bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing Strategy of Triboelectric Nanogenerator via Origami Pattern by Harvesting Mechanical Motion and Wind Flow
Authors: Chung Seh-Hoon , Kim Minsoo , Lin Zong-Hong , Koo Bonwook , Choi Dongwhi , Kim Dongseob , Lee Sangmin
Published: May 2024

Triboelectric nanogenerators (TENGs) are promising energy‐harvesting devices that generate electricity from mechanical energy. However, the electrical outputs of typical TENGs are limited because of the fundamental mechanism by which TENGs require a certain amount of space for contact‐separation motion. Therefore, we developed an origami‐based vertical/fluttering hybrid TENG (OVFH‐TENG), which is the innovative structure that can generate electricity from both vertical movement and wind flow which is generated by vertical movement. It consists of a vertical TENG and a fluttering TENG where vertical TENGs can generate electricity and wind flow from mechanical input and the fluttering TENGs can generate electricity from the wind flow which is generated by its own operation process. Thus, OVFH‐TENG can effectively harvest energy from vertical contact and fluttering motions with a single input. The optimized OVFH‐TENG generated a 34.7% higher output than the general contact‐separation TENG. Finally, the OVFH‐TENG was able to light 180 LEDs, which was not possible with a general contact‐separation TENG.
A Genetic Algorithm with Lower Neighborhood Search for the Three-Dimensional Multiorder Open-Size Rectangular Packing Problem
Authors: Yang Jianglong , Liu Huwei , Liang Kaibo , Shan Man , Kong Lingjie , Zhou Li
Published: May 2024

This paper addresses the multiorder open-dimension three-dimensional rectangular packing problem (3D-MOSB-ODRPP), which involves packing rectangular items from multiple orders into a single, size-adjustable container. We propose a novel metaheuristic approach combining a genetic algorithm with the Gurobi solver. The algorithm incorporates a lower neighborhood search strategy and is underpinned by a mathematical model representing the multiorder open-dimension packing scenario. Extensive experiments validate the effectiveness of the proposed approach. The LNSGA algorithm outperforms Gurobi and the traditional genetic algorithm in solution quality and computational efficiency. For small-scale instances, LNSGA achieves optimal values in most cases. LNSGA demonstrates significant optimization improvements over Gurobi and the genetic algorithm for large-scale instances. The superior performance is attributed to the effective integration of the lower neighborhood search mechanism and the Gurobi solver. This study offers valuable insights for optimizing the packing process in e-commerce warehousing and logistics operations.
Beyond the Neonate: A Delayed Presentation of Congenital Diaphragmatic Hernia in a 17‐Year‐Old
Authors: Vinton Vivienne , Posa Molly , Kelly Maria N. , Taylor Janice A. , Otero Jaclyn
Published: May 2024

Congenital diaphragmatic hernia (CDH) is a rare anomaly resulting from incomplete closure of pleuroperitoneal canals during fetal development, often presenting with acute respiratory distress in neonates. This case report highlights a 17‐year‐old female with recurrent episodes of acute left upper quadrant (LUQ) pain and no history of trauma or dietary change. A computerized tomography (CT) scan taken during her second presentation to the emergency department led to a diagnosis of left‐sided CDH. She later had a successful laparoscopic diaphragmatic repair surgery and has remained symptom‐free for over a year. Late‐presenting CDH indicates a rare subset of cases diagnosed after one month of age. Late presentations comprise 5–25% of cases and become increasingly rare with age. Unlike neonatal CDH, which is associated with several comorbidities, late presentations often manifest as a standalone anomaly. When the correct diagnosis is made, uncomplicated surgical repair yields excellent long‐term outcomes. However, delayed and incorrect diagnoses can result in serious morbidity. Late‐presenting CDH has diverse clinical presentations and can elude diagnostic imaging. As a result, there is a need for heightened clinical suspicion. This report aims to enhance awareness of late‐presenting CDH and explore challenges to prompt, accurate diagnosis. Ultimately, this study implores clinicians to consider this condition in patients with unexplained respiratory or gastrointestinal symptoms.
Figure S7 from Bile Acid Metabolism Mediates Cholesterol Homeostasis and Promotes Tumorigenesis in Clear Cell Renal Cell Carcinoma
Authors: Riscal Romain , Gardner Sarah M. , Coffey Nathan J. , Carens Madeleine , Mesaros Clementina , Xu Jimmy P. , Xue Yizheng , Davis Leah , Demczyszyn Sara , Vogt Austin , Olia Adam , Finan Jennifer M. , Godfrey Jason , Schultz David C. , Blair Ian A. , Keith Brian , Marmorstein Ronen , Skuli Nicolas , Simon M. Celeste
Published: May 2024

Figure S7
Supplementary Data from FUME-TCRseq Enables Sensitive and Accurate Sequencing of the T-cell Receptor from Limited Input of Degraded RNA
Authors: Baker Ann-Marie , Nageswaran Gayathri , Nenclares Pablo , Ronel Tahel , Smith Kane , Kimberley Christopher , Laclé Miangela M. , Bhide Shreerang , Harrington Kevin J. , Melcher Alan , Rodriguez-Justo Manuel , Chain Benny , Graham Trevor A.
Published: May 2024

Supplementary Tables 1 and 2, and Supplementary Figure 1
Supplementary Tables from NPEPPS Is a Druggable Driver of Platinum Resistance
Authors: Jones Robert T. , Scholtes Mathijs , Goodspeed Andrew , Akbarzadeh Maryam , Mohapatra Saswat , Feldman Lily Elizabeth , Vekony Hedvig , Jean Annie , Tilton Charlene B. , Orman Michael V. , Romal Shahla , Deiter Cailin , Kan Tsung Wai , Xander Nathaniel , Araki Stephanie P. , Joshi Molishree , Javaid Mahmood , Clambey Eric T. , Layer Ryan , Laajala Teemu D. , Parker Sarah J. , Mahmoudi Tokameh , Zuiverloon Tahlita C.M. , Theodorescu Dan , Costello James C.
Published: May 2024

