measurements were not available. Therefore, we could not confirm an association between UA elevation and changes in body composition. Another limitation is that UA can be affected by food intake; however, it was not possible to analyze this because of the nature of this study. Nevertheless, this study had several strengths. In this study, to minimize the factors affecting UA, we included children with no underlying medical conditions such as chronic disease, endocrine disease, brain disease, or chromosomal abnormalities. Furthermore, considering that the characteristics of UA are affected by puberty, only prepubertal patients were included; thus, it is considered a meaningful result compared with other studies that included pubertal patients. The characteristics of multicenter long-term prospective cohort studies may also lend greater significance to the statistical results of this study.In conclusion, serum UA levels are associated with height SDS. The result of a significant elevation in serum UA with an increase in height SDS after GH treatment was an interesting feature found during GH treatment. Further studies are needed to determine whether changes in serum UA levels caused by GH treatment are associated with changes in height and body composition, and to determine the role of UA in monitoring GH treatment.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by Institutional Review Board of Hallym University Kangdong Sacred Heart Hospital. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.JSY contributed to the data research and analyses and drafted the initial manuscript; YJS, EBK, and HJL designed the study and interpreted the findings; MJK critically reviewed the manuscript and contributed to the conception of the study; and ITH designed and conceptualized the study and critically reviewed the manuscript. All authors contributed to the article and approved the submitted version.We thank all the physicians who provided the data of patients included in the “LG Growth Study”; the authors would also like to thank LG Chem, Ltd., for assisting with the statistical analysis.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.


South Asians in general, and Asian Indians in particular, have higher risk of type 2 diabetes compared with white Europeans, and a younger age of onset. The reasons for the younger age of onset in relation to obesity, beta cell function and insulin sensitivity are under-explored.Two cohorts of Asian Indians, the ICMR-INDIAB cohort  and the DMDSC cohort , and one of white Europeans, the ESDC (East Scotland Diabetes Cohort), were used. Using a cross-sectional design, we examined the comparative prevalence of healthy, overweight and obese participants with young-onset diabetes, classified according to their BMI. We explored the role of clinically measured beta cell function in diabetes onset in Asian Indians. Finally, the comparative distribution of a partitioned polygenic score (pPS) for risk of diabetes due to poor beta cell function was examined. Replication of the genetic findings was sought using data from the UK Biobank.p<0.0001) lower in lean compared with obese individuals. Asian Indians in our study, and South Asians from the UK Biobank, had a higher number of risk alleles than white Europeans. After weighting the pPS for beta cell function, Asian Indians have lower genetically determined beta cell function than white Europeans (p<0.0001). The pPS was associated with age of diagnosis in Asian Indians but not in white Europeans. The pPS explained 2% of the variation in clinically measured beta cell function, and 1.2%, 0.97%, and 0.36% of variance in age of diabetes amongst Asian Indians with normal BMI, or classified as overweight and obese BMI, respectively.The prevalence of young-onset diabetes with normal BMI was 9.3% amongst white Europeans and 24–39% amongst Asian Indians. In Asian Indians with young-onset diabetes, after adjustment for family history of type 2 diabetes, sex, insulin sensitivity and HDL-cholesterol, stimulated C-peptide was 492 pmol/ml (IQR 353–616, The prevalence of lean BMI in young-onset diabetes is over two times higher in Asian Indians compared with white Europeans. This phenotype of lean, young-onset diabetes appears driven in part by lower beta cell function. We demonstrate that Asian Indians with diabetes also have lower genetically determined beta cell function.The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-022-05671-z. Diabetes prevalence is increasing, with a major burden of morbidity in South Asia. The International Diabetes Federation projects that by 2045 there will be 151.4 million indigenous South Asians with type 2 diabetes, almost doubling the present prevalence , 4. Sout2, the equivalent BMI in South Asian participants was only 22 kg/m2 ), across the regions of Tayside and Fife. Clinical data are made available through the Scottish Care Information–Diabetes Collaboration (SCI–DC) system . General1c . ParticiClinical data from Asian Indians with diabetes was obtained from Dr. Mohan’s Diabetes Specialities Centre (DMDSC). This is a privately run chain of single-speciality hospitals and clinics for the treatment of diabetes and comorbidities, and is a key site for diabetes research in India , 27, 28.In addition to the inclusion criterion of diagnosis of type 2 diabetes using the WHO criteria , in the 