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diff --git a/gnqa/paper2_eval/data/dataset/gpt4o/intermediate_files/gpt4o_cs_diabetes_7 b/gnqa/paper2_eval/data/dataset/gpt4o/intermediate_files/gpt4o_cs_diabetes_7 new file mode 100644 index 0000000..485f8f6 --- /dev/null +++ b/gnqa/paper2_eval/data/dataset/gpt4o/intermediate_files/gpt4o_cs_diabetes_7 @@ -0,0 +1,65 @@ +{ + "titles": [ + "2019 - (Epi)genomic heterogeneity of pancreatic islet function and failure in type 2 diabetes.pdf", + "2020 - Functional Genomics in Pancreatic \u03b2 Cells Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research.pdf", + "2016 - Dissecting diabetes metabolic disease.pdf", + "2020 - Functional Genomics in Pancreatic \u03b2 Cells Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research.pdf", + "2020 - Functional Genomics in Pancreatic \u03b2 Cells Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research.pdf", + "2020 - Functional Genomics in Pancreatic \u03b2 Cells Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research.pdf", + "2020 - Functional Genomics in Pancreatic \u03b2 Cells Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research.pdf", + "2019 - (Epi)genomic heterogeneity of pancreatic islet function and failure in type 2 diabetes.pdf", + "2020 - Functional Genomics in Pancreatic \u03b2 Cells Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research.pdf", + "2020 - Functional Genomics in Pancreatic \u03b2 Cells Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research.pdf" + ], + "extraction_id": [ + "57736895-897e-54e5-a735-aadcbd77cb63", + "5f8a0ddd-a0c7-5151-9b6a-e0980bb94aa6", + "998a92ba-e7fc-5553-b629-7b5797fbfafe", + "fe5bf2df-2eda-5ef0-8aad-79bbc5b898d6", + "0a3e3095-4789-505a-96b7-123a05078e95", + "ab61a462-21d3-50dc-afb3-3e1cdeb15b1f", + "ab61a462-21d3-50dc-afb3-3e1cdeb15b1f", + "4e73f54b-d265-594d-9fc1-9535a2d84672", + "a36cee80-5961-55e5-8ea4-8d4e1bc501a9", + "62d513ed-2dca-5f45-9da2-d847f92fc931" + ], + "document_id": [ + "b9bc63a5-e366-5685-bd7a-4732a8eeffb7", + "51350055-d53c-5692-ab53-337b8a8bafd6", + "eee2f79d-e093-52fb-871a-798fd859235e", + "51350055-d53c-5692-ab53-337b8a8bafd6", + "51350055-d53c-5692-ab53-337b8a8bafd6", + "51350055-d53c-5692-ab53-337b8a8bafd6", + "51350055-d53c-5692-ab53-337b8a8bafd6", + "b9bc63a5-e366-5685-bd7a-4732a8eeffb7", + "51350055-d53c-5692-ab53-337b8a8bafd6", + "51350055-d53c-5692-ab53-337b8a8bafd6" + ], + "id": [ + "chatcmpl-AIFppDyOUKllFXSAk1UvPBBd5ythq", + "f42c0f84-d2a8-5bf9-89c2-3dd182bfb235", + "1859f32b-8f5c-5c3c-9f4d-54193d37645d", + "df30dab3-a490-5497-a079-2741f9039f87", + "eadf2320-de70-5499-ade0-7aa9930ac091", + "99ccc9a2-865f-5d11-9b08-b26261d02fc9", + "1f114642-3f77-5346-89e8-394c433f66ff", + "57b9550d-0258-5a87-be57-976f471e5763", + "4b170851-2dbd-5c06-9e3a-188d30a00170", + "83053df5-47ac-59da-9c30-69740a64372d", + "6f0adc7f-54ce-5a70-a2ea-153e074ccbdf" + ], + "contexts": [ + "A variety of cellular and animal models have been developed and applied over the past few years to experimentally manipulate cis-regulatory elements and their target gene function as it related to beta cell/isletfunction, glucose homeostasis, and T2D pathogenesis. CRISPR/Cas9 hasrevolutionized our ability to modify genomes and epigenomes almost at will. Unsurprisingly, CRISPR (epi)genome editing tools can and have been used to target putative T2D target genes [54] orcis-REs[55] in beta", + "to how CRISPR/Cas9 technology may nd clinical application in patients with diabetes. Keywords: genome editing, beta cell, genome-wide association studies, maturity onset of diabetes of the young, stem cells, mouse models INTRODUCTION Type 2 diabetes (T2D) affects an estimated 425 million people worldwide, a number predicted to rise to 629 million by 2045 ( 1). The disease usually involves insulin resistance but is ultimately the result", + "hPSCs [48,49] for correcting the COL7A1 [50] anda1-antitrypsin genes [51]. Given the superior cutting ef ciency, CRISPR/Cas9 is increasingly becoming the favored choice for genome editing inhPSCs [16,52] . 3.2. Employing hPSCs and genome editing tools to study diabetes and metabolic syndromes In general, the strategy to carry out in vitro disease modeling of dia-", + "Due to its simplicity and adaptability, CRISPR has rapidly become the most popular genome editing tool available for the mammalian genome ( 50,63). Because NHEJ DNA repair often introduces unwanted indels at the Cas9 cutting site, CRISPR hasbeen used to knock-out genes by introducing frameshiftmutations, resulting in protein depletion ( 156,157). In the diabetes eld, CRISPR has also been adopted to study several genes in bcell lines and in human ES-derived bcells ( 21,151,", + "samples ( 236). CRISPR technology has been used recently to correct point mutations in patient-derived iPSCs to target