bluuebunny/crossref_metadata_2025 huggingface dataset:
Cone‐Beam Computed Tomography Assessment of Prevalence of Procedural Errors in Maxillary Posterior Teeth
Authors: Nouroloyouni Ahmad , Nazi Yousef , Mikaieli Xiavi Hesam , Noorolouny Sara , Kuzekanani Maryam , Plotino Gianluca , Walsh James Laurence , Sheikhfaal Behzad , Alyali Rashin , Tavakkol Elham
Published: December 2023

A range of procedural errors can occur when performing endodontic treatment on posterior teeth. These errors may decrease the success rate in endodontic practice. This study assessed the prevalence of procedural errors and the quality of endodontic treatments in maxillary molars and premolars using cone‐beam computed tomography (CBCT). CBCT scans from two private radiology centers were assessed retrospectively to ensure the same calculated sample size of 327 teeth for each of the four maxillary posterior tooth types (a total of 1,308 endodontically treated teeth). Image sets were evaluated for procedural errors categorized as follows: obturation length (overfilling or underfilling by >2 mm short of the root apex), missed canals, perforations, strip perforations (with extrusion of material into the furcation area), separated instruments in the root canal space, and root fracture. Data were analyzed with SPSS version 20 (SPSS Inc., Chicago, IL, USA), and frequency data was assessed using the Monte Carlo test at the 0.05 level of significance. The procedural errors most commonly reported in the present study were from most frequent to least frequent: underfilled canals (50.0%), missed canals (27.5%), overfilled canals (12.5%), apical perforations (5.0%), separated instruments (3.1%), and root fractures (1.9%). No strip perforations (with extrusion of material into the furcation area) were seen in the study (0%). Underfilled and missed root canals were the most frequent procedural errors identified in the present study. These findings underline the importance of more consideration of critical working length management during all stages of root canal treatment, greater awareness of root canal anatomy, and the use of imaging and diagnostic devices that enhance the ability to identify and treat root canals both safely and effectively.
Retrospective Study to Reduce Blood Transfusion Waste in Remote Island Healthcare Settings
Authors: Sakamoto Takamitsu , Mizuta Hiroyuki , Niiro Naohisa , Amagai Teruyoshi
Published: December 2023

Background. Tokunoshima is a remote island in the Amami Islands, 470 km southwest of the Kagoshima mainland. It has a population of 23,000 and consists of three towns: Tokunoshima, Isen, and Amagi. Three medical institutions on the island are responsible for blood transfusion medicine, but there is no blood stockpiling station on the island, and blood is stockpiled in each of the hospitals. Although Tokunoshima Tokushukai Hospital is responsible for 70% of transfusion medicine on Tokunoshima, it is difficult to maintain a sufficient amount of blood in stock considering disposal. Aim. To determine whether changing the distribution of blood types in a hospital’s stockpile would reduce the transfusion disposal rate. Methods. This was a retrospective survey. By changing the in-house stock of blood products for transfusions delivered to our hospital over 10 years from January 2013 to December 2017 (preintervention) and from January 2018 to December 2022 (postintervention), we compared the cost-saving effects of these two intervention strategies on disposal rates and blood inventories, as well as the survival rates of case profiles requiring transfusion interventions in hospital-donated transfusion and ABO-incompatible transfusion between two periods. The hospital's stock of RBC had changes that storage of type (A, B, O, AB) RBC from (4, 4, 4, 2) units in the pre-interventon to (2, 2, 6, 0) units in the postintervention. Results. The annual blood product waste rate decreased from 23.4% in the preintervention period to 17.9% in the post-intervention period. Conclusion. By changing the blood products stockpiled for transfusion medicine in Tokunoshima, the transfusion disposal rate can be reduced.
Vibrational Biospectroscopy in the Clinical Setting: Exploring the Impact of New Advances in the Field of Immunology
Authors: Kannan Siddarth , Callery Emma L. , Rowbottom Anthony W.
Published: December 2023

The investigation of pathological diseases largely relies on laboratory examinations. The ability to identify and characterise cells is an essential process for clinicians to reach an accurate diagnosis and inform appropriate treatments. There is currently a gap between the advancement of scientific knowledge on cellular and molecular pathways and the development of novel techniques capable of detecting subtle cellular changes associated with disease. Biospectroscopy is the use of spectroscopy techniques to investigate biological materials. Within a biological sample, important molecules such as lipids, carbohydrates, nucleic acids, and proteins are held together by chemical bonds; these bonds will vibrate following excitation with infrared light. By measuring the vibrational energy of each molecule present in a biological sample, a unique spectrum, known as the “molecular fingerprint” is generated. As disease-related changes in biological samples will be reflected in the molecular fingerprint, biospectroscopy is a well-placed candidate for the investigation of disease. Biospectroscopy has been gaining wider acceptance and application in the clinical setting over the past decade; however, it has yet to reach diagnostic laboratories and healthcare clinics as a routine platform for clinical assessment. Immunological disorders are complex, often demonstrating interaction across multiple molecular pathways which results in delayed diagnosis. Vibrational spectroscopy is being applied in many fields, and here we present a review of its use in cellular immunology. Potential benefits, including an enhanced definition of molecular processes and the use of spectroscopy in disease diagnosis, monitoring, and treatment response, are discussed. The translation of vibrational spectroscopic techniques into clinical practice offers rapid, noninvasive, and inexpensive methods to obtain information on the molecular composition of biological samples. The potential clinical benefits of biospectroscopy include providing a more prompt and accurate disease diagnosis, thus improving patient care and resulting in better health outcomes.
Effect of Oxygen Mixing Percentage on Mechanical and Microwave Dielectric Properties of SrBi4Ti4O15 Thin Films
Authors: Rambabu A. , Raju K. C. James , Kumar Polamarasetty P. , Nuvvula Ramakrishna S. S. , Khan Baseem
Published: December 2023

