bluuebunny/crossref_metadata_2025 huggingface dataset:
Instrumentalising the imagination: science fiction prototyping as posthumanist methodology
Authors: Szollosy Michael
Published: January 2025

Imagination and narrative are of vital importance in understanding how we conceive of our potential (disability) futures, and the role technology has in shaping our realities. The concept of ‘science fiction prototyping’ (SFP) is not only useful for articulating how narrative can be used to foster imaginations about potential future worlds, but also for creating a methodology through which we can understand how the imagination can work as a tool for co-designing better futures. Johnson’s conception of SFP (2011) serves as a useful starting place, but we need to more critically examine this (and related) conceptions. As Johnson himself admits, his is more of a ‘how-to book’ than a scholarly framework for research, and the key ideas that underpin his concept of SFP (eg, imagination, narrative) are underdeveloped. Most importantly, for all the claims as SFP being part of an exercise in ‘future casting’, the assumptions that are the foundations of Johnson’s book are resolutely and obsoletely humanist, despite co-design methodologies inherently reaching for something beyond the old humanist categories. By closely recontextualising SFP and examining its ideological origins, we will find important new directions to exploit and use in our work. Specifically, we explore how a more thoroughly conceived and developed SFP methodology is a posthumanist approach to co-design that better builds on a self-reflexive understanding of how cultural imaginations and our futures both shape and are shaped by our interactions with technology. This allows us to create a better methodology for a co-design practice that is more explicitly aware of how we use narratives and talk about our futures, and helps us to bridge co-design practice with more critical ways of thinking about how posthuman imaginations (personal, social, cultural, political) are constructed and instrumentalised.
Multiphysics Simulation of an Electrorefiner with Continuous Circulation of Molten Salt for Separation of Uranium and Neptunium
Authors: Sun Wenzhou , Yan Liuming , Jiang Tao , Peng Shuming , Yue Baohua
Published: January 2025

A 3-D continuous electrorefiner is designed and investigated using multiphysics simulation for the separation of uranium and neptunium from spent nuclear fuel in molten salt. The concentration distribution field, the electric field, the ionic flux density field, and the flow field are evaluated under galvanostatic and pulse electrorefining by numerical integration of the governing equations using finite element method. During the electrorefining without molten salt recirculation, the transport of the electroactive cations is controlled by diffusion and electromigration and high concentration gradient is built near electrodes. In a galvanostatic electrorefining with a current density of 50 A·m–2, the concentration of U3+ decreases to 26.7 mol·m–3 near cathode and increases to 62.5 mol·m–3 near anode within 40 s, and no co-deposition of uranium and neptunium occurs. In a galvanostatic electrorefining with a current density of 200 A·m–2, the concentration of U3+ decreases to 1.3 mol·m–3 near cathode and increases to 62.6 mol·m–3 near anode within 6.7 s, and the co-deposition of uranium and neptunium occurs after 0.28 mg of pure uranium is collected. With moderate molten salt recirculation, the transport of the electroactive cations is controlled by convection. The local concentrations of uranium ions approach steady near the electrodes within 32 s in a galvanostatic electrorefining of 50 A·m–2, and no co-deposition of uranium and neptunium occurs. Though the concentration of U3+ decreases to 21.1 mol·m–3 near cathode and increases to 62.6 mol·m–3 near anode within 6.7 s with a current density of 200 A·m–2, there is no co-deposition of uranium and neptunium occurred. In addition, it is proved that the pulse electrorefining does not improve the recovery of uranium compared with galvanostatic electrorefining with a corresponding average current.
Improved Asphalt Pavement Crack Detection Model Based on Shuffle Attention and Feature Fusion
Authors: Mamat Tursun , Dolkun Abdukeram , He Runchang , Zhang Yonghui , Nigat Zulipapar , Du Hanchen
Published: January 2025

Pavement distress is one of the most serious and prevalent diseases in pavement road detection. However, traditional methods for crack detection often suffer from low efficiency and limited accuracy, necessitating improvements in the accuracy of existing crack detection algorithms. Consequently, we propose the shuffle attention for you only look once version eight (SA‐YOLOv8) model, which is based on an enhanced framework. Initially, we establish the required dataset and classify images proportionally based on their states. Subsequently, we conduct comparative testing against the results of the original model, analyzing issues such as the oversight of shallow and small cracks, truncation in the recognition of single‐instance long cracks, and imprecise detection. We devise an improved detection approach based on YOLOv8. This method incorporates a small target detection layer to optimize the receptive field range, aiming to focus on identifying shallow and small cracks. Simultaneously, the Shuffle Attention mechanism and the transplanted spatial pyramid pooling‐fast (SPP‐F) reuse structure are introduced in the feature extraction network to enhance the model’s attention to detection targets. This augmentation improves the fusion of features for shallow small targets and overall and partial features of long cracks, thereby alleviating the precision of the model in crack detection. The experimental results demonstrate a stepwise improvement in the model’s mean average precision (mAP) with each enhancement to the original network. Initially, adding a small object detection layer increased the mAP by 3.4 percentage points, raising it to 68.2%. Subsequently, incorporating the spatial attention (SA) module resulted in a more substantial improvement, boosting the mAP by 8.7 percentage points to 73.5%. Finally, the addition of the transplanted SPP‐F module further enhanced accuracy, increasing the mAP by 0.7 percentage points from the previous stage, thus achieving a final mAP of 74.2%. Overall, these modifications resulted in a total improvement of 9.4 percentage points in mAP compared to the original model. In conclusion, the proposed SA‐YOLOv8s model effectively supports the automated recognition of asphalt road surface cracks, demonstrating applicability in practical scenarios. The recognition performance is notably favorable, demonstrating robustness in complex environments.
Supplementary Data from Targeted Degradation of SOS1 Exhibits Potent Anticancer Activity and Overcomes Resistance in KRAS-Mutant Tumors and BCR–ABL–Positive Leukemia
Authors: Luo Ziwei , Lin Chencen , Yu Chuwei , Yuan Changxian , Wu Wenyong , Xu Xiaowei , Sun Renhong , Jia Yan , Wang Yafang , Shen Jie , Wang Dingyan , Wang Sinan , Jiang Hualiang , Jiang Biao , Yang Xiaobao , Xie Chengying
Published: January 2025

