tbuckley/cabot-search huggingface dataset:
CLO22-094: Leg Length Discrepancy Following Limb Sparing Surgery in Pediatric and Adolescent Lower Extremity Bone Sarcomas: A Case Series
Authors: Angela W Zhang, Camille M Powers, Kathryn E Gallaway, Alexandra K Callan
Journal: Journal of the National Comprehensive Cancer Network (2022)

"CLO22-094: Leg Length Discrepancy Following Limb Sparing Surgery in Pediatric and Adolescent Lower Extremity Bone Sarcomas: A Case Series" published on 31 Mar 2022 by National Comprehensive Cancer Network.
IN-HOSPITAL OUTCOMES OF PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS INFECTION
Authors: Mohamed Zghouzi, Parveen Razvi, Amer N. Kadri, Abdul-Rahman M. Suleiman, Waqas Ullah, Yasar Sattar, Heba Osman, Nada Elmakshbr, Rashid Alhusain, Adam Chalek, Chaitu Dandu, Nasser M. Lakkis, M. Chadi Alraies
Journal: Journal of the American College of Cardiology (2022)
RED WINE REMODELS GUT MICROBIOTA INDEPENDENTLY OF TRIMETHYLAMINE N-OXIDE LEVELS
Authors: Elisa Haas, Mario J. Saad, Andrey Santos, Nicola Vitulo, Wilson Lemos, Aline Martins, Carolina R. Picossi, Desiderio Favarato, Peter Libby, Francisco Laurindo, Protasio Lemos Da Luz
Journal: Journal of the American College of Cardiology (2022)
Cellular stress signaling and the unfolded protein response in retinal degeneration: mechanisms and therapeutic implications
Authors: Todd McLaughlin, Andy Medina, Jacob Perkins, Maria Yera, Joshua J. Wang, Sarah X. Zhang
Journal: Molecular Neurodegeneration (2022)

Abstract Background The retina, as part of the central nervous system (CNS) with limited capacity for self-reparation and regeneration in mammals, is under cumulative environmental stress due to high-energy demands and rapid protein turnover. These stressors disrupt the cellular protein and metabolic homeostasis, which, if not alleviated, can lead to dysfunction and cell death of retinal neurons. One primary cellular stress response is the highly conserved unfolded protein response (UPR). The UPR acts through three main signaling pathways in an attempt to restore the protein homeostasis in the endoplasmic reticulum (ER) by various means, including but not limited to, reducing protein translation, increasing protein-folding capacity, and promoting misfolded protein degradation. Moreover, recent work has identified a novel function of the UPR in regulation of cellular metabolism and mitochondrial function, disturbance of which contributes to neuronal degeneration and dysfunction. The role of the UPR in retinal neurons during aging and under disease conditions in age-related macular degeneration (AMD), retinitis pigmentosa (RP), glaucoma, and diabetic retinopathy (DR) has been explored over the past two decades. Each of the disease conditions and their corresponding animal models provide distinct challenges and unique opportunities to gain a better understanding of the role of the UPR in the maintenance of retinal health and function. Method We performed an extensive literature search on PubMed and Google Scholar using the following keywords: unfolded protein response, metabolism, ER stress, retinal degeneration, aging, age-related macular degeneration, retinitis pigmentosa, glaucoma, diabetic retinopathy. Results and conclusion We summarize recent advances in understanding cellular stress response, in particular the UPR, in retinal diseases, highlighting the potential roles of UPR pathways in regulation of cellular metabolism and mitochondrial function in retinal neurons. Further, we provide perspective on the promise and challenges for targeting the UPR pathways as a new therapeutic approach in age- and disease-related retinal degeneration.
Abstract P5-05-10: Inhibition of FASN as a potential treatment of advanced therapy-resistant breast cancer
Authors: Henriette U Balinda
Journal: Cancer Research (2022)

