Guidance of development, validation, and evaluation of algorithms for populating health status in observational studies of routinely collected data (DEVELOP-RCD).

BACKGROUND: In recent years, there has been a growing trend in the utilization of observational studies that make use of routinely collected healthcare data (RCD). These studies rely on algorithms to identify specific health conditions (e.g. diabetes or sepsis) for statistical analyses. However, there has been substantial variation in the algorithm development and validation, leading to frequently suboptimal performance and posing a significant threat to the validity of study findings. Unfortunately, these issues are often overlooked. METHODS: We systematically developed guidance for the development, validation, and evaluation of algorithms designed to identify health status (DEVELOP-RCD). Our initial efforts involved conducting both a narrative review and a systematic review of published studies on the concepts and methodological issues related to algorithm development, validation, and evaluation. Subsequently, we conducted an empirical study on an algorithm for identifying sepsis. Based on these findings, we formulated specific workflow and recommendations for algorithm development, validation, and evaluation within the guidance. Finally, the guidance underwent independent review by a panel of 20 external experts who then convened a consensus meeting to finalize it. RESULTS: A standardized workflow for algorithm development, validation, and evaluation was established. Guided by specific health status considerations, the workflow comprises four integrated steps: assessing an existing algorithm's suitability for the target health status; developing a new algorithm using recommended methods; validating the algorithm using prescribed performance measures; and evaluating the impact of the algorithm on study results. Additionally, 13 good practice recommendations were formulated with detailed explanations. Furthermore, a practical study on sepsis identification was included to demonstrate the application of this guidance. CONCLUSIONS: The establishment of guidance is intended to aid researchers and clinicians in the appropriate and accurate development and application of algorithms for identifying health status from RCD. This guidance has the potential to enhance the credibility of findings from observational studies involving RCD.

The WUSCHEL-related homeobox transcription factor CsWOX3 negatively regulates fruit spine morphogenesis in cucumber (Cucumis sativus L.).

Cucumber (Cucumis sativus L.) is a widely cultivated crop with rich germplasm resources, holding significant nutritional value. It also serves as an important model for studying epidermal cell fate and sex determination. Cucumbers are covered with multicellular and unbranched trichomes, including a specific type called spines found on the surface of the fruit. The presence and density of these fruit spines determine the visual quality of cucumber fruits. However, the key regulatory genes and mechanisms underlying cucumber fruit spine development remain poorly understood. In this study, we identified a WUSCHEL-related homeobox (WOX) family gene CsWOX3, which functioned as a typical transcriptional repressor and played a negative role in fruit spine development. Spatial-temporal expression analysis revealed that CsWOX3 exhibited a relatively high expression level in the cucumber female floral organs, particularly in the fruit exocarp. Knockout of CsWOX3 using CRISPR/Cas9 resulted in a significant 2-to-3-fold increase in the diameter of fruit spines base, while overexpression led to a 17% decrease in the diameter compared to the wild-type. A SQUAMOSA PROMOTER BINDING PROTEIN-LIKE transcription factor CsSPL15 could directly bind and activate the expression of CsWOX3, thereby suppressing the expression of downstream auxin-related genes, such as CsARF18. Additionally, the RING-finger type E3 ubiquitin ligase CsMIEL1-like interacted with the HD domain of CsWOX3, which might result in the ubiquitination and subsequent alteration in protein stability of CsWOX3. Collectively, our study uncovered a WOX transcription factor CsWOX3 and elucidated its expression pattern and biological function. This discovery enhances our comprehension of the molecular mechanism governing cucumber fruit spine morphogenesis.

D-π-A type fluorescent dyes: Effect of π-bridge units on optical and G4 DNA binding properties.

