bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge on Management of Traumatic Dental Injury and Related Predictors in Taif, Saudi Arabia: A Cross‐Sectional Study
Authors: Shukr Bandar S. , Alshamrani Haifaa M. , Alzubaidi Mohammed A. , Alqarni Ali A. , Alzahrani Muaath H. , Altalhi Faisal K. , Alrizqi Abdulrahman A.
Published: February 2025

Objectives: This study was undertaken to investigate the knowledge and attitudes toward pediatric traumatic dental injury (TDI) among the population of Taif, as well as predictors of emergency management and intentions for future education, with an additional focus on the subpopulation of parents.

Methods: Data were collected from 345 participants using an anonymous questionnaire that was distributed online and contained four sections: demographics, questions regarding TDI knowledge and previous experiences, questions about the management of two clinical cases, and questions about the self‐reported capability to manage future TDIs and the motivation for future education/training. Adjusted linear and logistic regressions were utilized to assess the effect of the different predictors on the total knowledge score, self‐reported management capabilities, TDI learning importance, and future education/training interests.

Results: The findings revealed poor overall knowledge regarding TDI management, especially in avulsion incidents, with slightly better knowledge in the subpopulation of parents. In the total population, working in a governmental job (p‐value = 0.047) or as a freelancer (p‐value = 0.006) was associated with higher knowledge, while obtaining any previous TDI information was associated with sufficient management capabilities (p‐value = 0.001). Regarding the parent subpopulation, attending a previous TDI educational course was associated with higher knowledge (p‐value = 0.043). Similar to the total population, obtaining any previous TDI information was associated with sufficient management capabilities (p‐value = 0.001). However, receiving such information from professional resources was associated with lower management capabilities (p‐value = 0.033). No significant associations were observed regarding the outcomes of TDI learning importance and future education/training interests.

Conclusion: This study highlights significant gaps in the knowledge, awareness, and skills related to pediatric dental injuries and their management among the population of the Taif region. Targeted educational interventions are needed to increase public awareness and bridge the current gaps in knowledge and skills.
Optical Flow‐Based Structural Anomaly Detection in Seismic Events From Video Data Combined With Computational Cost Reduction Through Deep Learning
Authors: Wang Sifan , Saida Taisei , Nishio Mayuko
Published: February 2025

This study presents a novel approach for anomaly event detection in large‐scale civil structures by integrating transfer learning (TL) techniques with extended node strength network analysis based on video data. By leveraging TL with BEiT + UPerNet pretrained models, the method identifies structural Region‐of‐Uninterest (RoU), such as windows and doors. Following this identification, the extended node strength network uses rich visual information from the video data, concentrating on structural components to detect disturbances in the nonlinearity vector field within these components. The proposed framework provides a comprehensive solution for anomaly detection, achieving high accuracy and reliability in identifying deviations from normal behavior. The approach was validated through two large‐scale structural shaking table tests, which included both pronounced shear cracks and tiny cracks. The detection and quantitative analysis results demonstrated the effectiveness and robustness of the method in detecting varying degrees of anomalies in civil structural components. Additionally, the integration of TL techniques improved computational efficiency by approximately 10%, with a positive correlation observed between this efficiency gain and the proportion of structural RoUs in the video. This study advances anomaly detection in large‐scale structures, offering a promising approach to enhancing safety and maintenance practices in critical infrastructure.
Anlotinib versus placebo as adjuvant therapy for localized high-grade soft tissue sarcomas: a phase 2, double-blinded, randomized controlled trial
Authors: Wang Chunmeng , Hu Xianglin , Yang Lingge , Xu Yu , Zheng Biqiang , Yang Jilong , Liao Zhichao , Sun Zhengwang , Zhang Shengjian , Yu Lin , Yan Yan , Chen Yong , Fujiwara Tomohiro , Zhang Jianrong , Buhtoiarov Ilia N. , Sun Yangbai , Yan Wangjun
Published: February 2025

Purpose: We aimed to investigate the efficacy and safety of anlotinib as adjuvant targeted therapy for completely resected localized high-grade soft tissue sarcomas (STS). Patients and Methods: Patients with localized high-grade STS after complete resection were randomly assigned in a 1:1 ratio to receive either oral 12 mg anlotinib or placebo once daily on days 1-14 every 21 days as a cycle, with up to 6 cycles until disease relapse, unmanageable toxicity or death. The efficacy and safety were analyzed. This trial was the first trial exploring adjuvant targeted therapy for STS (NCT03951571). Results: Between June 2019 and November 2023, 88 patients were randomly assigned to receive anlotinib (n=44) or placebo (n=44). With a median follow-up of 30.95 months, the 1-year and 2-year disease-free survival (DFS) rates were 88% and 77% in the anlotinib group, compared to 64% and 58% in the placebo group. Compared to patients treated with surgery alone, patients receiving adjuvant anlotinib combined with surgery had a reduced risk of disease recurrence (HR 0.47 [95% CI 0.22~1.00, P=0.0445]). Based on the tumor histology, the reduced risk of disease recurrence with anlotinib versus placebo was observed in patients with myxofibrosarcoma (HR 0.54 [95% CI 0.17~1.65], P=0.2698) and undifferentiated pleomorphic sarcoma (HR 0.58 [95% CI 0.12~2.87], P=0.4971). Four patients discontinued anlotinib, including two for proteinuria/hematuria (2/44, 5%) and two for poor healing of surgical wound (2/44, 5%). Conclusions: Compared to surgery alone, adjuvant anlotinib following surgery reduces the incidence of disease relapse in localized high-grade STS, with acceptable toxicity.
Supplemental Figure 7 from Intra- and Extrahepatic Cholangiocarcinomas Display Differing Sensitivities to NK Cell Lysis and Modulate NK Cell Function through Shared and Distinct Pathways
Authors: Nguyen Ngan , Henrich Ian C.
Published: February 2025

Figure S7. Difference in relative immune abundance between iCCA and eCCA.
Supplemental Figure 5 from Intra- and Extrahepatic Cholangiocarcinomas Display Differing Sensitivities to NK Cell Lysis and Modulate NK Cell Function through Shared and Distinct Pathways
Authors: Nguyen Ngan , Henrich Ian C.
Published: February 2025