Supplementary figures and tables
Figure S7 from H4K20me3-Mediated Repression of Inflammatory Genes Is a Characteristic and Targetable Vulnerability of Persister Cancer Cells
Authors: Ramponi Valentina , Richart Laia , Kovatcheva Marta , Stephan-Otto Attolini Camille , Capellades Jordi , Lord Alice E. , Yanes Oscar , Ficz Gabriella , Serrano Manuel
Published: January 2025

Supplementary figure 7
Figure 7 from Targeted Degradation of SOS1 Exhibits Potent Anticancer Activity and Overcomes Resistance in KRAS-Mutant Tumors and BCR–ABL–Positive Leukemia
Authors: Luo Ziwei , Lin Chencen , Yu Chuwei , Yuan Changxian , Wu Wenyong , Xu Xiaowei , Sun Renhong , Jia Yan , Wang Yafang , Shen Jie , Wang Dingyan , Wang Sinan , Jiang Hualiang , Jiang Biao , Yang Xiaobao , Xie Chengying
Published: January 2025

Combination of SIAIS562055 and TKIs synergistically inhibits the growth of CML xenografts in vivo and enhances cell death in primary samples from patients with CML. A–D, K562-xenografted mice received vehicle, SIAIS562055 (30 mg/kg/day), imatinib (100 mg/kg/day), or their combination; then, relative tumor volumes (A), tumor weights (B), photo of tumors (C), and mice body weights (D) were determined at indicated times. Data are presented as mean ± SEM, n = 5. E, Western blot analysis of SOS1, pERK, and pSTAT5 in K562 xenograft tumors after treatment with vehicle, SIAIS562055, imatinib, or their combination. Data are shown as mean ± SEM, n = 5. F, Cell viability of three primary BCR–ABL+ samples from patients with CML treated with varying doses of SIAIS562055 or imatinib, alone or in combination, for 72 hours was assessed by CellTiter-Glo assay. Data are presented as mean ± SD, n = 3. G, Western blot analysis of the indicated proteins in primary samples from patients with CML under 24-hour exposure to SIAIS562055 or imatinib, alone or in combination. Statistical significance was assessed using two-tailed unpaired Student t test. *, P < 0.05; **, P < 0.01; ***, P < 0.001. qd, once a day.
Figure S6 from H4K20me3-Mediated Repression of Inflammatory Genes Is a Characteristic and Targetable Vulnerability of Persister Cancer Cells
Authors: Ramponi Valentina , Richart Laia , Kovatcheva Marta , Stephan-Otto Attolini Camille , Capellades Jordi , Lord Alice E. , Yanes Oscar , Ficz Gabriella , Serrano Manuel
Published: January 2025

Supplementary figure 6
Figure 5 from Targeted Degradation of SOS1 Exhibits Potent Anticancer Activity and Overcomes Resistance in KRAS-Mutant Tumors and BCR–ABL–Positive Leukemia
Authors: Luo Ziwei , Lin Chencen , Yu Chuwei , Yuan Changxian , Wu Wenyong , Xu Xiaowei , Sun Renhong , Jia Yan , Wang Yafang , Shen Jie , Wang Dingyan , Wang Sinan , Jiang Hualiang , Jiang Biao , Yang Xiaobao , Xie Chengying
Published: January 2025

SIAIS562055 inhibits the proliferation of CML cells in vitro. A, Western blot analysis of SOS1 in K562 cells treated with SIAIS562055 (1,000 nmol/L), SIAIS562092 (1,000 nmol/L), or BI-3406 (1,000 nmol/L) for 24 hours, with or without the pretreatment of MG132 (1,000 nmol/L) for 1 hour. B, Western blot analysis of SOS1, pERK, GSPT1, and IKZF3 in K562 cells treated with SIAIS562055, SIAIS562092, or BI-3406 for 24 hours. C, Western blot analysis of SOS1 and pERK in K562 cells treated with a time gradient of SIAIS562055 or SIAIS562092. Histogram shows the relative SOS1 levels. D, Western blot analysis of SOS1 and pERK in K562 cells treated with SIAIS562055 (1,000 nmol/L), SIAIS562092 (1,000 nmol/L), or BI-3406 (1,000 nmol/L) for 12 hours, followed by wash-out and incubation with fresh media for another 0, 24, 48, and 72 hours. Line chart shows the relative pERK levels. E, Western blot analysis of SOS1 and pERK in K562 and KU812 cells treated with SIAIS562055 for 24 hours in a concentration gradient. F, Antiproliferative effects in K562 and KU812 cells after treatment with SIAIS562055 for 72 hours. Line charts show the IC50 values of two-dimensional culture. Data are shown as mean ± SD, n = 3. **, P < 0.01; ***, P < 0.001; ns, not significant.
Figure 4 from Targeted Degradation of SOS1 Exhibits Potent Anticancer Activity and Overcomes Resistance in KRAS-Mutant Tumors and BCR–ABL–Positive Leukemia
Authors: Luo Ziwei , Lin Chencen , Yu Chuwei , Yuan Changxian , Wu Wenyong , Xu Xiaowei , Sun Renhong , Jia Yan , Wang Yafang , Shen Jie , Wang Dingyan , Wang Sinan , Jiang Hualiang , Jiang Biao , Yang Xiaobao , Xie Chengying
Published: January 2025