Fluorescent solvatochromic dyes that are sensitive to the nature of local microenvironmental, have been explored as probes in applications ranging from the imaging biomolecules to understanding of basic biomolecule functions. To expand the scope of fluorescent solvatochromic dyes for G-quadruplex (G4) DNA structures, and to illustrate the relationship between structure and properties, three newly designed D-π-A type fluorescent dyes were synthesized by introducing diarylimidazole to carbazole skeleton linked to benzene, furan or thiophene π-conjugated bridge and connected with pyridinium acceptor, respectively. Their structural characteristics, optical properties, and G4 DNA binding properties were discussed in detail. In general, the incorporation of furan and thiophene as π-conjugated bridges leads the better conjugation and molecular coplanarity with more efficient intramolecular charge transfer (ICT) effect compared with benzene bridge. The fluorescence intensities induced upon interaction were found that TP-6 with thiophene π-conjugated bridge had the strongest response toward G4 DNAs. In addition, the application of this dye as a fluorescent agent for living cell imaging was also demonstrated.

Analysis of the Economic Burden of Chronic Kidney Disease With Comorbidities Among Patients in Xuzhou, China.

Objectives: To analyze the costs and medication patterns of patients with chronic kidney disease (CKD) and comorbidities in Xuzhou, China, using a large electronic medical records database. Methods: Data were obtained from an electronic medical records database. The annual per-person and per-visit cost of hospitalization, as well as the proportions of those costs, are presented. Results: The majority of the participants were middle-aged men, and had medical insurance. Glomerulonephritis was the primary cause of CKD in patients with an identified etiology. The average per-visit cost of hospitalization for the CKD-renal anemia and CKD-mineral and bone disorder groups was 8,674.5 (5,154.3-13,949.6) and 8,182.6 (4,798.2-12,844.7) Yuan, respectively, which was greater than that of the other groups. The major expenses incurred were for diagnostics, drug usage, surgical procedures, laboratory tests and material costs. Conclusion: The substantial burden imposed by CKD with comorbidities indicates the importance of implementing public health strategies aimed at detecting and preventing these conditions in the general population. With the aging population, our nation may experience a greater CKD-related economic burden.

Blood Urine Nitrogen Trajectories of Acute Pancreatitis Patients in Intensive Care Units.

Objective: To identify subclasses of acute pancreatitis (AP) patients in the intensive care unit (ICU) by analyzing blood urea nitrogen (BUN) trajectories. Methods: AP patients in West China Hospital System (development cohort) and three public databases in the United States (validation cohort) were included. Latent class trajectory modelling was used to identify subclasses based on BUN trajectories within the first 21 days after ICU admission. Clinical characteristics and outcomes were compared, and results were externally validated. Results: The study comprised 2971 and 930 patients in the development and validation cohorts, respectively, with five subclasses: Class 1 ("Moderate-azotemia, slow decreasing"), Class 2 ("Non-azotemia"), Class 3 ("Severe-azotemia, slow decreasing"), Class 4 ("Moderate-azotemia, rapid increasing"), and Class 5 ('Moderate-azotemia, slow increasing) identified. Azotemia patients showed significantly higher 30-day mortality risk in development and validation cohorts. Specifically, Class 4 patients exhibited notably highest mortality risk in both the development cohort (HR 5.32, 95% CI 2.62-10.82) and validation cohort (HR 6.23, 95% CI 2.93-13.22). Regarding clinical characteristics, AP patients in Class 4 showed lower mean arterial pressure and a higher proportion of renal disease. We also created an online early classification model to further identify Class 4 patients among all patients with moderate azotemia at baseline. Conclusion: This multinational study uncovers heterogeneity in BUN trajectories among AP patients. Patients with "Moderate-azotemia, rapid increasing" trajectory, had a higher mortality risk than patients with severe azotemia at baseline. This finding complements studies that solely rely on baseline BUN for risk stratification and enhanced our understanding of longitudinal progression of AP.

Placebo effects of repetitive transcranial magnetic stimulation on negative symptoms and cognition in patients with schizophrenia spectrum disorders: a systematic review and meta-analysis.