Figure S5. Checkpoint expression on NK-92MI after co-culture.
Supplemental Figure 4 from Intra- and Extrahepatic Cholangiocarcinomas Display Differing Sensitivities to NK Cell Lysis and Modulate NK Cell Function through Shared and Distinct Pathways
Authors: Nguyen Ngan , Henrich Ian C.
Published: February 2025

Figure S4. Cytokine expression in NK and CCA cells after co-culture.
Supplemental Figure 11 from Intra- and Extrahepatic Cholangiocarcinomas Display Differing Sensitivities to NK Cell Lysis and Modulate NK Cell Function through Shared and Distinct Pathways
Authors: Nguyen Ngan , Henrich Ian C.
Published: February 2025

Figure S11. iCCA and eCCA NKLow patients have similar gene expression pathway signatures dominated by stroma-epithelial markers.
Supplemental Figure 10 from Intra- and Extrahepatic Cholangiocarcinomas Display Differing Sensitivities to NK Cell Lysis and Modulate NK Cell Function through Shared and Distinct Pathways
Authors: Nguyen Ngan , Henrich Ian C.
Published: February 2025

Figure 10. iCCA and eCCA NKHigh patients have distinct gene expression pathway signatures.
RNF6 Inhibits Lung Adenocarcinoma Cell Proliferation by Promoting Cyclin D2 Degradation
Authors: Sun Yuening , Jiang Liyang , Zhang Zubin , Zhu Rongrong , Liang Jingpei , Liu Ziyang , He Yuanming , Huang Zhenqian , Ling Chunhua , Zhou Xiumin , Mao Xinliang
Published: February 2025

The E3 ubiquitin ligase RING finger protein 6 (RNF6) has been widely recognized for its role in promoting tumorigenesis in multiple cancers. However, we found that it is downregulated in lung adenocarcinoma (LUAD), and the molecular rationale for this discrepancy remains unclear. In the present study, we find that RNF6, but not its ΔRING inactive form, inhibits LUAD cell proliferation and migration and sensitizes LUAD to chemotherapy. To understand the molecular mechanism, we utilize affinity purification/tandem mass spectrometry (MS-MS) to analyze RNF6-interacting proteins and find that cyclin D2 (CCND2), a key regulator of the G1–S transition in the cell cycle. RNF6 physically binds to CCND2 and mediates its K48-linked polyubiquitination and subsequent degradation. However, ΔRING RNF6 fails to mediate CCND2 for ubiquitination and degradation. Moreover, Thr280 is critically important for CCND2 stability. When Thr280 is mutated, CCND2 becomes more stable and less ubiquitinated by RNF6. Furthermore, RNF6 arrests LUAD cell cycle at the G1 phase by inhibiting the CCND2/phospho-Rb signaling pathway, which is consistent with decreased cell proliferation. Lastly, RNF6 curtails the growth of LUAD xenografts in vivo, associated with decreased CCND2 expression. Therefore, RNF6 is a novel E3 ligase of CCND2 and suppresses LUAD cell proliferation.

Implications: This study reveals a novel regulation on cell-cycle transition in LUAD and suggests the RNF6/CCND2 axis may represent an alternative therapeutic target for the treatment of LUAD.
Supplementary Table 14 from CTR-FAPI PET Enables Precision Management of Medullary Thyroid Carcinoma
Authors: Kong Ziren , Li Zhu , Cui Xi-Yang , Wang Jian , Xu Mengxin , Liu Yang , Chen Junyi , Ni Song , Zhang Zongmin , Fan Xiaowei , Huang Jiazhao , Lin Yansong , Sun Yuning , He Yuqin , Lin Xinfeng , Meng Tianyu , Li Han , Song Yixuan , Peng Boshizhang , An Changming , Gao Chenyan , Li Nan , Liu Chen , Zhu Yiming , Yang Zhi , Liu Zhibo , Liu Shaoyan
Published: February 2025

Representativeness of study participants
Supplementary Table 13 from CTR-FAPI PET Enables Precision Management of Medullary Thyroid Carcinoma
Authors: Kong Ziren , Li Zhu , Cui Xi-Yang , Wang Jian , Xu Mengxin , Liu Yang , Chen Junyi , Ni Song , Zhang Zongmin , Fan Xiaowei , Huang Jiazhao , Lin Yansong , Sun Yuning , He Yuqin , Lin Xinfeng , Meng Tianyu , Li Han , Song Yixuan , Peng Boshizhang , An Changming , Gao Chenyan , Li Nan , Liu Chen , Zhu Yiming , Yang Zhi , Liu Zhibo , Liu Shaoyan
Published: February 2025

Safety of the PET-CT regimens
Supplementary Table 12 from CTR-FAPI PET Enables Precision Management of Medullary Thyroid Carcinoma
Authors: Kong Ziren , Li Zhu , Cui Xi-Yang , Wang Jian , Xu Mengxin , Liu Yang , Chen Junyi , Ni Song , Zhang Zongmin , Fan Xiaowei , Huang Jiazhao , Lin Yansong , Sun Yuning , He Yuqin , Lin Xinfeng , Meng Tianyu , Li Han , Song Yixuan , Peng Boshizhang , An Changming , Gao Chenyan , Li Nan , Liu Chen , Zhu Yiming , Yang Zhi , Liu Zhibo , Liu Shaoyan
Published: February 2025

Pre- and post-surgical calcitonin level of surgical patients
Supplementary Table 11 from CTR-FAPI PET Enables Precision Management of Medullary Thyroid Carcinoma
Authors: Kong Ziren , Li Zhu , Cui Xi-Yang , Wang Jian , Xu Mengxin , Liu Yang , Chen Junyi , Ni Song , Zhang Zongmin , Fan Xiaowei , Huang Jiazhao , Lin Yansong , Sun Yuning , He Yuqin , Lin Xinfeng , Meng Tianyu , Li Han , Song Yixuan , Peng Boshizhang , An Changming , Gao Chenyan , Li Nan , Liu Chen , Zhu Yiming , Yang Zhi , Liu Zhibo , Liu Shaoyan
Published: February 2025