SIAIS562055 combined with KRAS inhibitors overcomes drug resistance. A, Western blot analysis of SOS1 in Ba/F3 cells transformed with or without KRAS mutation after treatment with SIAIS562055 (1,000 nmol/L) or BI-3406 (1,000 nmol/L) for 24 hours. B, Antiproliferative effects of SIAIS562055 on Ba/F3 cells transformed with or without KRAS mutations for 72 hours. Histogram shows the IC50 values of compounds in two-dimensional (2D) cultured cells. C, Cell proliferative inhibition of MIA PaCa-2 and MIA PaCa-2/R cells treated with AMG510 and MRTX849 for 72 hours. Histogram shows the IC50 values of compounds and resistance factors (RF) in 2D cultured cells. D, Western blot analysis of SOS1 by SIAIS562055 in MIA PaCa-2 and MIA PaCa-2/R cells for 72 hours. MIA PaCa-2/R xenograft-bearing mice received vehicle, SIAIS562055, and MRTX849, alone or in combination, then, the relative tumor volumes (E) and mouse body weights (F) were tested. qd, once a day. G, Western blot analysis of SOS1, pERK, and cleaved caspase-3 in MIA PaCa-2/R xenograft tumor tissues. Data about relative tumor volumes and body weights are presented as mean ± SEM, n = 5, whereas other statistical data are presented as mean ± SD, n = 3. **, P < 0.01; ***, P < 0.001.
Figure 1 from Targeted Degradation of SOS1 Exhibits Potent Anticancer Activity and Overcomes Resistance in KRAS-Mutant Tumors and BCR–ABL–Positive Leukemia
Authors: Luo Ziwei , Lin Chencen , Yu Chuwei , Yuan Changxian , Wu Wenyong , Xu Xiaowei , Sun Renhong , Jia Yan , Wang Yafang , Shen Jie , Wang Dingyan , Wang Sinan , Jiang Hualiang , Jiang Biao , Yang Xiaobao , Xie Chengying
Published: January 2025

SIAIS562055 selectively degrades SOS1. A, Chemical structure of SIAIS562055 (562055 for short). B, Ternary complex of SIAIS562055, E3 ligase CRBN, and SOS1 determined by computer simulation. C, Visual inspection and interaction fingerprint analysis of the ternary complex. D, SPR assay was used to test the binding affinity of SIAIS562055 with SOS1. E, HTRF assay of the SOS1 and KRAS interaction after treatment with SIAIS562055 or BI-3406 at different concentrations. Data are shown as mean ± SD, n = 3. F, Effects of SOS1 by SIAIS562055 (1,000 nmol/L), SIAIS562092 (562092 for short; 1,000 nmol/L), or BI-3406 (1,000 nmol/L) for 24 hours with or without pretreatment of MG132 (1,000 nmol/L) for 1 hour in NCI-H358 and GP2d cells. G, Western blot analysis of SOS1, pERK, GSPT1, and IKZF1/3 in NCI-H358 cells treated with SIAIS562055, SIAIS562092, or BI-3406 for 24 hours. Data are representative of three independent replicates.
Table S3 from TCTN1 Induces Fatty Acid Oxidation to Promote Melanoma Metastasis
Authors: Li Yinlam , Ming Ren , Zhang Tianyi , Gao Zixu , Wang Lu , Yang Yang , Shen Kangjie , Wei Chenlu , Zhu Yu , Li Jianrui , Zheng Shaoluan , Luo Zucheng , Ding Yiteng , Xuan Jiangying , Hu Qianrong , Yang Yanwen , Gu Jianying , Wei Chuanyuan
Published: January 2025

Table S3
Supplementary Figure S9 from SpatialDeX Is a Reference-Free Method for Cell-Type Deconvolution of Spatial Transcriptomics Data in Solid Tumors
Authors: Liu Xinyi , Tang Gongyu , Chen Yuhao , Li Yuanxiang , Li Hua , Wang Xiaowei
Published: January 2025

Supplementary Figure S9
Supplementary Figure S8 from SpatialDeX Is a Reference-Free Method for Cell-Type Deconvolution of Spatial Transcriptomics Data in Solid Tumors
Authors: Liu Xinyi , Tang Gongyu , Chen Yuhao , Li Yuanxiang , Li Hua , Wang Xiaowei
Published: January 2025

Supplementary Figure S8
Supplementary Figure S7 from SpatialDeX Is a Reference-Free Method for Cell-Type Deconvolution of Spatial Transcriptomics Data in Solid Tumors
Authors: Liu Xinyi , Tang Gongyu , Chen Yuhao , Li Yuanxiang , Li Hua , Wang Xiaowei
Published: January 2025

Supplementary Figure S7
Supplementary Figure S4 from SpatialDeX Is a Reference-Free Method for Cell-Type Deconvolution of Spatial Transcriptomics Data in Solid Tumors
Authors: Liu Xinyi , Tang Gongyu , Chen Yuhao , Li Yuanxiang , Li Hua , Wang Xiaowei
Published: January 2025

Supplementary Figure S4
Supplementary Figure S3 from SpatialDeX Is a Reference-Free Method for Cell-Type Deconvolution of Spatial Transcriptomics Data in Solid Tumors
Authors: Liu Xinyi , Tang Gongyu , Chen Yuhao , Li Yuanxiang , Li Hua , Wang Xiaowei
Published: January 2025

Supplementary Figure S3
Supplementary Figure S2 from SpatialDeX Is a Reference-Free Method for Cell-Type Deconvolution of Spatial Transcriptomics Data in Solid Tumors
Authors: Liu Xinyi , Tang Gongyu , Chen Yuhao , Li Yuanxiang , Li Hua , Wang Xiaowei
Published: January 2025

Supplementary Figure S2
Supplementary Data from Replication Stress Is an Actionable Genetic Vulnerability in Desmoplastic Small Round Cell Tumors
Authors: Kawai-Kawachi Asuka , Lenormand Madison M. , Astier Clémence , Herbel Noé , Cutrona Meritxell B. , Ngo Carine , Garrido Marlène , Eychenne Thomas , Dorvault Nicolas , Bordelet Laetitia , Song Feifei , Bouyakoub Ryme , Loktev Anastasia , Romo-Morales Antonio , Henon Clémence , Colmet-Daage Léo , Vibert Julien , Drac Marjorie , Brough Rachel , Schwob Etienne , Martella Oliviano , Pinna Guillaume , Shipley Janet M. , Mittnacht Sibylle , Zimmermann Astrid , Gulati Aditi , Mir Olivier , Le Cesne Axel , Faron Matthieu , Honoré Charles , Lord Christopher J. , Chabanon Roman M. , Postel-Vinay Sophie
Published: January 2025

