Patient-derived organoids predict personalized drug response and reveal alternative therapeutic options in glioblastoma.
The 3 matches
- [1] § Results › Transcriptomic analysis reveals potential mechanisms underlying both innate and acquired TMZ resistance in GBOs with MGMT methylation ↔ Code/RNA_analysis.R, lines 276–352 · score 0.69 · Gene Ontology, pathway enrichment, fold changes, DEGs, KEGG, GO
- [2] § Results › Transcriptomic analysis reveals potential mechanisms underlying both innate and acquired TMZ resistance in GBOs with MGMT methylation ↔ Code/RNA_analysis.R, lines 276–352 · score 0.56 · fold changes, expressed genes, enriched, DEGs, enrichment, pathways
- [3] § Results › Transcriptomic analysis reveals potential mechanisms underlying both innate and acquired TMZ resistance in GBOs with MGMT methylation ↔ Code/RNA_analysis.R, lines 51–104 · score 0.54 · mismatch repair, KEGG pathway, MMR, gene
Paper
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The authors' code
R · 352 lines · 13 KB · no license · 3 matches
- # rna analysis
- library(org.Hs.eg.db)
- library(clusterProfiler)
- library(GSEABase)
- library(GSVA)
- library(edgeR)
- library(tidyverse)
- library(ggthemes)
- library(ggpubr)
- library(dplyr)
- library(ComplexHeatmap)
- library(limma)
- library(pheatmap)
- library(RColorBrewer)
- library(enrichplot)
- # RNA expression correlation
- ## TMM normalize
- anno = read.delim("anno.txt", row.names = 1)
- ### load data
- counts <- read.delim("RNA_readcount.txt", sep="\t")
- colnames(counts)[3:14] <- colnames(counts)[3:14] %>% gsub("\\.","-",.)
- counts_dedup <- counts[,c(2:14)]
- counts_dedup <- counts_dedup[!duplicated(counts_dedup$Gene_id), ]
- ### normalize
- group=anno$Type
- count_input <- counts_dedup[,c(anno$RNA_ID)]
- row.names(count_input) <- counts_dedup$Gene_id
- y <- DGEList(counts=count_input, group=group)
- keep <- filterByExpr(y, group=group)
- y <- y[keep, , keep.lib.sizes=FALSE]
- y <- calcNormFactors(y)
- bcv <- 0.4 # well-controlled experiments are 0.4 for human data
- et <- exactTest(y, dispersion=bcv^2)
- top <- topTags(et)
- tmm_log <- cpm(y, log=TRUE)
- exp.df <- t(tmm_log)
- exp.df <- merge(anno, exp.df, by="row.names")
- ## draw
- pdf("RNA_cor_per_patient.pdf", 16, 4)
- exp.df %>% filter(Sample %in% c("GBO-001", "GBO-002", "GBO-003", "GBO-005", "GBO-008")) %>% column_to_rownames("RNA_ID") %>%
- select(Type, Patient, colnames(exp.df)[23:21125]) %>% pivot_longer(colnames(exp.df)[23:21125], names_to = "Gene", values_to = "Expression") %>%
- pivot_wider(names_from = Type , values_from = Expression ) %>%
- ggplot(aes(x=Tissue, y=Organoid)) +
- stat_density_2d(aes(fill = stat(level)), alpha=0.9, geom = "polygon", show.legend = T , color="black", size = 0.2, bins = 9) +
- scale_fill_distiller(palette = "Spectral") +
- theme_base() + stat_cor(method = "spearman") +
- facet_wrap(~ Patient, scales = "free", ncol = 5) + labs(x = "mRNA expression (Tissue)", y = "mRNA expression (Organoid)")
- dev.off()
- # KEGG pathway GSVA
- ## load data
- tpm_final <- read.delim("RNA_TPM.txt")
- colnames(tpm_final)[3:15] <- colnames(tpm_final)[3:15] %>% gsub("\\.","-",.)