Background: Negative symptoms and cognitive impairments are highly frequent in schizophrenia spectrum disorders (SSD), associated with adverse functional outcomes and quality of life. Repetitive transcranial magnetic stimulation (rTMS) has been considered a promising therapeutic option in SSD. However, placebo effects of rTMS on these symptoms remained unclear. Objective: To investigate placebo effects of rTMS on alleviating negative symptoms and cognitive impairment in patients with SSD and to explore potential moderators. Methods: We systematically searched five electronic databases up to 15 July 2023. Randomized, double-blind, sham-controlled trials investigating effects of rTMS on negative symptoms or cognition in patients with SSD were included. The pooled placebo effect sizes, represented by Hedges' g, were estimated using the random-effects model. Potential moderators were explored through subgroup analysis and meta-regression. Results: Forty-four randomized controlled trials with 961 patients (mean age 37.53 years; 28.1% female) in the sham group were included. Significant low-to-moderate pooled placebo effect sizes were observed for negative symptoms (g=0.44, p<0.001), memory (g=0.31, p=0.010), executive function (g=0.35, p<0.001), working memory (g=0.26, p=0.004), and processing speed (g=0.36, p=0.004). Subgroup analysis indicated that placebo effects were affected by sham stimulation methods, rTMS targeting approaches, and stimulation frequency. Conclusions: Placebo effects of rTMS on negative symptoms and cognition in patients with SSD are significant in a small-to-moderate magnitude, which might be mediated by rTMS parameters. Our findings will provide new insights for practitioners to further optimize and establish standardized rTMS protocols for future RCTs tackling cardinal symptoms in SSD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023390138.

Oral soluble shell prepared from OSA starch incorporated with tea polyphenols for the microencapsulation of Sichuan pepper oleoresin: Characterization, flavor stability, release mechanisms and its application in mooncake.

The market share of Sichuan pepper oleoresin (SPO) in the flavor industry is increasing steadily; however, its high volatility, low water solubility, and poor stability continue to pose significant challenges to application. The microencapsulation prepared by emulsion embedding and spray drying is considered as an effective technique to solve the above problems. Sodium octenyl succinate starch (OSA starch) and tea polyphenols (TPs) were used to develop OSA-TPs complex as encapsulants for SPO to prepare orally soluble microcapsules. And the optimum doping of TPs was determined. SPO microcapsules have good properties with high encapsulation efficiency up to 88.13 ± 1.48% and high payload up to 41.58 ± 1.86% with low water content and high heat resistance. The binding mechanism of OSA starch with TPs and its regulation mechanism and effect on SPOs were further analyzed and clarified. The binding mechanism between OSA starch and TPs was clarified in further analyses. The OSA-TPs complexes enhanced the rehydration, release in food matrix and storage stability of SPO, and exhibited good sensory immediacy. Flavor-improved mooncakes were successfully developed, achieving the combination of mooncake flavor and SPO flavor. This study provided a valuable way to prepare flavoring microcapsules suitable for the catering industry, opened up the combined application of SPO and bakery ingredients, and was of great practical value and significance for improving the processing quality of flavor foods, driving the development of the SPO industry, and enhancing the national dietary experience.

Treatment with immunosuppressants did not increase the risk of COVID-19 in pemphigus patients: A single-center survey-based study.

BACKGROUND: The prevalence and outcomes of coronavirus 2019 (COVID-19) among patients using glucocorticoids and immunosuppressants remain controversial. AIM: The study aims to investigate the impact of immunosuppressants especially glucocorticoids on patients in the Autoimmune Bullous Diseases Cohort of West China Hospital (AIBDWCH) during COVID-19. METHODS: We conducted a cross-sectional survey from December 7, 2022, to February 8, 2023, using questionnaires administered either face-to-face or by phone. COVID-19 cases were classified as confirmed, probable, or suspected according to World Health Organization criteria. Patients were divided into Group A (confirmed and probable cases) and Group B (suspected and other cases). The impact of glucocorticoids and immunosuppressive agents on COVID-19 disease and progression was evaluated with logistic regression models. RESULTS: This study included 111 patients with pemphigus. Overweight patients had a reduced risk of confirmed COVID-19 (odds ratio [OR] 0.35 [95 % CI 0.13-0.97], p = 0.045). Patients treated with a medium dose of prednisone during the pandemic had a lower incidence of COVID-19 compared to those on low doses, though the difference was not statistically significant. No independent effects of age, sex, comorbidities, and therapies were observed. No significant differences were found in COVID-19 symptoms among different therapy groups. CONCLUSIONS: Treatment with immunosuppressants, particularly glucocorticoids at low-to-medium doses, did not elevate COVID-19 risk in pemphigus patients. Consistent outcomes across treatments confirm the safety of these therapies during the pandemic.

