RADseq-based population genomic analysis and environmental adaptation of rare and endangered recretohalophyte Reaumuria trigyna.

Genetic diversity reflects the survival potential, history, and population dynamics of an organism. It underlies the adaptive potential of populations and their response to environmental change. Reaumuria trigyna is an endemic species in the Eastern Alxa and West Ordos desert regions in China. The species has been considered a good candidate to explore the unique survival strategies of plants that inhabit this area. In this study, we performed population genomic analyses based on restriction-site associated DNA sequencing to understand the genetic diversity, population genetic structure, and differentiation of the species. Analyses of 92,719 high-quality single-nucleotide polymorphisms (SNPs) indicated that overall genetic diversity of R. trigyna was low (HO  = 0.249 and HE  = 0.208). No significant genetic differentiation was observed among the investigated populations. However, a subtle population genetic structure was detected. We suggest that this might be explained by adaptive diversification reinforced by the geographical isolation of populations. Overall, 3513 outlier SNPs were located in 243 gene-coding sequences in the R. trigyna transcriptome. Potential sites under diversifying selection occurred in genes (e.g., AP2/EREBP, E3 ubiquitin-protein ligase, FLS, and 4CL) related to phytohormone regulation and synthesis of secondary metabolites which have roles in adaptation of species. Our genetic analyses provide scientific criteria for evaluating the evolutionary capacity of R. trigyna and the discovery of unique adaptions. Our findings extend knowledge of refugia, environmental adaption, and evolution of germplasm resources that survive in the Ordos area.

Stroke prevention in rural residents: development of a simplified risk assessment tool with artificial intelligence.

BACKGROUND: Limited studies have focused on the risk assessment of stroke in rural regions. Moreover, the application of artificial intelligence in stroke risk scoring system is still insufficient. This study aims to develop a simplified and visualized risk score with good performance and convenience for rural stroke risk assessment, which is combined with a machine learning (ML) algorithm. METHODS: Participants of the Henan Rural Cohort were enrolled in this study. The total participants (n = 38,322) were randomly split into a train set and a test set in the ratio of 7:3. An ML algorithm was used to select variables and the logistic regression was then applied to construct the scoring system. The C-statistic and the Brier score (BS) were used to evaluate the discrimination and calibration. The Framingham stroke risk profile (FSRP) and the self-reported stroke risk function (SRSRF) were chosen to be compared. RESULTS: The Rural Stroke Risk Score (RSRS) was produced in this study, including age, drinking status, triglyceride, type 2 diabetes mellitus, hypertension, waist circumference, and family history of stroke. On validation, the C-statistic was 0.757 (95% CI 0.749-0.765) and the BS was 0.058 in the test set. In addition, the discrimination of RSRS was 6.02% and 7.34% higher than that of the FSRP and SRSRF, respectively. CONCLUSIONS: A well-performed scoring system for assessing stroke risk in rural residents was developed in this study. This risk score would facilitate stroke screening and the prevention of cardiovascular disease in economically underdeveloped areas.

Can Professionalization Alleviate Job Burnout in Construction Workers in China? A Multivariable Mediating Model.

Burnout is at all-time highs across modern professions. As a typical labor-intensive industry, the high-pressure and task-driven nature of the construction industry makes construction workers more prone to burnout. It is still unclear whether increasing the professionalization level can lessen the many harmful consequences of job burnout on construction workers' employment. Therefore, this study examined the influencing mechanism of professionalization on job burnout in the construction industry. First, a theoretical model based on the conservation of resources (COR) theory was developed with workload, job insecurity, and work-family conflict as moderating variables. A reliable sample of 441 Chinese construction workers were then recruited in the investigation. The data analysis was supported by confirmatory factor analysis (CFA) and structural equation modeling (SEM). The results indicated that: (i) an increase in the professionalization level could be directly effective in alleviating job burnout among construction workers; (ii) workload and work-family conflict could play an independent and continuous mediating role between professionalization and job burnout; and (iii) while job insecurity caused by a low professionalization did not have a direct impact on job burnout, it could have an indirect impact on job burnout through workload and work-family conflict, respectively. This study enriches the literature on job burnout among construction workers, as well as provides a theoretical basis and practical management guidance for Chinese construction companies to alleviate job burnout in workers from a professionalization standpoint.

