tbuckley/cabot-search huggingface dataset:
IMPACT OF END STAGE RENAL DISEASE ON THE OUTCOMES OF HOSPITALIZED PATIENTS WITH INFECTIVE ENDOCARDITIS: ANALYSIS OF NATIONAL INPATIENT SAMPLE
Authors: Bharosa Sharma, Iriagbonse Asemota, Emmanuel Akuna, Smriti Khanal, Prajwal Shrestha, Raquel Soon-Shiong, Dennis Danso Kumi, Muhammad Usman Almani
Journal: Journal of the American College of Cardiology (2022)
Abstract P5-09-02: Tetrameric and monomeric gain-of-function mutant p53 interacts with chromatin
Authors: George Kwakye Annor
Journal: Cancer Research (2022)

Abstract In 80% of triple-negative breast cancers (TNBC) the TP53 gene is mutated, with a high occurrence of missense changed in the DNA binding domain. These mutations lead to loss of wild-type p53 (wtp53) function and some also create mutant p53 (mtp53) proteins with novel gain-of-function (GOF) tumor-promoting capabilities. We previously reported that mtp53 R273H interacts with replication-associated proteins including MCM2-7 and poly ADP-ribose polymerase (PARP1). Moreover, mtp53 is found on actively replicating nascent DNA. What remains unclear is which domains of mtp53 R273H are responsible for the protein’s chromatin-based replication activities. In this study, we tested whether the oligomerization state of mtp53 plays a role in oncogenic GOF activities. We destabilized tetramer formation by using site-directed mutagenesis to introduce oligomerization domain (OD) point mutations A347D, R337C, or L344P. The site-directed mutagenesis constructs were transiently transfected into p53-/- mammalian cell lines to evaluate the altered functions. The oligomerization state of mtp53 was assessed via glutaraldehyde crosslinking and western blot analyses. Western blot and qPCR analyses were used to test how OD mutations in plasmids expressing either wtp53 or R273H mtp53 regulated the targets p21, CDC7 and RRM2. We used chromatin fractionation and western blot analyses to compare the chromatin association of the R273H mtp53 (with variable OD mutants), PARP1, and MCM2 to assess how destabilizing tetramer formation influenced chromatin interactions. Compared to the tetrameric versions of wildtype (wt) and mutant (mt) p53, the wtp53-A347D and R273H-A347D were predominantly dimers, while wtp53-R337C, wtp53-L344P, mtp53 R273H-R337C, and mtp53R273H-L344P were predominantly monomers. When wtp53 tetramerization was blocked so was its ability to activate the cyclin-dependent kinase p21/waf. Interestingly, all oligomerization forms of mtp53 localized to the chromatin suggesting GOF does not require tetramer formation for all functions. Strikingly, all oligomerization mutants of R273H mtp53, compared to the tetrameric mtp53, had a stronger interaction with MCM2. When we examined the mtp53 GOF transcriptional target we found that only tetrameric mtp53 R273H activated the target gene RRM2. Our findings suggest that destabilizing tetramer formation reduced certain mtp53 R273H GOF oncogenic activities while activating others. These changes of functions require examination in the context of triple-negative breast cancers. Citation Format: George Kwakye Annor. Tetrameric and monomeric gain-of-function mutant p53 interacts with chromatin [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-09-02.
Takotsubo Syndrome: Pathophysiology, Emerging Concepts, and Clinical Implications
Authors: Trisha Singh, Hilal Khan, David T. Gamble, Caroline Scally, David E. Newby, Dana Dawson
Journal: Circulation (2022)

Takotsubo syndrome is a condition characterized by acute transient left ventricular systolic dysfunction, which at presentation can be challenging to distinguish from acute myocardial infarction. Although previously thought to be a benign, self-limiting condition, recent studies have confirmed that patients with takotsubo syndrome have persistent subtle ongoing cardiac dysfunction, and many continue to have limiting symptoms despite restoration of left ventricular ejection fraction. Moreover, these patients have a substantial burden of morbidity and mortality, as well, with high rates of subsequent major adverse cardiovascular events that approach those of patients with acute coronary syndrome. The mechanisms behind this condition remain elusive. Despite substantial research, the medical community continues to have an incomplete understanding of its underlying pathogenesis and pathophysiology. Catecholamine-induced myocardial injury is the most established and well-known theory, but this does not explain all the clinical features and presentations of the condition, and numerous other pathways and abnormalities are emerging. Because of the poor understanding of its underlying pathophysiology, there is a lack of evidence-based interventions to treat the acute episode, to avoid recurrences, and to prevent major adverse cardiovascular events. This highlights the need for further research to gain a better understanding of the underlying pathophysiology to inform appropriate randomized controlled trials of interventions targeting the causative pathways. Only then can evidence-based management strategies be established to improve clinical outcomes of this potentially lethal condition.