Aurivillus oxide thin films with nanostructures attained much interest due to their structural stability, outstanding ferroelectric, and dielectric properties. This manuscript reports the influence of oxygen mixing percentage (OMP) on structural, nanomechanical, and microwave dielectric properties of strontium bismuth titanate (SrBi4Ti4O15) thin films. SrBi4Ti4O15 films were successfully fabricated on fused silica substrates at room temperature, followed by annealed in a microwave furnace. The crystalline nature and purity of the phase was identified by X-ray diffraction. Nanomechanical properties of the SrBi4Ti4O15 films were studied using nanoindentation and nanoscratch tests. The best nanomechanical (hardness ∼6.9 GPa, Young’s modulus ∼120 GPa) properties were shown for films deposited around 50% of OMP. Microwave dielectric properties (dielectric constant and loss tangent at microwave frequencies 10 and 20 GHz) were extracted from the split postdielectric resonator technique.
A GIS Partial Discharge Pattern Recognition Method Based on Improved CBAM-ResNet
Authors: Hu Di , Chen Zhong , Yang Wei , Zhu Taiyun , Ke Yanguo , Yin Kaiyang
Published: December 2023

Different types of partial discharge (PD) cause different damages to gas-insulated substation (GIS), so it is very important to correctly identify the type of PD for evaluating the GIS insulation condition. The traditional PD pattern recognition algorithm has the limitations of low recognition accuracy and slow recognition speed in engineering applications. To effectively diagnose the GIS PD type and safeguard the safe and reliable operation of the distribution network, a GIS PD method based on improved CBAM-ResNet was proposed in this paper. And the improved CBAM-ResNet takes advantage of the residual neural network and attention mechanism. In particular, the channel attention module and the spatial attention module are connected in parallel in the improved CBAM. The experimental results showed that the GIS PD pattern recognition method proposed herein has a recognition rate of 93.58%, 95.00%, 93.55%, and 93.88% against the four PD types. Compared with the traditional PD pattern recognition algorithm, the algorithm has the advantages of a lightweight model and more accurate recognition results, which carry better engineering application values.
Supplementary Table S4 from Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression
Authors: Hsu Wen-Hao , LaBella Kyle A. , Lin Yiyun , Xu Ping , Lee Rumi , Hsieh Cheng-En , Yang Lei , Zhou Ashley , Blecher Jonathan M. , Wu Chang-Jiun , Lin Kangyu , Shang Xiaoying , Jiang Shan , Spring Denise J. , Xia Yan , Chen Peiwen , Shen John Paul , Kopetz Scott , DePinho Ronald A.
Published: December 2023

Supplementary Table S4 shows primers used for RT-qPCR and ChIP-qPCR
Supplementary Table S1 from Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression
Authors: Hsu Wen-Hao , LaBella Kyle A. , Lin Yiyun , Xu Ping , Lee Rumi , Hsieh Cheng-En , Yang Lei , Zhou Ashley , Blecher Jonathan M. , Wu Chang-Jiun , Lin Kangyu , Shang Xiaoying , Jiang Shan , Spring Denise J. , Xia Yan , Chen Peiwen , Shen John Paul , Kopetz Scott , DePinho Ronald A.
Published: December 2023

Supplementary Table S1 includes differentially expressed genes from 4 fibroblast subtypes
Supplementary Figure S6 from Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression
Authors: Hsu Wen-Hao , LaBella Kyle A. , Lin Yiyun , Xu Ping , Lee Rumi , Hsieh Cheng-En , Yang Lei , Zhou Ashley , Blecher Jonathan M. , Wu Chang-Jiun , Lin Kangyu , Shang Xiaoying , Jiang Shan , Spring Denise J. , Xia Yan , Chen Peiwen , Shen John Paul , Kopetz Scott , DePinho Ronald A.
Published: December 2023

Figure S6 illustrates the secretion of VEGFA by lipid-rich CAFs, which in turn promotes tumor angiogenesis.
Supplementary Figure S2 from Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression
Authors: Hsu Wen-Hao , LaBella Kyle A. , Lin Yiyun , Xu Ping , Lee Rumi , Hsieh Cheng-En , Yang Lei , Zhou Ashley , Blecher Jonathan M. , Wu Chang-Jiun , Lin Kangyu , Shang Xiaoying , Jiang Shan , Spring Denise J. , Xia Yan , Chen Peiwen , Shen John Paul , Kopetz Scott , DePinho Ronald A.
Published: December 2023

Figure S2 illustrates the identification and enrichment of lipid-rich CAFs
within the stroma of Kras*-driven CRC.
Supplementary Figure S1 from Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression
Authors: Hsu Wen-Hao , LaBella Kyle A. , Lin Yiyun , Xu Ping , Lee Rumi , Hsieh Cheng-En , Yang Lei , Zhou Ashley , Blecher Jonathan M. , Wu Chang-Jiun , Lin Kangyu , Shang Xiaoying , Jiang Shan , Spring Denise J. , Xia Yan , Chen Peiwen , Shen John Paul , Kopetz Scott , DePinho Ronald A.
Published: December 2023

Figure S1 demonstrates the enrichment of lipid-rich CAFs within the stroma of Kras*-driven CRC.
Supplementary Figure 9 from Formate Supplementation Enhances Antitumor CD8+ T-cell Fitness and Efficacy of PD-1 Blockade
Authors: Rowe Jared H. , Elia Ilaria , Shahid Osmaan , Gaudiano Emily F. , Sifnugel Natalia E. , Johnson Sheila , Reynolds Amy G. , Fung Megan E. , Joshi Shakchhi , LaFleur Martin W. , Park Joon Seok , Pauken Kristen E. , Rabinowitz Joshua D. , Freeman Gordon J. , Haigis Marcia C. , Sharpe Arlene H.
Published: December 2023

Supplementary Figure 9 shows tumor impacts of formate on and/or anti-PD-1 treatment on EO771 and 4T1 tumor growth & animal survival.
Supplementary Figure 8 from Formate Supplementation Enhances Antitumor CD8+ T-cell Fitness and Efficacy of PD-1 Blockade
Authors: Rowe Jared H. , Elia Ilaria , Shahid Osmaan , Gaudiano Emily F. , Sifnugel Natalia E. , Johnson Sheila , Reynolds Amy G. , Fung Megan E. , Joshi Shakchhi , LaFleur Martin W. , Park Joon Seok , Pauken Kristen E. , Rabinowitz Joshua D. , Freeman Gordon J. , Haigis Marcia C. , Sharpe Arlene H.
Published: December 2023