Non-covalent cyclic peptides simultaneously targeting Mpro and NRP1 are highly effective against Omicron BA.2.75.

Available vaccine-based immunity may at high risk of being evaded due to substantial mutations in the variant Omicron. The main protease (Mpro) of SARS-CoV-2 and human neuropilin-1 (NRP1), two less mutable proteins, have been reported to be crucial for SARS-CoV-2 replication and entry into host cells, respectively. Their dual blockade may avoid vaccine failure caused by continuous mutations of the SARS-CoV-2 genome and exert synergistic antiviral efficacy. Herein, four cyclic peptides non-covalently targeting both Mpro and NRP1 were identified using virtual screening. Among them, MN-2 showed highly potent affinity to Mpro (K d = 18.2 ± 1.9 nM) and NRP1 (K d = 12.3 ± 1.2 nM), which was about 3,478-fold and 74-fold stronger than that of the positive inhibitors Peptide-21 and EG3287. Furthermore, MN-2 exhibited significant inhibitory activity against Mpro and remarkable anti-infective activity against the pseudotyped variant Omicron BA.2.75 without obvious cytotoxicity. These data demonstrated that MN-2, a novel non-covalent cyclic peptide, is a promising agent against Omicron BA.2.75.

Identification of a Novel Potent CYP4Z1 Inhibitor Attenuating the Stemness of Breast Cancer Cells through Lead Optimization.

Pharmacological targeting cancer stem cells are emerging as a novel therapeutic modality for cancer treatment and prevention. Human cytochrome P450 enzyme CYP4Z1 represents a promising target for its potential role in attenuating the stemness of breast cancer cells. In order to develop potent and selective CYP4Z1 inhibitors, a series of novel N-hydroxyphenylformamidines were rationally designed and synthesized from a pan-CYP inhibitor HET0016. CYP4Z1 inhibitory activities of the newly synthesized derivatives were evaluated, and the structure-activity relationships (SARs) were summarized. Among them, compound 7c exhibited the best inhibitory activity with an IC50 value of 41.8 nM. Furthermore, it was found that 7c decreased the expression of stemness markers, spheroid formation, and metastatic ability as well as tumor-initiation capability in a concentration-dependent manner in vitro and in vivo. Altogether, compound 7c might be a potential lead compound to develop CYP4Z1 inhibitor with more favorable druggability for clinical application to treat breast cancer.

Dual-targeting cyclic peptides of receptor-binding domain (RBD) and main protease (Mpro) as potential drug leads for the treatment of SARS-CoV-2 infection.

The receptor-binding domain (RBD) and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) play a crucial role in the entry and replication of viral particles, and co-targeting both of them could be an attractive approach for the treatment of SARS-CoV-2 infection by setting up a "double lock" in the viral lifecycle. However, few dual RBD/Mpro-targeting agents have been reported. Here, four novel RBD/Mpro dual-targeting peptides, termed as MRs 1-4, were discovered by an integrated virtual screening scheme combining molecular docking-based screening and molecular dynamics simulation. All of them possessed nanomolar binding affinities to both RBD and Mpro ranging from 14.4 to 39.2 nM and 22.5-40.4 nM, respectively. Further pseudovirus infection assay revealed that the four selected peptides showed >50% inhibition against SARS-CoV-2 pseudovirus at a concentration of 5 µM without significant cytotoxicity to host cells. This study leads to the identification of a class of dual RBD/Mpro-targeting agents, which may be developed as potential and effective SARS-CoV-2 therapeutics.

The Impact of Climate Change Risks on Residential Consumption in China: Evidence from ARMAX Modeling and Granger Causality Analysis.