Multiplexed imaging mass cytometry of the chemokine milieus in melanoma characterizes features of the response to immunotherapy
Authors: Tobias Hoch, Daniel Schulz, Nils Eling, Julia Martínez Gómez, Mitchell P. Levesque, Bernd Bodenmiller
Journal: Science Immunology (2022)

Intratumoral immune cells are crucial for tumor control and antitumor responses during immunotherapy. Immune cell trafficking into tumors is mediated by binding of specific immune cell receptors to chemokines, a class of secreted chemotactic cytokines. To broadly characterize chemokine expression and function in melanoma, we used multiplexed mass cytometry-based imaging of protein markers and RNA transcripts to analyze the chemokine landscape and immune infiltration in metastatic melanoma samples. Tumors that lacked immune infiltration were devoid of most of the profiled chemokines and exhibited low levels of antigen presentation and markers of inflammation. Infiltrated tumors were characterized by expression of multiple chemokines. CXCL9 and CXCL10 were often localized in patches associated with dysfunctional T cells expressing the B lymphocyte chemoattractant CXCL13. In tumors with B cells but no B cell follicles, T cells were the sole source of CXCL13, suggesting that T cells play a role in B cell recruitment and potentially in B cell follicle formation. B cell patches and follicles were also enriched with TCF7+ naïve-like T cells, a cell type that is predictive of response to immune checkpoint blockade. Our data highlight the strength of targeted RNA and protein codetection to analyze tumor immune microenvironments based on chemokine expression and suggest that the formation of tertiary lymphoid structures may be accompanied by naïve and naïve-like T cell recruitment, which may contribute to antitumor activity.
NEW-ONSET ATRIAL FIBRILLATION AND RISK OF INCIDENT CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS OF COHORT STUDIES
Authors: Veena Gujju, Janeth Gomez-Perez, Siddharth Agarwal, Christian Fleming, Muhammad Faraz Anwaar, Shari Clifton, Jessica Reese, Abhishek Deshmukh, Zain Ul Abideen Asad
Journal: Journal of the American College of Cardiology (2022)
PERCEPTION OF ILLNESS STRATIFIED BY INVASIVE PHENOTYPE IN WOMEN WITH ISCHEMIA AND NO OBSTRUCTIVE CORONARY ARTERY DISEASE
Authors: Leslie Yingzhijie Tseng, Nukte Goc, Steffne Kunnirickal, Natalija Odanovic, Alexandra Schwann, Emily J. Cherlin, Leslie Curry, Erica Sarah Spatz, Samit Shah
Journal: Journal of the American College of Cardiology (2022)
EUGLYCEMIC DIABETIC KETOACIDOSIS AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT. A BITTERSWEET DIAGNOSIS
Authors: Hector Alfredo Garcia Gallardo, Carlos Antonio Gomez Gomez, J. Clemente Mendoza A, Javier Antezana, Nayeli García Hernández, Montserrat Carrillo Estrada
Journal: Journal of the American College of Cardiology (2022)
Integrated single-cell sequencing and histopathological analyses reveal diverse injury and repair responses in a participant with acute kidney injury: a clinical-molecular-pathologic correlation