Development of D-π-A organic dyes for discriminating HSA from BSA and study on dye-HSA interaction.

HSA (human serum albumin), a most abundant protein in blood serum, plays a key role in maintaining human health. Abnormal HSA level is correlated with many diseases, and thus has been used as an essential biomarker for therapeutic monitoring and biomedical diagnosis. Development of small-molecule fluorescent probes allowing the selective and sensitive recognition of HSA in in vitro and in vivo is of fundamental importance in basic biological research as well as medical diagnosis. Herein, we reported a series of new synthesized fluorescent dyes containing D-π-A constitution, which exhibited different optical properties in solution and solid state. Among them, dye M-H-SO3 with a hydrophilic sulfonate group at electron-acceptor part displayed selectivity for discrimination of HSA from BSA and other enzymes. Upon binding of dye M-H-SO3 with HSA, a significant fluorescence enhancement with a turn-on ratio about 96-fold was triggered. The detection limit was estimated to be âˆ¼ 40 nM. Studies on the interaction mechanism revealed that dye M-H-SO3 could bind to site III of HSA with a 1:1 binding stoichiometry. Furthermore, dye M-H-SO3 has been applied to determine HSA in real urine samples with good recoveries, which provided a useful method for HSA analysis in biological fluids.

Research on the coordinated development of provincial urbanization and carbon emission efficiency of construction industry in China.

BACKGROUND: Energy conservation and emission reduction policies restrict the economic and social development of all countries in the world, and the impact on China, which has low urbanization, is more serious. In the process of promoting urbanization, the pressure of carbon emission reduction in the construction industry has increased, and the high emissions of the construction industry have made the low-carbon development of cities face severe challenges. China is at a critical stage of urbanization development, and there is become a general consensus on how to improve the carbon emission efficiency of the construction industry. The interaction between urbanization and the carbon emission efficiency of the construction industry is a long-term and complex process. As one of the industries contributing to China's urbanization process and carbon emissions, it is of great practical significance to explore the coordination relationship between urbanization and the carbon emission efficiency of the construction industry (CEECI) to realize the goal of "double carbon", promoting urbanization construction and solving the problem of "green development". Taking 30 provinces in China as the research target area, the double weighted summation method and the undesirable output superefficiency window-EBM-DEA model are used to measure the provincial urbanization level and CEECI, respectively. Then, the coupling coordination degree model of the relative development index is introduced, and the spatial autocorrelation model and the spatial and temporal differentiation characteristics of the coordination level of urbanization and the CEECI are analysed. RESULTS: From 2010 to 2021, China's urbanization level increased steadily, but the growth rate gradually decreased. There were significant differences in urbanization levels among provinces. The eastern provinces have a higher level of urbanization but lack an impetus in the later period, while the western provinces have a lower level of urbanization but a faster growth rate. The low-carbon development trend of China's construction industry is good, and the overall development of the CEECI shows an "N" type, and the inflection points appear in 2013 and 2018. The interprovincial urbanization level is significantly different from that of the CEECI, and the development form of the central and western provinces is better than that of the eastern provinces. The coordination level of urbanization and the CEECI in China is transitioning from the running-in stage to the coordination stage, and the coupling coordination degree between systems is on the rise, while the relative development degree is on the decline. The spatial distribution pattern is in a dynamic state of change, and the overall distribution pattern is "high in the east and low in the central and western regions". The differences among provinces were significantly decreased, with 63.33% of provinces at the high running-in level. The provinces that entered the coordination stage were mainly located in the eastern region, and only Beijing was in the coordination stage by the end of the study. In addition, 90% of the provinces exhibited lagging efficiency, and only Jiangxi, Guangxi and Chongqing, which had low coordination levels maintained synchronous development of the two systems. The coordination level between provincial urbanization and the CEECI showed a positive spatial distribution, the global Moran index showed a "V" shape trend, and the spatial dependence of the coordination level between the two systems gradually weakened. In the local spatial distribution, there are two types of convergence: high and low. CONCLUSIONS: The coordination degree of urbanization and the CEECI analysed in this study is an extension of the research on the relationship between the two. By integrating the two into a unified framework, the method of combining quantitative and qualitative analysis is used to further explore the coordination relationship between the two, which not only enhances the scientificity and accuracy of the research but also extends the breadth and depth of relevant theoretical research. At the same time, according to the coordination type between urbanization and the CEECI, China should propose corresponding targeted coordination and optimization paths from the perspective of urbanization and low-carbon development of the construction industry to achieve high-quality development of China's economy and society.