Estimating the impact of climate change risks on residential consumption is one of the important elements of climate risk management, but there is too little research on it. This paper investigates the impact of climate change risks on residential consumption and the heterogeneous effects of different climate risk types in China by an ARMAX model and examines the Granger causality between them. Empirical results based on monthly data from January 2016 to January 2019 suggest a significant positive effect of climate change risks on residential consumption, but with a three-month lag period. If the climate risk index increases by 1 unit, residential consumption will increase by 1.29% after three months. Additionally, the impact of climate change risks on residential consumption in China mainly comes from drought, waterlogging by rain, and high temperature, whereas the impact of typhoons and cryogenic freezing is not significant. Finally, we confirmed the existence of Granger-causality running from climate change risks to residential consumption. Our findings establish the linkage between climate change risks and residential consumption and have some practical implications for the government in tackling climate change risks.

Microbiota dysbiosis in primary Sjögren's syndrome and the ameliorative effect of hydroxychloroquine.

The human microbiome plays an important role in autoimmune diseases. However, there is limited knowledge regarding the microbiota in individuals with primary Sjögren's syndrome (pSS). Here, we perform 16S ribosomal RNA gene sequencing of fecal, oral, and vaginal samples from a cohort of 133 individuals with pSS, 56 with non-pSS, and 40 healthy control (HC) individuals. Dysbiosis in the gut, oral, and vaginal microbiome is evident in patients with pSS, and oral samples demonstrate the greatest extent of microbial variation. Multiple key indicator bacteria and clinical characteristics are identified across different body sites, implying that microbial dysbiosis has important roles in the pathogenesis of pSS. Furthermore, we observe pSS-like dysbiosis in individuals with pre-clinical pSS or non-pSS-related disease, revealing that microbial shifts could appear prior to pSS. After hydroxychloroquine (HCQ) treatment, microbial dysbiosis in individuals with pSS is partially resolved, although the microbiota composition remain disordered. These results contribute to the overall understanding of the relationship between the microbiome and pSS.

Establishment of type 2 diabetes mellitus models using streptozotocin after 3 months high-fat diet in Bama minipigs.

In the past twenty years, the number of adults with diabetes has tripled. Most studies have been conducted using rodent models of type 2 diabetes mellitus (T2DM), and the developed drugs have low clinical conversion efficiency. Therefore, it is urgent to establish a more human-like large animal model to explore T2DM pathogenesis and formulate new disease prevention and control strategies. This study was designed to establish and validate a T2DM model using minipigs fed a high-fat or high-cholesterol/high-fat diet and injected with low-dose streptozotocin (STZ). We examined the influence of the STZ injection timing with a diet high in fat (HFD) compared with one high in cholesterol and fat (HCFD) on the atherosclerotic lesions accelerated by T2DM. Male Bama minipigs (n = 24) were randomly divided into five groups. The control group was fed a normal diet for 9 months. The STZ + HFD and STZ + HCFD groups were infused with 90 mg/kg STZ and then fed a high-fat diet or high-cholesterol and high-fat diet for 9 months, respectively. The HFD + STZ and HCFD + STZ groups were fed a high-fat diet or a high-cholesterol and high-fat diet, respectively, for 9 months (after 3 months, these pigs were injected intravenously with 90 mg/kg STZ). During the induction period, animal body weight, BMI, and serum GLU, INS, TG, TC, HDL-C, LDL-C, FFA, ALT, AST, CRE, and BUN were detected monthly intervals. IVGTT and insulin release tests were performed at 3-month intervals. At the end of the test, the coronary artery and abdominal aorta were examined by computed tomography and pathological observations, and the thickness of the basement membrane of the capillary of the retina and kidney glomerulus was measured under a transmission electron microscope. The serum glucose concentrations were normal in all groups except the HFD + STZ and HCFD + STZ groups. Animals fed an HFD for 9 months did not develop apparent atherosclerotic lesions, but atherosclerotic lesions were seen in the animals fed an HCFD. Hyperglycemia accelerated the formation of atherosclerotic lesions on the intimal surface of the abdominal aorta. Low-dose STZ after 3 months of HFD or HCFD successfully established a T2DM model in minipigs. The HFD did not induce apparent atherosclerotic lesions, but these were seen with the HCFD. Hyperglycemia accelerated atherosclerosis in the minipigs.