Authors: Rajasree Menon, Andrew S. Bomback, Blue B. Lake, Christy Stutzke, Stephanie M. Grewenow, Steven Menez, Vivette D. D’Agati, Sanjay Jain, Richard Knight, Stewart H. Lecker, Isaac Stillman, Steve Bogen, Laurence H. Beck, Sushrut Waikar, Gearoid M. McMahon, Astrid Weins, Mia R. Colona, Nir Hacohen, Paul J. Hoover, Mark Aulisio, William S. Bush, Dana C. Crawford, John O'toole, Emilio Poggio, John Sedor, Leslie Cooperman, Stacey Jolly, Leal Herlitz, Jane Nguyen, Agustin Gonzalez-Vicente, Ellen Palmer, Dianna Sendrey, Carissa Vinovskis, Petter M. Bjornstad, Paul Appelbaum, Jonathan M. Barasch, Andrew S. Bomback, Vivette D. D'Agati, Krzysztof Kiryluk, Karla Mehl, Pietro A. Canetta, Ning Shang, Olivia Balderes, Satoru Kudose, Shweta Bansal, Theodore Alexandrov, Helmut Rennke, Tarek M. El-Achkar, Yinghua Cheng, Pierre C. Dagher, Michael T. Eadon, Kenneth W. Dunn, Katherine J. Kelly, Timothy A. Sutton, Daria Barwinska, Michael J. Ferkowicz, Seth Winfree, Sharon Bledsoe, Marcelino Rivera, James C. Williams, Ricardo Melo Ferreira, Chirag R. Parikh, Celia P. Corona-Villalobos, Steven Menez, Avi Rosenberg, Sylvia E. Rosas, Neil Roy, Mark Williams, Evren U. Azeloglu, Cijang He, Ravi Iyengar, Jens Hansen, Yuguang Xiong, Brad Rovin, Samir Parikh, John P. Shapiro, Christopher R. Anderton, Ljiljana Pasa-Tolic, Dusan Velickovic, Jessica Lukowski, George Oliver, Joseph Ardayfio, Jack Bebiak, Keith Brown, Catherine E. Campbell, John Saul, Anna Shpigel, Christy Stutzke, Robert Koewler, Taneisha Campbell, Lynda Hayashi, Nichole Jefferson, Glenda V. Roberts, Roy Pinkeney, Olga Troyanskaya, Rachel Sealfon, Katherine R. Tuttle, Yury Goltsev, Kun Zhang, Blue B. Lake, Zoltan G. Laszik, Garry Nolan, Patrick Boada, Minnie Sarwal, Tara Sigdel, Paul J. Lee, Rita R. Alloway, E. Steve Woodle, Heather Ascani, Ulysses G.J. Balis, Jeffrey B. Hodgin, Matthias Kretzler, Chrysta Lienczewski, Laura H. Mariani, Rajasree Menon, Becky Steck, Yougqun He, Edgar Otto, Jennifer Schaub, Victoria M. Blanc, Sean Eddy, Ninive C. Conser, Jinghui Luo, Paul M. Palevsky, Matthew Rosengart, John A. Kellum, Daniel E. Hall, Parmjeet Randhawa, Mitchell Tublin, Raghavan Murugan, Michele M. Elder, James Winters, Charles E. Alpers, Kristina N. Blank, Jonas Carson, Ian H. De Boer, Ashveena L. Dighe, Jonathan Himmelfarb, Sean D. Mooney, Stuart Shankland, Kayleen Williams, Christopher Park, Frederick Dowd, Robyn L. McClelland, Stephen Daniel, Andrew N. Hoofnagle, Adam Wilcox, Stephanie M. Grewenow, Shweta Bansal, Kumar Sharma, Manjeri Venkatachalam, Guanshi Zhang, Annapurna Pamreddy, Hongping Ye, Richard Montellano, Robert D. Toto, Miguel Vazquez, Simon C. Lee, R. Tyler Miller, Orson W. Moe, Jose Torrealba, Nancy Wang, Asra Kermani, Kamalanathan Sambandam, Harold Park, S. Susan Hedayati, Christopher Y. Lu, Sanjay Jain, Anitha Vijayan, Joseph P. Gaut, Dennis Moledina, Francis P. Wilson, Ugochukwu Ugwuowo, Tanima Arora
Journal: Kidney International (2022)
PERIODONTITIS, ORAL HEALTHCARE PRACTICES, AND THE RISK OF ABDOMINAL AORTIC ANEURYSM: THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY
Authors: Romil Parikh, James Pankow, Pamela L. Lutsey, Lin Yee Chen, James Beck, Kunihiro Matsushita, Ryan T. Demmer, Weihong Tang
Journal: Journal of the American College of Cardiology (2022)
HOW WELL DO EXPERT READERS COMPARE TO ARTIFICIAL INTELLIGENCE QUANTITATIVE CT IN IDENTIFYING HIGH RISK PLAQUE?