Synergistic acceleration of machine learning and molecular docking for prostate-specific antigen ligand design.

Prostate-specific antigen (PSA) serves as a critical biomarker for the early detection and continuous monitoring of prostate cancer. However, commercial PSA detection methods primarily rely on antigen-antibody interactions, leading to issues such as high costs, stringent storage requirements, and potential cross-reactivity due to PSA variant sequence homology. This study is dedicated to the precise design and synthesis of molecular entities tailored for binding with PSA. By employing a million-level virtual screening to obtain potential PSA compounds and effectively guiding the synthesis using machine learning methods, the resulting lead compounds exhibit significantly improved binding affinity compared to those developed before by researchers using high-throughput screening for PSA, substantially reducing screening and development costs. Unlike antibody detection, the design of these small molecules offers promising avenues for advancing prostate cancer diagnostics. Furthermore, this study establishes a systematic framework for the rapid development of customized ligands that precisely target specific protein entities.

Handling time-varying treatments in observational studies: A scoping review and recommendations.

OBJECTIVE: Time-varying treatments are common in observational studies. However, when assessing treatment effects, the methodological framework has not been systematically established for handling time-varying treatments. This study aimed to examine the current methods for dealing with time-varying treatments in observational studies and developed practical recommendations. METHODS: We searched PubMed from 2000 to 2021 for methodological articles about time-varying treatments, and qualitatively summarized the current methods for handling time-varying treatments. Subsequently, we developed practical recommendations through interactive internal group discussions and consensus by a panel of external experts. RESULTS: Of the 36 eligible reports (22 methodological reviews, 10 original studies, 2 tutorials and 2 commentaries), most examined statistical methods for time-varying treatments, and only a few discussed the overarching methodological process. Generally, there were three methodological components to handle time-varying treatments. These included the specification of treatment which may be categorized as three scenarios (i.e., time-independent treatment, static treatment regime, or dynamic treatment regime); definition of treatment status which could involve three approaches (i.e., intention-to-treat, per-protocol, or as-treated approach); and selection of analytic methods. Based on the review results, a methodological workflow and a set of practical recommendations were proposed through two consensus meetings. CONCLUSIONS: There is no consensus process for assessing treatment effects in observational studies with time-varying treatments. Previous efforts were dedicated to developing statistical methods. Our study proposed a stepwise workflow with practical recommendations to assist the practice.

Physiological and transcriptomic analysis revealed that the accumulation of reactive oxygen species caused the low temperature sensitivity of Liriodendron × sinoamericanum.

Liriodendron × sinoamericanum is widely cultivated in southern China as an excellent wood and garden ornamental trees. However, its intolerance to low temperature limits its application to high latitudes. Understanding the molecular mechanism of low temperature sensitivity of Liriodendron × sinoamericanum is very important for its further application. In this study, combined with physiological and transcriptomic analysis, it was revealed that low temperature stress can lead to water loss and decreased photosynthetic capacity of Liriodendron × sinoamericanum leaves. The accelerated accumulation of reactive oxygen species (ROS) caused by the imbalance of cell REDOX homeostasis is one of the important reasons for the low temperature sensitivity. Further analysis showed that several transcription factors could be involved in regulating the synthesis and degradation of ROS, among which LsNAC72 and LsNAC73a could regulate the accumulation of O2- and H2O2 in leaves by affecting the expression level of LsAPX, LsSOD, LsPAO, and LsPOD.