Abstract INTRODUCTION: The majority of breast cancers are estrogen receptor (ERα) positive making endocrine therapy a mainstay for these patients. Unfortunately, resistance to endocrine therapy is a common occurrence. Fatty acid synthase (FASN) is a key enzyme in lipid biosynthesis and is overexpressed in more aggressive and therapy-resistant tumors, including breast cancers. METHODS: The effect of the FASN inhibitor TVB-3166 on ERα expression and cell growth was characterized in tamoxifen-resistant and fulvestrant-resistant cell lines, xenografts, and patient explants. Subcellular localization of ERα was assessed using subcellular fractionations. Palmitoylation and ubiquitination of ERα were assessed by immunoprecipitation. ERα and p-eIF2α protein levels were analyzed by western blotting after treatment with TVB-3166 with or without the addition of palmitate or BAPTA. RESULTS: TVB-3166 treatment leads to a marked inhibition of proliferation in tamoxifen-resistant and fulvestrant-resistant cells compared to the parental cells. Additionally, TVB-3166 significantly inhibited tamoxifen-resistant breast tumor growth in mice and decreased proliferation of primary tumor explants compared to untreated controls. FASN inhibition significantly reduced ERα levels most prominently in endocrine resistant cells and altered its subcellular localization. Furthermore, we showed that the reduction of ERα expression upon TVB-3166 treatment is mediated through the induction of endoplasmic reticulum stress. CONCLUSION: Our preclinical data provide evidence that FASN inhibition by TVB-3166 presents a promising therapeutic strategy for treatment of endocrine-resistant breast cancer. Further clinical development of FASN inhibitors for endocrine resistant breast cancer should be considered. Citation Format: Henriette U Balinda. Inhibition of FASN as a potential treatment of advanced therapy-resistant breast cancer [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 P5-05-10.
REAL-WORLD TREATMENT PATTERNS, HEALTHCARE RESOURCE UTILIZATION, AND COSTS AMONG PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION IN THE UNITED STATES
Authors: Lia Pizzicato, Vijay R. Nadipelli, Governor Samuel, Jianbin Mao, Stephan Lanes, John Butler, Rebecca S. Pepe, Hemant Phatak, Karim El-Kersh
Journal: Journal of the American College of Cardiology (2022)
Hospitalizations and Mortality From Non–SARS-CoV-2 Causes Among Medicare Beneficiaries at US Hospitals During the SARS-CoV-2 Pandemic
Authors: Alexander Dang, Ravi Thakker, Shuang Li, Erin Hommel, Hemalkumar B. Mehta, James S. Goodwin
Journal: JAMA Network Open (2022)

The increased hospital mortality rates from non-SARS-CoV-2 causes during the SARS-CoV-2 pandemic are incompletely characterized.
ISOLATED VALVE AMYLOIDOSIS IN AORTIC STENOSIS: A NEW CLINICAL SCENARIO?
Authors: Maddalena Conte, Maria Monti, Paolo Poggio, Laura Petraglia, Serena Cabaro, Dario Bruzzese, Pasquale Campana, Giuseppe Comentale, Aurelio Caruso, Maria G. Grimaldi, Emilia Zampella, Flora Cozzolino, Vittoria Monaco, Veronika Veronika Myasoedova, Vincenza Valerio, Adele Ferro, Michele Bellino, Gennaro Galasso, Pietro Pucci, Pietro Formisano, Emanuele Pilato, Alberto Cuocolo
Journal: Journal of the American College of Cardiology (2022)
ASSOCIATION BETWEEN SMOKING HISTORY AND RESPONSE TO ANTI-ARRHYTHMIC THERAPY IN ATRIAL FIBRILLATION PATIENTS ACROSS RACE-ETHNICITY
Authors: Baha’A Al-azzam, Ishita Aggarwal, Miles Barney, Annette Diaz, Pranati Sreepathy, Katherine Shapiro, Yining Chen, Miguel Perez, Atreya Mishra, Sreenivas Konda, Dawood Darbar
Journal: Journal of the American College of Cardiology (2022)
Endoscopic management of buried bumper syndrome: the balloon-dilation pull technique
Authors: Michiel Bronswijk, Marlies Maly, Christophe Snauwaert, Paul Christiaens
Journal: Endoscopy (2022)