Supplementary Tables 1-7
Supplementary methods and Figure S1-S12 from Mutant U2AF1-Induced Mis-Splicing of mRNA Translation Genes Confers Resistance to Chemotherapy in Acute Myeloid Leukemia
Authors: Jin Peng , Wang Xiaoling , Jin Qiqi , Zhang Yi , Shen Jie , Jiang Ge , Zhu Hongming , Zhao Ming , Wang Dan , Li Zeyi , Zhou Yan , Li Wenzhu , Zhang Wei , Liu Yabin , Wang Siyang , Jin Wen , Cao Yuncan , Sheng Guangying , Dong Fangyi , Wu Shishuang , Li Xiaoyang , Jin Zhen , He Mengke , Liu Xiaxin , Chen Luonan , Zhang Yunxiang , Wang Kankan , Li Junmin
Published: May 2024

Supplementary methods and Figure S1-S12
Supplementary Table S1-S20 from Mutant U2AF1-Induced Mis-Splicing of mRNA Translation Genes Confers Resistance to Chemotherapy in Acute Myeloid Leukemia
Authors: Jin Peng , Wang Xiaoling , Jin Qiqi , Zhang Yi , Shen Jie , Jiang Ge , Zhu Hongming , Zhao Ming , Wang Dan , Li Zeyi , Zhou Yan , Li Wenzhu , Zhang Wei , Liu Yabin , Wang Siyang , Jin Wen , Cao Yuncan , Sheng Guangying , Dong Fangyi , Wu Shishuang , Li Xiaoyang , Jin Zhen , He Mengke , Liu Xiaxin , Chen Luonan , Zhang Yunxiang , Wang Kankan , Li Junmin
Published: May 2024

Supplementary Table S1-S20
Figure S9 from DNA of Neutrophil Extracellular Traps Binds TMCO6 to Impair CD8+ T-cell Immunity in Hepatocellular Carcinoma
Authors: Song Mengjia , Zhang Chaoqi , Cheng Shaoyan , Ouyang Dijun , Ping Yu , Yang Jieying , Zhang YaoJun , Tang Yan , Chen Hao , Wang Qi-jing , Li Yong-qiang , He Jia , Xiang Tong , Zhang Yizhuo , Xia Jian-Chuan
Published: May 2024

TMCO6 plays a key role in CD8+ T cells interacting with NETs during HCC progression.
Figure S5 from DNA of Neutrophil Extracellular Traps Binds TMCO6 to Impair CD8+ T-cell Immunity in Hepatocellular Carcinoma
Authors: Song Mengjia , Zhang Chaoqi , Cheng Shaoyan , Ouyang Dijun , Ping Yu , Yang Jieying , Zhang YaoJun , Tang Yan , Chen Hao , Wang Qi-jing , Li Yong-qiang , He Jia , Xiang Tong , Zhang Yizhuo , Xia Jian-Chuan
Published: May 2024

Receiver operating characteristic curves analysis for NETs in HCC.
Supplementary Data 3 from PABPC1L Induces IDO1 to Promote Tryptophan Metabolism and Immune Suppression in Renal Cell Carcinoma
Authors: Shu Guannan , Chen Minyu , Liao Wuyuan , Fu Liangmin , Lin Mingjie , Gui Chengpeng , Cen Junjie , Lu Jun , Chen Zhenhua , Wei Jinhuan , Chen Wei , Wang Yinghan , Zhu Jiangquan , Zhao Tianxin , Liu Xiaonan , Jing Jiajia , Liu Guo-chang , Pan Yihui , Luo Junhang , Zhang Jiaxing
Published: May 2024

Supplementary Data 3
Figure S4 from DNA of Neutrophil Extracellular Traps Binds TMCO6 to Impair CD8+ T-cell Immunity in Hepatocellular Carcinoma
Authors: Song Mengjia , Zhang Chaoqi , Cheng Shaoyan , Ouyang Dijun , Ping Yu , Yang Jieying , Zhang YaoJun , Tang Yan , Chen Hao , Wang Qi-jing , Li Yong-qiang , He Jia , Xiang Tong , Zhang Yizhuo , Xia Jian-Chuan
Published: May 2024

The effects of tumor-derived TGF-β1 on NET formation.
Figure S2 from DNA of Neutrophil Extracellular Traps Binds TMCO6 to Impair CD8+ T-cell Immunity in Hepatocellular Carcinoma
Authors: Song Mengjia , Zhang Chaoqi , Cheng Shaoyan , Ouyang Dijun , Ping Yu , Yang Jieying , Zhang YaoJun , Tang Yan , Chen Hao , Wang Qi-jing , Li Yong-qiang , He Jia , Xiang Tong , Zhang Yizhuo , Xia Jian-Chuan
Published: May 2024

The representative dotplots used for gating strategies of flow staining for CD8+ T cells in in-vivo experiments.
Figure S10 from DNA of Neutrophil Extracellular Traps Binds TMCO6 to Impair CD8+ T-cell Immunity in Hepatocellular Carcinoma
Authors: Song Mengjia , Zhang Chaoqi , Cheng Shaoyan , Ouyang Dijun , Ping Yu , Yang Jieying , Zhang YaoJun , Tang Yan , Chen Hao , Wang Qi-jing , Li Yong-qiang , He Jia , Xiang Tong , Zhang Yizhuo , Xia Jian-Chuan
Published: May 2024

TGF-β1-signaling inhibition or TMCO6 deficiency combined with anti-PD-1 abolishes NET-driven HCC progression in vivo.
Supplementary Table S6 from ATG-101 Is a Tetravalent PD-L1×4-1BB Bispecific Antibody That Stimulates Antitumor Immunity through PD-L1 Blockade and PD-L1–Directed 4-1BB Activation
Authors: Yuwen Hui , Wang Huajing , Li Tengteng , Ren Yijing , Zhang Yun-kai , Chen Peng , Sun Ao , Bian Gang , Li Bohua , Flowers David , Presler Marc , Subramanian Kalyanasundaram , Xue Jia , Wang Jingjing , Lynch Kevin , Mei Jay , He Xiaowen , Shan Bo , Hou Bing
Published: May 2024

ATG-101 did not affecct cytokine release in monkey
Striking the Balance with a PD-L1×4–1BB Bispecific Antibody
Authors: Ha JongHoon , Grippin Adam J. , Kim Betty Y.S. , Jiang Wen
Published: May 2024