The Reliability and Validity of Recalled Body Shape and the Responsiveness of Obesity Classification Based on Recalled Body Shape Among the Chinese Rural Population.

Background: The reliability and validity of recalled body shape were unknown in China. This study was conducted to examine the reliability and validity of recalled body shape as well as the responsiveness of obesity classification by recalled body shape among the Chinese rural population. Methods: A total of 166 people from the Henan rural cohort were enrolled. The Spearman's correlation coefficient (SCC), intraclass correlation coefficient (ICC), and Cronbach's α were calculated to assess the reliability and validity of recalled body shape. Additionally, the receiver operator characteristic curve (ROC) was performed to assess the responsiveness. Results: The SCC between the twice recalled body shape ranged from 0.383 to 0.578, and the ICC ranged from 0.357 to 0.615. Besides, the Cronbach's α of the recalled body shape questionnaire was 0.845. At the age of 20-70, the SCC between recalled body shape and actual body mass index (BMI) and waist circumference (WC) ranged from 0.563 to 0.699 and 0.409 to 0.661, respectively. Furthermore, above the age of 20, the area under the curve (AUC) of classifying general obesity and abdominal obesity by recalled body shape ranged from 0.833 to 0.960 and 0.686 to 0.870, respectively. Conclusion: The results indicated that recalled body shape had moderate reliability, validity, and discriminative degree for earlier obesity among the Chinese rural population.

Highly Potent, Selective, Biostable, and Cell-Permeable Cyclic d-Peptide for Dual-Targeting Therapy of Lung Cancer.

The application of peptide drugs in cancer therapy is impeded by their poor biostability and weak cell permeability. Therefore, it is imperative to find biostable and cell-permeable peptide drugs for cancer treatment. Here, we identified a potent, selective, biostable, and cell-permeable cyclic d-peptide, NKTP-3, that targets NRP1 and KRASG12D using structure-based virtual screening. NKTP-3 exhibited strong biostability and cellular uptake ability. Importantly, it significantly inhibited the growth of A427 cells with the KRASG12D mutation. Moreover, NKTP-3 showed strong antitumor activity against A427 cell-derived xenograft and KRASG12D-driven primary lung cancer models without obvious toxicity. This study demonstrates that the dual NRP1/KRASG12D-targeting cyclic d-peptide NKTP-3 may be used as a potential chemotherapeutic agent for KRASG12D-driven lung cancer treatment.

Nonlaboratory-based risk assessment model for coronary heart disease screening: Model development and validation.

BACKGROUND: Identifying groups at high risk of coronary heart disease (CHD) is important to reduce mortality due to CHD. Although machine learning methods have been introduced, many require laboratory or imaging parameters, which are not always readily available; thus, their wide applications are limited. OBJECTIVE: The aim of this study was to develop and validate a simple, efficient, and joint machine learning model for identifying individuals at high risk of CHD using easily obtainable nonlaboratory parameters. METHODS: This prospective study used data from the Henan Rural Cohort Study, which was conducted in rural areas of Henan Province, China, between July 2015 and September 2017. A joint machine learning model was developed by selecting and combining four base machine learning algorithms, including logistic regression (LR), artificial neural network (ANN), random forest (RF), and gradient boosting machine (GBM). We used readily accessible variables, including demographics, medical and family history, lifestyle and dietary factors, and anthropometric data, to inform the model. The model was also externally validated by a cohort of individuals from the Dongfeng-Tongji cohort study. Model discrimination was assessed by using the area under the receiver operating characteristic curve (AUC), and calibration was measured by using the Brier score (BS). RESULTS: A total of 38 716 participants (mean [SD] age, 55.64[12.19] years; 23449[60.6%] female) from the Henan Rural Cohort Study and 17 958 subjects (mean [SD] age, 62.74 [7.59] years; 10,076 [56.1%] female) from the Dongfeng-Tongji cohort study were included in the analysis. Age, waist circumference, pulse pressure, heart rate, family history of CHD, education level, family history of type 2 diabetes mellitus (T2DM), and family history of dyslipidaemia were strongly associated with the development of CHD. In regard to internal validation, the model we built demonstrated good discrimination (AUC, 0.844 (95% CI 0.828-0.860)) and had acceptable calibration (BS, 0. 066). In regard to external validation, the model performed well with clearly useful discrimination (AUC, 0.792 (95% CI 0.774-0.810)) and robust calibration (BS, 0.069). CONCLUSIONS: In this study, the novel and simple, machine learning-based model comprising readily accessible variables accurately identified individuals at high risk of CHD. This model has the potential to be widely applied for large-scale screening of CHD populations, especially in medical resource-constrained settings. TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register. (Trial registration: ChiCTR-OOC-15006699. Registered 6 July 2015 - Retrospectively registered) http://www.chictr.org.cn/showproj.aspx?proj=11375.