Percutaneous endoscopic gastrostomy (PEG) placement facilitates safe and effective enteric feeding in the critically or chronically ill. However, long-term PEG feeding, improper feeding tube care, and potentially smaller or harder discs have been associated with development of buried bumper syndrome in approximately 1.5 % of patients [1] [2] [3] [4]. Although more and more techniques have been described and even dedicated tools developed [1] [2] [3] [4], simple balloon-assisted buried bumper management may carry several advantages [5].
The Need for Praxis in Combating the Race Idea in Bioethics: Theory, Reflection, and Action
Authors: Kayhan Parsi, Denise M. Dudzinski
Journal: The American Journal of Bioethics (2022)

"The Need for Praxis in Combating the Race Idea in Bioethics: Theory, Reflection, and Action." The American Journal of Bioethics, 22(3), pp. 4–5
Blocking UBE2N abrogates oncogenic immune signaling in acute myeloid leukemia
Authors: Laura Barreyro, Avery M. Sampson, Chiharu Ishikawa, Kathleen M. Hueneman, Kwangmin Choi, Mario A. Pujato, Somchai Chutipongtanate, Michael Wyder, Wendy D. Haffey, Eric O’Brien, Mark Wunderlich, Vighnesh Ramesh, Ellen M. Kolb, Cem Meydan, Yaseswini Neelamraju, Lyndsey C. Bolanos, Susanne Christie, Molly A. Smith, Madeline Niederkorn, Tomoya Muto, Santosh Kesari, Francine E. Garrett-Bakelman, Boris Bartholdy, Britta Will, Matthew T. Weirauch, James C. Mulloy, Zartash Gul, Stephen Medlin, Rhett A. Kovall, Ari M. Melnick, John P. Perentesis, Kenneth D. Greis, Elmar Nurmemmedov, William L. Seibel, Daniel T. Starczynowski
Journal: Science Translational Medicine (2022)

Dysregulation of innate immune signaling pathways is implicated in various hematologic malignancies. However, these pathways have not been systematically examined in acute myeloid leukemia (AML). We report that AML hematopoietic stem and progenitor cells (HSPCs) exhibit a high frequency of dysregulated innate immune-related and inflammatory pathways, referred to as oncogenic immune signaling states. Through gene expression analyses and functional studies in human AML cell lines and patient-derived samples, we found that the ubiquitin-conjugating enzyme UBE2N is required for leukemic cell function in vitro and in vivo by maintaining oncogenic immune signaling states. It is known that the enzyme function of UBE2N can be inhibited by interfering with thioester formation between ubiquitin and the active site. We performed in silico structure-based and cellular-based screens and identified two related small-molecule inhibitors UC-764864/65 that targeted UBE2N at its active site. Using these small-molecule inhibitors as chemical probes, we further revealed the therapeutic efficacy of interfering with UBE2N function. This resulted in the blocking of ubiquitination of innate immune- and inflammatory-related substrates in human AML cell lines. Inhibition of UBE2N function disrupted oncogenic immune signaling by promoting cell death of leukemic HSPCs while sparing normal HSPCs in vitro. Moreover, baseline oncogenic immune signaling states in leukemic cells derived from discrete subsets of patients with AML exhibited a selective dependency on UBE2N function in vitro and in vivo. Our study reveals that interfering with UBE2N abrogates leukemic HSPC function and underscores the dependency of AML cells on UBE2N-dependent oncogenic immune signaling states.
COMBINATORIAL MATURATION OF PATIENT STEM CELL-DERIVED ATRIAL CARDIOMYOCYTES UNMASKS ATRIAL FIBRILLATION CAUSED BY AN NPPA GENE MUTATION
Authors: Olivia Ly, Grace E. Brown, Hanna Chen, Liang Hong, Xinge Wang, Yong Duk Han, Mahmud Arif Pavel, Arvind Sridhar, Mark Maienschein-Cline, Brandon Chalazan, Sang Ging Ong, Khaled Abdelhady, Malek Massad, Lona E. Rizkallah, Jalees Rehman, Salman R. Khetani, Dawood Darbar
Journal: Journal of the American College of Cardiology (2022)
Universal Screening in Primary Care Practices by Self-administered Tablet vs Nursing Staff
Authors: David P. Miller, Kristie L. Foley, Richa Bundy, Ajay Dharod, Elena Wright, Mark Dignan, Anna C. Snavely
Journal: JAMA Network Open (2022)