Antibody-based immune checkpoint blockade therapy has revolutionized the field of cancer immunotherapy, yet its efficacy remains limited in immunologically cold tumors. Combining checkpoint inhibitors with costimulatory agonists improves tumoricidal activity of T cells but also can lead to off-target hepatotoxicity. Although bispecific antibodies confer tumor selectivity to alleviate undesirable adverse effects, toxicity concerns persist with increased dosing. In this issue of Cancer Research, Yuwen and colleagues introduce ATG-101, a tetravalent PD-L1×4–1BB bispecific antibody with high programmed death ligand 1 (PD-L1) affinity and low 4–1BB affinity, aiming to mitigate hepatotoxicity. ATG-101 demonstrates PD-L1–dependent 4–1BB activation, leading to selective T-cell activation within the tumor microenvironment. ATG-101 exhibits potent antitumor activity, even in large, immunologically cold, and monotherapy-resistant tumor models. Single-cell RNA sequencing reveals significant shifts of immune cell populations in the tumor microenvironment from protumor to antitumor phenotypes following ATG-101 treatment. In cynomolgus monkeys, no serious cytokine storm and hepatotoxicity are observed after ATG-101 treatment, indicating a broad therapeutic window for ATG-101 in cancer treatment. This study highlights the potential of tetravalent bispecific antibodies in cancer immunotherapy, with implications for various antibody-based treatment modalities across different fields.

See related article by Yuwen et al., p. 1680
Supplementary Data 1 from Targeting CCL2/CCR2 Signaling Overcomes MEK Inhibitor Resistance in Acute Myeloid Leukemia
Authors: Modak Rucha V. , de Oliveira Rebola Katia G. , McClatchy John , Mohammadhosseini Mona , Damnernsawad Alisa , Kurtz Stephen E. , Eide Christopher A. , Wu Guanming , Laderas Ted , Nechiporuk Tamilla , Gritsenko Marina A. , Hansen Joshua R. , Hutchinson Chelsea , Gosline Sara J.C. , Piehowski Paul , Bottomly Daniel , Short Nicholas , Rodland Karin , McWeeney Shannon K. , Tyner Jeffrey W. , Agarwal Anupriya
Published: May 2024

Suppl Figures 1-5 and list of tables 1-10
Supp Table S2 from Targeting CCL2/CCR2 Signaling Overcomes MEK Inhibitor Resistance in Acute Myeloid Leukemia
Authors: Modak Rucha V. , de Oliveira Rebola Katia G. , McClatchy John , Mohammadhosseini Mona , Damnernsawad Alisa , Kurtz Stephen E. , Eide Christopher A. , Wu Guanming , Laderas Ted , Nechiporuk Tamilla , Gritsenko Marina A. , Hansen Joshua R. , Hutchinson Chelsea , Gosline Sara J.C. , Piehowski Paul , Bottomly Daniel , Short Nicholas , Rodland Karin , McWeeney Shannon K. , Tyner Jeffrey W. , Agarwal Anupriya
Published: May 2024

Correlation and p values of cytokines and AUC for small molecules
Supplementary Figure S9 from Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma
Authors: Dermawan Josephine K. , Chiang Sarah , Singer Samuel , Jadeja Bhumika , Hensley Martee L. , Tap William D. , Movva Sujana , Maki Robert G. , Antonescu Cristina R.
Published: May 2024

Supplementary Figure S9. MSKCC ULMS cohort. Genomic variables (gene level point mutations and copy number changes and chromosomal arm level changes) are input into the OncoCast model using the elastic net (“ENET”) approach, with outcome being overall survival. Variable importance is assigned and visualized in a plot by selection frequency (the event frequency of that feature in the data) and Cox proportional hazard ratios. Dotted lines indicate threshold of 0.50 selection frequency and hazard ratio of 1.
Supplementary Table S4 from Tumor-Infiltrating Lymphocytes Refine Outcomes in Triple-Negative Breast Cancer Treated with Anthracycline-Free Neoadjuvant Chemotherapy
Authors: Martín Miguel , Yoder Rachel , Salgado Roberto , del Monte-Millán María , Álvarez Enrique L. , Echavarría Isabel , Staley Joshua M. , O'Dea Anne P. , Nye Lauren E. , Stecklein Shane R. , Bueno Coralia , Jerez Yolanda , Cebollero María , Bueno Oscar , García Saenz José Ángel , Moreno Fernando , Bohn Uriel , Gómez Henry , Massarrah Tatiana , Khan Qamar J. , Godwin Andrew K. , López-Tarruella Sara , Sharma Priyanka
Published: May 2024

Patient characteristics by enrolling study cohort
Supplementary Table S2 from Tumor-Infiltrating Lymphocytes Refine Outcomes in Triple-Negative Breast Cancer Treated with Anthracycline-Free Neoadjuvant Chemotherapy
Authors: Martín Miguel , Yoder Rachel , Salgado Roberto , del Monte-Millán María , Álvarez Enrique L. , Echavarría Isabel , Staley Joshua M. , O'Dea Anne P. , Nye Lauren E. , Stecklein Shane R. , Bueno Coralia , Jerez Yolanda , Cebollero María , Bueno Oscar , García Saenz José Ángel , Moreno Fernando , Bohn Uriel , Gómez Henry , Massarrah Tatiana , Khan Qamar J. , Godwin Andrew K. , López-Tarruella Sara , Sharma Priyanka
Published: May 2024

Baseline patient characteristics by availability of sTILs data
Supplementary Table S3 from Targeting SMAD3 Improves Response to Oxaliplatin in Esophageal Adenocarcinoma Models by Impeding DNA Repair
Authors: Ballout Farah , Lu Heng , Bhat Nadeem , Chen Lei , Peng Dunfa , Chen Zheng , Chen Steven , Sun Xiaodian , Giordano Silvia , Corso Simona , Zaika Alexander , McDonald Oliver , Livingstone Alan S. , El-Rifai Wael
Published: May 2024

Supplementary key resources table 3. Sequences of primers
Supplementary Table S2 from Targeting SMAD3 Improves Response to Oxaliplatin in Esophageal Adenocarcinoma Models by Impeding DNA Repair
Authors: Ballout Farah , Lu Heng , Bhat Nadeem , Chen Lei , Peng Dunfa , Chen Zheng , Chen Steven , Sun Xiaodian , Giordano Silvia , Corso Simona , Zaika Alexander , McDonald Oliver , Livingstone Alan S. , El-Rifai Wael
Published: May 2024