Authors: Rebecca Jonas, Rebecca Fisher, William F. Griffin, Habib Rahban, Shani Weerakoon, Hugo Marques, Ronald P. Karlsberg, Robert K. Zeman, Richard J. Katz, Robert S. Jennings, Tami R. Crabtree, Andrew D. Choi, James P. Earls
Journal: Journal of the American College of Cardiology (2022)
SEVERE PPM FOLLOWING TAVR IN SMALL ANNULUS IN SUPRA VERSUS INTRA-ANNULAR VALVE
Authors: Houman Khalili, Philippe Pibarot, Sammy Elmariah, Thomas Pilgrim, Brijeshwar Singh Maini, Anthony A. Bavry, Taishi Okuno, Karim Al-Azizi, Thomas Waggoner, Amr E. Abbas
Journal: Journal of the American College of Cardiology (2022)
NATIONWIDE STUDY ON THE PREVALENCE OF AORTIC STENOSIS AMONG RHEUMATOID ARTHRITIS PATIENTS- A DESCRIPTIVE ANALYSIS
Authors: Akshaya Gopalakrishnan, Saikrishna Patibandla, Pradeep Kumar Devarakonda, Daniel Brito, Samian Sulaiman, Sarath Reddy
Journal: Journal of the American College of Cardiology (2022)
High BMP4 expression in low/intermediate risk BCP-ALL identifies children with poor outcomes
Authors: Lidia M. Fernández-Sevilla, Jaris Valencia, Paula Ortiz-Sánchez, Alberto Fraile-Ramos, Pilar Zuluaga, Eva Jiménez, Rosa Sacedón, María V. Martínez-Sánchez, Janez Jazbec, Marusa Debeljak, Birthe Fedders, Martin Stanulla, Denis Schewe, Gunnar Cario, Alfredo Minguela, Manuel Ramírez, Alberto Varas, Ángeles Vicente
Journal: Blood (2022)

Pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) outcome has improved in the last decades, but leukemic relapses are still one of the main problems of this disease. Bone morphogenetic protein 4 (BMP4) was investigated as a new candidate biomarker with potential prognostic relevance, and its pathogenic role was assessed in the development of disease. A retrospective study was performed with 115 pediatric patients with BCP-ALL, and BMP4 expression was analyzed by quantitative reverse transcription polymerase chain reaction in leukemic blasts at the time of diagnosis. BMP4 mRNA expression levels in the third (upper) quartile were associated with a higher cumulative incidence of relapse as well as a worse 5-year event-free survival and central nervous system (CNS) involvement. Importantly, this association was also evident among children classified as having a nonhigh risk of relapse. A validation cohort of 236 patients with BCP-ALL supported these data. Furthermore, high BMP4 expression promoted engraftment and rapid disease progression in an NSG mouse xenograft model with CNS involvement. Pharmacological blockade of the canonical BMP signaling pathway significantly decreased CNS infiltration and consistently resulted in amelioration of clinical parameters, including neurological score. Mechanistically, BMP4 favored chemoresistance, enhanced adhesion and migration through brain vascular endothelial cells, and promoted a proinflammatory microenvironment and CNS angiogenesis. These data provide evidence that BMP4 expression levels in leukemic cells could be a useful biomarker to identify children with poor outcomes in the low-/intermediate-risk groups of BCP-ALL and that BMP4 could be a new therapeutic target to blockade leukemic CNS disease.