Supplementary File containing methods, figures and uncropped membranes.
Figure 3 from Replication Stress Is an Actionable Genetic Vulnerability in Desmoplastic Small Round Cell Tumors
Authors: Kawai-Kawachi Asuka , Lenormand Madison M. , Astier Clémence , Herbel Noé , Cutrona Meritxell B. , Ngo Carine , Garrido Marlène , Eychenne Thomas , Dorvault Nicolas , Bordelet Laetitia , Song Feifei , Bouyakoub Ryme , Loktev Anastasia , Romo-Morales Antonio , Henon Clémence , Colmet-Daage Léo , Vibert Julien , Drac Marjorie , Brough Rachel , Schwob Etienne , Martella Oliviano , Pinna Guillaume , Shipley Janet M. , Mittnacht Sibylle , Zimmermann Astrid , Gulati Aditi , Mir Olivier , Le Cesne Axel , Faron Matthieu , Honoré Charles , Lord Christopher J. , Chabanon Roman M. , Postel-Vinay Sophie
Published: January 2025

PARPi and ATRi combination elicits DNA damage, replication stress, and genomic instability in DSRCT cells. A–D, Quantification of γH2AX (A and B) or RAD51 foci (C and D) in JN1 (A and C) or R (B and D) cells exposed to DMSO control, PARPi talazoparib (Tala), ATRi M4344, or a combination of both for 72 hours. Cisplatin was used as the positive control. A minimum of 500 nuclei was analyzed per condition. Violin plots show the absolute number of foci per nucleus. Thick line, median; thin lines, bottom and top quartiles; two-way ANOVA and post hoc Dunn test. E and F, Western blots of pCHK1, CHK1, pRPA2, RPA2, γH2AX, H2AX, and cleaved-PARP1 (cPARP) in JN1 (E) or R (F) cells exposed to DMSO control, PARPi talazoparib or olaparib, ATRi M4344 or AZD6738, or a combination of both for 48 hours. G and H, Representative immunofluorescence images (G) and quantification (H) of micronuclei-positive cells in JN1 cells exposed to DMSO control, PARPi talazoparib, ATRi M4344, or a combination of both for 72 hours. A minimum of 500 cells was analyzed per condition. Mean ± SD; n = 3; one-way ANOVA and post hoc Dunn test. Arrows, micronuclei. Scale bar, 20 μm. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001; ns, not significant.
Supplementary Table S5 from LSD1 and CoREST2 Potentiate STAT3 Activity to Promote Enteroendocrine Cell Differentiation in Mucinous Colorectal Cancer
Authors: Ladaika Christopher A. , Ghobashi Ahmed H. , Boulton William C. , Miller Samuel A. , O’Hagan Heather M.
Published: January 2025

Gene regulatory network data.
Supplementary Figure S2 from LSD1 and CoREST2 Potentiate STAT3 Activity to Promote Enteroendocrine Cell Differentiation in Mucinous Colorectal Cancer
Authors: Ladaika Christopher A. , Ghobashi Ahmed H. , Boulton William C. , Miller Samuel A. , O’Hagan Heather M.
Published: January 2025

STAT3, JAK2, and calcium promote EEC differentiation.
Supplementary Figure S1 from LSD1 and CoREST2 Potentiate STAT3 Activity to Promote Enteroendocrine Cell Differentiation in Mucinous Colorectal Cancer
Authors: Ladaika Christopher A. , Ghobashi Ahmed H. , Boulton William C. , Miller Samuel A. , O’Hagan Heather M.
Published: January 2025

EnrichR and additional feature linkage maps.
Figure S5 from SOS1 Inhibition Enhances the Efficacy of KRASG12C Inhibitors and Delays Resistance in Lung Adenocarcinoma
Authors: Daley Brianna R. , Sealover Nancy E. , Finniff Bridget A. , Hughes Jacob M. , Sheffels Erin , Gerlach Daniel , Hofmann Marco H. , Kostyrko Kaja , LaMorte Joseph P. , Linke Amanda J. , Beckley Zaria , Frank Andrew M. , Lewis Robert E. , Wilkerson Matthew D. , Dalgard Clifton L. , Kortum Robert L.
Published: January 2025

KRASG12C-mutated cell lines show universal G12Ci:SHP2i synergy.
Data from LSD1 and CoREST2 Potentiate STAT3 Activity to Promote Enteroendocrine Cell Differentiation in Mucinous Colorectal Cancer
Authors: Ladaika Christopher A. , Ghobashi Ahmed H. , Boulton William C. , Miller Samuel A. , O’Hagan Heather M.
Published: January 2025

Abstract
Neuroendocrine cells have been implicated in therapeutic resistance and worse overall survival in many cancer types. Mucinous colorectal cancer (mCRC) is uniquely enriched for enteroendocrine cells (EEC), the neuroendocrine cells of the normal colon epithelium, as compared with non-mCRC. Therefore, targeting EEC differentiation may have clinical value in mCRC. In this study, single-cell multiomics uncovered epigenetic alterations that accompany EEC differentiation, identified STAT3 as a regulator of EEC specification, and discovered a rare cancer-specific cell type with enteric neuron–like characteristics. Furthermore, lysine-specific demethylase 1 (LSD1) and CoREST2 mediated STAT3 demethylation and enhanced STAT3 chromatin binding. Knockdown of CoREST2 in an orthotopic xenograft mouse model resulted in decreased primary tumor growth and lung metastases. Collectively, these results provide a rationale for developing LSD1 inhibitors that target the interaction between LSD1 and STAT3 or CoREST2, which may improve clinical outcomes for patients with mCRC.