Accuracy of [68Ga]Ga-CTR-FAPI PET-CT and traditional imaging in identifying MTC or non-MTC lesions
Supplementary Figure S10 from The UBA1–STUB1 Axis Mediates Cancer Immune Escape and Resistance to Checkpoint Blockade
Authors: Bao Yi , Cruz Gabriel , Zhang Yuping , Qiao Yuanyuan , Mannan Rahul , Hu Jing , Yang Fan , Gondal Mahnoor , Shahine Miriam , Kang Sarah , Mahapatra Somnath , Chu Alec , Choi Jae Eun , Yu Jiali , Lin Heng , Miner Stephanie J. , Robinson Dan R. , Wu Yi-Mi , Zheng Yang , Cao Xuhong , Su Fengyun , Wang Rui , Hosseini Noshad , Cieslik Marcin , Kryczek Ilona , Vaishampayan Ulka , Zou Weiping , Chinnaiyan Arul M.
Published: February 2025

Supplementary Figure S10. UBA1 inactivation upregulates interferon signaling in human cancer.
Supplementary Figure S1 from The UBA1–STUB1 Axis Mediates Cancer Immune Escape and Resistance to Checkpoint Blockade
Authors: Bao Yi , Cruz Gabriel , Zhang Yuping , Qiao Yuanyuan , Mannan Rahul , Hu Jing , Yang Fan , Gondal Mahnoor , Shahine Miriam , Kang Sarah , Mahapatra Somnath , Chu Alec , Choi Jae Eun , Yu Jiali , Lin Heng , Miner Stephanie J. , Robinson Dan R. , Wu Yi-Mi , Zheng Yang , Cao Xuhong , Su Fengyun , Wang Rui , Hosseini Noshad , Cieslik Marcin , Kryczek Ilona , Vaishampayan Ulka , Zou Weiping , Chinnaiyan Arul M.
Published: February 2025

Supplementary Figure S1. High expression of UBA1 is associated with low levels of intratumoral CD8+ T cells and predictive of ICB resistance and poor survival in ICB cohorts.
Supplementary Figure 3 from CTR-FAPI PET Enables Precision Management of Medullary Thyroid Carcinoma
Authors: Kong Ziren , Li Zhu , Cui Xi-Yang , Wang Jian , Xu Mengxin , Liu Yang , Chen Junyi , Ni Song , Zhang Zongmin , Fan Xiaowei , Huang Jiazhao , Lin Yansong , Sun Yuning , He Yuqin , Lin Xinfeng , Meng Tianyu , Li Han , Song Yixuan , Peng Boshizhang , An Changming , Gao Chenyan , Li Nan , Liu Chen , Zhu Yiming , Yang Zhi , Liu Zhibo , Liu Shaoyan
Published: February 2025

Correlation between [68Ga]Ga-CTR-FAPI uptake and FAP expression
Figure 4 from The UBA1–STUB1 Axis Mediates Cancer Immune Escape and Resistance to Checkpoint Blockade
Authors: Bao Yi , Cruz Gabriel , Zhang Yuping , Qiao Yuanyuan , Mannan Rahul , Hu Jing , Yang Fan , Gondal Mahnoor , Shahine Miriam , Kang Sarah , Mahapatra Somnath , Chu Alec , Choi Jae Eun , Yu Jiali , Lin Heng , Miner Stephanie J. , Robinson Dan R. , Wu Yi-Mi , Zheng Yang , Cao Xuhong , Su Fengyun , Wang Rui , Hosseini Noshad , Cieslik Marcin , Kryczek Ilona , Vaishampayan Ulka , Zou Weiping , Chinnaiyan Arul M.
Published: February 2025

UBA1 inhibition synergizes with anti–PD-1 therapy to control tumor growth. A, Change of volume over time of subcutaneous tumors derived from B16-F10 cells in C57BL/6 mice treated with the indicated agents (n = 5–6 mice, per group). α-PD-1: anti–PD-1; Combo: TAK-243 plus α-PD-1. B, Individual growth curves of tumors in mice treated as in A. Last treatment was administered on day 14 after the initial treatment. CR, complete response. C, Survival of mice treated in A. D, Change of volume over time of the indicted tumor models in their syngeneic hosts treated with the indicated agents (n = 5–10 mice per group). E, Evaluation of drug synergism, using CombPDX (44), for the combination of TAK-243 and anti–PD-1 in the indicated models, treated as in A and D. A combination index larger than zero was defined as synergistic (44). *, P < 0.05; ***, P < 0.001. F, Left: change of volume over time of subcutaneous tumors derived from Myc-CaP cells transfected with nontargeting sgRNA (control) or sgRNAs depleting Uba1 (sgUba1) in FVB mice treated with α-PD-1 or the control IgG (n = 5 mice per group). Right: Evaluation of synergism using CombPDX for the combination of Uba1-depletion (sgUba1) and anti-PD-1 in the indicated model. G, Flow cytometry measuring the absolute numbers of IFN-γ+ CD8+ T cells in the indicated tumors from syngeneic mice treated with the indicated agents. H, Tumor growth over time of Myc-CaP subcutaneous tumors in control, TAK-243–treated, or TAK-243–treated and anti-PD-1–treated (combo) FVB mice, with (α-CD8) or without (IgG) CD8+ T-cell depletion (n = 5 mice, per group). I, Tumor growth over time of CT26 subcutaneous tumors at naïve or rechallenged stage, in control, TAK-243–treated, anti–PD-1–treated, or TAK-243–treated and anti–PD-1–treated (combo) BALB/c mice. Rechallenge was performed 4 days after removal of the primary tumors by surgery (n = 6–8 mice, per group). All data are presented as mean ± SEM, except E (mean) and G (box and whisker plots). Statistics were acquired by two-way ANOVA in A, D, F, and H, by log-rank test in C, or by two-tailed Student’s t test in G.
Notification to AttendingPhysician from CTR-FAPI PET Enables Precision Management of Medullary Thyroid Carcinoma
Authors: Kong Ziren , Li Zhu , Cui Xi-Yang , Wang Jian , Xu Mengxin , Liu Yang , Chen Junyi , Ni Song , Zhang Zongmin , Fan Xiaowei , Huang Jiazhao , Lin Yansong , Sun Yuning , He Yuqin , Lin Xinfeng , Meng Tianyu , Li Han , Song Yixuan , Peng Boshizhang , An Changming , Gao Chenyan , Li Nan , Liu Chen , Zhu Yiming , Yang Zhi , Liu Zhibo , Liu Shaoyan
Published: February 2025