Supplementary key resources table 2. Reagents and kits
Supplementary Table S1 from The Irreversible FGFR Inhibitor KIN-3248 Overcomes FGFR2 Kinase Domain Mutations
Authors: Balasooriya Eranga R. , Wu Qibiao , Ellis Haley , Zhen Yuanli , Norden Bryanna L. , Corcoran Ryan B. , Mohan Adithi , Martin Eric , Franovic Aleksandra , Tyhonas John , Lardy Matthew , Grandinetti Kathryn B. , Pelham Robert , Soroceanu Liliana , Silveira Vanessa S. , Bardeesy Nabeel
Published: May 2024

Kinome Selectivity Analysis of KIN-3248 by MSA (Carna Biosciences*)
Supplementary Table S2 from Response Rate and Molecular Correlates to Encorafenib and Binimetinib in BRAF-V600E Mutant High-Grade Glioma
Authors: Schreck Karisa C. , Strowd Roy E. , Nabors Louis B. , Ellingson Benjamin M. , Chang Michael , Tan Sze K. , Abdullaev Zied , Turakulov Rust , Aldape Kenneth , Danda Neeraja , Desideri Serena , Fisher Joy , Iacoboni Michaella , Surakus Trisha , Rudek Michelle A. , Bettegowda Chetan , Grossman Stuart A. , Ye Xiaobu
Published: May 2024

Supplementary Table S2: Patient features.
Supplemental Table 7 from A Phase 0/I Pharmacokinetic and Pharmacodynamics and Safety and Tolerability Study of Letrozole in Combination with Standard Therapy in Recurrent High-Grade Gliomas
Authors: Desai Pankaj B. , Karve Aniruddha S. , Zawit Misam , Arora Priyanka , Dave Nimita , Awosika Joy , Li Ningjing , Fuhrman Bethany , Medvedovic Mario , Sallans Larry , Kendler Ady , DasGupta Biplab , Plas David , Curry Richard , Zuccarello Mario , Chaudhary Rekha , Sengupta Soma , Wise-Draper Trisha M.
Published: May 2024

Supplemental Table 7: List of GSEA genes
Supplemental Table 4 from A Phase 0/I Pharmacokinetic and Pharmacodynamics and Safety and Tolerability Study of Letrozole in Combination with Standard Therapy in Recurrent High-Grade Gliomas
Authors: Desai Pankaj B. , Karve Aniruddha S. , Zawit Misam , Arora Priyanka , Dave Nimita , Awosika Joy , Li Ningjing , Fuhrman Bethany , Medvedovic Mario , Sallans Larry , Kendler Ady , DasGupta Biplab , Plas David , Curry Richard , Zuccarello Mario , Chaudhary Rekha , Sengupta Soma , Wise-Draper Trisha M.
Published: May 2024

Supplemental Table 4: Detailed Adverse Events
Supplementary Table S3 from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

Baseline and treatment characteristics of patients treated with cytotoxic chemotherapy TS-1 (tegafur, gimeracil, and oteracil potassium) and cisplatin.
Supplementary Table S7 from Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma
Authors: Oliver-Caldes Aina , Español-Rego Marta , Zabaleta Aintzane , González-Calle Verónica , Navarro-Velázquez Sergio , Inogés Susana , de Cerio Ascensión López-Díaz , Cabañas Valentín , López-Muñoz Nieves , Rodríguez-Otero Paula , Reguera Juan Luis , Moreno David F. , Martínez-Cibrian Nuria , López-Corral Lucía , Pérez-Amill Lorena , Martin-Antonio Beatriz , Rosiñol Laura , Cid Joan , Tovar Natalia , Sáez-Peñataro Joaquín , López-Parra Miriam , Olesti Eulalia , Guillén Elena , Varea Sara , Rodríguez-Lobato Luis Gerardo , Battram Anthony M. , González Marta Sonia , Sánchez-Salinas Andrés , González-Navarro Azucena , Ortiz-Maldonado Valentín , Delgado Julio , Prósper Felipe , Juan Manel , Martínez-López Joaquín , Moraleda José M. , Mateos Maria Victoria , Urbano-Ispizua Álvaro , Paiva Bruno , Pascal Mariona , Fernández de Larrea Carlos
Published: May 2024

Table 7. Patients with positive antibodies against CART in the end-of-treatment (EOT) sample.
Supplementary Table S3 from Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma
Authors: Oliver-Caldes Aina , Español-Rego Marta , Zabaleta Aintzane , González-Calle Verónica , Navarro-Velázquez Sergio , Inogés Susana , de Cerio Ascensión López-Díaz , Cabañas Valentín , López-Muñoz Nieves , Rodríguez-Otero Paula , Reguera Juan Luis , Moreno David F. , Martínez-Cibrian Nuria , López-Corral Lucía , Pérez-Amill Lorena , Martin-Antonio Beatriz , Rosiñol Laura , Cid Joan , Tovar Natalia , Sáez-Peñataro Joaquín , López-Parra Miriam , Olesti Eulalia , Guillén Elena , Varea Sara , Rodríguez-Lobato Luis Gerardo , Battram Anthony M. , González Marta Sonia , Sánchez-Salinas Andrés , González-Navarro Azucena , Ortiz-Maldonado Valentín , Delgado Julio , Prósper Felipe , Juan Manel , Martínez-López Joaquín , Moraleda José M. , Mateos Maria Victoria , Urbano-Ispizua Álvaro , Paiva Bruno , Pascal Mariona , Fernández de Larrea Carlos
Published: May 2024

Table 3. Correlation between T-cell subsets in the apheresis with the proportion of CD8 central memory cells in the final product (FP).
Supplementary Figure S13 from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

Differential expression of markers before and after treatment.
Supplementary Figure S9 from Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma
Authors: Oliver-Caldes Aina , Español-Rego Marta , Zabaleta Aintzane , González-Calle Verónica , Navarro-Velázquez Sergio , Inogés Susana , de Cerio Ascensión López-Díaz , Cabañas Valentín , López-Muñoz Nieves , Rodríguez-Otero Paula , Reguera Juan Luis , Moreno David F. , Martínez-Cibrian Nuria , López-Corral Lucía , Pérez-Amill Lorena , Martin-Antonio Beatriz , Rosiñol Laura , Cid Joan , Tovar Natalia , Sáez-Peñataro Joaquín , López-Parra Miriam , Olesti Eulalia , Guillén Elena , Varea Sara , Rodríguez-Lobato Luis Gerardo , Battram Anthony M. , González Marta Sonia , Sánchez-Salinas Andrés , González-Navarro Azucena , Ortiz-Maldonado Valentín , Delgado Julio , Prósper Felipe , Juan Manel , Martínez-López Joaquín , Moraleda José M. , Mateos Maria Victoria , Urbano-Ispizua Álvaro , Paiva Bruno , Pascal Mariona , Fernández de Larrea Carlos
Published: May 2024