Supplementary Figure 8 shows a diagram of the CD8 depletion strategy and individual growth curves from CD8 depleted mice in main Figure 4.
Supplementary Table S3 from Structural Basis of PML-RARA Oncoprotein Targeting by Arsenic Unravels a Cysteine Rheostat Controlling PML Body Assembly and Function
Authors: Bercier Pierre , Wang Qian Qian , Zang Ning , Zhang Jie , Yang Chang , Maimaitiyiming Yasen , Abou-Ghali Majdouline , Berthier Caroline , Wu Chengchen , Niwa-Kawakita Michiko , Dirami Thassadite , Geoffroy Marie-Claude , Ferhi Omar , Quentin Samuel , Benhenda Shirine , Ogra Yasumitsu , Gueroui Zoher , Zhou Chun , Naranmandura Hua , de Thé Hugues , Lallemand-Breitenbach Valérie
Published: December 2023

Table displaying the cell lines used in this study with their origin/RRID
Supplementary Figure 6 from Formate Supplementation Enhances Antitumor CD8+ T-cell Fitness and Efficacy of PD-1 Blockade
Authors: Rowe Jared H. , Elia Ilaria , Shahid Osmaan , Gaudiano Emily F. , Sifnugel Natalia E. , Johnson Sheila , Reynolds Amy G. , Fung Megan E. , Joshi Shakchhi , LaFleur Martin W. , Park Joon Seok , Pauken Kristen E. , Rabinowitz Joshua D. , Freeman Gordon J. , Haigis Marcia C. , Sharpe Arlene H.
Published: December 2023

Supplementary Figure 6 shows the phenotype of B16-OVA tumor infiltrating Phgdh deficient OT-1 cells.
Supplementary Figure 5 from Formate Supplementation Enhances Antitumor CD8+ T-cell Fitness and Efficacy of PD-1 Blockade
Authors: Rowe Jared H. , Elia Ilaria , Shahid Osmaan , Gaudiano Emily F. , Sifnugel Natalia E. , Johnson Sheila , Reynolds Amy G. , Fung Megan E. , Joshi Shakchhi , LaFleur Martin W. , Park Joon Seok , Pauken Kristen E. , Rabinowitz Joshua D. , Freeman Gordon J. , Haigis Marcia C. , Sharpe Arlene H.
Published: December 2023

Supplementary Figure 5 shows Chimeric IMmune Editing (CHIME) can disrupt Phgdh causing loss of PHGDH expression and serine biosynthesis in CD8+ T cells.
Supplementary Figure 4 from Formate Supplementation Enhances Antitumor CD8+ T-cell Fitness and Efficacy of PD-1 Blockade
Authors: Rowe Jared H. , Elia Ilaria , Shahid Osmaan , Gaudiano Emily F. , Sifnugel Natalia E. , Johnson Sheila , Reynolds Amy G. , Fung Megan E. , Joshi Shakchhi , LaFleur Martin W. , Park Joon Seok , Pauken Kristen E. , Rabinowitz Joshua D. , Freeman Gordon J. , Haigis Marcia C. , Sharpe Arlene H.
Published: December 2023

Supplementary Figure 4 shows metabolite concentrations in the plasma and tumor interstitial fluid of B16-OVA tumor bearing mice.
Supplementary Table S1 from Structural Basis of PML-RARA Oncoprotein Targeting by Arsenic Unravels a Cysteine Rheostat Controlling PML Body Assembly and Function
Authors: Bercier Pierre , Wang Qian Qian , Zang Ning , Zhang Jie , Yang Chang , Maimaitiyiming Yasen , Abou-Ghali Majdouline , Berthier Caroline , Wu Chengchen , Niwa-Kawakita Michiko , Dirami Thassadite , Geoffroy Marie-Claude , Ferhi Omar , Quentin Samuel , Benhenda Shirine , Ogra Yasumitsu , Gueroui Zoher , Zhou Chun , Naranmandura Hua , de Thé Hugues , Lallemand-Breitenbach Valérie
Published: December 2023

Table displaying the primers used for site-directed mutagenesis.
Supplementary Figure 3 from Formate Supplementation Enhances Antitumor CD8+ T-cell Fitness and Efficacy of PD-1 Blockade
Authors: Rowe Jared H. , Elia Ilaria , Shahid Osmaan , Gaudiano Emily F. , Sifnugel Natalia E. , Johnson Sheila , Reynolds Amy G. , Fung Megan E. , Joshi Shakchhi , LaFleur Martin W. , Park Joon Seok , Pauken Kristen E. , Rabinowitz Joshua D. , Freeman Gordon J. , Haigis Marcia C. , Sharpe Arlene H.
Published: December 2023

Supplementary Figure 3 shows the cytotoxicity of previously activated CD8+ T cells with or without the SHMT inhibitor.
Supplementary Figure 2 from Formate Supplementation Enhances Antitumor CD8+ T-cell Fitness and Efficacy of PD-1 Blockade
Authors: Rowe Jared H. , Elia Ilaria , Shahid Osmaan , Gaudiano Emily F. , Sifnugel Natalia E. , Johnson Sheila , Reynolds Amy G. , Fung Megan E. , Joshi Shakchhi , LaFleur Martin W. , Park Joon Seok , Pauken Kristen E. , Rabinowitz Joshua D. , Freeman Gordon J. , Haigis Marcia C. , Sharpe Arlene H.
Published: December 2023

Supplementary Figure 2 shows the one carbon enzyme expression levels and serine biosynthesis following activation of CD8+ T cells with varying concentrations of anti-CD3.
Supplementary Figure S5 from Structural Basis of PML-RARA Oncoprotein Targeting by Arsenic Unravels a Cysteine Rheostat Controlling PML Body Assembly and Function
Authors: Bercier Pierre , Wang Qian Qian , Zang Ning , Zhang Jie , Yang Chang , Maimaitiyiming Yasen , Abou-Ghali Majdouline , Berthier Caroline , Wu Chengchen , Niwa-Kawakita Michiko , Dirami Thassadite , Geoffroy Marie-Claude , Ferhi Omar , Quentin Samuel , Benhenda Shirine , Ogra Yasumitsu , Gueroui Zoher , Zhou Chun , Naranmandura Hua , de Thé Hugues , Lallemand-Breitenbach Valérie
Published: December 2023

Figure S5 displays how B2 trimer is essential for PML-RARA microspeckle formation in progenitors and PML NB disruption as well as PML/RARA degradation ex vivo, as well as for PML NB formation and sumoylation in vivo
Supplementary Figure 14 from Formate Supplementation Enhances Antitumor CD8+ T-cell Fitness and Efficacy of PD-1 Blockade
Authors: Rowe Jared H. , Elia Ilaria , Shahid Osmaan , Gaudiano Emily F. , Sifnugel Natalia E. , Johnson Sheila , Reynolds Amy G. , Fung Megan E. , Joshi Shakchhi , LaFleur Martin W. , Park Joon Seok , Pauken Kristen E. , Rabinowitz Joshua D. , Freeman Gordon J. , Haigis Marcia C. , Sharpe Arlene H.
Published: December 2023