- tpm_final.df <- tpm_final[,c(2:15)]
- tpm_final.df <- tpm_final.df[!duplicated(tpm_final.df$Gene_id), ]
- tpm_final_mat = as.matrix(tpm_final.df %>% remove_rownames() %>% column_to_rownames("Gene_id"))
- kegg_geneSets = getGmt("c2.cp.kegg_medicus.v2023.2.Hs.symbols.gmt")
- ## run GSVA
- tpm_final_mat=as.matrix(tpm_final.df %>% remove_rownames() %>% column_to_rownames("Gene_id"))
- kegg_gsva=gsva(tpm_final_mat, kegg_geneSets, method="gsva", mx.diff=TRUE, verbose=FALSE, parallel.sz=1)
- kegg_gsva=data.frame(t(kegg_gsva), check.names = F, stringsAsFactors = F)
- gbo_rna_names = c("GBO-001-OR3-R", "GBO-002-OR5-R", "GBO-003-OR4-R", "GBO-005-OR4-R", "GBO-006-OR7-R", "GBO-008-OR-p-3-R", "GBO-019-OR2-R", "GBO-015-OR-R")
- ## draw
- pdf("KEGG_MMR_barplot_8GBO.pdf", 5, 5)
- kegg_gsva[gbo_rna_names,c("KEGG_MEDICUS_REFERENCE_MISMATCH_REPAIR", "KEGG_MEDICUS_REFERENCE_HOMOLOGOUS_RECOMBINATION")] %>%
- rownames_to_column("Sample") %>%
- pivot_longer(c("KEGG_MEDICUS_REFERENCE_MISMATCH_REPAIR", "KEGG_MEDICUS_REFERENCE_HOMOLOGOUS_RECOMBINATION"),
- names_to = "KEGG", values_to = "GSVA") %>%
- mutate(KEGG = gsub("KEGG_MEDICUS_REFERENCE_MISMATCH_REPAIR","Mismatch Repair", KEGG)) %>%
- filter(KEGG == "Mismatch Repair") %>%
- mutate(Sample = substr(Sample, 1, 7)) %>%
- ggplot(aes(x = Sample, y = GSVA)) +
- geom_bar(position=position_dodge(), stat="identity", color="black") +
- theme_base(base_size = 15) +
- theme(axis.text.x=element_text(color="black",angle = 45, hjust=1))+
- labs(x = NULL, y = "GSVA score", subtitle = "KEGG Mismatch Repair") +
- geom_hline(yintercept=0, size=0.1) +
- theme(panel.grid.major.y = element_line(color = 'gray80', linewidth = 0.5))
- dev.off()
- # enrichment analysis
- ## filter gene
- tpm_final.df %>% select("Gene_id", "GBO-005-OR4-R", "GBO-019-OR2-R") %>% remove_rownames() %>%
- column_to_rownames("Gene_id") %>%
- apply(2, function(x) {x > 5}) %>% as.data.frame %>% rowSums() %>%
- as.data.frame %>% rename(exp_thres = ".") %>%
- filter(exp_thres > 0) %>% row.names() -> gbo005_over5_gene_id
- ## select gene
- tpm_final.df %>% select("Gene_id", "GBO-005-OR4-R", "GBO-019-OR2-R") %>% filter(Gene_id %in% gbo005_over5_gene_id) %>%
- mutate(GBO005 = log2(`GBO-005-OR4-R` + 1)) %>% mutate(GBO005R = log2(`GBO-019-OR2-R` + 1)) %>%
- mutate(FC = GBO005R - GBO005) %>% filter(FC >= 2) %>% arrange(desc(FC)) %>% select(Gene_id) %>% deframe -> GBO5R_fc_over2
- ## enrichment analysis
- GBO5R_fc_over2_ego <-enrichGO(GBO5R_fc_over2, OrgDb='org.Hs.eg.db', keyType = "SYMBOL", ont = "ALL",
- pvalueCutoff = 0.05, pAdjustMethod = "BH",
- qvalueCutoff = 0.25, minGSSize = 10, maxGSSize = 500)
- ## draw
- pdf("GBO-019_FC_ego.dotplot.pdf", 7.5, 7)
- dotplot(GBO5R_fc_over2_ego %>% filter(ONTOLOGY == "BP"), showCategory = 15, label_format = 50,
- title="GBO-019, Biologial process")
- dev.off()
- # MGMT mRNA expression
- tpm.anno.df <- merge(anno, tpm_final.df %>% remove_rownames() %>% column_to_rownames("Gene_id") %>% t() , by="row.names")
- pdf("MGMT_mRNA_barplot.pdf", 4.5, 4)
- tpm.anno.df %>% filter(Type == "Organoid") %>% remove_rownames() %>% column_to_rownames("Row.names") %>%
- select("Sample", "MGMT") %>%
- ggplot(aes(x = Sample, y = MGMT)) +
