bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional NADPH oxidase 2 in T cells amplifies salt-sensitive hypertension and associated renal damage
Authors: Walton Samuel D. , Dasinger John Henry , Burns Emily C. , Cherian-Shaw Mary , Abais-Battad Justine M. , Mattson David L.
Published: June 2023

Our current work used the adoptive transfer of T cells that lack functional NADPH oxidase 2 into a genetically T cell-deficient Dahl salt-sensitive (SS) rat model. The results demonstrated that reactive oxygen species produced by NADPH oxidase 2 in T cells participate in the amplification of SS hypertension and associated renal damage and identifies a potential mechanism that exacerbates the salt-sensitive phenotype.
Exploring Prognostic Biomarkers of Acute Myeloid Leukemia to Determine Its Most Effective Drugs from the FDA‐Approved List through Molecular Docking and Dynamic Simulation
Authors: Alom Md. Murshid , Faruqe Md Omar , Molla Md. Khademul Islam , Rahman Md Motiur
Published: June 2023

Acute myeloid leukemia (AML) is a blood cancer caused by the abnormal proliferation and differentiation of hematopoietic stem cells in the bone marrow. The actual genetic markers and molecular mechanisms of AML prognosis are unclear till today. This study used bioinformatics approaches for identifying hub genes and pathways associated with AML development to uncover potential molecular mechanisms. The expression profiles of RNA‐Seq datasets, GSE68925 and GSE183817, were retrieved from the Gene Expression Omnibus (GEO) database. These two datasets were analyzed by GREIN to obtain differentially expressed genes (DEGs), which were used for performing the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein‐protein interaction (PPI), and survival analysis. The molecular docking and dynamic simulation were performed to identify the most effective drug/s for AML from the drug list approved by the Food and Drug Administration (FDA). By integrating the two datasets, 238 DEGs were identified as likely to be affected by AML progression. GO enrichment analyses exhibited that the upregulated genes were mainly associated with inflammatory response (BP) and extracellular region (CC). The downregulated DEGs were involved in the T‐cell receptor signalling pathway (BP), an integral component of the lumenal side of the endoplasmic reticulum membrane (CC) and peptide antigen binding (MF). The pathway enrichment analysis showed that the upregulated DEGs were mainly associated with the T‐cell receptor signalling pathway. Among the top 15 hub genes, the expression levels of ALDH1A1 and CFD were associated with the prognosis of AML. Four FDA‐approved drugs were selected, and a top‐ranked drug was identified for each biomarker through molecular docking studies. The top‐ranked drugs were further confirmed by molecular dynamic simulation that revealed their binding stability and confirmed their stable performance. Therefore, the drug compounds, enasidenib and gilteritinib, can be recommended as the most effective drugs against the ALDH1A1 and CFD proteins, respectively.
Study of the Effect of Drying on the Pore Structure and Rate of Oxygen Consumption and Heat Release of Immersed Lignite
Authors: Guo Wei , Zhang Chunhua , Dong Ziwen , Han Yongliang
Published: June 2023

To reveal the influence mechanism of the drying process of immersed coal on the spontaneous combustion characteristics, we measured the pore structure of coal with low-field nuclear magnetic resonance and conducted the temperature-programmed spontaneous combustion experiment. The results showed that the pore volume content of the pores with pore sizes of less than 100 nm was significantly reduced. The diameter range of 100–1000 nm was gradually generated after 8 h of coal drying, and the proportion of large pores and cracks larger than 1000 nm increased significantly during the drying process of the immersed coal. The oxygen consumption rate and the heat release rate were significantly affected by the degree of dryness and the temperature of coal samples in the temperature-programmed process. The turning point temperature was 140°C; below the turning point temperature, the raw coal had the fastest oxygen consumption and maximum heat release. When the coal temperature was higher than 140°C, the oxygen consumption rate and the heat release rate of the coal sample that was dried for 24 h were higher than those for the raw coal, followed by the samples that were dried for 8 h and dried for 48 h. The main reason is that the water content of the coal sample decreases to 11.4% and the porosity increases to 16.5% after drying for 24 h, while the proportion of pores or cracks larger than 1000 nm increases significantly to 87.17%, the largest increase range and the pore connectivity will reach the maximum.
Fabrication of Porous Ni-Co LDH Nanocomposites as Efficient Electrodes for Supercapacitors
Authors: Rosaiah P. , Vadivel S. , Prakash Nunna Guru , Dhananjaya Merum , Al-Asbahi Bandar Ali , Roy Soumyendu , Chalapathi U. , Park Si-Hyun
Published: June 2023

Nowadays, there is constant demand for the development of energy storage materials using advanced methodologies. In this scenario, a large-scale environmentally friendly synthesis was chosen to prepare Ni-Co-layered double hydroxide (LDH) composites for asymmetric supercapacitors. The developed materials had a flower-like porous architecture with very low dimensional layers and a large surface area. The developed Ni-Co/LDH composite electrodes showed impressive specific capacitance of 1095.1 F/g at a current density of 1 A/g and maintained 492.5 F/g even at a current density of 20 A/g. In particular, the Ni-Co/LDH composites maintained 86.9% of their initial capacitance even after 5000 cycles at a high current density of 2 A/g. Furthermore, an asymmetric supercapacitor with Ni-Co/LDH composites demonstrated an excellent energy density of 40.7 Wh/kg at a power density of 750 W/kg.
Interval Grey Hesitant Fuzzy Set and Its Applications in Decision-Making
Authors: Zhao Jingjie , Xie Wanli
Published: June 2023