This nonrandomized controlled trial investigates whether self-administered screening via an in-office tablet app was associated with improved detection of patients at risk for depression, injurious falls, or intimate partner violence compared with screening performed by clinicians.
AMFR drives allergic asthma development by promoting alveolar macrophage–derived GM-CSF production
Authors: Huihui Zhang, Ran Wei, Xinyi Yang, Lu Xu, Hongchao Jiang, Mengkai Li, Haixia Jiang, Haibo Zhang, Zhihong Chen, Feng Qian, Lei Sun
Journal: The Journal of Experimental Medicine (2022)

Alveolar macrophages (AMs) are specialized tissue-resident macrophages that orchestrate the immune response in allergic inflammation and asthma. However, what signals direct AMs to cross talk with other immune cells remains unclear. Here, we report that autocrine motility factor receptor (AMFR), an endoplasmic reticulum–resident E3 ubiquitin ligase, is upregulated in AMs of asthma and is critical for this condition. AMFR deficiency significantly decreased allergy-induced T helper 2 (Th2) and eosinophilic inflammation, with less granulocyte-macrophage colony-stimulating factor (GM-CSF) production in AMs. Mechanistically, following thymic stromal lymphopoietin (TSLP) stimulation, AMFR associated directly with cytokine-inducible SH2-containing protein (CIS), induced the ubiquitination of Lys48-linked polyubiquitination of CIS, and consequently blocked the inhibitory effect of CIS on signal transducer and activator of transcription 5 (STAT5) phosphorylation and the downstream pathway activation in AMs. In conclusion, our results demonstrate that AMFR serves a crucial role in promoting inflammation in asthma through regulating AM function, and may emerge as a new potential drug target for asthma therapy.
Hormonal Therapy Drug Switching, Out-of-Pocket Costs, and Adherence Among Older Women With Breast Cancer
Authors: Xuanzi Qin, Peter Huckfeldt, Jean Abraham, Douglas Yee, Beth A Virnig
Journal: JNCI Journal of the National Cancer Institute (2022)

Adherence to aromatase inhibitors (AIs) and tamoxifen has considerable survival benefits for postmenopausal women diagnosed with hormone receptor-positive breast cancer. Reduced out-of-pocket costs and treatment-related side effects could increase therapy adherence. Given that individuals' side effect profiles could differ across AIs, generic AI entry could facilitate switching between AIs to manage side effects and improve adherence.From Surveillance, Epidemiology, and End Results-Medicare, we selected women first diagnosed with hormone receptor-positive breast cancer at age 65+ years and initiated an AI within 1 year of diagnosis between January 1, 2007, and May 31, 2008, or June 1, 2011, and December 31, 2012, and followed them for up to 2 years (N = 20 677). We estimated changes in probabilities of adherence with and without switching for Part D enrollees with and without the low-income subsidy (LIS vs non-LIS) before and after generic entry using linear probability models. Tests of statistical significance are 2-sided.After generic entry reduced out-of-pocket costs of AIs (larger reduction for non-LIS), the percentage of women who ever switched from one AI to another AI increased from 8.8% to 14.6% for non-LIS and from 7.3% to 12.5% for LIS. Adherence without switching increased by 8.0 percentage points (pp) for non-LIS (P < .001) but decreased by 4.9 pp (P < .001) for LIS. Adherence with switching increased for both non-LIS (6.4 pp, P < .001) and LIS (4.4 pp, P < .001).Increased switching after generic entry contributed to increased adherence, suggesting switching allowed better management of treatment-related side effects. Subsidized women also experienced increased adherence with switching after generic entry, suggesting that patients and physicians might not understand Part D benefit design when making decisions.
Leaky gut model of the human intestinal mucosa for testing siRNA-based nanomedicine targeting JAK1
Authors: Olga Hartwig, Brigitta Loretz, Adrien Nougarede, Dorothée Jary, Eric Sulpice, Xavier Gidrol, Fabrice Navarro, Claus-Michael Lehr
Journal: Journal of Controlled Release (2022)

