Insulin-producing β-cells are destroyed in type 1 diabetes mellitus (T1DM), a chronic autoimmune disease that results in complete insulin insufficiency and metabolic dysfunction. According to a survival study that used p values, some hub genes are important for predicting and diagnosing illness. Scientists have inferred medicines to identify possible therapies that interact with the identified hub genes. The GSE10586 gene expression dataset from the Gene Expression Omnibus (GEO) was used for this investigation, which included 27 samples from 15 healthy controls and 12 diabetic patients. Normalization methods such as variance stabilization normalization (VSN) were used as part of the data pretreatment. A protein‒protein interaction (PPI) network was constructed, principal component analysis (PCA) was performed, heatmaps were created, and the Limma algorithm was used to analyze differential gene expression. Using DAVID v6.8 and KEGG pathway annotations, the functional enrichment of differentially expressed genes (DEGs) was evaluated. Furthermore, a computational study revealed CERS6 to be one of the potential hub genes. Four drugs, methotrexate, eliglustat, myriocin and statin, were the focus of further studies on the basis of predictions made via ChemSpider and PubChem database analysis. To determine the optimal binding positions of these drugs with CERS6, we used molecular docking techniques. The binding affinity of methotrexate was 8.48 kcal/mol, that of myriocin was 7.85 kcal/mol, that of eliglustat was − 6.62 kcal/mol, and that of serine was − 4.90 kcal/mol against the binding pocket’s active residues. To determine how consistently each drug interacted with the CERS6 protein over time, molecular dynamics (MD) simulations were run. Throughout the simulation intervals, both medications were confirmed to be stable, with minor alterations in the CERS6 protein loop region. Therefore, the investigation of structure-based drug design has potential for identifying specific therapeutic targets. Ten hub genes were identified via network analysis of differentially expressed genes. These hub genes could serve as novel targets for T1DM detection, prognosis, and targeting. CERS6 exhibited the highest degree of interaction. Methotrexate, eliglustat, myriocin and statins were identified as potential drugs for CERS6. Overall, these findings provide valuable insights that could pave the way for new experimental strategies in T1DM therapy.
Drug use disorders (DUDs) are emerging global public health challenges. Here we investigated the global and regional estimates of the prevalence and burden of DUDs, including amphetamine, cannabis, cocaine and opioid use disorders, from 1990 to 2023 for 204 countries and territories by using the Global Burden of Disease Study 2023. Overall, trends in global age-standardized disability-adjusted life-years of DUDs increased from 169.3 (95% uncertainty interval (95% UI), 134.4–203.9) per 100,000 people in 1990 to 212.0 (95% UI, 179.2–245.6) in 2023. In 2023, both prevalence and burden of DUDs were higher in high-income countries, particularly in the USA. The most prevalent DUDs in 2023 were cannabis use disorder (age-standardized prevalence, 270.8 (95% UI, 201.7–350.0) per 100,000 people) and opioid use disorder (205.9 (95% UI, 178.7–235.0)). Particularly, opioid use disorder showed a nearly twofold increase in prevalence and burden between 1990 and 2023. In 2023, compared with countries where cannabis use was illegal, countries permitting both recreational and medical cannabis use had higher prevalence rates for all types of DUDs. Proactive and effective policies are essential to mitigate the increasing global burden of DUDs.
Correction to: Nature Medicinehttps://doi.org/10.1038/s41591-025-04137-0, published online 16 January 2026. In the original version of this article, errors and omissions were identified in the Competing Interests statements of several authors among the GBD 2023 Substance Use Collaborators. Following a comprehensive review of all competing interest declarations, corrections were required for nine authors. The competing interests statement for S. Afzal was incomplete. The statement has been amended to include grants or contracts from the Dean Office, Institute of Public Health Lahore. The competing interests statement for L. Monasta was incomplete. The statement has been amended to include support for the present manuscript from the Italian Ministry of Health to the Institute for Maternal and Child Health – IRCCS Burlo Garofolo, with payments made to the institution under project RC 34/2027; all outside the submitted work. The competing interests statement for J.P.S. was incomplete. The statement has been amended to include support for the present manuscript from the Portuguese Foundation for Science and Technology, including payment of salary under contract reference 2021.01789.CEECIND/CP1662/CT0014; all outside the submitted work. The competing interests statement for L.M.L.R.S. contained inaccuracies regarding the sources of grants or contracts. The statement has been corrected to accurately reflect support received from SPRINT – Sport Physical Activity and Health Research & Innovation Center, Polytechnic of Guarda, 6300-559 Guarda, Portugal and RISE–Health, Faculty of Health Sciences, University of Beira Interior, 6201-506 Covilhã, Portugal. The competing interests statement for J.A.S. was incomplete. The statement has been amended to include stock or stock options in Atyr Pharmaceuticals. The competing interests statement for A.C.T. contained an incorrect NIH grant number. The grant number has been corrected from K34DA061696 to K24DA061696. The competing interests statements for B. Oancea, K. Krishan, and I. N. Soyiri were omitted from the version of this article initially published. The statements have now been added and read as follows: “B.O. reports grants from the Core Program within the Romanian National Research, Development, and Innovation Plan 2022–2027, carried out with the support of MRID, project no. 23020101 (SIA-PRO), contract no. 7N/2022, and project PNRR-I8 no. 842027778, contract no. 760096. K. Krishan reports non-financial support from the UGC Centre of Advanced Study (CAS II), awarded to the Department of Anthropology, and support from the RUSA 2.0 grant awarded by the Ministry of Education to Panjab University, Chandigarh, India; all outside the submitted work. I.N.S. reports a leadership or fiduciary role in another board, society, committee, or advocacy group, paid or unpaid, as a trustee of the Citizens Advice Bureau for Hull & East Riding, United Kingdom.” These errors have now been corrected in the HTML and PDF versions of the article. No other parts of the article have been changed.