The use of interval-valued hesitant fuzzy sets (IVHFS) can aid decision-makers in evaluating a variable using multiple interval numbers, making it a valuable tool for addressing decision-making problems. However, it fails to obtain information with greyness. The grey fuzzy set (GFS) can improve this problem but studies on it have lost the advantages of IVHFS. In order to improve the accuracy of decision-making and obtain more reasonable results, it is important to enhance the description of real-life information. We combined IVHFS and GFS and defined a novel fuzzy set named interval grey hesitant fuzzy set (IGHFS), in which possible degrees of grey numbers are designed to indicate the upper and lower limits of the interval number. Meanwhile, its basic operational laws, score function, entropy method, and distance measures are proposed. And then, a multicriteria decision-making (MCDM) model IGHFS-TOPSIS is developed based on them. Finally, an example of MOOC platform selection issues for teaching courses illustrates the effectiveness and feasibility of the decision model under the IGHFS.
Supplementary Video from Shortwave Infrared Imaging Enables High-Contrast Fluorescence-Guided Surgery in Neuroblastoma
Authors: Privitera Laura , Waterhouse Dale J. , Preziosi Alessandra , Paraboschi Irene , Ogunlade Olumide , Da Pieve Chiara , Barisa Marta , Ogunbiyi Olumide , Weitsman Gregory , Hutchinson J. Ciaran , Cross Kate , Biassoni Lorenzo , Stoyanov Danail , Sebire Neil , Beard Paul , De Coppi Paolo , Kramer-Marek Gabriela , Anderson John , Giuliani Stefano
Published: June 2023

Supplementary video showing fluorescence-guided resection of a subcutaneous model of Neuroblastoma injected with anti-GD2 fluorescence probes
Figure 8 from Shortwave Infrared Imaging Enables High-Contrast Fluorescence-Guided Surgery in Neuroblastoma
Authors: Privitera Laura , Waterhouse Dale J. , Preziosi Alessandra , Paraboschi Irene , Ogunlade Olumide , Da Pieve Chiara , Barisa Marta , Ogunbiyi Olumide , Weitsman Gregory , Hutchinson J. Ciaran , Cross Kate , Biassoni Lorenzo , Stoyanov Danail , Sebire Neil , Beard Paul , De Coppi Paolo , Kramer-Marek Gabriela , Anderson John , Giuliani Stefano
Published: June 2023

SWIR imaging achieves a higher TBR than NIR-I imaging. A, Normalized band images of exposed tumors at 24 hours post conjugates injection. Images show increased TBR at longer wavelengths. B, Normalized band images (900 and 1,300 nm only) 48, 72, and 96 hours after anti–GD2-IR800 and anti–GD2-IR12 administration. C, TBR versus wavelength band for each conjugate and control mice. Each line represents an individual (one individual per dye per time point). The TBR measured at 1,300 nm 72 hours post anti–GD2-IR12 injection was omitted as an outlier. The upper black line shows the fit of the combined anti–GD2-IR800 and anti–GD2-IR12 data. The lower black line shows the fit of the control data. The gray bands show the 95% confidence interval of the fit (simultaneous functional bounds).
Figure 7 from Shortwave Infrared Imaging Enables High-Contrast Fluorescence-Guided Surgery in Neuroblastoma
Authors: Privitera Laura , Waterhouse Dale J. , Preziosi Alessandra , Paraboschi Irene , Ogunlade Olumide , Da Pieve Chiara , Barisa Marta , Ogunbiyi Olumide , Weitsman Gregory , Hutchinson J. Ciaran , Cross Kate , Biassoni Lorenzo , Stoyanov Danail , Sebire Neil , Beard Paul , De Coppi Paolo , Kramer-Marek Gabriela , Anderson John , Giuliani Stefano
Published: June 2023

Biological evaluation of anti–GD2-IR800 and anti–GD2-IR12 using a preclinical NIR-I imaging system in vivo. A, IVIS Spectrum images of the exposed tumors at 24, 48, 72, and 96 hours postinjection of anti–GD2-IR800 (n = 3) and anti–GD2-IR12 (n = 3) in mice bearing subcutaneous LAN-1 neuroblastoma tumors. White dotted lines show the ROIs drawn to quantify tumor to background ratio. B, Graph bar showing fluorescence intensity of the tumor and the background at 24, 48, 72, and 96 hours post conjugates injection. C, Tumor-to-background ratio at 24, 48, 72, and 96 hours after the injection of the conjugates. Error bars represent the SE across individuals. D,Ex vivo fluorescence images of the resected organs. The white dotted lines delineate the regions used to quantify the fluorescence signals. E, MFI for each organ at each time point and for the background card (BG). Fluorescence intensity decreases over time, with the anti–GD2-IR800 being consistently brighter than the anti–GD2-IR12 (MFIIR800/MFIIR12 = 1.90 ± 0.36 for tumor, P = 10−20, three-way ANOVA). Error bars represent the SE across individuals. F, MFI of tumor relative to MFI of each organ at each time point. Data for control mice is shown in green in the graphs B, C, E, and F.
Supplementary Table from Ubiquitin Ligases Siah1a/2 Control Alveolar Macrophage Functions to Limit Carcinogen-Induced Lung Adenocarcinoma
Authors: Scortegagna Marzia , Du Yuanning , Bradley Linda M. , Wang Kun , Molinolo Alfredo , Ruppin Eytan , Murad Rabi , Ronai Ze'ev A.
Published: June 2023

Sup Table 3
Supplementary Fig 7 from Ubiquitin Ligases Siah1a/2 Control Alveolar Macrophage Functions to Limit Carcinogen-Induced Lung Adenocarcinoma
Authors: Scortegagna Marzia , Du Yuanning , Bradley Linda M. , Wang Kun , Molinolo Alfredo , Ruppin Eytan , Murad Rabi , Ronai Ze'ev A.
Published: June 2023

Sup Fig 7
Table S8 from An In Vivo CRISPR Screen Identifies That SNRPC Promotes Triple-Negative Breast Cancer Progression
Authors: Lu Xun-Xi , Yang Wen-Xiao , Pei Yu-Chen , Luo Hong , Li Xiao-Guang , Wang Yun-Jin , Zhang Guo-Liang , Ling Hong , Shao Zhi-Ming , Hu Xin
Published: June 2023

Table S8. Genes with changed Pol II peaks in SNRPC-KD CA1a cells.
Supplementary Fig 4 from Ubiquitin Ligases Siah1a/2 Control Alveolar Macrophage Functions to Limit Carcinogen-Induced Lung Adenocarcinoma
Authors: Scortegagna Marzia , Du Yuanning , Bradley Linda M. , Wang Kun , Molinolo Alfredo , Ruppin Eytan , Murad Rabi , Ronai Ze'ev A.
Published: June 2023