diabetes-relatedgene defects. To date, the most ef cient method used in iPSC is CRISPR/Cas9-based homology-directed repair (HDR). Here, a Cas9-mediated cut is generated adjacent to the site of interest. A homologous donor template with the intended nucleotidechange containing silent mutations in the gRNA sequence(167) can then be recombined by HDR. This approach has", + "in response to various stimuli including glucose aftertransplantation in an immunocompromised mouse model (230,231). However, the use of iPSC is controversial and there are some concerns over genetic and epigenetic variations iniPSCs which might affect cell function after differentiation ( 275). Manipulation of hESC/iPSC cells via CRISPR-Cas9 technology provides a platform for the correction of genomic mutations not only in diabetes but in other disease elds as well", + "RNP and single strand edDNA (ssDNA) donor which carriesdesired changes such as insertion of loxP site ( 255,259265). Using CRISPR-Cas9, leptin and leptin receptor knockout mice have been established as tools in diabetes and obesity research ( 160,255,256). Knock-in mouse models have also been established via HDR to achieve cell-speci c deletion of the gene ( 266). Genome Editing: Clinical Application in Diabetes An important goal in genetic research is to identify the genetic", + "CRISPR-Cas9 epigenome editing enables high-throughput screening for functionalregulatory elements in the human genome. Nature Biotechnology 35(6):561 e568. [58] Hodson, D.J., Mitchell, R.K., Marselli, L., Pullen, T.J., Gimeno Brias, S., Semplici, F., et al., 2014. ADCY5 couples glucose to insulin secretion in humanislets. Diabetes 63(9):3009 e3021 . [59] Zhou, Y., Park, S.-Y., Su, J., Bailey, K., Ottosson-Laakso, E., Shcherbina, L.,", + "free IPSCs from Human Pancreatic Cells Using the CRISPR-Cas9 System. J Vis Exp JoVE (2017). doi: 10.3791/56260 277. Millette K, Georgia S. Gene Editing and Human Pluripotent Stem Cells: Tools for Advancing Diabetes Disease Modeling and Beta-Cell Development. Curr Diabetes Rep (2017) 17:116. doi: 10.1007/s11892-017-0947-3Hu et al. Genome Editing of Pancreatic Beta Cells Frontiers in Endocrinology | www.frontiersin.org October 2020 | Volume 11 | Article 576632 19", + "DNA donors as templates, it is possible the nCas9-RT will beable to convert all variants at once. This new technique, however,is still in early development, and its editing ef ciency and side- effects remain to be seen.FUTURE PROSPECTIVES Recent technological developments around CRISPR-Cas9 and itsderivative technologies, combined with advances in humancellular models, should accelerate our understanding of theinterplay between diabetes risk-associated genetic variants and" + ], + "answer": "CRISPR/Cas9 technology can be used to study or treat genetic forms of diabetes in several ways: 1. **Genome and Epigenome Editing**: CRISPR/Cas9 has revolutionized the ability to modify genomes and epigenomes, allowing researchers to target specific genes associated with Type 2 Diabetes (T2D) and manipulate cis-regulatory elements related to beta cell function and glucose homeostasis [1]. 2. **Gene Knockout Studies**: CRISPR has been used to knock out genes by introducing frameshift mutations, which result in protein depletion. This approach has been adopted to study several genes in beta cell lines and human embryonic stem cell-derived beta cells, providing insights into the genetic basis of diabetes [4]. 3. **Correction of Point Mutations**: CRISPR technology has been used to correct point mutations in patient-derived induced pluripotent stem cells (iPSCs) targeting diabetes-related gene defects. The most efficient method for this is CRISPR/Cas9-based homology-directed repair (HDR), which involves generating a Cas9-mediated cut near the mutation site and using a homologous donor template to introduce the intended nucleotide change [5]. 4. **Disease Modeling**: CRISPR/Cas9 can be employed in human pluripotent stem cells (hPSCs) to model diabetes and metabolic syndromes in vitro. This allows researchers to study the disease mechanisms and test potential treatments in a controlled environment [3]. 5. **Animal Models**: CRISPR/Cas9 has been used to create knockout and knock-in mouse models, such as leptin and leptin receptor knockout mice, which serve as tools for diabetes and obesity research. These models help in understanding the genetic factors contributing to diabetes and testing therapeutic interventions [7]. Overall, CRISPR/Cas9 technology provides a powerful platform for both studying the genetic underpinnings of diabetes and developing potential gene therapies to treat the disease.", + "question": "How can CRISPR/Cas9 technology be used to study or treat genetic forms of diabetes?" +}
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