Comparing glycemic traits in defining diabetes among rural Chinese older adults.

BACKGROUND: We sought to identify the optimal cut-off of glycated hemoglobin (HbA1c) for defining diabetes and to assess the agreements of fasting plasma glucose (FPG), fasting serum glucose (FSG), and HbA1c in defining diabetes among rural older adults in China. METHODS: This population-based cross-sectional study included 3547 participants (age ≥61 years, 57.8% women) from the Multidomain Interventions to Delay Dementia and Disability in Rural China from 2018-2019; of these, 3122 had no previously diagnosed diabetes. We identified the optimal cut-off of HbA1c against FPG ≥7.0 mmol/L for defining diabetes by using receiver operating characteristic curve and Youden index. The agreements of FPG, FSG, and HbA1c in defining diabetes were assessed using kappa statistics. RESULTS: Among participants without previously diagnosed diabetes (n = 3122), the optimal HbA1c cut-off for defining diabetes was 6.5% (48 mmol/mol), with the sensitivity of 88.9%, specificity of 93.7%, and Youden index of 0.825. The correlation coefficients were 0.845 between FPG and FSG, 0.574 between FPG and HbA1c, and 0.529 between FSG and HbA1c in the total sample (n = 3547). The kappa statistic for defining diabetes was 0.962 between FSG and FPG, and 0.812 between HbA1c and FPG. CONCLUSIONS: The optimal cut-off of HbA1c for diagnosing diabetes against FPG >7.0 mmol/L is ≥6.5% in Chinese rural-dwelling older adults. The agreement in defining diabetes using FPG, FSG, and HbA1c is nearly perfect. These results have relevant implications for diabetes research and clinical practice among older adults in China. CLINICAL TRIAL REGISTRATION: The protocol of MIND-China was registered in the Chinese Clinical Trial Registry (ChiCTR, www.chictr.org.cn; registration no.: ChiCTR1800017758).

Validation and impact of algorithms for identifying variables in observational studies of routinely collected data.

BACKGROUND AND OBJECTIVES: Among observational studies of routinely collected health data (RCD) for exploring treatment effects, algorithms are used to identify study variables. However, the extent to which algorithms are reliable and impact the credibility of effect estimates is far from clear. This study aimed to investigate the validation of algorithms for identifying study variables from RCD, and examine the impact of alternative algorithms on treatment effects. METHODS: We searched PubMed for observational studies published in 2018 that used RCD to explore drug treatment effects. Information regarding the reporting, validation, and interpretation of algorithms was extracted. We summarized the reporting and methodological characteristics of algorithms and validation. We also assessed the divergence in effect estimates given alternative algorithms by calculating the ratio of estimates of the primary vs. alternative analyses. RESULTS: A total of 222 studies were included, of which 93 (41.9%) provided a complete list of algorithms for identifying participants, 36 (16.2%) for exposure, and 132 (59.5%) for outcomes, and 15 (6.8%) for all study variables including population, exposure, and outcomes. Fifty-nine (26.6%) studies stated that the algorithms were validated, and 54 (24.3%) studies reported methodological characteristics of 66 validations, among which 61 validations in 49 studies were from the cross-referenced validation studies. Of those 66 validations, 22 (33.3%) reported sensitivity and 16 (24.2%) reported specificity. A total of 63.6% of studies reporting sensitivity and 56.3% reporting specificity used test-result-based sampling, an approach that potentially biases effect estimates. Twenty-eight (12.6%) studies used alternative algorithms to identify study variables, and 24 reported the effects estimated by primary analyses and sensitivity analyses. Of these, 20% had differential effect estimates when using alternative algorithms for identifying population, 18.2% for identifying exposure, and 45.5% for classifying outcomes. Only 32 (14.4%) studies discussed how the algorithms may affect treatment estimates. CONCLUSION: In observational studies of RCD, the algorithms for variable identification were not regularly validated, and-even if validated-the methodological approach and performance of the validation were often poor. More seriously, different algorithms may yield differential treatment effects, but their impact is often ignored by researchers. Strong efforts, including recommendations, are warranted to improve good practice.