- geom_bar(position=position_dodge(), stat="identity", color="black") +
- theme_base(base_size = 15) +
- theme(axis.text.x=element_text(color="black",angle = 45, hjust=1))+
- geom_hline(yintercept=0, size=0.1) +
- labs(x = NULL, y = "TPM", subtitle = "MGMT RNA epxression") +
- theme(panel.grid.major.y = element_line(color = 'gray80', linewidth = 0.5))
- dev.off()
- # VEGFA, VEGFR expression
- pdf("VEGFA_VEGFR_tpm.pdf", 7, 4)
- tpm_final.df %>% filter(Gene_id %in% c("VEGFA", "FLT1", "KDR", "FLT4")) %>%
- pivot_longer(colnames(tpm_final.df)[-1], names_to = "Sample", values_to = "TPM") %>%
- mutate(Type = ifelse(grepl("-T-R" , Sample), "Tissue", "Organoid")) %>%
- mutate(log2TPM = log2(TPM+1)) %>%
- mutate(Gene_id = factor(Gene_id, levels = c("VEGFA", "FLT1", "KDR", "FLT4"))) %>%
- ggplot(aes(x=Type, y=log2TPM, fill=Type) ) + theme_base() +
- geom_dotplot(binaxis = "y", stackdir = "center", binpositions="all", binwidth = 0.3,color="black") +
- facet_grid(~ Gene_id)+ labs(y="log2 TPM", x =NULL) +
- theme(axis.text.x=element_text(color="black", angle = 45, hjust=1))
- dev.off()
- # Read TPM expression data and set gene IDs as row names
- GBO_TPM <- read.delim("GBM_GBO_TPM.txt")
- rownames(GBO_TPM) <- GBO_TPM$Gene_id
- # Keep only columns with "OR" in their names (GBO samples)
- GBO_TPM <- GBO_TPM[,grepl("OR", colnames(GBO_TPM))]
- # Filter out genes with low average expression (<5 TPM)
- GBO_TPM <- GBO_TPM[rowMeans(GBO_TPM) >= 5, ]
- # Filter out genes where ≤3 samples have expression >1
- GBO_TPM <- GBO_TPM %>%
- filter(rowSums(. > 1) > 3)
- # Log2 transform the data (adding 1 to avoid log(0))
- log_GBO_TPM.raw <- log2(GBO_TPM +1)
- # Save current row names as a new column for filtering
- log_GBO_TPM.raw$rownames <- rownames(log_GBO_TPM.raw)
- # Keep genes with expression >0 in more than 3 samples
- log_GBO_TPM <- log_GBO_TPM.raw %>%
- filter(rowSums(across(-rownames, ~ . > 0)) > 3)
- # Restore original row names after filtering
- rownames(log_GBO_TPM) <- rownames(GBO_TPM)
- ### Separate samples into TMZ-resistant and TMZ-sensitive groups
- # TMZ-resistant samples
- log_GBO_TPM.TMZ.resi <- log_GBO_TPM[,c("GBO.002.OR5.R", "GBO.003.OR4.R", "GBO.006.OR7.R")]
- rownames(log_GBO_TPM.TMZ.resi) <- rownames(log_GBO_TPM)
- # TMZ-sensitive samples
- log_GBO_TPM.TMZ.sens <- log_GBO_TPM[,c("GBO.001.OR3.R", "GBO.005.OR4.R", "GBO.008.OR.p.3.R")]
- rownames(log_GBO_TPM.TMZ.sens) <- rownames(log_GBO_TPM)
- ### Calculate fold-change between resistant and sensitive samples
- log_GBO_TPM <- log_GBO_TPM %>% select(-rownames)
- # Compute average expression per gene for each group
- resi.mean <- rowMeans(log_GBO_TPM.TMZ.resi)
- sens.mean <- rowMeans(log_GBO_TPM.TMZ.sens)
- fold.diff <- resi.mean - sens.mean
- # Select top 50 upregulated and top 50 downregulated genes (total 100)
- top_DEGs <- c(names(sort(fold.diff, decreasing=TRUE)[1:50]), names(sort(fold.diff)[1:50]))
- # Prepare data for the heatmap (excluding the last column if needed)
- data <- log_GBO_TPM[top_DEGs, -ncol(log_GBO_TPM)]
- # Rename columns for clarity
- colnames(data) <- c("GBO-001", "GBO-002", "GBO-003", "GBO-005", "GBO-006","GBO-008")
- # Define sample types for each column