Notification to Attending Physician
Supplementary Materials&Methods from Survivin Promotes Stem Cell Competence for Skin Cancer Initiation
Authors: Canato Sara , Sarate Rahul , Carvalho-Marques Sofia , Maia Soares Raquel , Song Yura , Monteiro-Ferreira Sara , Vieugué Pauline , Liagre Mélanie , Grossi Giancarlo , Cardoso Erik , Dubois Christine , Conway Edward M. , Schenone Silvia , Sánchez-Danés Adriana , Blanpain Cédric
Published: February 2025

Genetic sequence of the Survivin GOF-IRES-mCherry mice generated
Supplementary Figure S4 from Glioblastoma Cortical Organoids Recapitulate Cell-State Heterogeneity and Intercellular Transfer
Authors: Mangena Vamsi , Chanoch-Myers Rony , Sartore Rafaela , Paulsen Bruna , Gritsch Simon , Weisman Hannah , Hara Toshiro , Breakefield Xandra O. , Breyne Koen , Regev Aviv , Chung Kwanghun , Arlotta Paola , Tirosh Itay , Suvà Mario L.
Published: February 2025

Supplementary Figure S4 describes widespread transfer of endogenous malignant transcripts in GCOs, related to Figure 4.
Supplementary Table 6 from Tumor-Intrinsic Kinome Landscape of Pancreatic Cancer Reveals New Therapeutic Approaches
Authors: Xu Yi , Peng Xianlu L. , East Michael P. , McCabe Ian C. , Stroman Grace C. , Jenner Madison R. , Chan Priscilla S. , Morrison Ashley B. , Shen Emily C. , Hererra Silvia G. , Joisa Chinmaya U. , Rashid Naim U. , Iuga Alina C. , Gomez Shawn M. , Miller-Phillips Lisa , Boeck Stefan , Heinemann Volker , Haas Michael , Ormanns Steffen , Johnson Gary L. , Yeh Jen Jen
Published: February 2025

Supplementary Table 6.overall_survival
Supplementary Figure S3 from Glioblastoma Cortical Organoids Recapitulate Cell-State Heterogeneity and Intercellular Transfer
Authors: Mangena Vamsi , Chanoch-Myers Rony , Sartore Rafaela , Paulsen Bruna , Gritsch Simon , Weisman Hannah , Hara Toshiro , Breakefield Xandra O. , Breyne Koen , Regev Aviv , Chung Kwanghun , Arlotta Paola , Tirosh Itay , Suvà Mario L.
Published: February 2025

Supplementary Figure S3 describes GFP transfer process in GCOs, related to Figure 3.
Supplementary Figure S2 from Glioblastoma Cortical Organoids Recapitulate Cell-State Heterogeneity and Intercellular Transfer
Authors: Mangena Vamsi , Chanoch-Myers Rony , Sartore Rafaela , Paulsen Bruna , Gritsch Simon , Weisman Hannah , Hara Toshiro , Breakefield Xandra O. , Breyne Koen , Regev Aviv , Chung Kwanghun , Arlotta Paola , Tirosh Itay , Suvà Mario L.
Published: February 2025

Supplementary Figure S2 describes malignant cell states in GCOs, related to Figure 2.
GFP sequence for transcriptome alignment from Glioblastoma Cortical Organoids Recapitulate Cell-State Heterogeneity and Intercellular Transfer
Authors: Mangena Vamsi , Chanoch-Myers Rony , Sartore Rafaela , Paulsen Bruna , Gritsch Simon , Weisman Hannah , Hara Toshiro , Breakefield Xandra O. , Breyne Koen , Regev Aviv , Chung Kwanghun , Arlotta Paola , Tirosh Itay , Suvà Mario L.
Published: February 2025

Text file shows the GFP sequence from pLV-CMV-GFP used to align GFP reads from scRNA-seq data.
Supplementary Figures S1-S6 from Tumor-Intrinsic Kinome Landscape of Pancreatic Cancer Reveals New Therapeutic Approaches
Authors: Xu Yi , Peng Xianlu L. , East Michael P. , McCabe Ian C. , Stroman Grace C. , Jenner Madison R. , Chan Priscilla S. , Morrison Ashley B. , Shen Emily C. , Hererra Silvia G. , Joisa Chinmaya U. , Rashid Naim U. , Iuga Alina C. , Gomez Shawn M. , Miller-Phillips Lisa , Boeck Stefan , Heinemann Volker , Haas Michael , Ormanns Steffen , Johnson Gary L. , Yeh Jen Jen
Published: February 2025

Supplementary Data Figure 1. PDX show high correlation within the same patient line across different runs compared to different patient lines on the same run. Supplementary Data Figure 2. Mouse kinase expression is not line specific and does not associate with tumor molecular subtype. Supplementary Data Figure 3. Molecular subtyping in PDX model recapitulates basal-like and classical tumor specific subtypes. Supplementary Data Figure 4. Subtype specific kinase expression is associated with gene expression in PDX tumors. Supplementary Data Figure 5. Kinase expression from patients reflects the PDAC PDX kinome. Supplementary Data Figure 6. Overall survival (OS) and treatment response of patients who received EGFR inhibitors.
Contents of Supplementary Tables from DNAJB1-PRKACA Fusion Drives Fibrolamellar Liver Cancer through Impaired SIK Signaling and CRTC2/p300-Mediated Transcriptional Reprogramming
Authors: Gritti Ilaria , Wan Jinkai , Weeresekara Vajira , Vaz Joel M. , Tarantino Giuseppe , Bryde Tenna Holgersen , Vijay Vindhya , Kammula Ashwin V. , Kattel Prabhat , Zhu Songli , Vu Phuong , Chan Marina , Wu Meng-Ju , Gordan John D. , Patra Krushna C. , Silveira Vanessa S. , Manguso Robert T. , Wein Marc N. , Ott Christopher J. , Qi Jun , Liu David , Sakamoto Kei , Gujral Taranjit S. , Bardeesy Nabeel
Published: February 2025