Sup Fig 4
Table S3 from An In Vivo CRISPR Screen Identifies That SNRPC Promotes Triple-Negative Breast Cancer Progression
Authors: Lu Xun-Xi , Yang Wen-Xiao , Pei Yu-Chen , Luo Hong , Li Xiao-Guang , Wang Yun-Jin , Zhang Guo-Liang , Ling Hong , Shao Zhi-Ming , Hu Xin
Published: June 2023

Table S3. MAGeCK ranking of screen genes in DCIS and CA1a.
Table S2 from An In Vivo CRISPR Screen Identifies That SNRPC Promotes Triple-Negative Breast Cancer Progression
Authors: Lu Xun-Xi , Yang Wen-Xiao , Pei Yu-Chen , Luo Hong , Li Xiao-Guang , Wang Yun-Jin , Zhang Guo-Liang , Ling Hong , Shao Zhi-Ming , Hu Xin
Published: June 2023

Table S2. sgRNA sequences of RBP genes in the CRISPR/Cas9 library.
Supplementary Table S4-6 from An In Vivo CRISPR Screen Identifies That SNRPC Promotes Triple-Negative Breast Cancer Progression
Authors: Lu Xun-Xi , Yang Wen-Xiao , Pei Yu-Chen , Luo Hong , Li Xiao-Guang , Wang Yun-Jin , Zhang Guo-Liang , Ling Hong , Shao Zhi-Ming , Hu Xin
Published: June 2023

Table S4. Primers used in qPCR assays.Table S5. The association of SNRPC expression with patients’ characteristics.Table S6. Univariate and multivariate analysis of DFS in all patients.
Supplementary Fig 2 from Ubiquitin Ligases Siah1a/2 Control Alveolar Macrophage Functions to Limit Carcinogen-Induced Lung Adenocarcinoma
Authors: Scortegagna Marzia , Du Yuanning , Bradley Linda M. , Wang Kun , Molinolo Alfredo , Ruppin Eytan , Murad Rabi , Ronai Ze'ev A.
Published: June 2023

Sup Fig 2
Table S3 from Proteomic Profiling of Extracellular Matrix Components from Patient Metastases Identifies Consistently Elevated Proteins for Developing Nanobodies That Target Primary Tumors and Metastases
Authors: Jailkhani Noor , Clauser Karl R. , Mak Howard H. , Rickelt Steffen , Tian Chenxi , Whittaker Charles A. , Tanabe Kenneth K. , Purdy Stephen R. , Carr Steven A. , Hynes Richard O.
Published: June 2023

Supplementary Table S3
Supplementary Table 2 from CellMinerCDB: NCATS Is a Web-Based Portal Integrating Public Cancer Cell Line Databases for Pharmacogenomic Explorations
Authors: Reinhold William C. , Wilson Kelli , Elloumi Fathi , Bradwell Katie R. , Ceribelli Michele , Varma Sudhir , Wang Yanghsin , Duveau Damien , Menon Nikhil , Trepel Jane , Zhang Xiaohu , Klumpp-Thomas Carleen , Micheal Samuel , Shinn Paul , Luna Augustin , Thomas Craig , Pommier Yves
Published: June 2023

Tissues of origin
Supplementary Figure 1 from CellMinerCDB: NCATS Is a Web-Based Portal Integrating Public Cancer Cell Line Databases for Pharmacogenomic Explorations
Authors: Reinhold William C. , Wilson Kelli , Elloumi Fathi , Bradwell Katie R. , Ceribelli Michele , Varma Sudhir , Wang Yanghsin , Duveau Damien , Menon Nikhil , Trepel Jane , Zhang Xiaohu , Klumpp-Thomas Carleen , Micheal Samuel , Shinn Paul , Luna Augustin , Thomas Craig , Pommier Yves
Published: June 2023

BAX versus SN38
Table 1 from Prospective Analysis Reveals Associations between Carbohydrate Intakes, Genetic Predictors of Short-Chain Fatty Acid Synthesis, and Colorectal Cancer Risk
Authors: Watling Cody Z. , Kelly Rebecca K. , Murphy Neil , Gunter Marc , Piernas Carmen , Bradbury Kathryn E. , Schmidt Julie A. , Key Timothy J. , Perez-Cornago Aurora
Published: June 2023

Baseline characteristics by lowest and highest quartile of intake of whole grain starch, refined grain starch, and fiber in 114,217 UK Biobank participants.
Supplementary Data from Chi3l1 Is a Modulator of Glioma Stem Cell States and a Therapeutic Target in Glioblastoma
Authors: Guetta-Terrier Charlotte , Karambizi David , Akosman Bedia , Zepecki John P. , Chen Jia-Shu , Kamle Suchitra , Fajardo J. Eduardo , Fiser Andras , Singh Ritambhara , Toms Steven A. , Lee Chun Geun , Elias Jack A. , Tapinos Nikos
Published: June 2023

Supplementary Data and figure legends
Figure S5 from Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation and Progression
Authors: DeBlasi Janine M. , Falzone Aimee , Caldwell Samantha , Prieto-Farigua Nicolas , Prigge Justin R. , Schmidt Edward E. , Chio Iok In Christine , Karreth Florian A. , DeNicola Gina M.
Published: June 2023

Supplementary Fig. S5 shows lung tumor analysis data in the KrasG12D/+; p53fl/fl model with single copy Nrf2 deletion.
Figure S4 from Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation and Progression
Authors: DeBlasi Janine M. , Falzone Aimee , Caldwell Samantha , Prieto-Farigua Nicolas , Prigge Justin R. , Schmidt Edward E. , Chio Iok In Christine , Karreth Florian A. , DeNicola Gina M.
Published: June 2023

