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Item ISPAD Clinical Practice Consensus Guidelines 2024: Screening, Staging, and Strategies to Preserve Beta-Cell Function in Children and Adolescents with Type 1 Diabetes(Karger, 2024) Haller, Michael J.; Bell, Kirstine J.; Besser, Rachel E. J.; Casteels, Kristina; Couper, Jenny J.; Craig, Maria E.; Larsson, Helena Elding; Jacobsen, Laura; Lange, Karin; Oron, Tal; Sims, Emily K.; Speake, Cate; Tosur, Mustafa; Ulivi, Francesca; Ziegler, Anette-G.; Wherrett, Diane K.; Marcovecchio, M. Loredana; Pediatrics, School of MedicineThe International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This guideline serves as an update to the 2022 ISPAD consensus guideline on staging for type 1 diabetes (T1D). Key additions include an evidence-based summary of recommendations for screening for risk of T1D and monitoring those with early-stage T1D. In addition, a review of clinical trials designed to delay progression to Stage 3 T1D and efforts seeking to preserve beta-cell function in those with Stage 3 T1D are included. Lastly, opportunities and challenges associated with the recent US Food and Drug Administration (FDA) approval of teplizumab as an immunotherapy to delay progression are discussed. The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This guideline serves as an update to the 2022 ISPAD consensus guideline on staging for type 1 diabetes (T1D). Key additions include an evidence-based summary of recommendations for screening for risk of T1D and monitoring those with early-stage T1D. In addition, a review of clinical trials designed to delay progression to Stage 3 T1D and efforts seeking to preserve beta-cell function in those with Stage 3 T1D are included. Lastly, opportunities and challenges associated with the recent US Food and Drug Administration (FDA) approval of teplizumab as an immunotherapy to delay progression are discussed.Item Systems biology approach to stage-wise characterization of epigenetic genes in lung adenocarcinoma(Springer Nature, 2013-12-26) Pradhan, Meeta P.; Desai, Akshay; Palakal, Mathew J.; Biomedical Engineering and Informatics, Luddy School of Informatics, Computing, and EngineeringBackground: Epigenetics refers to the reversible functional modifications of the genome that do not correlate to changes in the DNA sequence. The aim of this study is to understand DNA methylation patterns across different stages of lung adenocarcinoma (LUAD). Results: Our study identified 72, 93 and 170 significant DNA methylated genes in Stages I, II and III respectively. A set of common 34 significant DNA methylated genes located in the promoter section of the true CpG islands were found across stages, and these were: HOX genes, FOXG1, GRIK3, HAND2, PRKCB, etc. Of the total significant DNA methylated genes, 65 correlated with transcription function. The epigenetic analysis identified the following novel genes across all stages: PTGDR, TLX3, and POU4F2. The stage-wise analysis observed the appearance of NEUROG1 gene in Stage I and its re-appearance in Stage III. The analysis showed similar epigenetic pattern across Stage I and Stage III. Pathway analysis revealed important signaling and metabolic pathways of LUAD to correlate with epigenetics. Epigenetic subnetwork analysis identified a set of seven conserved genes across all stages: UBC, KRAS, PIK3CA, PIK3R3, RAF1, BRAF, and RAP1A. A detailed literature analysis elucidated epigenetic genes like FOXG1, HLA-G, and NKX6-2 to be known as prognostic targets. Conclusion: Integrating epigenetic information for genes with expression data can be useful for comprehending in-depth disease mechanism and for the ultimate goal of better target identification.