List of contents of each Supplementary Table
Supplementary Table S7 from Copper Drives Remodeling of Metabolic State and Progression of Clear Cell Renal Cell Carcinoma
Authors: Bischoff Megan E. , Shamsaei Behrouz , Yang Juechen , Secic Dina , Vemuri Bhargav , Reisz Julie A. , D’Alessandro Angelo , Bartolacci Caterina , Adamczak Rafal , Schmidt Lucas , Wang Jiang , Martines Amelia , Venkat Jahnavi , Tcheuyap Vanina Toffessi , Biesiada Jacek , Behrmann Catherine A. , Vest Katherine E. , Brugarolas James , Scaglioni Pier Paolo , Plas David R. , Patra Krushna C. , Gulati Shuchi , Landero Figueroa Julio A. , Meller Jarek , Cunningham John T. , Czyzyk-Krzeska Maria F.
Published: February 2025

Genes expressed in spatial clusters
Supplementary Table S4 from Copper Drives Remodeling of Metabolic State and Progression of Clear Cell Renal Cell Carcinoma
Authors: Bischoff Megan E. , Shamsaei Behrouz , Yang Juechen , Secic Dina , Vemuri Bhargav , Reisz Julie A. , D’Alessandro Angelo , Bartolacci Caterina , Adamczak Rafal , Schmidt Lucas , Wang Jiang , Martines Amelia , Venkat Jahnavi , Tcheuyap Vanina Toffessi , Biesiada Jacek , Behrmann Catherine A. , Vest Katherine E. , Brugarolas James , Scaglioni Pier Paolo , Plas David R. , Patra Krushna C. , Gulati Shuchi , Landero Figueroa Julio A. , Meller Jarek , Cunningham John T. , Czyzyk-Krzeska Maria F.
Published: February 2025

Metabolomic fluxes
Supplementary Figure S7 from Copper Drives Remodeling of Metabolic State and Progression of Clear Cell Renal Cell Carcinoma
Authors: Bischoff Megan E. , Shamsaei Behrouz , Yang Juechen , Secic Dina , Vemuri Bhargav , Reisz Julie A. , D’Alessandro Angelo , Bartolacci Caterina , Adamczak Rafal , Schmidt Lucas , Wang Jiang , Martines Amelia , Venkat Jahnavi , Tcheuyap Vanina Toffessi , Biesiada Jacek , Behrmann Catherine A. , Vest Katherine E. , Brugarolas James , Scaglioni Pier Paolo , Plas David R. , Patra Krushna C. , Gulati Shuchi , Landero Figueroa Julio A. , Meller Jarek , Cunningham John T. , Czyzyk-Krzeska Maria F.
Published: February 2025

Bulk RNA and spatial transcriptomics analysis of ccRCC.
Supplementary Figure S6 from Copper Drives Remodeling of Metabolic State and Progression of Clear Cell Renal Cell Carcinoma
Authors: Bischoff Megan E. , Shamsaei Behrouz , Yang Juechen , Secic Dina , Vemuri Bhargav , Reisz Julie A. , D’Alessandro Angelo , Bartolacci Caterina , Adamczak Rafal , Schmidt Lucas , Wang Jiang , Martines Amelia , Venkat Jahnavi , Tcheuyap Vanina Toffessi , Biesiada Jacek , Behrmann Catherine A. , Vest Katherine E. , Brugarolas James , Scaglioni Pier Paolo , Plas David R. , Patra Krushna C. , Gulati Shuchi , Landero Figueroa Julio A. , Meller Jarek , Cunningham John T. , Czyzyk-Krzeska Maria F.
Published: February 2025

Characterization of subpopulations of cancer cells identified by scRNA-seq.
Data from CTR-FAPI PET Enables Precision Management of Medullary Thyroid Carcinoma
Authors: Kong Ziren , Li Zhu , Cui Xi-Yang , Wang Jian , Xu Mengxin , Liu Yang , Chen Junyi , Ni Song , Zhang Zongmin , Fan Xiaowei , Huang Jiazhao , Lin Yansong , Sun Yuning , He Yuqin , Lin Xinfeng , Meng Tianyu , Li Han , Song Yixuan , Peng Boshizhang , An Changming , Gao Chenyan , Li Nan , Liu Chen , Zhu Yiming , Yang Zhi , Liu Zhibo , Liu Shaoyan
Published: February 2025

Abstract
Medullary thyroid carcinoma (MTC) can only be cured through the excision of all metastatic lesions, but current clinical practice fails to localize the disease in 29% to 60% of patients. Previously, we developed a fibroblast activation protein inhibitor (FAPI)-based covalent targeted radioligand (CTR) for improved detection sensitivity and accuracy. In this first-in-class clinical trial, we head-to-head compared [68Ga]Ga-CTR-FAPI PET-CT and [18F]fluorodeoxyglucose ([18F]FDG) PET-CT in 50 patients with MTC. The primary endpoint was the patient-based detection rate, with [68Ga]Ga-CTR-FAPI exhibiting higher detection than [18F]FDG (98% vs. 66%, P = 0.0002). This improved detection was attributed to increased tumor uptake (maximum standardized uptake value = 11.71 ± 9.16 vs. 2.55 ± 1.73, P < 0.0001). Diagnostic accuracy, validated on lesions with gold-standard pathology, was greater for [68Ga]Ga-CTR-FAPI compared with [18F]FDG (96.7% vs. 43.3%, P < 0.0001). Notably, the management of 32% of patients was altered following [68Ga]Ga-CTR-FAPI PET-CT, and the surgical plan was changed for 66.7% of patients. Overall, [68Ga]Ga-CTR-FAPI PET-CT provided superior detection and diagnostic accuracy compared with [18F]FDG PET-CT, enabling precision management of patients with MTC.

Significance: In this first-in-class clinical trial of CTR, [68Ga]Ga-CTR-FAPI demonstrated an improved patient-based detection rate (98%), tumor uptake (maximum standardized uptake value = 11.71 ± 9.16), and pathology-validated diagnostic accuracy (96.7%) compared with the currently approved method in MTC treatment. It directly altered management in 32% of patients, enabling precision diagnosis and management of MTC.