Figure 9. Cytokine levels in the peripheral blood of patients treated with ARI0002h
Supplementary Figure S8 from Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma
Authors: Oliver-Caldes Aina , Español-Rego Marta , Zabaleta Aintzane , González-Calle Verónica , Navarro-Velázquez Sergio , Inogés Susana , de Cerio Ascensión López-Díaz , Cabañas Valentín , López-Muñoz Nieves , Rodríguez-Otero Paula , Reguera Juan Luis , Moreno David F. , Martínez-Cibrian Nuria , López-Corral Lucía , Pérez-Amill Lorena , Martin-Antonio Beatriz , Rosiñol Laura , Cid Joan , Tovar Natalia , Sáez-Peñataro Joaquín , López-Parra Miriam , Olesti Eulalia , Guillén Elena , Varea Sara , Rodríguez-Lobato Luis Gerardo , Battram Anthony M. , González Marta Sonia , Sánchez-Salinas Andrés , González-Navarro Azucena , Ortiz-Maldonado Valentín , Delgado Julio , Prósper Felipe , Juan Manel , Martínez-López Joaquín , Moraleda José M. , Mateos Maria Victoria , Urbano-Ispizua Álvaro , Paiva Bruno , Pascal Mariona , Fernández de Larrea Carlos
Published: May 2024

Figure 8. B-cell kinetics after ARI0002h infusion until study withdrawal.
Supplementary Figure S2 from Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma
Authors: Oliver-Caldes Aina , Español-Rego Marta , Zabaleta Aintzane , González-Calle Verónica , Navarro-Velázquez Sergio , Inogés Susana , de Cerio Ascensión López-Díaz , Cabañas Valentín , López-Muñoz Nieves , Rodríguez-Otero Paula , Reguera Juan Luis , Moreno David F. , Martínez-Cibrian Nuria , López-Corral Lucía , Pérez-Amill Lorena , Martin-Antonio Beatriz , Rosiñol Laura , Cid Joan , Tovar Natalia , Sáez-Peñataro Joaquín , López-Parra Miriam , Olesti Eulalia , Guillén Elena , Varea Sara , Rodríguez-Lobato Luis Gerardo , Battram Anthony M. , González Marta Sonia , Sánchez-Salinas Andrés , González-Navarro Azucena , Ortiz-Maldonado Valentín , Delgado Julio , Prósper Felipe , Juan Manel , Martínez-López Joaquín , Moraleda José M. , Mateos Maria Victoria , Urbano-Ispizua Álvaro , Paiva Bruno , Pascal Mariona , Fernández de Larrea Carlos
Published: May 2024

Figure 2. PD-1 and TIGIT expression over time in two patients with available bone marrow samples until withdrawal of the study
Supplementary Figure S2 from Circulating microRNA Analysis in a Prospective Co-clinical Trial Identifies MIR652–3p as a Response Biomarker and Driver of Regorafenib Resistance Mechanisms in Colorectal Cancer
Authors: Hedayat Somaieh , Cascione Luciano , Cunningham David , Schirripa Marta , Lampis Andrea , Hahne Jens C. , Tunariu Nina , Hong Sung Pil , Marchetti Silvia , Khan Khurum , Fontana Elisa , Angerilli Valentina , Delrieux Mia , Nava Rodrigues Daniel , Procaccio Letizia , Rao Sheela , Watkins David , Starling Naureen , Chau Ian , Braconi Chiara , Fotiadis Nicos , Begum Ruwaida , Guppy Naomy , Howell Louise , Valenti Melanie , Cribbes Scott , Kolozsvari Bernadett , Kirkin Vladimir , Lonardi Sara , Ghidini Michele , Passalacqua Rodolfo , Elghadi Raghad , Magnani Luca , Pinato David J. , Di Maggio Federica , Ghelardi Filippo , Sottotetti Elisa , Vetere Guglielmo , Ciracì Paolo , Vlachogiannis Georgios , Pietrantonio Filippo , Cremolini Chiara , Cortellini Alessio , Loupakis Fotios , Fassan Matteo , Valeri Nicola
Published: May 2024

Supplementary Figure S2. Changes in MIR652-3p expression upon anti-angiogenic treatment.
Supplementary Data 1 from Mesenchymal Stem/Stromal Cell Therapy for Radiation-Induced Xerostomia in Previous Head and Neck Cancer Patients: A Phase II Randomized, Placebo-Controlled Trial
Authors: Jakobsen Kathrine Kronberg , Carlander Amanda-Louise Fenger , Todsen Tobias , Melchiors Jacob , Paaske Natasja , Østergaard Madsen Anne Kathrine , Kloch Bendtsen Simone , Mordhorst Christine , Stampe Helene , Kastrup Jens , Ekblond Annette , Haack-Sørensen Mandana , Farhadi Mohammad , Maare Christian , Friborg Jeppe , Lynggaard Charlotte D. , Werner Hauge Anne , Christensen Robin , Grønhøj Christian , von Buchwald Christian
Published: May 2024

Supplementary data
Supplementary Table S1 from Ataxia-Telangiectasia Mutated Loss-of-Function Displays Variant and Tissue-Specific Differences across Tumor Types
Authors: Pilié Patrick G. , Giuliani Virginia , Wang Wei-Lien , McGrail Daniel J. , Bristow Christopher A. , Ngoi Natalie Y.L. , Kyewalabye Keith , Wani Khalida M. , Le Hung , Campbell Erick , Sanchez Nora S. , Yang Dong , Gheeya Jinesh S. , Goswamy Rohit Vivek , Holla Vijaykumar , Shaw Kenna Rael , Meric-Bernstam Funda , Liu Chiu-Yi , Ma XiaoYan , Feng Ningping , Machado Annette A. , Bardenhagen Jennifer P. , Vellano Christopher P. , Marszalek Joseph R. , Rajendra Eeson , Piscitello Desiree , Johnson Timothy I. , Likhatcheva Maria , Elinati Elias , Majithiya Jayesh , Neves Joana , Grinkevich Vera , Ranzani Marco , Luzarraga Marina Roy , Boursier Marie , Armstrong Lucy , Geo Lerin , Lillo Giorgia , Tse Wai Yiu , Lazar Alexander J. , Kopetz Scott E. , Geck Do Mary K. , Lively Sarah , Johnson Michael G. , Robinson Helen M.R. , Smith Graeme C.M. , Carroll Christopher L. , Di Francesco M. Emilia , Jones Philip , Heffernan Timothy P. , Yap Timothy A.
Published: May 2024

