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8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever).
Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice.
Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice.Allium leafminer, Phytomyza gymnostoma Loew (Diptera Agromyzidae), is an invasive pest of allium crops in North America. Spinosyn insecticides, spinetoram and spinosad, have been effective choices for managing P. gymnostoma infestations in allium crops, but their use should be optimized for economical and resistance management purposes. In New York from 2018 through 2020, performance of each spinosyn insecticide was evaluated by making two applications spaced either 1 or 2 wk apart beginning at various intervals after P. gymnostoma was first detected in the field; a weekly spray program also was included. Results indicated that weekly applications of each spinosyn insecticide provided ≥98% reduction of P. gymnostoma densities in scallions and leeks relative to the untreated control. Spinetoram applied twice, regardless of initial timing and duration between sprays, provided an acceptable level of P. gynostoma control (71 to 98% reduction in densities relative to the untreated control). Spinosad also was effective when applied twice (85 to 95% reduction in densities relative to the untreated control), but not when sprays were made consecutively beginning when P. gymnostoma was first detected and not when the P. gymnostoma infestation was extremely high (i.e., 38 insects per plant in the untreated control). Management of P. gymnostoma with spinosyns can be successful with only two applications, but control tended to be best when first applied 2 to 3 wk after initial detection. Optimizing applications of spinetoram and spinosad will save growers time, reduce insecticide costs, and mitigate resistance development without significantly increasing the risk of yield reduction.
The longitudinal evidence between detailed parameters of smoking status and type 2 diabetes among young adults has been limited. We evaluated this association in young Korean adults.
This nationwide cohort study included 3 026 551 adults aged 20 to 39 years who underwent Korean National Health Insurance Service health examinations in 2009 and were followed up until the end of 2017. The participants were categorized according to smoking status, smoking duration, and smoking amount. The hazard ratios (HRs) and 95% CIs for type 2 diabetes were estimated using multivariable Cox proportional hazard regression analysis.
During 8.2 years of follow-up, 71 952 cases of type 2 diabetes newly developed. Compared with never-smokers, independently increased HRs of type 2 diabetes were observed in ex-smokers (1.06, 95% CI = 1.04-1.09) and current smokers (1.39, 1.36-1.42). In these two groups, the type 2 diabetes risk increased with greater smoking duration and amount (p for trend <.001). The HRs of type 2 diabetereduce the incidence of type 2 diabetes.Leveraging large-scale electronic health record (EHR) data to estimate survival curves for clinical events can enable more powerful risk estimation and comparative effectiveness research. However, use of EHR data is hindered by a lack of direct event time observations. Selleckchem Fulvestrant Occurrence times of relevant diagnostic codes or target disease mentions in clinical notes are at best a good approximation of the true disease onset time. On the other hand, extracting precise information on the exact event time requires laborious manual chart review and is sometimes altogether infeasible due to a lack of detailed documentation. Current status labels-binary indicators of phenotype status during follow-up-are significantly more efficient and feasible to compile, enabling more precise survival curve estimation given limited resources. Existing survival analysis methods using current status labels focus almost entirely on supervised estimation, and naive incorporation of unlabeled data into these methods may lead to biased estimates. In this article, we propose Semisupervised Calibration of Risk with Noisy Event Times (SCORNET), which yields a consistent and efficient survival function estimator by leveraging a small set of current status labels and a large set of informative features. In addition to providing theoretical justification of SCORNET, we demonstrate in both simulation and real-world EHR settings that SCORNET achieves efficiency akin to the parametric Weibull regression model, while also exhibiting semi-nonparametric flexibility and relatively low empirical bias in a variety of generative settings.
Food-related quality of life (FRQoL) encompasses the psychosocial elements of eating and drinking. The FRQoL of children and adolescents with inflammatory bowel disease has not yet been assessed. This study aimed to evaluate the utility of the validated FR-Qol-29 instrument in children with Crohn's disease (CD).
Children diagnosed with CD, a shared home environment healthy sibling, and healthy control subjects 6 to 17 years of age were recruited to this single-center, prospective, cross-sectional study. Children or their parent or guardian completed the FR-QoL-29 instrument. Internal consistency was assessed by completing Cronbach's α. Construct validity was established by correlating the CD FR-QoL-29 sum scores with the Physician Global Assessment and Pediatric Crohn Disease Activity Index scores. The discriminant validity was analyzed using a 1-way analysis of variance, and a Spearman's correlation coefficient test was completed to identify any correlations associated with FRQoL.