Supplementary Figure 14 shows the effects of formate treatment on TCF1 and TIM3 expression in B16-OVA specific CD8+ T cells
Supplementary Figure S4 from Structural Basis of PML-RARA Oncoprotein Targeting by Arsenic Unravels a Cysteine Rheostat Controlling PML Body Assembly and Function
Authors: Bercier Pierre , Wang Qian Qian , Zang Ning , Zhang Jie , Yang Chang , Maimaitiyiming Yasen , Abou-Ghali Majdouline , Berthier Caroline , Wu Chengchen , Niwa-Kawakita Michiko , Dirami Thassadite , Geoffroy Marie-Claude , Ferhi Omar , Quentin Samuel , Benhenda Shirine , Ogra Yasumitsu , Gueroui Zoher , Zhou Chun , Naranmandura Hua , de Thé Hugues , Lallemand-Breitenbach Valérie
Published: December 2023

Figure S4 illustrates how trivalent arsenic binding to C213 in the B2 trimer leads to PML NB aggregation, and defective sumoylation and degradation of the trimer mutants, as well as the role of C213 mutants on PML partner localization and sumoylation
Supplementary Figure 13 from Formate Supplementation Enhances Antitumor CD8+ T-cell Fitness and Efficacy of PD-1 Blockade
Authors: Rowe Jared H. , Elia Ilaria , Shahid Osmaan , Gaudiano Emily F. , Sifnugel Natalia E. , Johnson Sheila , Reynolds Amy G. , Fung Megan E. , Joshi Shakchhi , LaFleur Martin W. , Park Joon Seok , Pauken Kristen E. , Rabinowitz Joshua D. , Freeman Gordon J. , Haigis Marcia C. , Sharpe Arlene H.
Published: December 2023

Supplementary Figure 13 shows the effects of formate treatment on tumor infiltrating bystander cells.
Supplementary Figure 10 from Formate Supplementation Enhances Antitumor CD8+ T-cell Fitness and Efficacy of PD-1 Blockade
Authors: Rowe Jared H. , Elia Ilaria , Shahid Osmaan , Gaudiano Emily F. , Sifnugel Natalia E. , Johnson Sheila , Reynolds Amy G. , Fung Megan E. , Joshi Shakchhi , LaFleur Martin W. , Park Joon Seok , Pauken Kristen E. , Rabinowitz Joshua D. , Freeman Gordon J. , Haigis Marcia C. , Sharpe Arlene H.
Published: December 2023

Supplementary Figure 10 shows individual mouse growth curves from those depicted in main Figure 4.
Supplementary Figure 1 from Formate Supplementation Enhances Antitumor CD8+ T-cell Fitness and Efficacy of PD-1 Blockade
Authors: Rowe Jared H. , Elia Ilaria , Shahid Osmaan , Gaudiano Emily F. , Sifnugel Natalia E. , Johnson Sheila , Reynolds Amy G. , Fung Megan E. , Joshi Shakchhi , LaFleur Martin W. , Park Joon Seok , Pauken Kristen E. , Rabinowitz Joshua D. , Freeman Gordon J. , Haigis Marcia C. , Sharpe Arlene H.
Published: December 2023

Supplementary Figure 1 shows the approach for rapid magnetic bead based separation of OT-1 cells and peptide pulsed splenocytes for metabolomic analysis.
Supplementary Table S2 from p53 Gain-of-Function Mutation Induces Metastasis via BRD4-Dependent CSF-1 Expression
Authors: Efe Gizem , Dunbar Karen J. , Sugiura Kensuke , Cunningham Katherine , Carcamo Saul , Karaiskos Spyros , Tang Qiaosi , Cruz-Acuña Ricardo , Resnick-Silverman Lois , Peura Jessica , Lu Chao , Hasson Dan , Klein-Szanto Andres J. , Taylor Alison M. , Manfredi James J. , Prives Carol , Rustgi Anil K.
Published: December 2023

Supplementary Table S2. List of antibodies and dilutions used in the study.
Supplementary Table S1 from p53 Gain-of-Function Mutation Induces Metastasis via BRD4-Dependent CSF-1 Expression
Authors: Efe Gizem , Dunbar Karen J. , Sugiura Kensuke , Cunningham Katherine , Carcamo Saul , Karaiskos Spyros , Tang Qiaosi , Cruz-Acuña Ricardo , Resnick-Silverman Lois , Peura Jessica , Lu Chao , Hasson Dan , Klein-Szanto Andres J. , Taylor Alison M. , Manfredi James J. , Prives Carol , Rustgi Anil K.
Published: December 2023

Supplementary Table S1. List of oligonucleotides used in the study.
Supplementary Figure S4 from p53 Gain-of-Function Mutation Induces Metastasis via BRD4-Dependent CSF-1 Expression
Authors: Efe Gizem , Dunbar Karen J. , Sugiura Kensuke , Cunningham Katherine , Carcamo Saul , Karaiskos Spyros , Tang Qiaosi , Cruz-Acuña Ricardo , Resnick-Silverman Lois , Peura Jessica , Lu Chao , Hasson Dan , Klein-Szanto Andres J. , Taylor Alison M. , Manfredi James J. , Prives Carol , Rustgi Anil K.
Published: December 2023

Supplementary Figure S4. Depletion of Brd4 reduces Csf1 secretion and ESCC tumor cell invasion.
Supplementary Figure S2 from p53 Gain-of-Function Mutation Induces Metastasis via BRD4-Dependent CSF-1 Expression
Authors: Efe Gizem , Dunbar Karen J. , Sugiura Kensuke , Cunningham Katherine , Carcamo Saul , Karaiskos Spyros , Tang Qiaosi , Cruz-Acuña Ricardo , Resnick-Silverman Lois , Peura Jessica , Lu Chao , Hasson Dan , Klein-Szanto Andres J. , Taylor Alison M. , Manfredi James J. , Prives Carol , Rustgi Anil K.
Published: December 2023