16S rRNA gene sequencing analysis of gut microbiome in a mini-pig diabetes model.

BACKGROUND: Currently, increasing attention is being paid to the important role of intestinal microbiome in diabetes. However, few studies have evaluated the characteristics of gut microbiome in diabetic miniature pigs, despite it being a good model animal for assessing diabetes. METHODS: In this study, a mini-pig diabetes model (DM) was established by 9-month high-fat diet (HFD) combined with low-dose streptozotocin, while the animals fed standard chow diet constituted the control group. 16S ribosomal RNA (rRNA) gene sequencing was performed to assess the characteristics of the intestinal microbiome in diabetic mini-pigs. RESULTS: The results showed that microbial structure in diabetic mini-pigs was altered, reflected by increases in levels of Coprococcus_3 and Clostridium_sensu_stricto_1, which were positively correlated with diabetes, and decreases in levels of the bacteria Rikenellaceae, Clostridiales_vadinBB60_group, and Bacteroidales_RF16_group, which were inversely correlated with blood glucose and insulin resistance. Moreover, PICRUSt-predicted pathways related to the glycolysis and Entner-Doudoroff superpathway, enterobactin biosynthesis, and the l-tryptophan biosynthesis were significantly elevated in the DM group. CONCLUSION: These results reveal the composition and predictive functions of the intestinal microbiome in the mini-pig diabetes model, further verifying the relationship between HFD, gut microbiome, and diabetes, and providing novel insights into the application of the mini-pig diabetes model in gut microbiome research.

Association between serum uric acid and carotid atherosclerosis in elderly postmenopausal women: A hospital-based study.

BACKGROUND: Carotid atherosclerosis (CAS) is associated with increased cardiovascular risk and implicated in 20-30% of strokes. METHODS: 504 patients were included in this study. The detailed medical history and the results of physical examination, carotid ultrasound examination, and routine laboratory tests were collected. Logistic regression analyses were conducted to analyze the relationship between the SUA and the presence of carotid plaques. And the relationship between SUA and the progression of CAS was analyzed by multiple linear regression. The effect of hormone replacement therapy (HRT) on CAS has also be evaluated. RESULTS: 412 patients (81.7%) had carotid plaques of different sizes by carotid ultrasound examination. We found a positive association between the level of SUA and the probability of having carotid plaque by univariate logistic regression (OR: 2.01, 95% CI: 1.83-2.19, p = 0.003). At 2 years post-discharge, we found that 1 mg/dL increase in SUA levels was expected to 0.946% increase in plaque score and 0.026 cm increase in carotid intima-media thickness, separately. Moreover, patients treated by long-term HRT (≥5 years) had a lower level of SUA and blood lipid and the less change of plaque score and carotid intima-media thickness than patients without HRT. CONCLUSION: The presence and progression of CAS had significantly positive associations with the level of SUA. And the HRT may have the ability to prevent the presence and progression of CAS. However, the safety and long-term outcome of HRT on CAS should be evaluated in further studies.

Discovery of potent and noncovalent KRASG12D inhibitors: Structure-based virtual screening and biological evaluation.