- sample_types <- c("TMZ-sensitive", "TMZ-resistant", "TMZ-resistant",
- "TMZ-sensitive", "TMZ-resistant", "TMZ-sensitive")
- # Set colors for sample types
- type_colors <- c("TMZ-sensitive" = "yellow", "TMZ-resistant" = "purple")
- # Create column annotation data frame
- annotation <- data.frame(Type = sample_types)
- rownames(annotation) <- colnames(data)
- # Define annotation colors for both column and row annotations
- ann_colors <- list(
- Type = c("TMZ-sensitive" = "yellow", "TMZ-resistant" = "purple"),
- `TMZ-resist Expr` = c("Upregulated" = "brown", "Downregulated" = "darkgreen")
- )
- # Create row annotation indicating whether genes are up- or downregulated
- annotation_row <- data.frame(`TMZ-resist Expr` = factor(c(rep("Upregulated", 50), rep("Downregulated", 50))))
- rownames(annotation_row) <- rownames(data)
- colnames(annotation_row) <- "TMZ-resist Expr"
- # Plot the heatmap with row scaling and clustering
- pheatmap(
- as.matrix(data),
- annotation_col = annotation,
- annotation_colors = ann_colors,
- annotation_row = annotation_row,
- annotation_names_row = FALSE,
- scale = "row", # Standardize by rows
- cluster_rows = TRUE,
- cluster_cols = TRUE,
- color=colorRampPalette(c("blue", "white", "red"))(100),
- show_rownames=TRUE
- )
- #Figure 4C, Figure S6
- # Load TPM expression data and set row names to gene IDs
- GBO_TPM <- read.delim("GBM_GBO_TPM.txt")
- rownames(GBO_TPM) <- GBO_TPM$Gene_id
- # Keep only columns with "OR" in their names (GBO samples)
- GBO_TPM <- GBO_TPM[,grepl("OR", colnames(GBO_TPM))]
- # Log2 transform the TPM data (adding 1 to avoid log(0))
- log_GBO_TPM <- log2(GBO_TPM +1)
- ### Separate samples into TMZ-resistant and TMZ-sensitive groups
- log_GBO_TPM.TMZ.resi <- log_GBO_TPM[,c("GBO.002.OR5.R", "GBO.003.OR4.R", "GBO.006.OR7.R")]
- log_GBO_TPM.TMZ.sens <- log_GBO_TPM[,c("GBO.001.OR3.R", "GBO.005.OR4.R", "GBO.008.OR.p.3.R")]
- # Calculate fold changes between resistant and sensitive samples
- resi.mean <- rowMeans(log_GBO_TPM.TMZ.resi)
- sens.mean <- rowMeans(log_GBO_TPM.TMZ.sens)
- fold.diff <- resi.mean - sens.mean
- # Print average expression for each group (for reference)
- mean(resi.mean)
- mean(sens.mean)
- # Plot a histogram of the fold changes
- hist(fold.diff, breaks=200, xlim=c(-3,3), xlab="Fold Change", main = "Histogram of GBO RNA expression FC")
- # Calculate p-value for all genes (estimating differential expressions)
- # Welch Two Sample t-test
- # Calculate p-values using the Wilcoxon test for each gene
- p.val <- sapply(1:nrow(log_GBO_TPM.TMZ.resi), function(i)
- wilcox.test(as.matrix(log_GBO_TPM.TMZ.resi[i,]),
- as.matrix(log_GBO_TPM.TMZ.sens[i,]), paired = FALSE)$p.value)
- # Adjust p-values using Benjamini-Hochberg FDR
- FDR <- round(p.adjust(p.val, 'BH'),3)
- fData <- data.frame(Accession=rownames(log_GBO_TPM.TMZ.resi), FC=fold.diff, p.value=p.val, FDR=FDR)
- fData
- ### Gene Ontology Enrichment Analysis
- # Identify differentially expressed genes (DEGs)
- fData$DEG.UP <- fData$FC > 1
- fData$DEG.DOWN <- fData$FC < -1
- # Select only DEGs (either up or down)
- DEG <- fData[fData$DEG.UP | fData$DEG.DOWN,]
- # Order DEGs by fold change (highest first)