Supplementary Figure S2. Trp53R172H-dependent Csf-1/Csf-1r signaling promotes metastasis only in the presence of p53-R172H, but not p53 null or wild-type p53.
Data from Spatial and Temporal Mapping of Breast Cancer Lung Metastases Identify TREM2 Macrophages as Regulators of the Metastatic Boundary
Authors: Yofe Ido , Shami Tamar , Cohen Noam , Landsberger Tomer , Sheban Fadi , Stoler-Barak Liat , Yalin Adam , Phan Truong San , Li Baoguo , Monteran Lea , Scharff Ye'ela , Giladi Amir , Elbaz Miriam , David Eyal , Gurevich-Shapiro Anna , Gur Chamutal , Shulman Ziv , Erez Neta , Amit Ido
Published: December 2023

Abstract
Cancer mortality primarily stems from metastatic recurrence, emphasizing the urgent need for developing effective metastasis-targeted immunotherapies. To better understand the cellular and molecular events shaping metastatic niches, we used a spontaneous breast cancer lung metastasis model to create a single-cell atlas spanning different metastatic stages and regions. We found that premetastatic lungs are infiltrated by inflammatory neutrophils and monocytes, followed by the accumulation of suppressive macrophages with the emergence of metastases. Spatial profiling revealed that metastasis-associated immune cells were present in the metastasis core, with the exception of TREM2+ regulatory macrophages uniquely enriched at the metastatic invasive margin, consistent across both murine models and human patient samples. These regulatory macrophages (Mreg) contribute to the formation of an immune-suppressive niche, cloaking tumor cells from immune surveillance. Our study provides a compendium of immune cell dynamics across metastatic stages and niches, informing the development of metastasis-targeting immunotherapies.
Significance:
Temporal and spatial single-cell analysis of metastasis stages revealed new players in modulating immune surveillance and suppression. Our study highlights distinct populations of TREM2 macrophages as modulators of the microenvironment in metastasis, and as the key immune determinant defining metastatic niches, pointing to myeloid checkpoints to improve therapeutic strategies.

This article is featured in Selected Articles from This Issue, p. 2489
Data from p53 Gain-of-Function Mutation Induces Metastasis via BRD4-Dependent CSF-1 Expression
Authors: Efe Gizem , Dunbar Karen J. , Sugiura Kensuke , Cunningham Katherine , Carcamo Saul , Karaiskos Spyros , Tang Qiaosi , Cruz-Acuña Ricardo , Resnick-Silverman Lois , Peura Jessica , Lu Chao , Hasson Dan , Klein-Szanto Andres J. , Taylor Alison M. , Manfredi James J. , Prives Carol , Rustgi Anil K.
Published: December 2023

Abstract
TP53 mutations are frequent in esophageal squamous cell carcinoma (ESCC) and other SCCs and are associated with a proclivity for metastasis. Here, we report that colony-stimulating factor-1 (CSF-1) expression is upregulated significantly in a p53-R172H–dependent manner in metastatic lung lesions of ESCC. The p53-R172H–dependent CSF-1 signaling, through its cognate receptor CSF-1R, increases tumor cell invasion and lung metastasis, which in turn is mediated in part through Stat3 phosphorylation and epithelial-to-mesenchymal transition (EMT). In Trp53R172H tumor cells, p53 occupies the Csf-1 promoter. The Csf-1 locus is enriched with histone 3 lysine 27 acetylation (H3K27ac), which is likely permissive for fostering an interaction between bromodomain-containing domain 4 (BRD4) and p53-R172H to regulate Csf-1 transcription. Inhibition of BRD4 not only reduces tumor invasion and lung metastasis but also reduces circulating CSF-1 levels. Overall, our results establish a novel p53-R172H–dependent BRD4–CSF-1 axis that promotes ESCC lung metastasis and suggest avenues for therapeutic strategies for this difficult-to-treat disease.
Significance:
The invasion–metastasis cascade is a recalcitrant barrier to effective cancer therapy. We establish that the p53-R172H–dependent BRD4-CSF-1 axis is a mediator of prometastatic properties, correlates with patient survival and tumor stages, and its inhibition significantly reduces tumor cell invasion and lung metastasis. This axis can be exploited for therapeutic advantage.

This article is featured in Selected Articles from This Issue, p. 2489
Cancer in 2023
Authors:   AACR Cancer Progress Report 2023 Steering Committee
Published: December 2023

Excerpts from the 13th edition of the annual AACR Cancer Progress Report (https://cancerprogressreport.aacr.org/progress/) to U.S. Congress and the public highlight current challenges in achieving the goal of the Cancer Moonshot to reduce the cancer death rate in the United States by 50% by 2047 and a call to action for robust, sustained support of medical research funding is issued.
Precision Oncology: 2023 in Review
Authors: Murciano-Goroff Yonina R. , Suehnholz Sarah P. , Drilon Alexander , Chakravarty Debyani
Published: December 2023

This article presents a review of recent major advances in precision oncology and the future implications of these advances, specifying the iterative progress achieved from the end of 2022 through 2023. We discuss the different classes of precision oncology drugs and associated biomarkers as well as the improvements in clinical trial design that have enabled the efficient testing of these drugs.
Supplementary Figure 9 from Activating Transcription Factor 5 Promotes Neuroblastoma Metastasis by Inducing Anoikis Resistance
Authors: Banerjee Debarshi , Boboila Shuobo , Okochi Shunpei , Angelastro James M. , Kadenhe-Chiweshe Angela V. , Lopez Gonzalo , Califano Andrea , Connolly Eileen P. , Greene Lloyd A. , Yamashiro Darrell J.
Published: December 2023

Supplementary Figure 9 shows that BMF knockdown rescues ATF5 loss-induced reduction of anchorage-independent cell viability
Supplementary Figure 8 from Activating Transcription Factor 5 Promotes Neuroblastoma Metastasis by Inducing Anoikis Resistance
Authors: Banerjee Debarshi , Boboila Shuobo , Okochi Shunpei , Angelastro James M. , Kadenhe-Chiweshe Angela V. , Lopez Gonzalo , Califano Andrea , Connolly Eileen P. , Greene Lloyd A. , Yamashiro Darrell J.
Published: December 2023

Supplementary Figure S8 shows that BMF overexpression reduces the anchorage-independent viability of BE(2)-C and SK-N-DZ cells.
Supplementary Figure 4 from Activating Transcription Factor 5 Promotes Neuroblastoma Metastasis by Inducing Anoikis Resistance
Authors: Banerjee Debarshi , Boboila Shuobo , Okochi Shunpei , Angelastro James M. , Kadenhe-Chiweshe Angela V. , Lopez Gonzalo , Califano Andrea , Connolly Eileen P. , Greene Lloyd A. , Yamashiro Darrell J.
Published: December 2023