KRASG12D, the most common oncogenic KRAS mutation, is a promising target for the treatment of pancreatic cancer. Herein, we identified four potent and noncovalent KRASG12D inhibitors (hits 1-4) by using structure-based virtual screening and biological evaluation. The in vitro assays indicated that the four compounds had sub-nanomolar affinities for KRASG12D and showed a dose-dependent inhibitory effect on human pancreatic cancer cells. In particular, the hit compound 3 was the most promising candidate and significantly inhibited the tumor growth of pancreatic cancer in tumor-bearing mice. The hit compound 3 represented a promising starting point for structural optimization in hit-to-lead development. This study shows that hit compound 3 provides a basis for the development of the treatment of cancer driven by KRASG12D.

Bioresponsive micro-to-nano albumin-based systems for targeted drug delivery against complex fungal infections.

As a typical human pathogenic fungus, Cryptococcus neoformans is a life-threatening invasive fungal pathogen with a worldwide distribution causing ∼700,000 deaths annually. Cryptococcosis is not just an infection with multi-organ involvement, intracellular survival and extracellular multiplication of the fungus also play important roles in the pathogenesis of C. neoformans infections. Because adequate accumulation of drugs at target organs and cells is still difficult to achieve, an effective delivery strategy is desperately required to treat these infections. Here, we report a bioresponsive micro-to-nano (MTN) system that effectively clears the C. neoformans in vivo. This strategy is based on our in-depth study of the overexpression of matrix metalloproteinase 3 (MMP-3) in infectious microenvironments (IMEs) and secreted protein acidic and rich in cysteine (SPARC) in several associated target cells. In this MTN system, bovine serum albumin (BSA, a natural ligand of SPARC) was used for the preparation of nanoparticles (NPs), and then microspheres were constructed by conjugation with a special linker, which mainly consisted of a BSA-binding peptide and an MMP-3-responsive peptide. This MTN system was mechanically captured by the smallest capillaries of the lungs after intravenous injection, and then hydrolyzed into BSA NPs by MMP-3 in the IMEs. The NPs further targeted the lung tissue, brain and infected macrophages based on the overexpression of SPARC, reaching multiple targets and achieving efficient treatment. We have developed a size-tunable strategy where microspheres "shrink" to NPs in IMEs, which effectively combines active and passive targeting and may be especially powerful in the fight against complex fungal infections.

The Association Between Ideal Cardiovascular Health and Health-Related Quality of Life in Adults: A Population-Based Cross-Sectional Study.

Objectives: The study aimed to explore the association between Ideal cardiovascular health (ICH) and health-related quality of life (HRQoL) using the European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L) among rural population. Methods: This study included 20,683 participants aged 18-79 years from "the Henan Rural Cohort study". Generalized linear and Tobit regression models were employed to explore the associations of ICH with EQ-5D-5L utility scores and visual analogue scale (VAS) scores, respectively. Results: The mean EQ-5D-5L utility scores and VAS scores were 0.962 ± 0.095 and 79.52 ± 14.02, respectively. Comparing with poor CVH participants (EQ-5D-5L utility scores and VAS scores: 0.954 ± 0.111 and 78.44 ± 14.29), people with intermediate and ideal CVH had higher EQ-5D-5L utility scores (0.969 ± 0.079 and 0.959 ± 0.099) and VAS scores (80.43 ± 13.65 and 79.28 ± 14.14). ICH scores were positively correlated with EQ-5D-5L utility scores (0.007 (0.004, 0.009)) and VAS scores (0.295 (0.143, 0.446)), respectively. Conclusions: Higher ICH scores is positive associated with better HRQoL in rural population, which suggests that improvement of cardiovascular health may help to enhance HRQoL among rural population.

Discovery of a Dual Tubulin and Poly(ADP-Ribose) Polymerase-1 Inhibitor by Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking, and Biological Evaluation.