Supplementary Fig. S4 shows the H-scores by tumor grade of Nrf2 and Nqo1 immunohistochemical staining in KrasG12D/+; p53fl/fl and KrasG12D/+; p53fl/fl; Keap1R554Q/R554Q mouse models with single copy Nrf2 deletion.
Data from Proteomic Profiling of Extracellular Matrix Components from Patient Metastases Identifies Consistently Elevated Proteins for Developing Nanobodies That Target Primary Tumors and Metastases
Authors: Jailkhani Noor , Clauser Karl R. , Mak Howard H. , Rickelt Steffen , Tian Chenxi , Whittaker Charles A. , Tanabe Kenneth K. , Purdy Stephen R. , Carr Steven A. , Hynes Richard O.
Published: June 2023

Abstract
Metastases are hard to detect and treat, and they cause most cancer-related deaths. The relative lack of therapies targeting metastases represents a major unmet clinical need. The extracellular matrix (ECM) forms a major component of the tumor microenvironment in both primary and metastatic tumors, and certain ECM proteins can be selectively and abundantly expressed in tumors. Nanobodies against ECM proteins that show selective abundance in metastases have the potential to be used as vehicles for delivery of imaging and therapeutic cargoes. Here, we describe a strategy to develop phage-display libraries of nanobodies against ECM proteins expressed in human metastases, using entire ECM-enriched preparations from triple-negative breast cancer (TNBC) and colorectal cancer metastases to different organs as immunogens. In parallel, LC-MS/MS-based proteomics were used to define a metastasis-associated ECM signature shared by metastases from TNBC and colorectal cancer, and this conserved set of ECM proteins was selectively elevated in other tumors. As proof of concept, selective and high-affinity nanobodies were isolated against an example protein from this signature, tenascin-C (TNC), known to be abundant in many tumor types and to play a role in metastasis. TNC was abundantly expressed in patient metastases and widely expressed across diverse metastatic sites originating from several primary tumor types. Immuno-PET/CT showed that anti-TNC nanobodies bind TNBC tumors and metastases with excellent specificity. We propose that such generic nanobodies against tumors and metastases are promising cancer-agnostic tools for delivery of therapeutics to tumor and metastatic ECM.
Significance:
Nanobodies specific for extracellular matrix markers commonly expressed in primary tumors and metastases are promising agents for noninvasive detection of tumors and metastases and potential tools for targeted therapy.
Supplementary Table S2 from Genomic Profiling of Radiation-Induced Sarcomas Reveals the Immunologic Characteristics and Its Response to Immune Checkpoint Blockade
Authors: Hong Dong-Chun , Yang Jing , Sun Cong , Liu Yuan-Tao , Shen Lu-Jun , Xu Bu-Shu , Que Yi , Xia Xiaojun , Zhang Xing
Published: June 2023

Differentially expressed genes (DEG), possible fusion genes and alternative splicing events, and the anti-tumor immunity scores and proliferation module scores of each sample.
Supplementary Table S2 from Integrative Single-Cell and Bulk Transcriptomes Analyses Identify Intrinsic HNSCC Subtypes with Distinct Prognoses and Therapeutic Vulnerabilities
Authors: Dai Yibin , Wang Ziyu , Xia Yingchao , Li Jin , Wu Yaping , Wang Yanling , Jiang Hongbing , Cheng Jie
Published: June 2023

iCMS classifier (marker genes) & biological enrichment
Supplementary Table S1 from Genomic Profiling of Radiation-Induced Sarcomas Reveals the Immunologic Characteristics and Its Response to Immune Checkpoint Blockade
Authors: Hong Dong-Chun , Yang Jing , Sun Cong , Liu Yuan-Tao , Shen Lu-Jun , Xu Bu-Shu , Que Yi , Xia Xiaojun , Zhang Xing
Published: June 2023

Clinical characteristics of patients in RIS group and SARC group as a whole, or for WES, or for mRNA- seq.
Supplementary Figure S4 from Genomic Profiling of Radiation-Induced Sarcomas Reveals the Immunologic Characteristics and Its Response to Immune Checkpoint Blockade
Authors: Hong Dong-Chun , Yang Jing , Sun Cong , Liu Yuan-Tao , Shen Lu-Jun , Xu Bu-Shu , Que Yi , Xia Xiaojun , Zhang Xing
Published: June 2023

The landscape of copy number variants and results for blood detection.༈A༉Top genes in copy number changes in RIS and SARC groups filtered by COSMIC gene list.༈B༉Top genes in copy number changes in RIFS and FS subtypes.༈C༉Top genes in copy number changes in RIOS and OS subtypes.(D and E༉Flow cytometry (D) and ELISA (E) results of immune cells and cytokines in peripheral blood from patients.
Supplementary Figures 1 from Integrative Single-Cell and Bulk Transcriptomes Analyses Identify Intrinsic HNSCC Subtypes with Distinct Prognoses and Therapeutic Vulnerabilities
Authors: Dai Yibin , Wang Ziyu , Xia Yingchao , Li Jin , Wu Yaping , Wang Yanling , Jiang Hongbing , Cheng Jie
Published: June 2023

Supplementary Figures
Supplementary Figure S1 from Genomic Profiling of Radiation-Induced Sarcomas Reveals the Immunologic Characteristics and Its Response to Immune Checkpoint Blockade
Authors: Hong Dong-Chun , Yang Jing , Sun Cong , Liu Yuan-Tao , Shen Lu-Jun , Xu Bu-Shu , Que Yi , Xia Xiaojun , Zhang Xing
Published: June 2023

The flowchart showing patient screening and identification, and analysis steps for mRNA-seq and WES data. FS: fibrosarcoma; OS: osteosarcoma.
Supplementary Table S1 from Patient-Specific Targeting of the T-Cell Receptor Variable Region as a Therapeutic Strategy in Clonal T-Cell Diseases
Authors: Lucero Olivia M. , Lee Ji-Ann , Bowman Jenna , Johnson Kara , Sapparapu Gopal , Thomas John K. , Fan Guang , Chang Bill H. , Thiel-Klare Karina , Eide Christopher A. , Okada Craig , Palazzolo Mike , Lind Evan , Kosaka Yoko , Druker Brian J. , Lydon Nicholas , Bowers Peter M.
Published: June 2023