Significance: STAT3 activity mediated by LSD1 and CoREST2 induces enteroendocrine cell specification in mucinous colorectal cancer, suggesting disrupting interaction among LSD1, CoREST2, and STAT3 as a therapeutic strategy to target neuroendocrine differentiation.
Figure S2 from A Novel Lipid Nanoparticle NBF-006 Encapsulating Glutathione S-Transferase P siRNA for the Treatment of KRAS-Driven Non–small Cell Lung Cancer
Authors: Cina Cima , Majeti Bharat , O’Brien Zhihong , Wang Li , Clamme Jean Pierre , Adami Roger , Tsang Kwok Yin , Harborth Jens , Ying Wenbin , Zabludoff Sonya
Published: January 2025

in vivo regulation of GSTP, PCNA and PARP
Supplementary Table 1 from PARP7 Inhibitors and AHR Agonists Act Synergistically across a Wide Range of Cancer Models
Authors: Chen Huadong , Gou Xuxu , Mao Ying , O’Leary Patrick C. , Diolaiti Morgan E. , Ashworth Alan
Published: January 2025

Supplementary Table 1. List of Primers used for gene cloning
Supplementary Figure 5 from PARP7 Inhibitors and AHR Agonists Act Synergistically across a Wide Range of Cancer Models
Authors: Chen Huadong , Gou Xuxu , Mao Ying , O’Leary Patrick C. , Diolaiti Morgan E. , Ashworth Alan
Published: January 2025

Supplementary Fig. 5 PARP7 inhibitor or inactivation can reverse AHR agonist induced AHR degradation and increase nuclear AHR
Supplementary Figure 4 from PARP7 Inhibitors and AHR Agonists Act Synergistically across a Wide Range of Cancer Models
Authors: Chen Huadong , Gou Xuxu , Mao Ying , O’Leary Patrick C. , Diolaiti Morgan E. , Ashworth Alan
Published: January 2025

Supplementary Fig. 4 AHR mediates the synergistic lethal of AHRa and PARP7i
Figure S7 from A Small-Molecule BCL6 Inhibitor as an Anti-Proliferative Agent for Diffuse Large B-Cell Lymphoma
Authors: Xing Yajing , Guo Weikai , Wu Min , Xie Jiuqing , Huang Dongxia , Hu Pan , Zhou Miaoran , Zhang Lin , Zhong Yadong , Liu Mingyao , Chen Yihua , Yi Zhengfang
Published: January 2025

Figure S7. H&E staining of liver, spleen, lung and kidney from subcutaneous tumor xenografts mice treated with FX1 and WK692. Scale bars, 50 μm.
Supplemental Figure 4 from Tumor-Specific Antigen Delivery for T-cell Therapy via a pH-Sensitive Peptide Conjugate
Authors: Yurkevicz Annali M. , Liu Yanfeng , Katz Samuel G. , Glazer Peter M.
Published: January 2025

Treatment with SIINFEKL alone in vivo does not impact tumor growth. A, Tumor growth curves of B16-F10 melanoma tumors in OT1 mice, treated with SIINFEKL or untreated as indicated. Statistical comparisons by two-way RM-ANOVA. B, Survival curves from (A). Statistical comparisons by Log-rank (Mantel–Cox) test, n=8 mice per group.
Figure S9 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Authors: Gamma Jay M. , Liu Qiang , Beauchamp Erwan , Iyer Aishwarya , Yap Megan C. , Zak Zoulika , Ekstrom Cassidy , Pain Rony , Kostiuk Morris A. , Mackey John R. , Brandwein Joseph , Wang Jean C.Y. , Berthiaume Luc G.
Published: January 2025

Supplementary Figure S9: Zelenirstat causes ER stress and Apoptosis in AML Cell Lines U937, and KG-1 cell lines were incubated with zelenirstat for up to 72 hours, then lysed and proteins analyzed by western blot. Representative blots of 3 biological replicates. Band intensity was determined using Image Studio Lite, and each sample normalized to actin. Differences between treatment groups determined using one-way ANOVA.
Figure S7 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Authors: Gamma Jay M. , Liu Qiang , Beauchamp Erwan , Iyer Aishwarya , Yap Megan C. , Zak Zoulika , Ekstrom Cassidy , Pain Rony , Kostiuk Morris A. , Mackey John R. , Brandwein Joseph , Wang Jean C.Y. , Berthiaume Luc G.
Published: January 2025

Figure S7: SFKs respond similarly to zelenirstat. AML cell lines were pre-treated with 1µM zelenirstat for 48 hours, then stimulated with 100 ng/mL SCF & FL. Levels of indicated Src-family kinases were analyzed by western blot.
FIgure S1 from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Authors: Gamma Jay M. , Liu Qiang , Beauchamp Erwan , Iyer Aishwarya , Yap Megan C. , Zak Zoulika , Ekstrom Cassidy , Pain Rony , Kostiuk Morris A. , Mackey John R. , Brandwein Joseph , Wang Jean C.Y. , Berthiaume Luc G.
Published: January 2025

Supplementary Figure S1: NMT1 and NMT2 have distinct expression patterns. NMT1 is consistently expressed in ∼1 400 CCLE cell lines and ∼11 000 TCGA patient samples. NMT2 is more variable and entirely absent in some cells. Expression measured by RNASeq and expressed as Log2(TPM+1). Data extracted from DepMap (CCLE, Expression Public 23Q2) and TCGA (via TCGABiolinks).
Supplementary Figure 5 from Riluzole Enhancing Anti-PD-1 Efficacy by Activating cGAS/STING Signaling in Colorectal Cancer
Authors: Liang Beiyuan , Khan Misbah , Storts Hayden , Zhang Evan H. , Zheng Xinru , Xing Xuanxuan , Claybon Hazel , Wilson Jenna , Li Chunjie , Jin Ning , Fishel Richard , Miles Wayne O. , Wang Jing J.
Published: January 2025