Supplementary Figure 4 shows that decreased ATF5 expression does not alter the invasiveness of BE(2)-C cells in vitro
Supplementary Figure 17 from Activating Transcription Factor 5 Promotes Neuroblastoma Metastasis by Inducing Anoikis Resistance
Authors: Banerjee Debarshi , Boboila Shuobo , Okochi Shunpei , Angelastro James M. , Kadenhe-Chiweshe Angela V. , Lopez Gonzalo , Califano Andrea , Connolly Eileen P. , Greene Lloyd A. , Yamashiro Darrell J.
Published: December 2023

Supplementary Figure 17 shows that CP-dn-ATF5 reduces tumor growth and metastasis of SK-N-DZ in vivo
Supplementary Figure 16 from Activating Transcription Factor 5 Promotes Neuroblastoma Metastasis by Inducing Anoikis Resistance
Authors: Banerjee Debarshi , Boboila Shuobo , Okochi Shunpei , Angelastro James M. , Kadenhe-Chiweshe Angela V. , Lopez Gonzalo , Califano Andrea , Connolly Eileen P. , Greene Lloyd A. , Yamashiro Darrell J.
Published: December 2023

Supplementary Figure 16 shows that CP-d/n-ATF5 inhibits growth of BE(2)-C tumors and increases apoptosis
Supplementary Figure 15 from Activating Transcription Factor 5 Promotes Neuroblastoma Metastasis by Inducing Anoikis Resistance
Authors: Banerjee Debarshi , Boboila Shuobo , Okochi Shunpei , Angelastro James M. , Kadenhe-Chiweshe Angela V. , Lopez Gonzalo , Califano Andrea , Connolly Eileen P. , Greene Lloyd A. , Yamashiro Darrell J.
Published: December 2023

Supplementary Figure 15 shows that CP-d/n-ATF5 treatment does not induce BMF under adherent conditions
Supplementary Figure 1 from Activating Transcription Factor 5 Promotes Neuroblastoma Metastasis by Inducing Anoikis Resistance
Authors: Banerjee Debarshi , Boboila Shuobo , Okochi Shunpei , Angelastro James M. , Kadenhe-Chiweshe Angela V. , Lopez Gonzalo , Califano Andrea , Connolly Eileen P. , Greene Lloyd A. , Yamashiro Darrell J.
Published: December 2023

Supplementary Figure 1 shows that ATF5 is expressed in neuroblastoma cell lines.
FIGURE 6 from Activating Transcription Factor 5 Promotes Neuroblastoma Metastasis by Inducing Anoikis Resistance
Authors: Banerjee Debarshi , Boboila Shuobo , Okochi Shunpei , Angelastro James M. , Kadenhe-Chiweshe Angela V. , Lopez Gonzalo , Califano Andrea , Connolly Eileen P. , Greene Lloyd A. , Yamashiro Darrell J.
Published: December 2023

CP-d/n-ATF5 induces anoikis and inhibits neuroblastoma growth and metastasis in vivo. A, Effects of CP-dn-ATF5 on the expression of ATF5 and apoptosis-related BCL-2 proteins in suspension cells. Immunoblot of proapoptotic and antiapoptotic proteins in BE(2)-C and SK-N-DZ suspension cells at 72 hours after CP-d/n-ATF5 treatment. β-Actin was used as a loading control. Densitometric analysis was performed using ImageJ. B, BMF knockdown inhibits CP-d/n-ATF5–induced anoikis of BE(2)-C and SK-N-DZ cells. Adherent cells were treated with or without siBMFs (50 nmol/L) as indicated for 24 hours and then seeded in nonadherent plates. CP-d/n-ATF5 (200 µmol/L) was added, and 72 hours later, anoikis was evaluated. C, Kaplan–Meier analysis of survival of mice bearing BE(2)-C tumors, treated with vehicle (n = 7) or CP-d/n-ATF5 (50 mg/kg; n = 7). Treatment was started 7 days after cell implantation, once daily for the first 3 days, and then twice weekly. P < 0.01, log-rank (Mantel–Cox). D, Quantification of liver bioluminescence flux (photons/second) by ex vivo imaging at the time of euthanasia from mice bearing BE(2)-C tumors described in C. Vehicle (n = 7), CP-d/n-ATF5 (n = 6). E, Quantification of bioluminescence in bone marrow homogenate measured at the time of euthanasia (RLU/# BM cells, RLU: Relative luciferase unit). Vehicle (n = 7), CP-d/n-ATF5 (n = 6). F, Quantification of CTC measured at the time of euthanasia by bioluminescence of blood. Vehicle (n = 7), CP-d/n-ATF5 (n = 6). G, Twelve hours after intracardiac injection of BE(2)-C cells, blood was collected for (left) quantification of CTC by measurement of blood bioluminescence and (right) for measurement of apoptosis in isolated BE(2)-C CTC. Mice were treated with CP-d/n-ATF5 (n = 9) or vehicle (n = 9) immediately after intracardiac injection. H, BE(2)-C cells were injected intracardially and then treated with vehicle (n = 8) or CP-d/n-ATF5 (n = 10). Whole-body bioluminescence flux was then monitored for subsequent tumor cell growth. I, Representative bioluminescence images showing metastatic growth of BE(2)-C in mice treated with vehicle or CP-dn-ATF5 at day 38 of the experiment described in H. J, Quantification of total flux (photons/second) by ex vivo liver bioluminescence at time of euthanasia (day 38). K, Quantification of bioluminescence in bone marrow homogenate at the time of euthanasia (day 38). L, RT-PCR analysis of ATF5, BMF, and ACTB (internal control) in BE(2)-CTC from K. *, P < 0.05; **, P < 0.01; ***, P < 0.001.
FIGURE 3 from Activating Transcription Factor 5 Promotes Neuroblastoma Metastasis by Inducing Anoikis Resistance
Authors: Banerjee Debarshi , Boboila Shuobo , Okochi Shunpei , Angelastro James M. , Kadenhe-Chiweshe Angela V. , Lopez Gonzalo , Califano Andrea , Connolly Eileen P. , Greene Lloyd A. , Yamashiro Darrell J.
Published: December 2023