Complex in vitro models of human immune cells and intestinal mucosa may have a translation-assisting role in the assessment of anti-inflammatory compounds. Chronic inflammation of the gastrointestinal tract is a hallmark of inflammatory bowel diseases (IBD). In both IBD entities, Crohn's disease and ulcerative colitis, impaired immune cell activation and dysfunctional epithelial barrier are the common pathophysiology. Current therapeutic approaches are targeting single immune modulator molecules to stop disease progression and reduce adverse effects. Such molecular targets can be difficult to assess in experimental animal models of colitis, due to the disease complexity and species differences. Previously, a co-culture model based on human epithelial cells and monocytes arranged in a physiological microenvironment was used to mimic inflamed mucosa for toxicological and permeability studies. The leaky gut model described here, a co-culture of Caco-2, THP-1 and MUTZ-3 cells, was used to mimic IBD-related pathophysiology and for combined investigations of permeability and target engagement of two Janus kinase (JAK) inhibitors, tofacitinib (TOFA) and a JAK1-targeting siRNA nanomedicine. The co-culture just before reaching confluency of the epithelium was used to mimic the compromised intestinal barrier. Delivery efficacy and target engagement against JAK1 was quantified via downstream analysis of STAT1 protein phosphorylation after IFN-γ stimulation. Compared to a tight barrier, the leaky gut model showed 92 ± 5% confluence, a barrier function below 200 Ω*cm2, and enhanced immune response to bacteria-derived lipopolysaccharides. By confocal microscopy we observed an increased accumulation of siJAK1-nanoparticles within the sub-confluent regions leading to uptake into immune cells near the epithelium. A concentration-dependent downregulation of JAK/STAT pathway was observed for siJAK1-nanoparticles (10 ± 12% to 16 ± 12%), whereas TOFA inhibition was 86 ± 2%, compared to untreated cells. By mimicking the status of severely damaged epithelium, like in IBD, the leaky gut model holds promise as a human in vitro system to evaluate the efficacy of anti-inflammatory drugs and nanomedicines.
EMERGENT USE OF VENO-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION (VA-ECMO) IN A PATIENT WITH CARDIAC ARREST CAUSED BY PHEOCHROMOCYTOMA
Authors: Jonathan Nichols, Esther Shao, Laura Onderko, Aaron Shaikh, Szymon L. Wiernek
Journal: Journal of the American College of Cardiology (2022)
Blocking CD47 promotes antitumour immunity through CD103+ dendritic cell–NK cell axis in murine hepatocellular carcinoma model
Authors: Shuai Wang, Qinchuan Wu, Tianchi Chen, Rong Su, Caixu Pan, Junjie Qian, Hechen Huang, Shengyong Yin, Haiyang Xie, Lin Zhou, Shusen Zheng
Journal: Journal of Hepatology (2022)
SYMPTOMATIC NON-SUSTAINED VENTRICULAR TACHYCARDIA ASSOCIATED WITH RESOLVED MILD COVID-19
Authors: Muhammad Adil Sheikh, Kevin Schrader, Omar Siddiqui, Yasser Al-Khadra, Raj Patel, Manjari R. Regmi, Zurain Niaz, Robert Kropp, Venkata Missula, Luke Schiller, Prashanth Singanallur, Mohamad Sukkari, Michael Gleason, Daniel Holtz, Abhishek Kalidas Kulkarni
Journal: Journal of the American College of Cardiology (2022)
Abstract P3-02-06: A phase II study of 68Ga-ABY-025 PET for non-invasive quantification of HER2 expression in breast cancer
Authors: Ali Alhuseinalkhudhur, Henrik Lindman, Per Liss, Tora Sundin, Fredrik Y Frejd, Johan Hartman, Victor Iyer, Mark Lubberink, Irina Velikyan, Jens Sörensen
Journal: Cancer Research (2022)