Supplementary Table S1. (A) List of published datasets used to compile the distributionof TCRVB Gene Usage across T-cell NHL. (B) TCR Vβ usage in 314 patients with T-cellNHL by disease type. Note that both the IMGT and Wei et al nomenclature are listed.
Supplementary Figure S3 from Patient-Specific Targeting of the T-Cell Receptor Variable Region as a Therapeutic Strategy in Clonal T-Cell Diseases
Authors: Lucero Olivia M. , Lee Ji-Ann , Bowman Jenna , Johnson Kara , Sapparapu Gopal , Thomas John K. , Fan Guang , Chang Bill H. , Thiel-Klare Karina , Eide Christopher A. , Okada Craig , Palazzolo Mike , Lind Evan , Kosaka Yoko , Druker Brian J. , Lydon Nicholas , Bowers Peter M.
Published: June 2023

Supplementary Figure 3: Vβ monoclonal antibodies induce antibody dependentcellular cytotoxicity of target cells.
Supplementary Figure S1 from Patient-Specific Targeting of the T-Cell Receptor Variable Region as a Therapeutic Strategy in Clonal T-Cell Diseases
Authors: Lucero Olivia M. , Lee Ji-Ann , Bowman Jenna , Johnson Kara , Sapparapu Gopal , Thomas John K. , Fan Guang , Chang Bill H. , Thiel-Klare Karina , Eide Christopher A. , Okada Craig , Palazzolo Mike , Lind Evan , Kosaka Yoko , Druker Brian J. , Lydon Nicholas , Bowers Peter M.
Published: June 2023

Supplementary Figure S1. Immunophenotype of Patient's T-LGL cells.
Data from Multicenter randomized double-blind phase III trial of donafenib in progressive radioactive iodine-refractory differentiated thyroid cancer
Authors: Lin Yansong , Qin Shukui , Yang Hui , Shi Feng , Yang Aimin , Han Xingmin , Liu Bin , Li Zhiyong , Ji Qinghai , Tang Lijun , Deng Zhiyong , Ding Yong , Fu Wei , Xie Xianhe , Li Linfa , He Xiaohui , Lv Zhongwei , Ma Qingjie , Shen Zan , Guo Zhuming , Chen Zhendong , Cui Yali , Tan Jian , Gao Zairong , Jing Shanghua , Lu Keyi , Luo Xianyang , Zhang Yuan , Fang Yong , Li Zhendong , Cheng Yizhuang , Lei Shangtong , Luan Sha , Chen Guang , Wang Guihua , Wu Liqing , Liu Lingling
Published: June 2023

Abstract
Purpose: The phase II/III study of donafenib was initiated when there was no available treatment indicated for Chinese patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Donafenib, an oral tyrosine kinase inhibitor (TKI), showed good efficacy and tolerability in the phase II study. We aimed to further evaluate the antitumour activity and safety of donafenib in Chinese RAIR-DTC patients. Patients and Methods: This multicenter, double-blind, placebo-controlled, phase III study enrolled 191 patients with progressive RAIR-DTC and randomized in a ratio of 2:1 to donafenib (300 mg twice daily, n=128) or matched placebo (n=63). An open-label donafenib treatment period was allowed upon disease progression. The primary endpoint was progression-free survival (PFS) assessed by the independent review committee. The second endpoints include objective response rate (ORR), disease control rate (DCR), safety, etc. Results: Donafenib demonstrated prolonged median PFS over placebo (12.9 vs. 6.4 months, HR 0.39, 95% CI 0.25-0.61, p<0.0001) in Chinese RAIR-DTC patients. Improved ORR (23.3% vs. 1.7%, p=0.0002) and DCR (93.3% vs. 79.3%,p=0.0044) were observed in the donafenib group over placebo. For donafenib, the most common grade ≥3 treatment-related adverse events included hypertension (13.3%) and hand-foot syndrome (12.5%), 42.2% underwent dose reduction or interruption and 6.3% experienced discontinuation. Conclusions: Donafenib was well-tolerated, and demonstrated clinical benefit in terms of improved PFS, ORR and DCRin patients with RAIR-DTC. The results suggest that donafenib could be a new treatment option for RAIR-DTC patients.
Translation and Psychometric Properties of the Persian Version of the Feeding/Swallowing Impact Survey in Iranian Mothers
Authors: Mokhlesin Maryam , Ebadi Abbas , Yadegari Fariba , Ghoreishi Zahra Sadat
Published: June 2023

Introduction: Feeding is an interactive process between a child and a caregiver, and its early and chronic problems can affect the stress and quality of life of parents. Since the health and support of caregivers can affect the child’s disability and performance, it is important to consider the impact of feeding and swallowing disorders on caregivers. Hence, the present study aimed to translate and investigate the validity and reliability of the Feeding/Swallowing Impact Survey (FS-IS) in Persian. Methods: This methodological study consisted of two phases: translating the test to Persian (P-FS-IS) and evaluating psychometric properties including face and content validity (through experts’ opinions and cognitive interviews), construct validity (by known-group validity and exploratory factor analysis), and reliability of the questionnaire (by internal consistency and test-retest reliability). The present study was performed on 97 Iranian mothers of children with cerebral palsy aged 2–18 years with swallowing impairments. Results: Exploratory factor analysis rendered two factors with a cumulative variance of 59.71%. When evaluating known-group validity, the questionnaire scores were significantly different across the groups with different severity of the disorder (F(2, 94) = 57.1, p ≤ 0.001). P-FS-IS had a high internal consistency with Cronbach’s alpha of 0.95, and there was an appropriate intra-class correlation coefficient of 0.97 for the total questionnaire. Conclusion: P-FS-IS has good validity and reliability and is a suitable questionnaire for assessing the impact of pediatric feeding and swallowing disorders on Persian language mothers. This scale can be used in research and clinical settings to evaluate and determine therapeutic goals.
Brincar nas, com e apesar das telas
Authors: Albuquerque Luciana Santos Guilhon , Perry Cassia Patricia Barroso , Andrade Marina Teixeira , Sancovschi Beatriz , Nasciutti Laura Freire , Martins Thalita Cristina Ferreira
Published: June 2023