Depletion of ATF5 induces anoikis and decreases metastasis of neuroblastoma cells. A and B, Viability of BE(2)-C and SK-N-DZ suspension cells in poly-HEMA–coated plates, expressing Dox-inducible shATF5-1 or shATF5-2 at different timepoints after Dox treatment. Mean ± SD. C and D, Quantification of anoikis of BE(2)-C and SK-N-DZ suspension cells cultured as in A and B at different timepoints after Dox addition. Mean ± SD. E, Quantification of whole-body bioluminescence flux (photons/second) in mice 24 hours after intracardiac injection of BE(2)-C-shATF5-2 cells, + Dox (n = 9); −Dox, (n = 9). Mice were maintained on drinking water containing Dox (2 mg/mL) from 3 days before injection to the time of euthanasia. F, Bioluminescent images at 24 hours after intracardiac injection under conditions described in E. G, Quantification of bioluminescence of blood from mice collected 12 and 24 hours after intracardiac injection under conditions described in E. H, Quantification of apoptosis of BE(2)-C-shATF5-2 CTCs isolated from mice 12 hours after intracardiac injection and treatment ± Dox (see E and Materials and Methods), + Dox (n = 5), −Dox, (n = 5). I, RT-PCR analyses of ATF5 and ACTB in circulating BE(2)-C-shATF5-2 cells isolated after 12 hours. J, Time course of whole-body bioluminescence flux in mice treated as in E. + Dox (n = 8); −Dox, (n = 9). The mice were monitored for metastatic spread by bioluminescence and euthanized at day 31. K, Quantification of total flux (photons/second) by ex vivo liver bioluminescence at the time of euthanasia (day 31). L, Quantification of bioluminescence in bone marrow homogenates at the time of euthanasia (day 31). *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.
Histological Reaction in the Round Window Membrane after Cochlear Implant Insertion in Nonhuman Primates
Authors: Picciafuoco Sebastian , Manrique-Huarte Raquel , De Abajo Jorge , de Linera-Alperi Marta Alvarez , Gallego Maria Antonia , Manrique Manuel
Published: December 2023

Introduction: The primary objective of this article was to determine if any histological alterations occur in the round window (RW) and adjacent anatomical structures of an animal model with normal hearing when a cochlear implant (CI) electrode array is inserted. Furthermore, this article aims to relate these histological alterations to the auditory changes generated. Methods: Cochlear implantation was performed, following the principles of minimally traumatic surgery (MTS), in 15 ears of nonhuman primates (Macaca fascicularis) (Mf) with normal hearing. Auditory brainstem-evoked potentials (ABR) using clicks and tones were used prior to surgery and during a 6-month follow-up period. Histological evaluation was carried out, analyzing the position of the electrode array with respect to the round window membrane (RWM), its percentage of occupation and integrity, the presence of intracochlear damage, and the tissue reaction provoked, the latter of which was quantified in the temporal bones. Results: Surgery was performed on all 15 ears without relevant incidences. Regarding histology, the electrode array in the RW of all ears presented a lateral position with respect to the modiolus. No lesions affecting the integrity of the RW were observed. The mean value of the array’s occupation in the RW was 25%. Tissue reaction, in the form of fibrosis, was observed in all ears and more intensely in the trans-RWM and post-RWM areas. In all ears, the electrodes remained on the scala tympani. No profound hearing impairment was recorded in any ear, being the mean loss of 25.4 dB when comparing presurgical thresholds with those collected 6 months after implantation in ABR click and 24.4 dB in ABR tone burst. Conclusions: The animal model and Hybrid L-14 (HL14) electrode array were optimal for implementing a surgical technique similar to that routinely performed on humans. Mild histological alterations were observed in the round window membrane and adjacent anatomical structures from the insertion of a cochlear implant electrode array. Following the minimally invasive technique, levels of hearing preservation were satisfactory, reaching a pre-post difference of 25.4 dB in the ABR click and 24.4 dB for a high-frequency tone burst. Complete hearing impairment was not observed in either ear. Correlation between the severity of histological alterations and hearing changes recorded in the ABR studies was observed.
Fine-Needle Aspiration Biopsy as a Diagnostic Modality for Orbital Adnexal Lymphoma
Authors: Dan Nicole , Norin Cecilia , Dafgård Kopp Eva , Strömberg Olga , Tani Edneia , Bohman Elin
Published: December 2023

Introduction: The aim of this study was to evaluate fine-needle aspiration biopsy (FNAB) as a diagnostic tool for lymphoproliferative orbital lesions in light of recent improvements in cytomorphological and immunologic analyses. Method: Retrospective case series including all orbital FNABs with a lymphoproliferative outcome at Karolinska University Hospital, Stockholm, Sweden during the period 2005–2015. Results: Of the 38 patients included, 31 (82%) were conclusively diagnosed as having lymphoma according to the first FNAB. Disease in 20 patients (65%) could be subclassified. The diagnosis in 7 patients (18%) was either inconclusive, suggestive of lymphoma, or reactive lymphatic infiltrate. These 7 patients were re-investigated, and the initial suspected diagnosis of malignant lymphoma was confirmed in four. Two of the remaining 3 patients were initially diagnosed as having non-lymphoproliferative disease; however, this was later changed to a lymphoproliferative diagnosis following reinvestigation, while the results of both reFNAB and incisional biopsy were inconclusive in the third. Conclusion: In the majority of the 38 patients, a definitive diagnosis of lymphoma could be made based on FNAB alone, using cytomorphological and immunological workup, and subclassification was possible in 20 patients (65%). Primary low-grade malignant orbital lymphomas are traditionally treated with low-dose radiotherapy regardless of subtype, and incisional biopsy was not needed to initiate treatment. Our findings suggest that FNAB is a valid first option for the diagnosis of suspected orbital lymphomas due to the minimal risk of complications compared to incisional biopsy, and the fact that it can be performed as an outpatient procedure with no anesthesia.
Abstract 14914: Vascular Remodelling Can Be Alleviated by Stem Cell Exosomes in Pulmonary Arterial Hypertension via HIF-1α and Runx2 Signalling Pathway
Authors: Wang Mei-Tzu , LIN Kun-Chang , Huang Wei-Chun
Published: December 2023

Introduction:
Pulmonary arterial hypertension (PAH) is characterized by extensive pulmonary arterial remodelling. Although mesenchymal stem cell (MSC)-derived exosomes provide protective effects in PAH, MSCs exhibit limited senescence during in vitro expansion compared to the induced pluripotent stem cells (iPSCs).