1c, BMI, systolic and diastolic blood pressure (SBP and DBP), total cholesterol, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), triacylglycerol, serum creatinine and liver enzymes. These were measured in the fasted state. LDL-C was calculated using the Friedewald formula. Information such as family history of diabetes in first-degree relatives, fasting and postprandial C-peptide, HOMA-B and HOMA of insulin sensitivity (HOMA-S) were available. HOMA-B and HOMA-S were calculated from fasting C-peptide and glucose using the HOMA calculator [Clinical variables were analysed only from the INSPIRED DMDSC cohort. Variables included age of diagnosis, sex, HbAlculator –31.n = 1513) were used to examine the relationship between the pPS, age at diagnosis and BMI. Replication in the UK Biobank was undertaken using individuals diagnosed with type 2 diabetes [pPS for type 2 diabetes risk have been developed , 33. We diabetes . We compdiabetes . Informa2 and >25 kg/m2 as normal BMI and obesity [2, and obesity was defined as BMI >30 kg/m2. We then examined risk factors for young lean-onset diabetes in Asian Indians in the DMDSC cohort. Finally, a comparison of the pPS for beta cell function in Asian Indians (DMDSC) and white Europeans (ESDC) with type 2 diabetes was undertaken. Details of the statistical methods used are provided in ESM Cross-sectional analyses were undertaken using the timepoint of diabetes diagnosis in all cohorts. Young-onset diabetes was defined as diagnosis at or under the age of 40 years . Sensiti obesity , 40. NorFor the Indian cohort, ethics approval was granted by the National Institute for Health Research Global Health Research Unit on Global Diabetes Outcomes Research, Institutional Ethics Committee of Madras Diabetes Research Foundation, Chennai, India . For the Scottish cohort, ethical approval for the study was provided by the Tayside Medical Ethics Committee (REF:053/04) The study was performed in accordance with the Declaration of Helsinki.A total of 1712 Asian Indians from the ICMR-INDIAB cohort, 54,989 Asian Indians from the DMDSC cohort and 42,563 white Europeans from the ESDC, all with newly diagnosed type 2 diabetes, were categorised by their age at diagnosis and BMI : 45.9% in the ICMR-INDIAB cohort and 57.8% in the DMDSC cohort. Similarly, 72.9% of white Europeans were obese on the basis of their BMI (>30 kg/m2). However, a shift of distribution was observed for young-onset diabetes with normal BMI: 39% of Indians from the ICMR-INDIAB study and 24% of Indians from the DMDSC cohort were classified as having normal BMI (<23 kg/m2), in contrast with 9.3% of white Europeans (<25 kg/m2) . A sensitivity analysis using population-derived age cut-offs showed similar results   and older diagnosed (>40 years). The distribution of clinical and anthropometric features across age groups is described in Table An examination of trends across BMI categories in the two age groups is provided in ESM Table The observation of impaired beta cell function in young lean Asian Indians persisted after adjusting for sex, family history of diabetes, HDL-C and insulin sensitivity . The approximate percentage of white Europeans with eight or more risk alleles was 25%, whereas that for South Asians or Asian Indians was 45%. The difference in the empirical distribution of risk alleles between the two ethnicities was significant      Fig. . Higher ESM Fig. , but no ESM Fig. . In AsiaESM Fig. , with thn = 1513). We used linear regression models stratified by BMI to predict age at diagnosis using the pPS in Asian Indians. We observed that the maximum variance explained was in those with normal BMI (R2 = 1.2%), with decreasing variance for overweight individuals (R2 = 0.97%) and obese individuals (R2 = 0.36%)  better than in those classified as overweight or obese.As far as we are aware, this study is the first to use non-migrant populations and ethnicity-specific BMI thresholds to highlight that the age of diabetes onset in Asian Indians is dramatically lower than in white Europeans, and that young onset is characterised by a two to four times higher prevalence of individuals with normal BMI. Further, we show that, amongst Asian Indians, this group  has a lower beta cell function. Using pPS values, we demonstrate that Asian Indians have a higher genetic burden of risk variants for lower beta cell function. Finally, we demonstrate that the pPS predicts age of diabetes diagnosis in those with normal BMI (n = 1153) predominantly comprises individuals of Asian Indian descent (n = 700). In contrast, the white population in UK Biobank comprises a mixture of individuals of English, Welsh, Irish and Scottish origin, as well as of other European descent living in the UK. In contrast, the white Scottish population in the ESDC is from the local population of Tayside, Scotland.Although this study is focused on Asian Indians, many studies have used less specific South Asian populations, which may include people from Afghanistan, Pakistan, India, Bangladesh, Nepal, Bhutan and Sri Lanka etc. This is an important distinction, as genetic studies have shown significant heterogeneity in these populations that may be reflected in different clinical phenotypes , 42. AddWe used two methods to determine young onset: a single threshold of young-onset diabetes (<40 years) and ethnicity-determined mean age of diagnosis