Comparison of clinical characteristics and disease burden between early- and late-onset type 2 diabetes patients: a population-based cohort study.

BACKGROUND: The clinical characteristics of early-onset type 2 diabetes (T2D) patients are not fully understood. To address this gap, we conducted a cohort study to evaluate clinical characteristics and disease burden in the new-onset T2D population, especially regarding the progression of diseases. METHODS: This cohort study was conducted using a population-based database. Patients who were diagnosed with T2D were identified from the database and were classified into early- (age < 40) and late-onset (age ≥ 40) groups. A descriptive analysis was performed to compare clinical characteristics and disease burden between early- and late-onset T2D patients. The progression of disease was compared using Kaplan‒Meier analysis. RESULTS: A total of 652,290 type 2 diabetic patients were included. Of those, 21,347 were early-onset patients, and 300,676 were late-onset patients. Early-onset T2D patients had poorer glycemic control than late-onset T2D patients, especially at the onset of T2D (HbA1c: 9.3 [7.5, 10.9] for early-onset vs. 7.7 [6.8, 9.2] for late-onset, P < 0.001; random blood glucose: 10.9 [8.0, 14.3] for early-onset vs. 8.8 [6.9, 11.8] for late-onset, P < 0.001). Insulin was more often prescribed for early-onset patients (15.2%) than for late-onset patients (14.8%). Hypertension (163.0 [28.0, 611.0] days) and hyperlipidemia (114.0 [19.0, 537.0] days) progressed more rapidly among early-onset patients, while more late-onset patients developed hypertension (72.7% vs. 60.1%, P < 0.001), hyperlipidemia (65.4% vs. 51.0%, P < 0.001), cardiovascular diseases (66.0% vs. 26.7%, P < 0.001) and chronic kidney diseases (5.5% vs. 2.1%, P < 0.001) than early-onset patients. CONCLUSIONS: Our study results indicate that patients with newly diagnosed early-onset T2D had earlier comorbidities of hypertension and hyperlipidemia. Both clinical characteristics and treatment patterns suggest that the degree of metabolic disturbance is more severe in patients with early-onset type 2 diabetes. This highlights the importance of promoting healthy diets or lifestyles to prevent T2D onset in young adults.

Reporting, handling, and interpretation of time-varying drug treatments in observational studies using routinely collected healthcare data.

BACKGROUND: Time-varying drug treatments are common in studies using routinely collected health data (RCD) for assessing treatment effects. This study aimed to examine how these studies reported, handled, and interpreted time-varying drug treatments. METHODS: A systematic search was conducted on PubMed from 2018 to 2020. Eligible studies were those used RCD to explore drug treatment effects. We summarized the reporting characteristics and methods employed for handling time-varying treatments. Logistic regressions were performed to investigate the association between study characteristics and the reporting of time-varying treatments. RESULTS: Two hundred and fifty-six studies were included, and 225 (87.9%) studies involved time-varying treatments. Of these, 24 (10.7%) reported the proportion of time-varying treatments and 105 (46.7%) reported methods used to handle time-varying treatments. Multivariable logistic regression showed that medical studies, prespecified protocol, and involvement of methodologists were associated with a higher likelihood of reporting the methods applied to handle time-varying treatments. Among the 105 studies that reported methods, as-treated analyses were the most commonly used analysis sets, which were employed in 73.9%, 75.3% and 88.2% of studies that reported approaches for treatment discontinuation, treatment switching and treatment add-on. Among the 225 studies involved time-varying treatments, 27 (12.0%) acknowledged the potential bias introduced by treatment change, of which 14 (51.9%) suggested that potential biases may impact acceptance or rejection of the null hypothesis. CONCLUSIONS: Among observational studies using RCD, the underreporting about the presence and methods for handling time-varying treatments was largely common. The potential biases due to time-varying treatments have frequently been disregarded. Collaborative endeavors are strongly needed to enhance the prevailing practices.