See related commentary by Witney, p. 264
Data from The UBA1–STUB1 Axis Mediates Cancer Immune Escape and Resistance to Checkpoint Blockade
Authors: Bao Yi , Cruz Gabriel , Zhang Yuping , Qiao Yuanyuan , Mannan Rahul , Hu Jing , Yang Fan , Gondal Mahnoor , Shahine Miriam , Kang Sarah , Mahapatra Somnath , Chu Alec , Choi Jae Eun , Yu Jiali , Lin Heng , Miner Stephanie J. , Robinson Dan R. , Wu Yi-Mi , Zheng Yang , Cao Xuhong , Su Fengyun , Wang Rui , Hosseini Noshad , Cieslik Marcin , Kryczek Ilona , Vaishampayan Ulka , Zou Weiping , Chinnaiyan Arul M.
Published: February 2025

Abstract
How cancer cells escape immune surveillance and resist immune checkpoint blockade (ICB) remains to be fully elucidated. By screening candidate genes frequently gained in cancer, we identified expression of ubiquitin-like modifier-activating enzyme 1 (UBA1) as being the most negatively correlated with signatures related to effector CD8+ T cells. High UBA1 expression was strongly predictive of treatment resistance and poor survival in ICB cohorts. Functional studies revealed that UBA1 mediated immune escape to promote tumor growth. Immune profiling further showed that Uba1 overexpression or depletion markedly decreased or increased functional intratumoral CD8+ T cells, respectively. Importantly, a selective UBA1 inhibitor, TAK-243, significantly synergized with ICB in multiple syngeneic models. Mechanistically, depletion or inactivation of the UBA1–STUB1 axis stabilized a key IFN pathway component (JAK1), enhanced IFN signaling, and elevated key immune modulators, including CXCL9, CXCL10, and MHC class I. Our study warrants clinical evaluation of the combination of UBA1 inhibitors and ICB.
Significance:
Our study reveals UBA1 as a predictive biomarker for clinical outcomes in ICB cohorts, mediating cancer immune evasion and ICB resistance. We further highlight JAK1 stabilization as a key mechanism of UBA1 inhibition and nominate the UBA1–STUB1 axis as an immuno-oncology therapeutic target to improve the efficacy of ICB.
Data from Predisposition Footprints in the Somatic Genome of Wilms Tumors
Authors: Treger Taryn D. , Wegert Jenny , Wenger Anna , Coorens Tim H.H. , Al-Saadi Reem , Kemps Paul G. , Kennedy Jonathan , Parks Conor , Anderson Nathaniel D. , Hodder Angus , Letunovska Aleksandra , Jung Hyunchul , Ogbonnah Toochi , Trinh Mi K. , Lee-Six Henry , Morcrette Guillaume , van den Heuvel-Eibrink Marry M. , Drost Jarno , van Boxtel Ruben , Bertrums Eline J.M. , Goemans Bianca F. , Antoniou Evangelia , Reinhardt Dirk , Streitenberger Heike , Ziegler Barbara , Bartram Jack , Hutchinson John C. , Vujanic Gordan M. , Vokuhl Christian , Chowdhury Tanzina , Furtwängler Rhoikos , Graf Norbert , Pritchard-Jones Kathy , Gessler Manfred , Behjati Sam
Published: February 2025

Abstract
Approximately 10% of children with cancer harbor a mutation in a predisposition gene. In children with the kidney cancer Wilms tumor, the prevalence is as high as 30%. Certain predispositions are associated with defined histological and clinical features, suggesting differences in tumorigenesis. To investigate this, we assembled a cohort of 137 children with Wilms tumor, of whom 71 had a pathogenic germline or mosaic variant. We examined 237 neoplasms (including two secondary leukemias), utilizing whole-genome sequencing, RNA sequencing, and genome-wide methylation, validating our findings in an independent cohort. Tumor development differed in children harboring a predisposition, depending on the variant gene and its developmental timing. Differences pervaded the repertoire of driver events, including high-risk mutations, the clonal architecture of normal kidneys, and the relatedness of neoplasms from the same individual. Our findings indicate that predisposition may preordain Wilms tumorigenesis, suggesting a variant-specific approach to managing children merits consideration.

Significance: Tumors that arise in children with a cancer predisposition may develop through the same mutational pathways as sporadic tumors. We examined this question in the childhood kidney cancer, Wilms tumor. We found that certain predispositions dictate the genetic development of tumors, with clinical implications for these children.

See related commentary by Brzezinski and Malkin, p. 258
Data from Tumor-Intrinsic Kinome Landscape of Pancreatic Cancer Reveals New Therapeutic Approaches
Authors: Xu Yi , Peng Xianlu L. , East Michael P. , McCabe Ian C. , Stroman Grace C. , Jenner Madison R. , Chan Priscilla S. , Morrison Ashley B. , Shen Emily C. , Hererra Silvia G. , Joisa Chinmaya U. , Rashid Naim U. , Iuga Alina C. , Gomez Shawn M. , Miller-Phillips Lisa , Boeck Stefan , Heinemann Volker , Haas Michael , Ormanns Steffen , Johnson Gary L. , Yeh Jen Jen
Published: February 2025

Abstract
Effective therapies for pancreatic ductal adenocarcinoma (PDAC) have been largely elusive. In this study, we perform multiplexed kinase inhibitor bead mass spectrometry on 102 patient-derived xenografts derived from 14 unique primary PDACs to define the tumor-intrinsic kinome landscape. Our findings uncover three kinome subgroups making up two tumor-intrinsic kinome subtypes that we call kinotypes. The kinotypes show enrichment of different kinase classes and recapitulate previously described molecular subtypes, basal-like and classical. The kinotype characterizing basal-like tumors shows enrichment of receptor tyrosine kinases, whereas the kinotype characterizing classical tumors is enriched in understudied kinases involved in Wnt signaling and immune pathways. We validate our findings in two clinical trials and show that only patients with basal-like tumors derive significant benefit from EGFR inhibitors. Our results provide a comprehensive tumor-intrinsic kinome landscape of PDAC that strongly supports actionable kinotype-specific kinase targets and provides a roadmap for kinase inhibitor therapy in PDAC.
Significance:
We provide a comprehensive tumor-intrinsic kinome landscape that provides a roadmap for the use of kinase inhibitors in PDAC treatment approaches.
Figure 2 from Age at First Full-term Pregnancy and Other Reproductive Factors Are Associated with Mammographic Breast Density in Postmenopausal Women: A Study in Flanders, Belgium
Authors: Vandeloo Magda J. , Kellen Eliane , Fang Carolyn Y. , Ross Eric A. , Vancoillie Liesbeth , Bruckers Liesbeth M. , Neven Kristof Y. , Bijnens Esmée M. , Nawrot Tim S. , Van Ongeval Chantal
Published: February 2025