Supplementary Table S1
Supplementary Data 1 from Infiltrative Vessel Co-optive Growth Pattern Induced by IQGAP3 Overexpression Promotes Microvascular Invasion in Hepatocellular Carcinoma
Authors: Tang Miaoling , Zhang Shuxia , Yang Meisongzhu , Feng Rongni , Lin Jinbin , Chen Xiaohong , Xu Yingru , Yu Ruyuan , Liao Xinyi , Li Ziwen , Li Xincheng , Li Man , Zhang Qiliang , Chen Suwen , Qian Wanying , Liu Yuanji , Song Libing , Li Jun
Published: May 2024

Supplementary material
Supplementary Figure S5 from Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series
Authors: Anselmino Nicolas , Labanca Estefania , Shepherd Peter D.A. , Dong Jiabin , Yang Jun , Song Xiaofei , Nandakumar Subhiksha , Kundra Ritika , Lee Cindy , Schultz Nikolaus , Zhang Jianhua , Araujo John C. , Aparicio Ana M. , Subudhi Sumit K. , Corn Paul G. , Pisters Louis L. , Ward John F. , Davis John W. , Vazquez Elba S. , Gueron Geraldine , Logothetis Christopher J. , Futreal Andrew , Troncoso Patricia , Chen Yu , Navone Nora M.
Published: May 2024

CDK12 loss of function in MDA PCa PDX
Data from Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma
Authors: Dermawan Josephine K. , Chiang Sarah , Singer Samuel , Jadeja Bhumika , Hensley Martee L. , Tap William D. , Movva Sujana , Maki Robert G. , Antonescu Cristina R.
Published: May 2024

AbstractPurpose:
Leiomyosarcomas (LMS) are clinically and molecularly heterogeneous tumors. Despite recent large-scale genomic studies, current LMS risk stratification is not informed by molecular alterations. We propose a clinically applicable genomic risk stratification model.
Experimental Design:
We performed comprehensive genomic profiling in a cohort of 195 soft tissue LMS (STLMS), 151 primary at presentation, and a control group of 238 uterine LMS (ULMS), 177 primary at presentation, with at least 1-year follow-up.
Results:
In STLMS, French Federation of Cancer Centers (FNCLCC) grade but not tumor size predicted progression-free survival (PFS) or disease-specific survival (DSS). In contrast, in ULMS, tumor size, mitotic rate, and necrosis were associated with inferior PFS and DSS. In STLMS, a 3-tier genomic risk stratification performed well for DSS: high risk: co-occurrence of RB1 mutation and chr12q deletion (del12q)/ATRX mutation; intermediate risk: presence of RB1 mutation, ATRX mutation, or del12q; low risk: lack of any of these three alterations. The ability of RB1 and ATRX alterations to stratify STLMS was validated in an external AACR GENIE cohort. In ULMS, a 3-tier genomic risk stratification was significant for both PFS and DSS: high risk: concurrent TP53 mutation and chr20q amplification/ATRX mutations; intermediate risk: presence of TP53 mutation, ATRX mutation, or amp20q; low risk: lack of any of these three alterations. Longitudinal sequencing showed that most molecular alterations were early clonal events that persisted during disease progression.
Conclusions:
Compared with traditional clinicopathologic models, genomic risk stratification demonstrates superior prediction of clinical outcome in STLMS and is comparable in ULMS.
Data from Landscape of Baseline and Acquired Genomic Alterations in Circulating Tumor DNA with Abemaciclib Alone or with Endocrine Therapy in Advanced Breast Cancer
Authors: Goetz Matthew P. , Hamilton Erika P. , Campone Mario , Hurvitz Sara A. , Cortes Javier , Johnston Stephen , Llombart-Cussac Antonio , Kaufman Peter A. , Toi Masakazu , Jerusalem Guy , Graham Hillary , Wang Hong , Jansen Valerie M. , Litchfield Lacey M. , Martin Miguel
Published: May 2024

AbstractPurpose:
To identify potential predictors of response and resistance mechanisms in patients with hormone receptor–positive (HR+), HER2-negative (HER2−) advanced breast cancer (ABC) treated with the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor abemaciclib ± endocrine therapy (ET), baseline and acquired genomic alterations in circulating tumor DNA (ctDNA) were analyzed and associated with clinical outcomes.
Experimental Design:
MONARCH 3: postmenopausal women with HR+, HER2− ABC and no prior systemic therapy in the advanced setting were randomly assigned to abemaciclib or placebo plus nonsteroidal aromatase inhibitor (NSAI). nextMONARCH: women with HR+, HER2− metastatic breast cancer that progressed on/after prior ET and chemotherapy were randomly assigned to abemaciclib alone (two doses) or plus tamoxifen. Baseline and end-of-treatment plasma samples from patients in MONARCH 3 and nextMONARCH (monotherapy arms) were analyzed to identify somatic genomic alterations. Association between genomic alterations and median progression-free survival (mPFS) was assessed.
Results:
Most patients had ≥1 genomic alteration detected in baseline ctDNA. In MONARCH 3, abemaciclib+NSAI was associated with improved mPFS versus placebo+NSAI, regardless of baseline alterations. ESR1 alterations were less frequently acquired in the abemaciclib+NSAI arm than placebo+NSAI. Acquired alterations potentially associated with resistance to abemaciclib ± NSAI included RB1 and MYC.
Conclusions:
In MONARCH 3, certain baseline ctDNA genomic alterations were prognostic for ET but not predictive of abemaciclib response. Further studies are warranted to assess whether ctDNA alterations acquired during abemaciclib treatment differ from other CDK4/6 inhibitors. Findings are hypothesis generating; further exploration is warranted into mechanisms of resistance to abemaciclib and ET.