- DEG <- DEG[order(DEG$FC, decreasing=T),]
- # Convert gene symbols to Entrez IDs using org.Hs.eg.db
- entrezID <- bitr(DEG$Accession, fromType = "SYMBOL",
- toType = "ENTREZID",
- OrgDb = org.Hs.eg.db)
- # Create a named vector of fold changes with Entrez IDs as names
- FC <- DEG$FC
- names(FC) <- entrezID$ENTREZID
- FC
- # Perform GO enrichment analysis (for all ontologies)
- ego <- enrichGO(entrezID$ENTREZID,
- OrgDb = "org.Hs.eg.db",
- ont = "ALL",
- readable = TRUE,
- pvalueCutoff = 0.01,
- qvalueCutoff = 0.05,
- universe = FC)
- # Plot GO enrichment results with a dot plot, split by ontology
- pdf("GO_dotplot_TMZresponse.pdf", height=16, width=12)
- dotplot(ego, split = "ONTOLOGY", showCategory = 20, font.size = 12, label_format = 50) +
- facet_grid(ONTOLOGY ~ ., scale = "free_y") +
- geom_count() +
- scale_size_area(max_size = 8)
- dev.off()
- # Perform KEGG pathway enrichment analysis
- kk <- enrichKEGG(entrezID$ENTREZID,
- organism = 'hsa',
- pvalueCutoff = 0.01,
- qvalueCutoff = 0.05)
- pdf("KEGG_dotplot_TMZresponse.pdf", height=16, width=12)
- # Plot KEGG enrichment results using a dot plot
- dotplot(kk, font.size = 10, showCategory = 20) +
- geom_count() +
- scale_size_area(max_size = 5)
- dev.off()
RNA_analysis.R at commit 3bd53b6, no license · at the source
Overview
13 affiliations
- Graduate School of Stem Cell and Regeneration Biology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
- KAIST Stem Cell Center, KAIST, Daejeon 34141, Republic of Korea
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
- SG BioScience, Inc., Seoul 02637, Republic of Korea
- Department of Biological Sciences, Chungnam National University, Daejeon 34134, Republic of Korea
- Department of Medical Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
- Department of Neurosurgery, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon 35015, Republic of Korea
- Department of Neurosurgery, Yeungnam University Hospital, Yeungnam University School of Medicine, Daegu 42415, Republic of Korea
- Department of Neurosurgery, Dongsan Medical Center, Keimyung University School of Medicine, Daegu 41931, Republic of Korea
- Department of Neurosurgery, Dong-A University Hospital, Dong-A University, College of Medicine, Busan 49201, Republic of Korea
- Department of Neurosurgery, Soonchunhyang University Hospital Cheonan, Soonchunhyang University School of Medicine, Cheonan 31151, Republic of Korea
- Department of Neurosurgery, Konkuk University Medical Center, Seoul 05030, Republic of Korea
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
Abstract
The abstract is not reproduced here: the paper's license (CC BY-NC-ND) does not allow it. Read it in the paper, at the publisher or on Europe PMC.
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SGMedical/GBO
3bd53b6dc092698e780cb000c474f91f8e6ebba8, 14 February 2025Availability: 1 check, the latest on 27 September 2026: the link answers
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3 files
- Code/
Genomic_analysis.R , R, 272 lines - Code/
RNA_analysis.R , R, 352 lines, 3 matches - README.md, Text, 5 lines
The paper's code and data availability statement is in the Data section.