Fig. . Using eThe phenomenon of lean, young onset of diabetes is particularly pronounced amongst Asian Indian men, who are more likely than women to have healthy waist circumferences when diagnosed young. There is no clear evidence of dyslipidaemia in the young-onset normal weight group compared with those with higher BMI. Given the reciprocal relationship between beta cell function and insulin sensitivity, it is not surprising that the insulin sensitivity based on the surrogate estimate of HOMA-S was higher in the lean young group compared with the obese young group. The genetic studies establish that it is the beta cell deficiency that is causal, with the increased HOMA-S secondary to this.It is worth noting that the substantive proportion of young-onset diabetes in Indians occurred in those classified as obese on the basis of BMI (54% in the ICMR-INDIAB cohort and 57% in the DMDSC cohort); this group also has lower insulin sensitivity and higher ALT levels. This is suggestive of higher ectopic fat deposition, as ALT is a reasonable correlate of ectopic fat, consistent with the hypothesis of the ‘thin–fat’ phenotype that has been suggested to predispose Asian Indians to type 2 diabetes , 23, 43.Our results suggest that the preponderance of young and lean Asian Indians developing diabetes is driven by poor beta cell function. The demographics of India are changing, with more urbanisation and a shift to sedentary jobs . It is lRunweighted = 12%, p=0.04; Rweighted = 14%, p=0.01). Notably, in the discovery study (INSPIRED DMDSC and ESDC), these SNPs had no pleiotropic effects on other glycaemic traits or diabetes risk factors, making them powerful genetic instruments. If these SNPs are not causal variants, they are tagging the causal variants through high linkage disequilibrium. It is possible that the linkage disequilibrium structure in these regions may differ between individuals of European and Asian ancestry. However, a recent trans-ancestral study of glycaemic traits has replicated many of these signals and reported that, overall, 80% of SNPs identified in single-ancestry studies of glycaemic traits showed no evidence of between-ancestry heterogeneity [As yet, there has been no conclusive genetic study of beta cell function, HDL-C, obesity, lipodystrophy etc. in individuals of Asian Indian or, more broadly, South Asian ancestry. This prevents us from utilising an ethnicity-specific polygenic risk score. It is possible that such a study would produce a different or expanded set of candidate SNPs for beta cell function, as the pPS used in this study has been derived from studies in white European populations. Furthermore, studies on causal genetic variants of beta cell function are not available. Instead, the SNPs used have been shown to be statistically associated with diabetes risk due to poor beta cell function . In our ogeneity . The ass1c at diagnosis is high. It is likely that the true age of onset is lower than the age recorded. However, this differential bias is likely to underestimate our finding of early age of diabetes onset with lean BMI.Due to the lack of routine screening for diabetes in the Indian population, HbAAnother limitation is the lack of comparison of glycaemic traits between the two ethnicities, particularly C-peptide levels. However, we do not expect to see a different relationship between BMI (as a measure of adiposity) and glycaemic traits in white Europeans than in Asian Indians, i.e. diabetes onset with low BMI is likely to be associated with beta cell failure . Our conThe availability of an intensively phenotyped cohort of non-migrant Asian Indians is novel, and inclusion of data on glycaemic traits, such as fasted and stimulated C-peptide levels, anthropometric traits such as BMI and waist circumference, lipid traits and family history, is unique. Availability of genetic data is an added advantage. The comparative distribution of the pPS between white Europeans and Asian Indians demonstrates an unbiased estimate of the genetic burden of lower beta cell function in Asian Indians. Furthermore, the observed difference in burden of risk alleles was replicated using the UK Biobank, comparing broader ethnic group of South Asians with white British individuals. The results are consistent with the prevailing hypothesis that beta cell function is lower in Asian Indians and more broadly in South Asian populations , 23, whiThe data were obtained from a private healthcare centre in India, and are more likely to reflect the situation in middle- and upper middle-class residents of urban India. However, no evidence exists suggesting that the underlying genetic architecture in urban and rural India is different. Therefore, we expect that the phenotype of diabetes driven by lower beta cell function will persist in rural areas. Indeed, this is clearly evidenced by the high rates of impaired fasting glucose prevalence observed in these settings . MoreoveThese results show that lower clinically and genetically determined beta cell function contributes to the higher burden of younger-onset type 2 diabetes in Asian Indians. Our results are supported by clinical clustering studies showing that, in contrast to white Europeans, Asian Indians with young-onset diabetes have a preponderance of insulin deficiency, suggesting a role of beta cell dysfunction , 48.ESM 1(PDF 702 KB)