Este trabalho está inserido em uma pesquisa que buscou explorar as articulações forjadas entre crianças e telas durante o isolamento físico imposto pela pandemia da COVID-19. O objetivo aqui foi analisar como as brincadeiras se desenrolaram nesse momento tão especial, levando em conta a presença das telas. Nossos principais referenciais teóricos foram a psicanálise e a Teoria Ator-Rede e adotamos a cartografia como metodologia, a fim de explorar o campo em toda sua fluidez e complexidade. Utilizamos questionários online e entrevistas com responsáveis e crianças. Foi possível observar que as crianças não deixaram de brincar por causa das telas, mas puderam construir múltiplas e singulares articulações, brincaram nas, com e apesar das telas.
Abstract 06: Feasibility Of Accelerated Code Team Activation With Code Button Triggered Smartphone Notifications
Authors: Couperus Cody , Dezman Zach , Friedrich Rebekah , Gurmu Samuel , Lemkin Dan , Morris Nicholas
Published: June 2023

Introduction:
In-hospital cardiac arrest mortality has improved only modestly in the past decade. Prior studies support the role of earlier defibrillation and epinephrine administration to improve outcomes. Timely code team activation facilitates expedient interventions and may provide an opportunity for quality improvement. We sought to accelerate the time to code team activation and increase the early distribution of patient-specific data to improve targeted treatments.

Methods:
We mapped code blue buttons present behind each patient bed to patient data through the Electronic Health Record. Use of the code blue button sent patient-specific data including admitting diagnosis, recent procedural history, presence of difficult airway, and most recent potassium, bicarbonate, troponin, and hemoglobin levels through a secure text messaging system to the code blue teams’ smartphones. Simultaneously, the code blue button contacted the hospital operator who activated the code blue team through traditional methods including overhead page and pager alerts. We piloted the system on four medicine inpatient units from November 2019 through May 2022. In our analysis, we evaluated the time from code blue button press to smartphone message receipt vs overhead page, time to epinephrine administration, and survival to hospital discharge.

Results:
There were 35 cardiac arrest events on the participating hospital units. The code blue button was the primary mode of code team activation for 12/35 (34.3%) of the events. The code team received smartphone notifications a median of 78 seconds (IQR = 47-127 seconds) before traditional notifications. The initial rhythm was non-shockable for 34/35 (97.1%) of the patients. The median time to documented epinephrine administration for codes activated with or without the code button was 2:57 and 4:00 (IQR = 0:34-6:07 vs. 2:07-4:30; p = 0.89). Survival to hospital discharge was 3/12 (25.0%) for codes activated with the code button and 4/23 (17.4%) when activated by other methods (p = 0.61).

Conclusion:
Implementation of a smartphone-based code button activated notification system reduced the time to code team activation by over one minute. Further evaluation in larger cohorts is necessary to assess the effect on patient outcomes.
Abstract 10026: Augmentation of Slow Repolarizing Potassium Channel (I
Ks
) Links Truncated Titin Mutations to Atrial Fibrillation
Authors: Ly Olivia T , Jiang Xinghang , Chen Hanna , Arif Pavel Mahmud , Brown Grace , Sridhar Arvind , Tofovic David , Marszalek Richard , Vanoye Carlos , George Alfred L , KHETANI SALMAN , Rehman Jalees , Saxena Ankur , Darbar Dawood
Published: June 2023

Introduction:
Rare titin-truncating variants (
TTN
tv) are associated with early-onset atrial fibrillation (AF) but the pathogenic mechanisms and therapeutic implications remain unclear. To determine the function of a highly conserved immunoglobulin-like domain of the A-band of
TTN
, a region enriched in AF-associated variants, we employed CRISPR-Cas9-mediated deletion of 9 amino acids (Δ9) in human induced pluripotent stem cells and then derived atrial cardiomyocytes (hiPSC-aCMs) for electrophysiological (EP) analysis.

Hypothesis:
We hypothesized that the
TTN
-Δ9 mutation results in augmentation of the slow delayed rectifier potassium current (I
Ks
) resulting in shortened action potential duration (APD).

Methods:
TTN
-WT hiPSC-aCMs (healthy control) and
TTN
-Δ9 hiPSC-aCMs (isogenic mutant) were matured with metabolic conditioning, electrical stimulation, co-culture with atrial fibroblasts, and micropatterning. We used transmission electron microscopy (TEM) to assess sarcomeric defects, RNA-sequencing and RT-qPCR to assess molecular ion channel remodeling, and high throughput automated patch clamp and optical voltage mapping to assess the EP properties of
TTN
-Δ9 hiPSC-aCMs. We also performed targeted pharmacological inhibition of I
Ks
.

Results:
We showed that
TTN
-Δ9 hiPSC-aCMs displayed disrupted organization and myofibril assembly (
Fig. 1A-B
), upregulated voltage-gated potassium channel complexes and increased
KCNQ1
expression (
Fig 1C-D
), and shortened APD (
Fig. 1E-F
). I
Ks
was significantly augmented in
TTN
-Δ9 hiPSC-aCMs (
Fig. 1G-H
). Infusion of the I
Ks
-specific blocker HMR-1556, and not I
Kr
blocker dofetilide, fully restored the shortened APD
90
and partially recovered defects in contractility in
TTN
-Δ9 hiPSC-aCMs compared to
TTN
-WT hiPSC-aCMs (
Fig. 1I-J
).