Dual inhibition of tubulin and poly(ADP-ribose) polymerase-1 (PARP-1) may become an attractive approach for cancer therapy. Here, we discover a dual tubulin/PARP-1 inhibitor (termed as TP-3) using structure-based virtual screening. TP-3 shows strong dual inhibitory effects on both tubulin and PARP-1. Cellular assays reveal that TP-3 shows superior antiproliferative activities against human cancer cells, including breast, liver, ovarian, and cervical cancers. Further studies indicate that TP-3 plays an antitumor role through multiple mechanisms, including the disturbance of the microtubule network and the PARP-1 DNA repairing function, accumulation of DNA double-strand breaks, inhibition of the tube formation, and induction of G2/M cell cycle arrest and apoptosis. In vivo assessment indicates that TP-3 inhibits the growth of MDA-MB-231 xenograft tumors in nude mouse with no notable side effects. These data demonstrate that TP-3 is a dual-targeting, high-efficacy, and low-toxic antitumor agent.

Nonlaboratory-Based Risk Assessment Model For Type 2 Diabetes Mellitus Screening in Chinese Rural Population: A Joint Bagging-Boosting Model.

Diabetes mellitus is one of the major public health problems in the world due to its high prevalence and medical costs. The prevention effort necessitates reliable risk assessment models which can effectively identify high-risk individuals and enable healthcare practitioners to initiate appropriate preventive interventions. However, diabetes risk assessment models based on data analysis face multiple challenges, such as class imbalance and low identification rate. To cope with these challenges, this paper proposed an analytical framework based on data-driven approaches using large population data from the Henan Rural Cohort Study. A joint bagging-boosting model (JBM) was developed and validated. For the convenience of large-scale population screening, our study excluded laboratory variables and collinearity variables using the maximum likelihood ratio method to obtain accessibility variables. Then, we explored the effects of different methods for dealing with the unbalanced nature of the available data, including over-sampling and under-sampling methods. Finally, to improve the overall model performance, a joint model which combined the bagging and boosting algorithms with the stacking algorithm was constructed. The model we built demonstrated good discrimination, with an area under the curve (AUC) value of 0.885, and acceptable calibration (Brier score = 0.072). Compared with the benchmark model, the proposed framework improved the AUC value of the overall model performance by 13.5%, and the recall increased from 0.744 to 0.847. The proposed model contributes to the personalized management of diabetes, especially in medical resource-poor settings.

Associations of midpoint of sleep and night sleep duration with type 2 diabetes mellitus in Chinese rural population: the Henan rural cohort study.

BACKGROUND: The study aimed to investigate the independent and combined effects of midpoint of sleep and night sleep duration on type 2 diabetes mellitus (T2DM) in areas with limited resources. METHODS: A total of 37,276 participants (14,456 men and 22,820 women) were derived from the Henan Rural Cohort Study. Sleep information was assessed based on the Pittsburgh Sleep Quality Index. Logistic regression models and restricted cubic splines were used to estimate the relationship of the midpoint of sleep and night sleep duration with T2DM. RESULTS: Of the 37,276 included participants, 3580 subjects suffered from T2DM. The mean midpoint of sleep among the Early, Intermediate and Late groups were 1:05 AM ±23 min, 1:56 AM ±14 min, and 2:57 AM ±34 min, respectively. Compared to the Intermediate group, adjusted odds ratios (ORs) and 95% confidence interval (CI) of T2DM were 1.13 (1.04-1.22) and 1.14 (1.03-1.26) in the Early group and the Late group. Adjusted OR (95% CI) for T2DM compared with the reference (7- h) was 1.28 (1.08-1.51) for longer (≥ 10 h) night sleep duration. The combination of late midpoint of sleep and night sleep duration (≥ 9 h) increased 38% (95% CI 10-74%) prevalence of T2DM. These associations were more obvious in women than men. CONCLUSIONS: Late and early midpoint of sleep and long night sleep duration were all associated with higher prevalence of T2DM. Meanwhile, midpoint of sleep and night sleep duration might have combined effects on the prevalence of T2DM, which provided potential health implications for T2DM prevention, especially in rural women. TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699 ). Date of registration: 2015-07-06.