Supplemental figure 5 and legend
Supplementary Figure 1 from Riluzole Enhancing Anti-PD-1 Efficacy by Activating cGAS/STING Signaling in Colorectal Cancer
Authors: Liang Beiyuan , Khan Misbah , Storts Hayden , Zhang Evan H. , Zheng Xinru , Xing Xuanxuan , Claybon Hazel , Wilson Jenna , Li Chunjie , Jin Ning , Fishel Richard , Miles Wayne O. , Wang Jing J.
Published: January 2025

Supplemental figure 1 and legend
Supplementary Table S5 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Table S5. Region of interest analysis data reported as %ID/cc of the [89Zr]PEG-DFB1-TLZ3 on on different subcutaneous tumors from Day 1-4 post injection. (n = 4)
Supplementary Table S18 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Table S18. Organ biodistribution analysis data in %ID/Organ tissue for 89Zr labeled nanocarriers at 72 h in nude mice inoculated with 22rv1 cells via intracardiac injection. (n = 4)
Supplementary Table S17 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Table S17. Organ biodistribution analysis data in %ID/g tissue for 89Zr labeled nanocarriers at 72 h in nude mice inoculated with 22rv1 cells via intracardiac injection. (n = 4)
Supplementary Table S12 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Table S12. Organ biodistribution analysis data in %ID/g tissue for 89Zr labeled nanocarriers at 96 h in mice model bearing LTL-610 subcutaneous tumors. (n = 4)
Supplementary Figure S3 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Figure S3. Ex vivo tumor biodistribution, (a) %ID per gram and (b) %ID per organ of nude mice bearing different tumor models including prostate cancer (22rv1, PC3, DU145), colorectal cancer (CT26), and pancreatic cancer (BxPC3) at 24h and 72 h post-injection of [89Zr]PEG-DFB1-TLZ3. The respective (c) tumor uptakes, (d) tumor to muscle ratio, and (e) tumor to blood ratio of the same mice. (n = 4, mean ± SD) (f) Autoradiographic images of tumor sections from mouse model bearing different preclinical cancer xenograft at 72h post-injection of [89Zr]PEG-DFB1-TLZ3.
Supplementary Figure S21 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Figure S21. Autoradiographic images and H&E staining images of metastatic tumor, and kedney sections from day 1 to day 4 post injection of [89Zr]PEG-DFB1-TLZ3 in nude mice inoculated with 22rv1 cells in the left kidney capsule. (NA = Data not available)
Supplementary Figure S16 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Figure S16. (a) White light images of LTL-610 tumors, and the respective (b) autoradiographic images of tumor sections on day 4 post injection of [89Zr]PEG-DFB4.
Supplementary Table 1 from Targeting Tumor Antigen 5T4 Using CAR T Cells for the Treatment of Acute Myeloid Leukemia
Authors: Harrop Richard , Blount Daniel G. , Khan Naeem , Soyombo Mayowa , Moyce Laura , Drayson Mark T. , Down Jenny , Lawson Michelle A. , O’Connor Deirdre , Nimmo Rachael , Lad Yatish , Souberbielle Bernard , Mitrophanous Kyriacos , Ettorre Anna
Published: January 2025

Supplementary Table 1A. Disease information on 5T4+ AML samples ranked by rMFI (all >1.5). Supplementary Table 1B. 5T4+ AML samples ranked by MFC % (all >20%).
Supplementary Figure 3 from Targeting Tumor Antigen 5T4 Using CAR T Cells for the Treatment of Acute Myeloid Leukemia
Authors: Harrop Richard , Blount Daniel G. , Khan Naeem , Soyombo Mayowa , Moyce Laura , Drayson Mark T. , Down Jenny , Lawson Michelle A. , O’Connor Deirdre , Nimmo Rachael , Lad Yatish , Souberbielle Bernard , Mitrophanous Kyriacos , Ettorre Anna
Published: January 2025

Supplementary Figure 3. Expression of 5T4 on Kasumi-1 cells and on the putative leukaemic stem cell population within Kasumi-1 cells
Supplementary Figure S1 from PET Imaging Using 89Zr-Labeled StarPEG Nanocarriers Reveals Heterogeneous Enhanced Permeability and Retention in Prostate Cancer
Authors: Meher Niranjan , Bidkar Anil P. , Wadhwa Anju , Bobba Kondapa Naidu , Dhrona Suchi , Dasari Chandrashekhar , Mu Changhua , Fong Cyril O.Y. , Cámara Juan A. , Ali Umama , Basak Megha , Bulkley David , Steri Veronica , Fontaine Shaun D. , Zhu Jun , Oskowitz Adam , Aggarwal Rahul R. , Sriram Renuka , Chou Jonathan , Wilson David M. , Seo Youngho , Santi Daniel V. , Ashley Gary W. , VanBrocklin Henry F. , Flavell Robert R.
Published: January 2025

Supplementary Figure S1. (a) Zeta potential of the StarPEG conjugates PEG-DFB4 and PEG-DFB1-TLZ3 with an average surface charge of -4.04±0.21 mV and -1.41±0.22 mV, respectively (n = 3). (b) TEM images of PEG-DFB4 and PEG-DFB1-TLZ3 showing the formation of nanoparticles in the range of 10 to 15 nm. TEM samples were prepared by dropcasting the water solution (0.25 mg/mL) of respective StarPEG on carbon coated copper grid of 200 mesh.
Supplementary Table S4 from Loss of PI5P4Kα Slows the Progression of a Pten Mutant Basal Cell Model of Prostate Cancer
Authors: Triscott Joanna , Lehner Marika , Benjak Andrej , Reist Matthias , Emerling Brooke M. , Ng Charlotte K.Y. , de Brot Simone , Rubin Mark A.
Published: January 2025

Table S4. GSEA pathways from Fig. 6
Table S4 from The Distinct Roles of NEIL1 and XPA in Limiting Aflatoxin B1–Induced Mutagenesis in Mice
Authors: Luzadder Michael M. , Minko Irina G. , Vartanian Vladimir L. , Davenport Marten , Fedorov Lev M. , McCullough Amanda K. , Lloyd R. Stephen
Published: January 2025