Correlation between MBD and age at FFTP. Plots (A and B) show the association of the VBD [in ln (%)] and GLAND [in ln (cm³)] with age at FFTP (in years). Breakpoint is indicated as a red dotted line at 25.7 years.
Determination of the relationship between electromyography-proven oxaliplatin-related peripheral neuropathy and serum uric acid level
Authors: Tanriverdi Ozgur , Dilmen Yavuz Selim , Arslan Burak , Kutlu Gulnihal , Alkan Ali
Published: February 2025

Introduction: Although different risk factors for oxaliplatin-associated chronic peripheral neuropathy have been identified and the predictive value of neuroinflammatory cytokines has often been emphasized, a clearly accepted predictive biomarker with economical, reproducible, and easily accessible properties has not yet been identified. In this study, we aimed to determine the relationship between serum uric level measured at the time of diagnosis and oxaliplatin-related peripheral neuropathy, based on literature information on the relationship between diabetic neuropathy and serum uric acid level.
Methods: In the study, 166 patients with colon adenocarcinoma, who were clinically thought to have grade 1-2 neuropathy in their follow-up after completing the adjuvant mFOLFOX6 regimen without dose reduction for 6 months, were grouped as those with or without peripheral neuropathy according to electromyography results. Demographic, clinical, laboratory and treatment-related characteristics, as well as serum uric acid levels at diagnosis, were determined as study variables and the groups were compared. Based on the presence of peripheral neuropathy, an ROC curve was drawn for serum uric acid level, cut-off was determined and multivariable logistic (binary) regression analysis was also applied to determine independent risk factors that may affect peripheral neuropathy. If the P value was below 0.05, it was considered statistically significant.
Results: It was determined that 29% of the patients (n = 48) had peripheral neuropathy proven by electromyography. It was determined that the majority of patients with peripheral neuropathy were women, above 65 years of age, low body mass index, high body surface area, and smokers. While the serum uric acid level of all patients was 5.1 mg/dl (1.9- 9.1), it was significantly higher in patients with peripheral neuropathy than in those without neuropathy (p = 0.0012). We found that ORPN may develop in patients with SUA levels higher than 5.96 mg/dL in men and 6.04 mg/dL in women at the time of diagnosis, and these cut-off values had a sensitivity of 40% and a specificity of 95.40% in men, respectively, while the sensitivity in women was 84.6% and the specificity was 83.87%. In multivariable analysis, female gender, smoking, high body surface area and high serum uric acid level were determined to be independent predictors for all patients.
Conclusion: Despite the limitations of the study, it was concluded that the possibility of developing oxaliplatin-induced peripheral neuropathy may be high in patients with high serum uric acid levels. This study needs to be repeated prospectively and evaluated in larger cohorts.
REAL-WORLD OUTCOMES OF ANTI-EGFR RECHALLENGE GUIDED BY LIQUID BIOPSY IN METASTATIC COLORECTAL CANCER
Authors: Roque Ricardo , Antunes Santos Rita , Santos Luis Guilherme , Coelho Rita , Viera Fernandes Isabel , Cunha Gonçalo , Gonçalves Marta , Paulo Judy , Bonito Nuno
Published: February 2025

INTRODUCTION: In patients with metastatic colorectal cancer (mCRC) without RAS/BRAF somatic variants, first-line anti-EGFR antibodies plus chemotherapy improve survival. Retreatment of responders with anti-EGFR rechallenge accumulates less evidence for benefit when compared with other available third-line treatments.

MATERIAL AND METHODS: A unicentric retrospective cohort of patients with somatic RAS/BRAF wild type (wt) mCRC, treated with irinotecan/cetuximab within the definition of rechallenge, was selected between 2018 and 2023. Liquid biopsy for confirmation of RAS/BRAF status was required previously to rechallenge. Outcomes measured were disease control and overall response rate (ORR) at first response evaluation, overall survival (OS) and progression-free survival (PFS). Toxicities were reported and graded according to Common Terminology Criteria for Adverse Events.

RESULTS: Sixteen patients received irinotecan/cetuximab rechallenge, with a median follow-up of 12.8 months (2.6-46.5). Eighty one percent were male with a median age of 63 years (51-84). Rechallenge was prescribed as third-line therapy in 88%. Overall, 31% achieved partial response and 56% disease control. Median PFS for rechallenge was 5.3 months (IC95% 3.3-7.4) and median OS was 12.7 months (IC95% 8.3-17.1). Sixty-two adverse events were reported, 11% grade 3, none leading to discontinuation of treatment. Seventy-five percent of the patients had acneiform rash of any grade. In subgroup analysis, development of grade ≥2 rash (n=9) correlated with superior PFS than grade 1 or absence of rash [HR 0.30 (IC95% 0.1-1.0), p=0.05].

DISCUSSION: Despite the absence of randomized phase III trials comparing rechallenge and other available therapies for third-line treatment of RAS/BRAF wt mCRC, cumulating evidence allows for the use of anti-EGFR rechallenge in patients selected by liquid biopsy that may benefit from disease response. Skin toxicity emerges as a potential biomarker for response in anti-EGFR rechallenge.

CONCLUSIONS: In our cohort, in accordance with previous studies, anti-EGFR rechallenge in liquid biopsy confirmed RAS/BRAF wt mCRC showed clinically relevant response rates and disease-free survival, in third line treatment and beyond.
How and Why Does Leader Anger Expression Influence Employees’ Deviant Innovation? Ability-Based Mianzi Stress and Workplace Anxiety Explanations of the Curvilinear Moderated Relations
Authors: Wang Yingdong
Published: February 2025

Leader anger expression affects leadership effectiveness and employees’ work status. Based on the theory of emotion as social information, we theorized a serial curvilinear mediated moderation model that links leader anger expression to deviant innovation under weak versus strong supervisor’s organizational embodiment. The results of our field of 289 employees showed that the mediated relationship between leader anger expression and deviant innovation was non-linear. Moreover, this non-linear mediated relationship was moderated by supervisor’s organizational embodiment such that, under strong supervisor’s organizational embodiment, the indirect effect via ability-based Mianzi stress and workplace anxiety was positive at high levels of leader anger expression, while, under conditions of supervisor’s organizational embodiment, the indirect effect via ability-based Mianzi stress was insignificant at low levels of leader anger expression, the indirect effect via workplace anxiety was negative as low levels of leader anger expression and positive at intermediate to high levels. We discussed the theoretical and practical implications for current and future leader anger expression research.
Want to Increase US Pension Fund Investment in Africa? Focus on the Actors Influencing the Asset Allocation Levers
Authors: Preston Daniel
Published: February 2025