Conclusion:
Our findings suggest that augmentation of I
Ks
contributes to the pathogenic mechanism of
TTN
-mediated AF, pointing to I
Ks
as a potential therapeutic target.
Abstract 10088: Electronic Cigarette Use and Chest Pain Report in US Adults
Authors: Behrooz Leili , Xie Wubin , Goghari Aboli , Robertson Rose M , Bhatnagar Aruni , Stokes Andrew , Hamburg Naomi M
Published: June 2023

Electronic cigarettes (e-cigarettes) are advertised as a healthier alternative for combustible cigarettes and have become the most commonly used smoking product. There is limited data regarding the association of e-cigarettes and risk of cardiovascular disease (CVD). We assessed the association of chest pain reports across tobacco product use groups. We used data from the Population Assessment of Tobacco and Health (PATH) study which is a nationally representative longitudinal study of tobacco use behavior and health effects. We categorized tobacco use patterns into 4 groups: cigarette use, dual use, e-cigarette use, and non-use. Participants were asked if they have ever had chest pain and if they have had chest pain in the past 30 days. Binominal regression models were used to examine the association between tobacco use categories and the 2 chest pain outcomes. We adjusted for covariates including age, sex, race, education, BMI, hypercholesterolemia, hypertension, current use of other combustible tobacco products, secondhand smoke exposure, marijuana use in the past 30 days, recreational drug use and history of respiratory diseases. The cohort included 9,284 participants after excluding those with established CVD and those with missing outcome or exposure data. The Mean age was 57 (SD±11) years and 54% of participants were female. Among the participants, 3,020 were exclusive cigarette users, 213 were dual users, 175 were exclusive e-cigarette users (94% were former smokers), and 5,876 were non-users. Compared to non-use, combustible cigarette use had 1.48 (95% CI, 1.27, 1.73) odds of ever having chest pain and 1.72 (95% CI, 1.4, 2.11) odds of having chest pain in the past 30 days. Dual use was associated with 1.52 (CI 95%, 1.05, 2.19) odds of chest pain ever and 1.82 (95% CI, 1.17, 2.83) odds of 30 days chest pain. Exclusive e-cigarette use had 0.78 (95% CI, 0.49, 1.26) odds of ever having chest pain and 0.75 (95% CI, 0.39, 1.42) odds of having chest pain in the past 30 days. Our findings suggest that compared to non-use, exclusive e-cigarette use has similar rates of chest pain; whereas dual use and combustible cigarette use have increased rates of chest pain outcomes.
Abstract 10116: A Stratified Analysis of the Risk Associated With Low Body Mass Index for Patients After Percutaneous Coronary Intervention
Authors: Horikoshi Takeo , Nakamura Takamitsu , Yoshizaki Toru , Watanabe Yousuke , Nakamura Jun , Uematsu Manabu , Makino Aritaka , Kobayashi Tsuyoshi , Saito Yukio , Obata Jyun-ei , Sawanobori Takao , Takano Hajime , umetani ken , Watanabe Akinori , Asakawa Tetsuya , Sato Akira
Published: June 2023

Introduction:
The relationship between low body mass index (BMI) and prognostic factors for patients with coronary artery disease, commonly observed in elderly individuals in Japan, is important. Few studies have evaluated the prognosis for patients with low BMI after percutaneous coronary intervention (PCI). We analyzed the risk associated with low BMI for patients after PCI using a multivariable-adjusted model and data from a prospective cohort registry.

Methods:
This prospective, multicenter registry included 5965 consecutive patients with coronary artery disease who underwent successful PCI. The patients were followed-up clinically for up to 3 years or until the occurrence of major adverse cardiac events. The primary endpoint was defined as a composite of all-cause death and nonfatal myocardial infarction.

Results:
During the follow-up period, primary events occurred in 639 (10.7%) patients. A risk analysis of the primary endpoint adjusted for the multivariable model showed a significant increase in risk for elderly individuals, underweight individuals[HR 1.43 (95% CI, 1.10-1.85),
P
< 0.001], those with diabetes mellitus (DM), peripheral artery disease, low left ventricular ejection fraction or acute coronary syndrome (ACS), and smokers. A stratified adjusted risk analysis based on BMI levels showed that the risk associated with underweight status was significantly pronounced for male patients, those aged 60-74 years, those with DM or ACS.

Conclusions:
Underweight patients with several risk factors were at significantly increased risk after PCI. Furthermore, the risk associated with low BMI was significantly more pronounced for men, individuals aged 60-74 years, patients with DM or ACS.
Abstract 10128: Recombinant Human Placental Growth Factor-2 Treatment in Porcine Ischemic Cardiomyopathy
Authors: Wu Ming , Pokreisz Peter , Claus Piet , Gillijns Hilde , Caluwe Ellen , Janssens Tom , Reyns Geert , Kindt Nele , Collen Desire , Janssens Stefan
Published: June 2023

Background:
Placental growth factor (PlGF)-2 induces neovascularization and improves myocardial function in atherosclerotic rodent myocardial ischemia models without stimulating plaque angiogenesis. This promising therapeutic profile of PlGF-2 warrants a double blind, randomized, and placebo-controlled feasibility and efficacy study in a large animal model, representative of human disease.

Methods:
We induced myocardial infarction (MI) in domestic pigs using a 75 min balloon occlusion of the mid-LAD followed by reperfusion. After 4 w, we randomized pigs with marked LV dysfunction (LVEF<40%) to continuous IV infusion of 5, 15, 45 μg/kg/day rhPlGF-2 or PBS (CON) for 2 w using osmotic pumps. We evaluated treatment effect 8 w after MI using comprehensive MRI analysis of LV function and structure and performed postmortem histological analyses of LV vascularization and fibrotic remodeling.

Results:
In the pilot study (3 pigs/dose), PIGF plasma concentrations showed stable and sustained dose-dependent increases for 28 days without organ-specific side effects or systemic toxicity. Myocardial Ischemia/reperfusion induced LV dysfunction at 4 w (infarct size, 16±4 % of LV mass, n=42; LVEF, 34±4 %, range 19%-40%). In the dose escalation study using 5 (n=10), 15 or 45 μg/kg/day PlGF (n=11 per group), global LV function, and regional myocardial blood flow at rest or during stress, and infarct size did not differ between CON (n=10) and PlGF (Figure 1). Capillary densities and extent of LV interstitial fibrosis in infarct core and border zone were comparable between CON and PlGF.