Abstract Introduction/Aim: 68Ga-ABY-025 is a small-protein HER2-binder which has shown promising results in evaluating HER2 receptor status in earlier studies in breast cancer (BC). The aim of the current study was to investigate the role of 68Ga-ABY-025 PET imaging in relation to histopathology and treatment response. Methods: This single-center Phase II study consecutively included neoadjuvant patients with stage 2/3 BC (n=22) and recurrent metastatic BC (rMBC, n=18). All patients had at least one HER2-positive/borderline biopsy before inclusion and underwent 68Ga-ABY-025 PET at baseline followed by FDG PET/CT and biopsies for pathology analysis as part of study. FDG PET/CT was repeated after 2 cycles of treatment and glycolytic tumor burden (FDG2-FDG1)/FDG1) was calculated for up to five largest lesions in each patient. A reduction in glycolytic tumor burden &amp;gt;30% was considered good metabolic response. Uptake values (ABY-SUV) from 68Ga-ABY-025 PET in tumor lesions were compared with standard pathology analysis of tumor biopsies. Data was evaluated using regression and ROC analysis. Results: Biopsies for HER2 showed 32 positive, 3 borderline and 5 negative lesions. 68Ga-ABY-025 PET produced high-contrast images with ABY-SUV ranging from 0 to 50. Correlation of ABY-SUV and HER2 score from biopsies did not reach significance. HER2-targeted therapy in stage 2/3 BC resulted in a larger metabolic response (mean reduction of glycolytic tumor burden 70±26%) than in rMBC (mean reduction 25±61%, p&amp;lt;0.001). ABY-SUV correlated negatively with change in glycolytic tumor burden (p&amp;lt;0.0001) and ABY-SUV&amp;gt;6.0 predicted good metabolic response in soft-tissue tumors (AUC 0.82, 95% confidence interval 0.75-0.89, p&amp;lt;0.0001), corrected for neoadjuvant/recurrent setting. Using this cut-off, ABY SUV and invasive HER2 score were discordant in 12 of 40 patients (30%) - 6 with stage 2/3 BC and 6 with rMBC. Of the discordant cases, 68Ga-ABY-025 PET predicted the response correct in 7 cases (3 with stage 2/3 BC and 4 with rMBC) compared to biopsy-based pathology with correct prediction in 5 cases. Conclusion: 68Ga-ABY-025 PET is a potentially useful non-invasive indicator of in-vivo HER2 receptor status in breast cancer and might predict early response to HER2-targeted therapies. A larger multi-center study has been initiated to confirm these results. Citation Format: Ali Alhuseinalkhudhur, Henrik Lindman, Per Liss, Tora Sundin, Fredrik Y Frejd, Johan Hartman, Victor Iyer, Mark Lubberink, Irina Velikyan, Jens Sörensen. A phase II study of 68Ga-ABY-025 PET for non-invasive quantification of HER2 expression in breast cancer [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 P3-02-06.
THE REAL-WORLD PERFORMANCE OF CONTEMPORARY SELF-EXPANDING TRANSCATHETER AORTIC VALVE REPLACEMENT IN PATIENTS WITH LEFT VENTRICULAR OUTFLOW TRACT CALCIUM
Authors: Giorgio Medranda, Toby Rogers, Brian Case, Syed Ali, Cheng Zhang, John C. Wang, Gaby Weissman, Lowell F. Satler, Itsik Ben-Dor, Ron Waksman
Journal: Journal of the American College of Cardiology (2022)