Advance Research on the Pre-Harvest Sprouting Trait in Vegetable Crop Seeds.

Pre-harvest sprouting (PHS), the germination of seeds on the plant prior to harvest, poses significant challenges to agriculture. It not only reduces seed and grain yield, but also impairs the commodity quality of the fruit, ultimately affecting the success of the subsequent crop cycle. A deeper understanding of PHS is essential for guiding future breeding strategies, mitigating its impact on seed production rates and the commercial quality of fruits. PHS is a complex phenomenon influenced by genetic, physiological, and environmental factors. Many of these factors exert their influence on PHS through the intricate regulation of plant hormones responsible for seed germination. While numerous genes related to PHS have been identified in food crops, the study of PHS in vegetable crops is still in its early stages. This review delves into the regulatory elements, functional genes, and recent research developments related to PHS in vegetable crops. Meanwhile, this paper presents a novel understanding of PHS, aiming to serve as a reference for the study of this trait in vegetable crops.

Association between dietary vitamin C and abdominal aortic calcification among the US adults.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality, and vascular calcification has been highly correlated with CVD events. Abdominal aortic calcification (AAC) has been shown to predict subclinical CVD and incident CVD events. However, the relationship between vitamin C and abdominal aortic calcification remains unclear. OBJECTIVE: To investigate the relationship of dietary vitamin C with AAC among the adult population in the US. METHODS: The National Health and Nutrition Examination Survey (NHANES) 2013-2014 provided the data for the cross-sectional study. 2297 subjects (1089 males) were included in the study. Two scoring systems, AAC 24-point scale (Kauppila) and AAC 8-point scale (Schousboe), were used for the measurement of AAC score. Dietary vitamin C intake was calculated as the average of two rounds of 24-h interview recall data and classified in tertiles for analysis. We applied weighted multiple regression analyses to assess the relationship of dietary vitamin C with AAC score and the risk of having AAC. To ensure the robustness of the findings, subgroup and sensitivity analyses were performed. Additionally, smooth curve fittings, using generalized additive models (GAM) were employed to visualize potential nonlinear relationships. Furthermore, an exploratory analysis on the relationship of vitamin C supplements with AAC was also conducted. RESULTS: The results showed that higher dietary vitamin C intake was related to a reduction in AAC score (AAC-24: ß = -0.338, 95% confidence interval [CI] -0.565, -0.111, P = 0.004; AAC-8: ß = -0.132, 95%CI -0.217, -0.047, P = 0.002), and lower risk of AAC (odds ratio [OR] = 0.807, 95%CI 0.659, 0.989, P = 0.038). However, the relationship of vitamin C supplements with AAC was not identified. CONCLUSIONS: The study revealed that higher intake of dietary vitamin C rather than vitamin C supplements was related to reduced AAC score and lower risk of AAC, indicating that diets rich in vitamin C are recommended due to its potential benefits for protecting against vascular calcification and CVD among the adult population in the US.

Sequentially Controlled Recognition of Different Proteins Using Programmable Protein Imprinted Nanospheres.

Although protein imprinted materials with multiple templates are developed to selectively separate different proteins, it is difficult to achieve the programmed adsorption and separation of different proteins using one material, because the available protein imprinted materials are constructed through irreversible crosslinking and their structures are unprogrammable and non-reconstructive. Herein, a novel nanosphere (MS@PTL-g-PNIPAM) is designed, which not only is temperature and pH responsive but also can dynamically reversibly crosslink/de-crosslink under ultraviolet light of different wavelengths. With the help of the dynamically reversible photo-crosslinking, the nanospheres can be repeatedly programmed into protein imprinted nanospheres toward different target proteins. Moreover, the prepared imprinted nanospheres can easily achieve the controlled rebinding and release of target proteins, benefiting from the introduced temperature- and pH-responsive moieties. As a consequence, this study realizes the specific separation of different target proteins from protein mixture and the real bovine blood sequentially by programming one material. It is resource saving, time saving, recyclable, and it will provide convenience for protein imprinted materials to use in the blood purification, drug delivery, and virus detection.