Increased platelet aggregation in patients with decompensated cirrhosis indicates higher risk of further decompensation and death
Authors: Alberto Zanetto, Elena Campello, Cristiana Bulato, Sabrina Gavasso, Fabio Farinati, Francesco Paolo Russo, Daniela Tormene, Patrizia Burra, Marco Senzolo, Paolo Simioni
Journal: Journal of Hepatology (2022)
Harnessing the Therapeutic Potential of Biomacromolecules through Intracellular Delivery of Nucleic Acids, Peptides, and Proteins
Authors: Yu Tian, Matthew V. Tirrell, James L. LaBelle
Journal: Advanced Healthcare Materials (2022)

Biomacromolecules have long been at the leading edge of academic and pharmaceutical drug development and clinical translation. With the clinical advances of new therapeutics, such as monoclonal antibodies and nucleic acids, the array of medical applications of biomacromolecules has broadened considerably. A major on-going effort is to expand therapeutic targets within intracellular locations. Owing to their large sizes, abundant charges, and hydrogen-bond donors and acceptors, advanced delivery technologies are required to deliver biomacromolecules effectively inside cells. In this review, strategies used for the intracellular delivery of three major forms of biomacromolecules: nucleic acids, proteins, and peptides, are highlighted. An emphasis is placed on synthetic delivery approaches and the major hurdles needed to be overcome for their ultimate clinical translation.
CLO22-042: Long Survival in Small-Cell Lung Cancer With Central Nervous System Metastasis: Relationship Between Survival and Metastasis Chronology (SMALLBRAIN Project)
Authors: Javier Diaz-Santos, Carmen Reyna-Fortes, Ana Godoy-Ortiz, Cristina Garcia-Gonzalez, Vanesa Gutierrez-Calderon, Antonio Rueda-Dominguez
Journal: Journal of the National Comprehensive Cancer Network (2022)

"CLO22-042: Long Survival in Small-Cell Lung Cancer With Central Nervous System Metastasis: Relationship Between Survival and Metastasis Chronology (SMALLBRAIN Project)" published on 31 Mar 2022 by National Comprehensive Cancer Network.
Abstract P5-08-12: Efficacy of futibatinib, an irreversible fibroblast growth factor receptor (FGFR) inhibitor, in breast cancer models with FGFR alterations
Authors: Turcin Saridogan, Argun Akcakanat, Ming Zhao, Kurt W. Evans, Erkan Yuca, Stephen Scott, Bryce P. Kirby, Xiaofeng Zheng, Senthil Damodaran, Funda Meric-Bernstam
Journal: Cancer Research (2022)

Abstract Purpose: Several FGFR alterations have been found in breast cancer, however, their role as a therapeutic target in breast has been controversial. Futibatinib (TAS-120; Taiho) is a novel, selective pan-FGFR inhibitor which irreversibly binds to and inhibits FGFR1-4 at nanomolar concentrations. We sought to determine the efficacy of futibatinib in breast cancer models with differing FGFR alterations. Experimental Design: In vivo, antitumor efficacy was evaluated by tumor growth curves and event-free survival in a panel of patient-derived xenografts (PDXs) from breast cancer patients with different FGFR1-4 alterations. Genomic alterations in the PDXs were characterized by next generation sequencing. Correlation of FGFR gene expression in matched patient tumors and PDXs was analyzed by RNA sequencing. In vitro, FGFR2 Y375C mutant and FGFR2-BICC1 fusion expressing MCF10A cell lines were generated, and effect on cell proliferation, colony formation assay, and cell signaling was assessed with and without futibatinib. Frequency of FGFR mutations and FGFR2 amplification was compiled from internal and public databases. Results: Breast cancer PDXs varied in their expression of FGFR1-4. FGFR gene expression significantly correlated between matched patient tumors and PDXs derived from them, however, PDXs had higher levels of FGFR3 and FGFR4 expression compared to patient samples. Futibatinib inhibited tumor growth in three of 10 PDX models, with tumor stabilization in a FGFR2 amplified model and prolonged tumor regression (more than 110 days) in a PDX bearing a FGFR2 Y375C mutation. In vitro, expression of FGFR2 Y375C, as well as FGFR2-BICC fusion in normal-like MCF10A cells enhanced growth, colony formation ability and FGFR signaling. Cells expressing FGFR2 Y375C as well as FGFR2-BICC fusions were more sensitive to futibatinib. In the five breast cancer genomic series we analyzed, FGFR2 mutations and amplifications were found in 1.1%-2.6% and 1.4%-2.5%, respectively. Conclusions: Futibatinib had single agent activity of selected breast cancer PDX models. FGFR2 activating mutations and amplification may represent rare but promising therapeutic targets to FGFR inhibition. Citation Format: Turcin Saridogan, Argun Akcakanat, Ming Zhao, Kurt W. Evans, Erkan Yuca, Stephen Scott, Bryce P. Kirby, Xiaofeng Zheng, Senthil Damodaran, Funda Meric-Bernstam. Efficacy of futibatinib, an irreversible fibroblast growth factor receptor (FGFR) inhibitor, in breast cancer models with FGFR alterations [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-08-12.