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Read it in the paper: doi.org/10.1016/j.xcrm.2026.102850.
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Recorded: type, language, journal, volume, issue, pages, dates, 24 authors, 7 keywords, 16 MeSH terms, 5 funders, 80 references, 15 RRIDs.
Cite
This paper
Park, J., Qiu, M., Cho, E. J., Seo, S., Moon, J.-H., Kim, M., Mun, H., Yun, H., Park, H., Lim, A., Kang, Y., Oh, J.-w., Youk, H., Kim, S.-H., Seo, Y., Kwon, S. M., Sung, K. S., Oh, H.-J., Cho, K. R., . . . Yoon, K.-J. (2026). Patient-derived organoids predict personalized drug response and reveal alternative therapeutic options in glioblastoma. Cell reports. Medicine, 7(7), 102850. https://
BibTeX
@article{park2026patient
author = {Park, Jisu and Qiu, Meiyu and Cho, Eun Jeong and Seo, Sanghee and Moon, Ji-Hoon and Kim, Minji and Mun, Hyemin and Yun, Hyounji and Park, Hoewon and Lim, Arim and Kang, Younsoo and Oh, Jeong-woo and Youk, Heejeong and Kim, Seon-Hwan and Seo, Yeongbeom and Kwon, Sae Min and Sung, Kyoung Su and Oh, Hyuk-Jin and Cho, Kyung Rae and Yoon, Kyungtae and Kim, Nam-Shik and Jang, Se Jin and Kim, Kyung Hwan and Yoon, Ki-Jun},
title = {{Patient-derived organoids predict personalized drug response and reveal alternative therapeutic options in glioblastoma}},
journal = {Cell reports. Medicine},
year = {2026},
month = jun,
volume = {7},
number = {7},
pages = {102850},
publisher = {Elsevier},
issn = {2666-3791},
doi = {10.1016/
url = {https://
pmid = {42276053},
pmcid = {PMC13400186}
}
RIS
TY - JOUR
AU - Park, Jisu
AU - Qiu, Meiyu
AU - Cho, Eun Jeong
AU - Seo, Sanghee
AU - Moon, Ji-Hoon
AU - Kim, Minji
AU - Mun, Hyemin
AU - Yun, Hyounji
AU - Park, Hoewon
AU - Lim, Arim
AU - Kang, Younsoo
AU - Oh, Jeong-woo
AU - Youk, Heejeong
AU - Kim, Seon-Hwan
AU - Seo, Yeongbeom
AU - Kwon, Sae Min
AU - Sung, Kyoung Su
AU - Oh, Hyuk-Jin
AU - Cho, Kyung Rae
AU - Yoon, Kyungtae
AU - Kim, Nam-Shik
AU - Jang, Se Jin
AU - Kim, Kyung Hwan
AU - Yoon, Ki-Jun
TI - Patient-derived organoids predict personalized drug response and reveal alternative therapeutic options in glioblastoma
T2 - Cell reports. Medicine
J2 - Cell Rep Med
PY - 2026
DA - 2026/
VL - 7
IS - 7
SP - 102850
SN - 2666-3791
PB - Elsevier
DO - 10.1016/
UR - https://
LA - en
ER -
CSL-JSON
{
"id": "10.1016/
"type": "article-journal",
"title": "Patient-derived organoids predict personalized drug response and reveal alternative therapeutic options in glioblastoma",
"container-title": "Cell reports. Medicine",
"author": [
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"family": "Park",
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"family": "Jang",
"given": "Se Jin"
},
{
"family": "Kim",
"given": "Kyung Hwan"
},
{
"family": "Yoon",
"given": "Ki-Jun"
}
],
"container-title-short":
"volume": "7",
"issue": "7",
"page": "102850",
"DOI": "10.1016/
"PMID": "42276053",
"PMCID": "PMC13400186",
"ISSN": "2666-3791",
"publisher": "Elsevier",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
[
2026,
6,
11
]
]
}
}
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