See related commentary by Wander and Bardia, p. 2008
Data from Targeting SMAD3 Improves Response to Oxaliplatin in Esophageal Adenocarcinoma Models by Impeding DNA Repair
Authors: Ballout Farah , Lu Heng , Bhat Nadeem , Chen Lei , Peng Dunfa , Chen Zheng , Chen Steven , Sun Xiaodian , Giordano Silvia , Corso Simona , Zaika Alexander , McDonald Oliver , Livingstone Alan S. , El-Rifai Wael
Published: May 2024

AbstractPurpose:
TGFβ signaling is implicated in the progression of most cancers, including esophageal adenocarcinoma (EAC). Emerging evidence indicates that TGFβ signaling is a key factor in the development of resistance toward cancer therapy.
Experimental Design:
In this study, we developed patient-derived organoids and patient-derived xenograft models of EAC and performed bioinformatics analysis combined with functional genetics to investigate the role of SMAD family member 3 (SMAD3) in EAC resistance to oxaliplatin.
Results:
Chemotherapy nonresponding patients showed enrichment of SMAD3 gene expression when compared with responders. In a randomized patient-derived xenograft experiment, SMAD3 inhibition in combination with oxaliplatin effectively diminished tumor burden by impeding DNA repair. SMAD3 interacted directly with protein phosphatase 2A (PP2A), a key regulator of the DNA damage repair protein ataxia telangiectasia mutated (ATM). SMAD3 inhibition diminished ATM phosphorylation by enhancing the binding of PP2A to ATM, causing excessive levels of DNA damage.
Conclusions:
Our results identify SMAD3 as a promising therapeutic target for future combination strategies for the treatment of patients with EAC.
Genotoxicity Associated with Retroviral CAR Transduction of ATM-Deficient T Cells
Authors: Rozenbaum Meir , Fluss Reut , Marcu-Malina Victoria , Sarouk Ifat , Meir Amilia , Elitzur Sarah , Zinger Tal , Jacob-Hirsch Jasmine , Saar Efrat G. , Rechavi Gideon , Jacoby Elad
Published: May 2024

Somatic variants in DNA damage response genes such as ATM are widespread in hematologic malignancies. ATM protein is essential for double-strand DNA break repair. Germline ATM deficiencies underlie ataxia–telangiectasia (A–T), a disease manifested by radiosensitivity, immunodeficiency, and predisposition to lymphoid malignancies. Patients with A–T diagnosed with malignancies have poor tolerance to chemotherapy or radiation. In this study, we investigated chimeric antigen receptor (CAR) T cells using primary T cells from patients with A–T (ATM−/−), heterozygote donors (ATM+/−), and healthy donors. ATM−/− T cells proliferate and can be successfully transduced with CARs, though functional impairment of ATM−/− CAR T-cells was observed. Retroviral transduction of the CAR in ATM−/− T cells resulted in high rates of chromosomal lesions at CAR insertion sites, as confirmed by next-generation long-read sequencing. This work suggests that ATM is essential to preserve genome integrity of CAR T-cells during retroviral manufacturing, and its lack poses a risk of chromosomal translocations and potential leukemogenicity.

Significance: CAR T-cells are clinically approved genetically modified cells, but the control of genome integrity remains largely uncharacterized. This study demonstrates that ATM deficiency marginally impairs CAR T-cell function and results in high rates of chromosomal aberrations after retroviral transduction, which may be of concern in patients with DNA repair deficiencies.
Scalp Rosacea Treated with Topical Ivermectin
Authors: Dall'Oglio Federica , Nasca Maria Rita , Guglielmi Giulia , Micali Giuseppe
Published: May 2024

Introduction: Scalp rosacea is often misdiagnosed or overlooked, and few reports deal with this peculiar localization. Furthermore, the pharmacological approach to scalp rosacea remains a therapeutic challenge, as no topical and/or systemic drugs have been approved for this specific area so far. Case Presentation: A series of 5 adult patients affected by inflammatory rosacea and concurrent scalp involvement, confirmed by dermoscopy and histopathology with negative microbiologic swabs, and effectively treated with ivermectin 1% cream once daily for 12 weeks is presented. Conclusion: Our experience, although limited, suggests that evaluation of rosacea subjects should also include the scalp and that the treatment with ivermectin 1% cream may be effective on scalp rosacea.
Impact of Arterial Calcification on Cardiovascular and Renal Outcomes in Kidney Transplant Patients
Authors: Ha Joohyung , Jeong Jong Cheol , Ryu Jung-Hwa , Kim Myung-Gyu , Huh Kyu Ha , Lee Kyo Won , Jung Hee-Yeon , Kang Kyung Pyo , Ro Han , Han Seungyeup , Seok Kim Beom , Yang Jaeseok ,   on behalf of the KNOW-KT Study Group
Published: May 2024

Introduction: Coronary artery calcification score (CACS) and abdominal aortic calcification score (AACS) are both well-established markers of vascular stiffness, and previous studies have shown that a higher CACS is a risk factor for chronic kidney disease (CKD) progression. However, the impact of pretransplant CACS and AACS on cardiovascular and renal outcomes in kidney transplant patients has not been established. Methods: We included 944 kidney transplant recipients from the KoreaN cohort study for Outcome in patients With Kidney Transplantation (KNOW-KT) cohort and categorized them into three groups (low, medium, and high) according to baseline CACS (0, 0 < and ≤100, >100) and AACS (0, 1–4, >4). The low (0), medium (0 < and ≤ 100), and high (>100) CACS groups each consisted of 462, 213, and 225 patients, respectively. Similarly, the low (0), medium (1–4), and high (>4) AACS groups included 638, 159, and 147 patients, respectively. The primary outcome was the occurrence of cardiovascular events. The secondary outcomes were all-cause mortality and composite kidney outcomes, which comprised of >50% decline in the estimated glomerular filtration rate and graft loss. Cox regression analysis was used to investigate the association between baseline CACS/AACS and outcomes. Results: The high CACS group (N = 462) faced a significantly higher risk for cardiovascular outcomes (adjusted hazard ratio [aHR], 5.97; 95% confidence interval [CI], 2.01–17.7) and all-cause mortality (aHR, 2.74; 95% CI, 1.27–5.92) compared to the low CACS group (N = 225). Similarly, the high AACS group (N = 638) had an elevated risk for cardiovascular outcomes (aHR, 2.38; 95% CI, 1.16–4.88). Furthermore, the addition of CACS to prediction models improved prediction indices for cardiovascular outcomes. However, the risk of renal outcomes did not differ among CACS or AACS groups. Conclusion: Pretransplant arterial calcification, characterized by high CACS or AACS, is an independent risk factor for cardiovascular outcomes and mortality in kidney transplant patients.
Application of Nanoparticles as Novel Adsorbents in Blood Purification Strategies
Authors: Shen Yue , Shen Yuqi , Bi Xiao , Shen Aiwen , Wang Yifeng , Ding Feng
Published: May 2024