VARIABILITY OF LEFT VENTRICULAR GLOBAL LONGITUDINAL STRAIN AND RIGHT VENTRICULAR FREE WALL STRAIN IN PATIENTS WITH OBESITY AND CARDIOVASCULAR RISK FACTORS
Authors: Renzo Mogollon, Raja Shekar Jadav, Mohamed Badawy, Mariana Garcia-Arango, Juan A. Quintero-Martinez, Sandra Cordova-Madera, Amy L. Dichak, Sorin V. Pislaru, Patricia A. Pellikka, Garvan C. Kane, Hector R. Villarraga
Journal: Journal of the American College of Cardiology (2022)
PRE-ADMISSION ORAL ANTICOAGULATION IS ASSOCIATED WITH FEWER THROMBOTIC COMPLICATIONS IN PATIENTS ADMITTED WITH COVID-19
Authors: David Louis, Kevin Kennedy, Marwan Saad, Gregory Salber, Hafiz Muhammad Imran, Tyler Wark, Cullen Soares, Dhairyasheel Ghosalkar, Rasan Cherala, Athena Poppas, J. Dawn Abbott, Herbert D. Aronow
Journal: Journal of the American College of Cardiology (2022)
A role for complement blockade in kidney transplantation
Authors: Diana Karpman, Zivile Bekassy, Anne Grunenwald, Lubka T. Roumenina
Journal: Cellular and Molecular Immunology (2022)

Kidney transplantation is a life-saving procedure for patients with end-stage renal failure, but unfortunately, only a limited number of patients benefit from this procedure due to organ shortage.Moreover, even after transplantation, the graft can be lost due to antibody-mediated rejection (AMR).A recent study by Schmitz et al. in Nature Communications [1] provides new hope to prevent AMR and prolong renal allograft survival.The authors inhibited the innate immune complement cascade at the level of its central component C3 and successfully prevented the tissue injury mediated by donor-specific antibodies (DSAs) in a primate model.After kidney transplantation, graft function can be impaired by various injurious processes.HLA incompatibility between the donor and the recipient contributes to the development of AMR.
Once Viewed as a Promising COVID-19 Treatment, Convalescent Plasma Falls Out of Favor
Authors: Rita Rubin
Journal: JAMA (2022)

Chenguang Shen, PhD; Zhaoqin Wang, PhD; Fang Zhao, PhD; Yang Yang, MD; Jinxiu Li, MD; Jing Yuan, MD; Fuxiang Wang, MD; Delin Li, PhD; Minghui Yang, PhD; Li Xing, MM; Jinli Wei, MM; Haixia Xiao, PhD; Yan Yang, MM; Jiuxin Qu, MD; Ling Qing, MM; Li Chen, MD; Zhixiang Xu, MM; Ling Peng, MM; Yanjie Li, MM; Haixia Zheng, MM; Feng Chen, MM; Kun Huang, MM; Yujing Jiang, MM; Dongjing Liu, MD; Zheng Zhang, MD; Yingxia Liu, MD; Lei Liu, MD