Sixty children or theealthy siblings also have poorer FRQoL than control subjects. Several clinical factors are associated with poorer FRQoL in children with CD including age and level of nutritional risk (weight, height, and body mass index). Further research is required validate these findings and to develop strategies for the prevention or treatment of impaired FRQoL in children with CD.
Preterm birth is defined by the onset of labor at a gestational age shorter than 37 weeks, and it can lead to premature birth and impose a threat to newborns' health. The Puerto Rico PROTECT cohort is a well-characterized prospective birth cohort that was designed to investigate environmental and social contributors to preterm birth in Puerto Rico, where preterm birth rates have been elevated in recent decades. To elucidate possible relationships between metabolites and preterm birth in this cohort, we conducted a nested case-control study to conduct untargeted metabolomic characterization of maternal plasma of 31 women who experienced preterm birth and 69 controls who underwent full-term labor at 24-28 gestational weeks.
A total of 333 metabolites were identified and annotated with liquid chromatography/mass spectrometry. Subsequent weighted gene correlation network analysis shows that the fatty acid and carene-enriched module has a significant positive association (P = 8e-04, FDR = 0.006) with preterm budy demonstrates the involvement of lipids, particularly fatty acids, in the pathogenesis of preterm birth.
Schistosomiasis, or bilharzia, is a parasitic disease caused by trematode flatworms of the genus Schistosoma. Infection by Schistosoma mansoni in humans results when cercariae emerge into water from freshwater snails in the genus Biomphalaria and seek out and penetrate human skin. The snail Biomphalaria straminea is native to South America and is now also present in Central America and China, and represents a potential vector host for spreading schistosomiasis. To date, genomic information for the genus is restricted to the neotropical species Biomphalaria glabrata. This limits understanding of the biology and management of other schistosomiasis vectors, such as B. straminea.
Using a combination of Illumina short-read, 10X Genomics linked-read, and Hi-C sequencing data, our 1.005 Gb B. straminea genome assembly is of high contiguity, with a scaffold N50 of 25.3 Mb. Transcriptomes from adults were also obtained. Developmental homeobox genes, hormonal genes, and stress-response genes were identified, and revariety of phenomena related to snail vectors of schistosomiasis, as well as evolutionary and genomics questions related to molluscs more widely.
Data-independent acquisition (DIA) has become an important approach in global, mass spectrometric proteomic studies because it provides in-depth insights into the molecular variety of biological systems. However, DIA data analysis remains challenging owing to the high complexity and large data and sample size, which require specialized software and vast computing infrastructures. Most available open-source DIA software necessitates basic programming skills and covers only a fraction of a complete DIA data analysis. In consequence, DIA data analysis often requires usage of multiple software tools and compatibility thereof, severely limiting the usability and reproducibility.
To overcome this hurdle, we have integrated a suite of open-source DIA tools in the Galaxy framework for reproducible and version-controlled data processing. The DIA suite includes OpenSwath, PyProphet, diapysef, and swath2stats. We have compiled functional Galaxy pipelines for DIA processing, which provide a web-based graphical user interface to these pre-installed and pre-configured tools for their use on freely accessible, powerful computational resources of the Galaxy framework. This approach also enables seamless sharing workflows with full configuration in addition to sharing raw data and results. We demonstrate the usability of an all-in-one DIA pipeline in Galaxy by the analysis of a spike-in case study dataset. Additionally, extensive training material is provided to further increase access for the proteomics community.
The integration of an open-source DIA analysis suite in the web-based and user-friendly Galaxy framework in combination with extensive training material empowers a broad community of researches to perform reproducible and transparent DIA data analysis.
The integration of an open-source DIA analysis suite in the web-based and user-friendly Galaxy framework in combination with extensive training material empowers a broad community of researches to perform reproducible and transparent DIA data analysis.
Disease complications, the onset of secondary phenotypes given a primary condition, can exacerbate the long-term severity of outcomes. However, the exact cause of many of these cross-phenotype associations is still unknown. One potential reason is shared genetic etiology-common genetic drivers may lead to the onset of multiple phenotypes. Disease-disease networks (DDNs), where nodes represent diseases and edges represent associations between diseases, can provide an intuitive way of understanding the relationships between phenotypes. Using summary statistics from a phenome-wide association study (PheWAS), we can generate a corresponding DDN where edges represent shared genetic variants between diseases. Such a network can help us analyze genetic associations across the diseasome, the landscape of all human diseases, and identify potential genetic influences for disease complications.
To improve the ease of network-based analysis of shared genetic components across phenotypes, we developed the humaN disEase phenoType MAp GEnerator (NETMAGE), a web-based tool that produces interactive DDN visualizations from PheWAS summary statistics.