Background: Blood purification therapy for patients overloaded with metabolic toxins or drugs still needs improvement. Blood purification therapies, such as in hemodialysis or peritoneal dialysis can profit from a combined application with nanoparticles. Summary: In this review, the published literature is analyzed with respect to nanomaterials that have been customized and functionalized as nano-adsorbents during blood purification therapy. Liposomes possess a distinct combined structure composed of a hydrophobic lipid bilayer and a hydrophilic core. The liposomes which have enzymes in their aqueous core or obtain specific surface modifications of the lipid bilayer can offer appreciated advantages. Preclinical and clinical experiments with such modified liposomes show that they are highly efficient and generally safe. They may serve as indirect and direct adsorption materials both in hemodialysis and peritoneal dialysis treatment for patients with renal or hepatic failure. Apart from dialysis, nanoparticles made of specially designed metal and activated carbon have also been utilized to enhance the removal of solutes during hemoadsorption. Results are a superior adsorption capacity and good hemocompatibility shown during the treatment of patients with toxication or end-stage renal disease. In summary, nanomaterials are promising tools for improving the treatment efficacy of organ failure or toxication. Key Messages: (i) The pH-transmembrane liposomes and enzyme-loaded liposomes are two representatives of liposomes with modified aqueous inner core which have been put into practice in dialysis. (ii) Unmodified or physiochemically modified liposomal bilayers are ideal binders for lipophilic protein-bound uremic toxins or cholestatic solutes, thus liposome-supported dialysis could become the next-generation hemodialysis treatment of artificial liver support system. (iii) Novel nano-based sorbents featuring large surface area, high adsorption capacity and decent biocompatibility have shown promise in the treatment of uremia, hyperbilirubinemia, intoxication, and sepsis. (vi) A major challenge of production lies in avoiding changes in physical and chemical properties induced by manufacturing and sterilizing procedures.
Endoscopic Diagnosis of Epithelial Subtypes of Superficial Non-Ampullary Duodenal Epithelial Tumors using Magnifying Narrow-Band Imaging
Authors: Kurata Yoshiyuki , Hirose Takashi , Kakushima Naomi , Nakaguro Masato , Okumura Yuki , Tanaka Hitoshi , Fujishiro Mitsuhiro , Kawashima Hiroki
Published: May 2024

Introduction: Superficial non-ampullary duodenal epithelial tumors (SNADETs) include low-grade adenoma (LGA) and high-grade adenoma or carcinoma (HGA/Ca) and are classified into two different epithelial subtypes, gastric-type (G-type) and intestinal-type (I-type). We attempted to distinguish them by endoscopic characteristics including magnifying endoscopy with narrow-band imaging (M-NBI). Methods: Various endoscopic and M-NBI findings of 286 SNADETs were retrospectively reviewed and compared between G- and I-types and histological grades. M-NBI findings were divided into four patterns based on the following vascular patterns; absent, network, intrastructural vascular (ISV), and unclassified. Lesions displaying a single pattern were classified as mono-pattern and those displaying multiple patterns as mixed-pattern. Lesions showing CDX2 positivity were categorized as I-types and those showing MUC5AC or MUC6 positivity were categorized as G-types based on immunohistochemistry. Results: Among 286 lesions, 23 (8%) were G-type and 243 (85%) were I-type. More G-type lesions were located oral to papilla (91.3 vs. 45.6%, p < 0.001), and had protruding morphology compared to those of I-types (65.2 vs. 14.4%, p < 0.001). The major M-NBI pattern was ISV in G-type (78.2 vs. 26.3%, p < 0.001), and absent for I-type (0 vs. 34.5%, p = 0.003). Three endoscopic characteristics; location oral to papilla, protruding morphology, and major M-NBI pattern (ISV) were independent predictors for G-type. Mixed-pattern was more common in HGA/Ca than LGA for I-type (77.0 vs. 58.8%, p = 0.01); however, there was no difference for those in G-type. Conclusion: Endoscopic findings including M-NBI are useful to differentiate epithelial subtypes.
A Novel Macrophage Subpopulation Conveys Increased Genetic Risk of Coronary Artery Disease
Authors: Jiang Jiahao , Hiron Thomas K. , Agbaedeng Thomas A. , Malhotra Yashaswat , Drydale Edward , Bancroft James , Ng Esther , Reschen Michael E. , Davison Lucy J. , O’Callaghan Chris A.
Published: May 2024

BACKGROUND:

Coronary artery disease (CAD), the leading cause of death worldwide, is influenced by both environmental and genetic factors. Although over 250 genetic risk loci have been identified through genome-wide association studies, the specific causal variants and their regulatory mechanisms are still largely unknown, particularly in disease-relevant cell types such as macrophages.

METHODS:

We utilized single-cell RNA-seq and single-cell multiomics approaches in primary human monocyte–derived macrophages to explore the transcriptional regulatory network involved in a critical pathogenic event of coronary atherosclerosis—the formation of lipid-laden foam cells. The relative genetic contribution to CAD was assessed by partitioning disease heritability across different macrophage subpopulations. Meta-analysis of single-cell RNA-seq data sets from 38 human atherosclerotic samples was conducted to provide high-resolution cross-referencing to macrophage subpopulations in vivo.

RESULTS:

We identified 18 782 cis-regulatory elements by jointly profiling the gene expression and chromatin accessibility of >5000 macrophages. Integration with CAD genome-wide association study data prioritized 121 CAD-related genetic variants and 56 candidate causal genes. We showed that CAD heritability was not uniformly distributed and was particularly enriched in the gene programs of a novel CD52-hi lipid-handling macrophage subpopulation. These CD52-hi macrophages displayed significantly less lipoprotein accumulation and were also found in human atherosclerotic plaques. We investigated the cis-regulatory effect of a risk variant rs10488763 on
FDX1
, implicating the recruitment of AP-1 and C/EBP-β in the causal mechanisms at this locus.

CONCLUSIONS:

Our results provide genetic evidence of the divergent roles of macrophage subsets in atherogenesis and highlight lipid-handling macrophages as a key subpopulation through which genetic variants operate to influence disease. These findings provide an unbiased framework for functional fine-mapping of genome-wide association study results using single-cell multiomics and offer new insights into the genotype-environment interactions underlying atherosclerotic disease.