Conclusions:
In this blinded randomized controlled trial, rhPIGF-2 did not improve global cardiac function in a porcine model of chronic ischemic cardiomyopathy, and failed to recapitulate therapeutic neovascularization reported in rodents. Our data emphasize the critical need for robust double blind, placebo controlled trials in representative large animal models before clinical translation.
Abstract 10130: Relationship Between Perceived and Measured Diet Quality Improvements in a Randomized Weight Loss Trial
Authors: Cheng Jessica , Costacou Tina , Sereika Susan M , Rockettewagner Bonny , Kriska Andrea M , Klem Mary Lou , Conroy Margaret B , Parmanto Bambang , Burke Lora E
Published: June 2023

Background:
Cross-sectional evidence suggests individuals overestimate their consumption of healthful foods. However, how perceived diet quality (PDQ) relates to diet quality calculated from standard methods is unclear. Examining study participants' misperceptions of either diet quality, and/or improvements in diet quality, may enhance our understanding of factors that influence the effectiveness of dietary interventions.

Methods:
The Healthy Eating Index (HEI-2015) was calculated pre- and post-intervention from dietary recalls in this randomized weight loss trial. Participant self-perception of pre-intervention and post-intervention diet quality was rated on a scale of 0 to 100 at the 12-month post-intervention time point. Agreement between perceived and calculated diet quality was examined using Bland-Altman method. Good agreement between measures was considered scores within 6 points.

Results:
Participants with complete HEI and PDQ data (n=116) was similar to the total sample and mostly female (79%), white (84%), and with median (q1, q3) age of 51.5 (35.5, 58.5) years. A quarter of participants had good agreement between HEI and PDQ scores at 12 months with differences between scores ranging from -44.8 to 29.9 points. Most of the disagreement arose from PDQ scores being higher (mean [std] 67.6 [18.5]) than HEI scores (mean [std] 56.4 [13.6]). Only 12% of participants had good agreement between change in HEI and change in PDQ scores with differences ranging from -68.4 to 39.6 points. Again, disagreement mainly arose from higher perceived improvement in diet quality (mean=18.6 points) compared to improvement in HEI scores (mean=1.3 points).

Discussion:
The diet quality of weight loss-seeking adults is less than ideal with little evidence of improvement; however, the majority of participants appear to perceive their diet quality and improvements in diet quality as better than measured. Future studies might consider the effect of better aligning participants’ perceptions with reality.
Abstract 10149: Clinical Predictors of Medical Therapy-Induced Improvement in Left Ventricular Function in Patients Diagnosed With Heart Failure With Reduced Ejection Fraction (HFrEF): The Intermountain Healthcare Experience
Authors: Muhlestein Joseph B , May Heidi T , Bair Tami L , Knight Stacey , Le Viet T , Horne Benjamin D , Knowlton Kirk U , Anderson Jeffrey L
Published: June 2023

Introduction:
When patients (pts) are diagnosed with HFrEF, it is hoped that medical therapy will improve their left ventricular ejection fraction (LVEF). However, which baseline clinical characteristics may predict an improvement in LVEF after medical treatment remains unclear.

Methods:
Pts with a baseline LVEF ≤35% and a follow-up LVEF ≥180 days later were categorized according to the change in LVEF identified between the baseline and follow-up LVEF’s (Increased [ΔLVEF ≥+10%]; No change [ΔLVEF=-9% to +9%]; Decreased [ΔLVEF ≥-10%]). Baseline characteristics and follow-up death rates were collected. Independent predictors of an improved LVEF were determined by logistic regression.

Results:
Qualifying HFrEF pts totaled 5,632 and were categorized by ΔLVEF as follows: Increased = 3,074 (54.6%); No change = 2,193 (38.9%); Decreased = 365 (6.5%). Baseline characteristics and independent predictors of an increase in LVEF are shown in the figure. During a median follow-up of 6.2 years, the death rate was 35.3%, 60.0%, and 72.6% (p<0.0001) in patients with an increase, no change, or decrease in LVEF, respectively.

Conclusions:
In patients diagnosed with HFrEF and initiated on medical therapy, an increase in LVEF predicted a lower death rate. The strongest predictors of an increase in LVEF included female gender, the absence of ASCVD, a low initial BNP, a narrow QRS duration, and the presence of atrial fibrillation, pulmonary hypertension, and statin use. Explanations for these findings remain to be determined.
Abstract 10169: Do Beta-Blockers Confer Cardiovascular Protection in Patients With Stable Coronary Artery Disease in the Contemporary Era?
Authors: Godoy Lucas C , Farkouh Michael E , Austin Peter , Shah Baiju , Qiu Feng , Jackevicius Cynthia , Wijeysundera Harindra C , Krumholz Harlan M , Ko Dennis T
Published: June 2023

Introduction:
Previous studies have failed to show a cardioprotective benefit of beta-blockers in patients with stable coronary artery disease (CAD). These studies, however, were frequently limited by either small or heterogenous populations. We aimed to determine the association between beta-blocker therapy and long-term cardiovascular events in patients with angiographically-documented stable CAD.

Methods:
We identified all patients ≥ 66 years undergoing elective coronary angiography in Ontario, Canada from 2009 to 2019, who had significant coronary stenoses. Patients with heart failure or recent myocardial infarction (MI) were excluded. We used a new user design by defining beta-blocker use as ≥1 prescription claims in the 90 days preceding or after coronary angiography and excluded those with beta-blocker use in the previous year. The main outcome was a composite of all-cause mortality, hospitalization for heart failure or MI. Propensity score and inverse probability of treatment weighting were used to deal with confounding.

Results:
We included 28,039 patients (mean age: 73.0 ± 5.6y; 66.2% male), 12,695 (45.3%) were treated with beta-blockers. The 5-year rate of the primary outcome in the weighted cohort was 14.3% in the beta-blocker group and 16.1% in the no beta-blocker group (HR: 0.92; 95% CI: 0.86 to 0.98; p=0.006), which was primarily driven by reductions in MI (HR: 0.87; 95% CI: 0.77 to 0.99; p=0.031). No significant difference was observed regarding all-cause death (HR: 0.95; 95% CI: 0.88 to 1.02) and hospitalization for heart failure (HR: 0.93; 95% CI: 0.82 to 1.06). Findings were consistent across subgroups, including sex, age, diabetes, and previous revascularization (p-interaction > 0.1; Figure).

Conclusions:
In patients with angiographically-documented stable CAD without heart failure or a recent MI, beta-blockers were associated with a significant reduction in the composite of all-cause mortality, hospitalization for heart failure or MI.