Aflatoxin-induced mutation subtypes
Table S14 from The Distinct Roles of NEIL1 and XPA in Limiting Aflatoxin B1–Induced Mutagenesis in Mice
Authors: Luzadder Michael M. , Minko Irina G. , Vartanian Vladimir L. , Davenport Marten , Fedorov Lev M. , McCullough Amanda K. , Lloyd R. Stephen
Published: January 2025

Mutation frequencies of SBS subtypes in the Chr13 and Chr19 targets
Data from N-Linked Fucosylated Glycans Are Biomarkers for Prostate Cancer with a Neuroendocrine and Metastatic Phenotype
Authors: Ippolito Joseph E. , Hartig Jordan P. , Bejar Kaitlyn , Nakhoul Hani , Sehn Jennifer K. , Weimholt Cody , Grimsley Grace , Nunez Elena , Trikalinos Nikolaos A. , Chatterjee Deyali , Kim Eric H. , Mehta Anand S. , Angel Peggi M. , Troyer Dean A. , Leach Robin J. , Corey Eva , Wu Jennifer D. , Drake Richard R.
Published: January 2025

Abstract
Prostate cancer is a heterogeneous disease with a spectrum of pathology and outcomes ranging from indolent to lethal. Although there have been recent advancements in prognostic tissue biomarkers, limitations still exist. We leveraged matrix-assisted laser desorption/ionization imaging of formalin-fixed, paraffin embedded prostate cancer specimens to determine if N-linked glycans expressed in the extracellular matrix of lethal neuroendocrine prostate cancer were also expressed in conventional prostate adenocarcinomas that were associated with poor outcomes. We found that N-glycan fucosylation was abundant in neuroendocrine prostate cancer as well as adenocarcinomas at the time of prostatectomy that eventually developed recurrent metastatic disease. Analysis of patient-derived xenografts revealed that this fucosylation signature was enriched differently across metastatic disease organ sites, with the highest abundance in liver metastases. These data suggest that N-linked fucosylated glycans could be an early tissue biomarker for poor prostate cancer outcomes.

Implications: These studies identify that hyper-fucosylated N-linked glycans are enriched in neuroendocrine prostate cancer and conventional prostate adenocarcinomas that progress to metastatic disease, thus advancing biomarker discovery and providing insights into mechanisms underlying metastatic disease.
Figure 3 from Depletion of Adipose Stroma-Like Cancer-Associated Fibroblasts Potentiates Pancreatic Cancer Immunotherapy
Authors: Rupert Joseph , Daquinag Alexes , Yu Yongmei , Dai Yulin , Zhao Zhongming , Kolonin Mikhail G.
Published: January 2025

The effects of Pdgfrb+ CAF vs. ASC-like CAF depletion on the TME. Shown are representative analyses of tumors from Figs. 1 and 2. A, t-distributed stochastic neighbor embedding clusters with cell populations identified based on heatmap analysis (not shown) show changes in labeled populations. B, Changes in frequencies of cells corresponding to labeled populations in A. C, IPA analysis of scRNA-seq data of gene expression in KPC cells and CAFs from (A) identifying top genes and pathways induced (orange) or suppressed (blue). D, Quantification of top pathways’ induction (orange) or suppression (blue) in CAFs from A. AP, Antigen Presenting CAF; FC, fold change; MY, myCAFS; Neut, neutrophil.
Neuroimaging-based responses to blood pressure augmentation in acute ischaemic stroke: A systematic review
Authors: Goh Rudy , El-Masri Shaddy , Zweck Daniel , Spicer Dominic , Ng Felix , Bacchi Stephen , Jannes Jim , Kleinig Timothy
Published: January 2025

Background: In acute ischaemic stroke, the key treatment to reduce infarct growth is reperfusion, achieved through thrombolysis, endovascular thrombectomy or endogenous reperfusion. Prior to definitive reperfusion therapy, blood pressure augmentation may enhance cerebral perfusion and reduce interim infarct growth. This study aims to summarise the existing evidence from randomised controlled trials on the use of imaging for patient selection and the assessment of blood pressure augmentation in acute ischaemic stroke.

A systematic review was conducted of the databases PubMed, EMBASE, and Cochrane library in accordance with the PRISMA guidelines. The systematic review was prospectively registered on PROSPERO.

Summary: Initial searches returned 266 results, of which 4 fulfilled inclusion criteria. Most identified studies did not utilise imaging for patient selection and the assessment of blood pressure augmentation in ischaemic stroke. Only two studies utilised magnetic resonance imaging (MRI) and/or magnetic resonance perfusion (MRP) imaging for patient selection, while one study used non-contrast CT brain. No studies utilised CT perfusion imaging for patient selection or outcome assessment post-blood pressure augmentation. There is also a lack of evidence regarding the association between specific perfusion imaging parameters, such as cerebral blood volume and delay time, and clinical outcomes post blood pressure augmentation.

Key Messages: Imaging is a potentially valuable surrogate marker of cerebral perfusion, yet it has not been routinely used for patient selection and assessment in blood pressure augmentation in acute ischaemic stroke trials. Additional research is required to determine its utility in assessing the efficacy of blood pressure augmentation in ischaemic stroke.
Correlation between Neuroimaging Scores and Carotid Artery Ultrasound Features in Cerebral Small Vessel Disease Patients
Authors: Xu Yun , Song Yifan , Tang Tieqi , Jia Weili , Xu Huijuan , Li Yu , Guo Yu , Wang Xiaorui , Liu Ruihong
Published: January 2025