A large financing gap exists to meet the development needs of the African continent. This article focuses on US pension funds as potential candidates for increased investment by identifying the organizations and individuals with the most agency in determining asset allocations to African countries. Research and analysis indicate that external investment consultants, investment indexing firms, and the trustees hold the most agency. Asset managers, senior-level professional staff, and investment committee members have significant power, but to a lesser extent. Knowledge of relative agency should improve efforts by organizations seeking to increase US pension fund investment in Africa.
Achievements, difficulties, and goals of the Spanish Society for Music Education (SEM-EE): A phenomenological study
Authors: Álamo Orellana Ana , Martínez-Rodríguez Marta
Published: February 2025

The Spanish Society for Music Education ( Sociedad para la Educación Musical del Estado Español, SEM-EE in its Spanish acronym), has been dedicated to music education for almost half a century. Even so, it is currently difficult to find studies on its activity or impact. The aim of this study is to learn about the achievements, difficulties, and goals for SEM-EE that have emerged along the way and will come in the future. This has been done through a qualitative phenomenological study, analyzing 18 interviews carried out with members of the boards of directors, and codified through Atlas.ti software program. The results show that some of the greatest achievements of this organization have been to carry out activities, facilitate the connection between professionals from different fields of music education, and the promotion of music research. The lack of support, both institutional and from the educational community, along with scarce economic resources were some of the most noted difficulties. Future goals point to promoting more dialog with the administration, and the improvement of technological resources. The implications of this work can be relevant for music teaching professionals interested in the advancement of music education based on bringing together different collectives.
The structure of the bilingual lexicon: Evidence from a semantic blocked word translation task with Chinese–English bilinguals
Authors: Zhang Yong , Shuai Yuhan , Xiao Chengyan , Ji Feng , Damian Markus F.
Published: February 2025

The question of how the mental lexicon of bilinguals is organized to incorporate more than a single language is of long-standing interest. Evidence regarding the structure of the bilingual system comes from word translation tasks, with a central issue whether translation speed, on the one hand, and semantic effects, on the other, are asymmetric dependent on direction of translation. We report a study in which unbalanced Chinese–English bilinguals translated words either in forward (first language to second language, i.e. L1 to L2) or backward (L2 to L1) direction. Words were presented in sets of semantically homogeneous or heterogeneous experimental blocks (‘semantic blocked naming/translation’). We found substantially faster forward than backward translation speed, as well as an inhibitory semantic effect which was larger in backward than in forward translation. We suggest that a word presented in L2 leads to a less stable/rich conceptual activation than one presented in L1, which in subsequent translation leads to slower translation times and larger semantic effects in backward than in forward translation. Results are informative with regard to the structure and organization of the bilingual lexicon.
Aspirin does not confer protection against major ischemic vascular events in patients diagnosed with rheumatoid arthritis
Authors: Gao Chao , Hou Qiqi , Cao Hongxia , Li Cangtuo , Peng Xu , Han Quanle , Wu Shouling , Li Kangbo
Published: February 2025

Objective

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammatory arthritis and extra-articular involvement. Patients with RA are at increased risk of developing cardiovascular diseases. This retrospective cohort study aimed to determine whether acetylsalicylic acid (aspirin [ASA]) protects against major ischemic vascular events in patients diagnosed with RA.

Methods

Patients with RA were recruited from a population of 118, 500 participants who were enrolled into the Kailuan Cohort Study between 2014 and 2016. Information regarding demographic characteristics, anthropometric measures, and medical histories were documented. Patients with RA who underwent ASA therapy were propensity score matched at a ratio of 1:4 with patients with RA who did not receive ASA. The risk of ischemic vascular events (myocardial infarction and ischemic stroke) was examined. The relationship between ASA therapy and major ischemic vascular events was analyzed by Cox proportional hazards regression.

Results

A total of 939 patients with RA were included (189 who received ASA and 750 who did not). During the 3.3-year follow-up, six and 35 major ischemic vascular events occurred in the ASA and non-ASA groups, respectively, with no significant between-group difference in the cumulative incidence of such events. Cox proportional hazards regression analysis showed that ASA therapy was not associated with major vascular ischemic events and its subtypes.

Conclusions

ASA did not confer protection against major ischemic vascular events in patients diagnosed with RA.
Led Watch: A ‘Go To’ and A ‘Must Have’
Authors: Brodrick James
Published: February 2025

The DOE's Lighting Facts program encourages the design community and other stakeholders to simply ‘read the label’
A Process Evaluation Revealed That Flexibility Was Key to Delivering Nutrition Education to Vulnerable Tribal Groups in India
Authors: Mockshell Jonathan , Ritter Thea , Garrett James
Published: February 2025

Background

This study is a process evaluation of a nutrition education intervention that is part of a large-scale development program targeting vulnerable tribal groups in Odisha, India.

Objective

The objectives are to examine whether the intervention is operating as planned (implementation fidelity), investigate potential pathways to achieve greater impact, and provide recommendations on how to design nutrition education interventions in similar contexts.

Methods

A program impact pathway forms the basis of this process evaluation, tracing inputs, processes, outputs, outcomes, and impacts. The study's mixed-methods approach includes semistructured interviews, focus group discussions, and Process Net-Mapping. Narrative analysis was applied to examine the transcripts. Data were analyzed in the context of the program impact pathway.

Results

The intervention was not delivered as intended (low implementation fidelity). Flexibility was key in providing nutrition education to beneficiaries despite challenges, such as the inability to utilize behavior change communication, inadequate funding, and language and cultural barriers. Despite low fidelity, the qualitative results show that the intervention improved awareness of nutrition and health among beneficiaries.

Conclusions

Providing adequate resources for training frontline workers and beneficiaries is required for nutrition education programs to achieve their desired effectiveness and impact. Utilizing existing organizations, integration into production-based interventions, and incorporating easy-to-understand nutrition models, practical demonstrations, and videos would increase frontline worker and beneficiary engagement and understanding, leading to improved maternal and child nutritional and health outcomes.