Hypothesis:
In this study, we determined the efficacy and mechanism of iPSC-derived exosomes (iPSC-Exo) in attenuating PAH in rats with monocrotaline (MCT)-induced pulmonary hypertension.

Methods:
Both prophylactic and therapeutic iPSC-Exo treatment effectively prevented the wall thickening and muscularization of pulmonary arterioles, improved the right ventricular systolic pressure, and alleviated the right ventricular hypertrophy in MCT-induced PAH rats.

Results:
Pulmonary artery smooth muscle cells (PASMC) derived from MCT-treated rats (MCT-PASMC) developed more proliferative and pro-migratory phenotypes, which were attenuated by the iPSC-Exo treatment. Moreover, the proliferation and migration of MCT-PASMC were reduced by iPSC-Exo with suppression of PCNA, cyclin D1, MMP-1, and MMP-10, which are mediated via the HIF-1α and PAK1/AKT/Runx2 pathways.

Conclusions:
IPSC-Exo are effective at preventing and reversing pulmonary hypertension by reducing pulmonary vascular remodelling and may provide an iPSC-free therapy for the treatment of PAH.
Abstract 16594: Impact of Anemia on Long-Term Clinical Outcome in Patients With Mildly Reduced Left Ventricular Systolic Function After Acute Myocardial Infarction
Authors: Seung Jaeho , Shin Sang Hoon , Shin Chang Yong , lee junghyuck , Kim Do Young , kim yeo reum , Lee Hyun Ki , Jung Moon Kyung , Roh Kyung Hoon , KIM YONGHEE , Kim Jin-jin , Hwang Byung-Hee , Chang Kiyuk
Published: December 2023

Background:
Anemia may confer a poor prognosis among patients with acute coronary syndrome. However, contemporary data are lacking on the prognostic importance of anemia in patients with mildly reduced left ventricular (LV) systolic function after acute myocardial infarction (AMI).

Methods:
AMI patients receiving percutaneous coronary intervention were consecutively enrolled from January 2004 to August 2014. A total of 2,172 patients with mild LV systolic dysfunction: LV ejection fraction 40 49% as measured by echocardiography, were divided according to the presence of anemia. Anemia was defined as a hemoglobin level <14 g/dL in men and <12 g/dL in women. All-cause mortality within a follow-up period was compared in groups of patients with and without anemia.

Results:
Median follow-up duration was 56.9 months (interquartile range 34.5 to 85.7 months). Patients with anemia were older, more likely to have diabetes and hypertension, but the two groups did not differ in sex and presence of dyslipidemia. The prescription rates of beta-blockers and angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists at discharge were similar in both groups, but those of potent P2Y12 inhibitors and statins were lower in patients with anemia. Patients with anemia had greater all-cause mortality (19.3% vs. 36.7%). Anemia was an independent predictor of all-cause mortality after adjusting confounding risk factors (hazard ratio: 1.301, confidence interval: 1.053-1.607, p=0.030).

Conclusion:
In patients with mildly reduced LV systolic function after AMI, anemia is associated with poorer outcome independently of coexisting risk factors.
LncRNA
PSMB8-AS1
Instigates Vascular Inflammation to Aggravate Atherosclerosis
Authors: Li Shu , He Run-Chao , Wu Shao-Guo , Song Yu , Zhang Ke-Lan , Tang Mao-Lin , Bei Yan-Rou , Zhang Ting , Lu Jin-Bo , Ma Xin , Jiang Min , Qin Liang-Jun , Xu Yudan , Dong Xian-Hui , Wu Jia , Dai Xiaoyan , Hu Yan-Wei
Published: December 2023

BACKGROUND:

Increasing evidence suggests that long noncoding RNAs play significant roles in vascular biology and disease development. One such long noncoding RNA,
PSMB8-AS1
, has been implicated in the development of tumors. Nevertheless, the precise role of
PSMB8-AS1
in cardiovascular diseases, particularly atherosclerosis, has not been thoroughly elucidated. Thus, the primary aim of this investigation is to assess the influence of
PSMB8-AS1
on vascular inflammation and the initiation of atherosclerosis.

METHODS:

We generated
PSMB8-AS1
knockin and
Apoe
(Apolipoprotein E) knockout mice (

Apoe
−/−
PSMB8-AS1
KI

) and global
Apoe
and proteasome subunit-β type-9 (
Psmb9
) double knockout mice (

Apoe
−/−
Psmb9
−/−

). To explore the roles of
PSMB8-AS1
and
Psmb9
in atherosclerosis, we fed the mice with a Western diet for 12 weeks.

RESULTS:

Long noncoding RNA
PSMB8-AS1
is significantly elevated in human atherosclerotic plaques. Strikingly,

Apoe
−/−
PSMB8-AS1
KI

mice exhibited increased atherosclerosis development, plaque vulnerability, and vascular inflammation compared with

Apoe
−/−

mice. Moreover, the levels of VCAM1 (vascular adhesion molecule 1) and ICAM1 (intracellular adhesion molecule 1) were significantly upregulated in atherosclerotic lesions and serum of

Apoe
−/−
PSMB8-AS1
KI

mice. Consistently, in vitro gain- and loss-of-function studies demonstrated that
PSMB8-AS1
induced monocyte/macrophage adhesion to endothelial cells and increased VCAM1 and ICAM1 levels in a PSMB9-dependent manner. Mechanistic studies revealed that
PSMB8-AS1
induced
PSMB9
transcription by recruiting the transcription factor NONO (non-POU domain-containing octamer-binding protein) and binding to the
PSMB9
promoter. PSMB9 (proteasome subunit-β type-9) elevated VCAM1 and ICAM1 expression via the upregulation of ZEB1 (zinc finger E-box-binding homeobox 1).
Psmb9
deficiency decreased atherosclerotic lesion size, plaque vulnerability, and vascular inflammation in

Apoe
−/−

mice in vivo. Importantly, endothelial overexpression of
PSMB8-AS1
-increased atherosclerosis and vascular inflammation were attenuated by
Psmb9
knockout.

CONCLUSIONS:

PSMB8-AS1
promotes vascular inflammation and atherosclerosis via the NONO
/
PSMB9/ZEB1 axis. Our findings support the development of new long noncoding RNA–based strategies to counteract atherosclerotic cardiovascular disease.