Introduction: The recently proposed cerebral small vessel disease (CSVD) score system may help capture the overall burden of CSVD. This study aimed to investigate the associations between carotid artery ultrasound features and the burden score and cognitive performance of CSVD patients. Methods: This is a cross-sectional analysis of an ongoing prospective study. From May 2019 to October 2023, 287 patients with at least one neuroimaging marker of CSVD were recruited and underwent carotid ultrasound examination, brain magnetic resonance imaging (MRI) scans, and neuropsychological assessment. Carotid artery properties, including carotid plaque, intima-media thickness (IMT), β stiffness index (β-index), Peterson’s elastic modulus (PEM), and pulse wave velocity-β (PWV-β), were calculated. The CSVD score was graded according to MRI evaluation. Participants were classified as having cognitive impairment (CI) or normal cognitive function (NCF) according to Montreal Cognitive Assessment (MoCA) scale. Results: A total of 209 eligible patients were included in the final analysis. A significant difference was revealed regarding the CSVD score between CI and NCF participants (p < 0.001). After adjusted for covariates, increased IMT (OR = 1.11, 95% CI: 1.04–1.37, p = 0.030) and PWV-β (OR = 1.24, 95% CI: 1.09–1.51, p = 0.006) were both associated with the presence of CI. IMT and PWV-β were also associated with worse performance on attention and processing speed (IMT: β = −0.13, p = 0.011; PWV-β: β = −0.21, p = 0.011), and executive function (IMT: β = −0.20, p = 0.024; PWV-β: β = −0.33, p = 0.008). Additionally, PEM was negatively associated with executive function (β = −0.20, p = 0.009). Furthermore, binary logistic regression indicated that IMT (OR = 1.45, 95% CI: 1.18–2.01, p = 0.006), β-index (OR = 1.30, 95% CI: 1.10–1.64, p = 0.008) and PWV-β (OR = 1.23, 95% CI: 1.01–1.89, p = 0.047) were independently related to a moderate to severe CSVD burden score. Conclusions: Carotid artery atherosclerosis and stiffness are associated with the burden score and cognitive performance of CSVD patients. Noninvasive ultrasound parameters of the carotid artery are capable of discriminating high-risk individuals with CSVD.
Single-Cell Transcriptomics Identifies Selective Lineage-Specific Regulation of Genes in Aortic Smooth Muscle Cells in Mice
Authors: Shukla Shalabh , Jana Sayantan , Sanford Nicole , Lee Chloe Y. , Liu Li , Cheng Paul , Quertermous Thomas , Dichek David A.
Published: January 2025

BACKGROUND:

Smooth muscle cells (SMCs) of the proximal thoracic aorta are derived from second heart field (SHF) and cardiac neural crest (CNC) lineages. Recent studies, both in vitro and in vivo, have implied relevance of lineage-specific SMC functions in the pathophysiology of thoracic aortic diseases; however, whether 2 lineage-derived SMCs have any predisposed transcriptional differences in the control aorta remains unexplored.

METHODS:

Single-cell RNA sequencing and single-nucleus assay for transposase-accessible chromatin sequencing were performed on isolated cells from the aortic root and ascending aortas of 14-week-old SHF-traced (
Mef2c-Cre

+/0

-Yfp

+/0

) and CNC-traced (
Wnt1-Cre

+/0

-Yfp

+/0

) male mice. RNA in situ hybridization was performed for spatial expression of selected differentially expressed genes (DEGs) of both lineages.

RESULTS:

Lineage stratification of SMCs in the proximal thoracic aorta was identified using antibody-based immunofluorescence staining. Single-cell RNA sequencing recognized 12 consistently upregulated DEGs (
Des
,
Tnnt2
,
Hand2os1
,
Psd
,
Gpc3
,
Meis2
,
Dcn
,
Gm34030
,
Palld
,
Nrtn
,
Lum
, and
Cfh
) in SHF-derived SMCs and 9 consistently upregulated DEGs (
Ccn5
,
Ccdc42
,
Tes
,
Eln
,
Aebp1
,
Galnt6
,
Ccn2
,
Aopep
, and
Wtip
) in CNC-derived SMCs. RNA in situ hybridization validated upregulated expressions of selective SHF-specific DEGs at the aortic root. We found SHF-derived SMCs contain a distinct, large subpopulation of SMCs that is enriched with
Des
and
Tnnt2
expressions. Single-nucleus assay for transposase-accessible chromatin analysis further confirmed higher chromosomal accessibility for upregulated DEGs of SHF-derived SMCs.

CONCLUSIONS:

The present study recognizes the presence of limited but distinct transcriptomic differences between CNC-derived and SHF-derived SMCs in the control proximal thoracic aorta.
Brain morphology normative modelling platform for abnormality and centile estimation: Brain MoNoCle
Authors: Little Bethany , Alyas Nida , Surtees Alexander , Winston Gavin P , Duncan John S , Cousins David A , Taylor John-Paul , Taylor Peter , Leiberg Karoline , Wang Yujiang
Published: January 2025

Normative models of brain structure estimate the effects of covariates such as age and sex using large samples of healthy controls. These models can then be applied to, for example, smaller clinical cohorts to distinguish disease effects from other covariates. However, these advanced statistical modelling approaches can be difficult to access, and processing large healthy cohorts is computationally demanding. Thus, accessible platforms with pre-trained normative models are needed. We present such a platform for brain morphology analysis as an open-source web application https://cnnplab.shinyapps.io/BrainMoNoCle/, with six key features: (i) user-friendly web interface, (ii) individual and group outputs, (iii) multi-site analysis, (iv) regional and whole-brain analysis, (v) integration with existing tools, and (vi) featuring multiple morphology metrics. Using a diverse sample of 3,276 healthy controls across 21 sites, we pre-trained normative models on various metrics. We validated the models with a small sample of individuals with bipolar disorder, showing outputs that aligned closely with existing literature only after applying our normative modelling. Using a cohort of people with temporal lobe epilepsy, we showed that individual-level abnormalities were in line with seizure lateralisation. Finally, with the ability to investigate multiple morphology measures in the same framework, we found that biological covariates are better explained in specific morphology measures, and for applications, only some measures are sensitive to the disease process. Our platform offers a comprehensive framework to analyse brain morphology in clinical and research settings. Validations confirm the superiority of normative models and the advantage of investigating a range of brain morphology metrics together.