tbuckley/cabot-search huggingface dataset:
ST-ELEVATION MYOCARDIAL INFARCTION AMONG CARDIAC AMYLOIDOSIS PATIENTS; A NATIONAL READMISSION DATABASE STUDY
Authors: Tarec Micho Ulbeh, Mohammed M. Uddin, Tanveer Mir, Jasmeet Kaur, Mohammed Amir Babu, Ibrahim Youssef, M. Chadi Alraies, Mujeeb Sheikh
Journal: Journal of the American College of Cardiology (2022)
Identification of Acute Mesenteric Ischemia on 18F-FDG PET/CT
Authors: Mathew V. Smith, Ming Yang, Michael C. Roarke
Journal: Clinical Nuclear Medicine (2021)

Abstract Acute mesenteric ischemia resulting in bowel necrosis is a surgical emergency. First identification of acute mesenteric ischemia with FDG PET/CT is uncommon, because patients with bowel ischemia are usually diagnosed by other imaging methods such as CT. Nevertheless, prompt imager recognition of the PET/CT findings of mesenteric ischemia and necrosis is critical for proper triage of the patient to potentially lifesaving interventions. We present a 39-year-old woman with portal vein thrombosis who was sent for 18 F-FDG PET/CT evaluation of a suspected pancreatic head neoplasm but was unexpectedly found to have ischemic and necrotic small bowel secondary to mesenteric venous infarction.
54P Overall survival in patients with metastatic lung cancer from 2000 to 2020: Implementation of innovative strategies in a real-world setting
Authors: C. Basse, M. Carton, M. Milder, S. Beaucaire Danel, C. Daniel, P. Du Rusquec, A. Livartowski, N. Girard
Journal: Annals of Oncology (2022)
Dose-Adjusted Etoposide, Doxorubicin, and Cyclophosphamide With Vincristine and Prednisone Plus Rituximab Therapy in Children and Adolescents With Primary Mediastinal B-Cell Lymphoma: A Multicenter Phase II Trial
Authors: G. A. Amos Burke, Veronique Minard-Colin, Anne Aupérin, Sarah Alexander, Marta Pillon, Rafael Delgado, József Zsíros, Anne Uyttebroeck, Peggy Dartigues, Rodney R. Miles, Bernarda Kazanowska, Alan K. Chiang, Stéphanie Haouy, Catherine M. Bollard, Monika Csoka, Keith Wheatley, Donald A. Barkauskas, Peter C. Adamson, Gilles Vassal, Catherine Patte, Thomas G. Gross
Journal: Journal of Clinical Oncology (2021)

A dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone plus rituximab (DA-EPOCH-R) regimen has been shown to deliver excellent survival for adults with primary mediastinal large B-cell lymphoma (PMLBL) without the use of radiotherapy. No international prospective evaluation of this regimen has previously been reported in children and adolescents.
Artificial intelligence-based assessments of colonoscopic withdrawal technique: a new method for measuring and enhancing the quality of fold examination
Authors: Wei Liu, Yu Wu, Xianglei Yuan, Jingyu Zhang, Yao Zhou, Wanhong Zhang, Peipei Zhu, Zhang Tao, Long He, Bing Hu, Zhang Yi
Journal: Endoscopy (2022)

Background This study aimed to develop an artificial intelligence (AI)-based system for measuring fold examination quality (FEQ) of colonoscopic withdrawal technique. We also examined the relationship between the system’s evaluation of FEQ and FEQ scores from experts, and adenoma detection rate (ADR) and withdrawal time of colonoscopists, and evaluated the system’s ability to improve FEQ during colonoscopy. Methods First, we developed an AI-based system for measuring FEQ. Next, 103 consecutive colonoscopies performed by 11 colonoscopists were collected for evaluation. Three experts graded FEQ of each colonoscopy, after which the recorded colonoscopies were evaluated by the system. We further assessed the system by correlating its evaluation of FEQ against expert scoring, historical ADR, and withdrawal time of each colonoscopist. We also conducted a prospective observational study to evaluate the systemʼs performance in enhancing fold examination. Results The system’s evaluations of FEQ of each endoscopist were significantly correlated with expertsʼ scores (r = 0.871, P &lt; 0.001), historical ADR (r = 0.852, P = 0.001), and withdrawal time (r = 0.727, P = 0.01). For colonoscopies performed by colonoscopists with previously low ADRs (&lt; 25 %), AI assistance significantly improved the FEQ, evaluated by both the AI system (0.29 [interquartile range (IQR) 0.27–0.30] vs. 0.23 [0.17–0.26]) and experts (14.00 [14.00–15.00] vs. 11.67 [10.00–13.33]) (both P &lt; 0.001). Conclusion The system’s evaluation of FEQ was strongly correlated with FEQ scores from experts, historical ADR, and withdrawal time of each colonoscopist. The system has the potential to enhance FEQ.
The four different modes of psychological explanation, and their proper evaluative schemas
Authors: Michael Gilead
Journal: Behavioral and Brain Sciences (2022)

Abstract I apply Benjamin's (1941) taxonomy of common scientific “modes of explanation” to the psychological context. I argue that: (i) in a “naming” mode, generalizability is not necessary; (ii) in an “analysis,” generalizability is desired; (iii) in a “causal ontology,” generalizability is merely one of the means to an end (theory-challenge); (iv) in a “synthesis,” generalizability is (eventually) critical. A better appreciation of the diversity in psychologists' modes of explanation is crucial for cogent meta-psychological discussions.
Abstract P021: Performance Of Pooled Cohort Equations And MESA Risk Score Across Race/Ethnicity And Socioeconomic Status To Estimate 10-year Cardiovascular Risk In Diverse New England Cohort
Authors: Aniket N Zinzuwadia, Chunying Li, Hesam Dashti, Lin Chen, Brian Cade, Elizabeth Karlson, Nina Paynter, Samia Mora, Olga Demler
Journal: Circulation (2022)

Introduction: The Pooled Cohort Equations (PCE) are the clinical standard for risk estimation of 10-year ASCVD risk, but they have not been extensively validated in minority populations or compared with newer risk estimation calculators such as the Multi-Ethnic Study of Atherosclerosis (MESA) 10-year CHD risk score. Methods: We collected 20-year electronic medical record data (1997-2017) from 34,138 patients in New England (age range in 2007: 55-75). These patients were not on statins and had no documented ASCVD event between 1997 and 2007. Cardiovascular risk factors were collected to calculate PCE and MESA (excluding coronary calcium) scores in 2007. 10-year incident ASCVD events were recorded using ICD codes (2007-17). Risk estimates were evaluated in the total population, race/ethnicity subgroups, and by socioeconomic status (SES) (quintiles of median community income). Results: Overall, PCE and MESA scores had similar discriminative performance (c-statistic: 0.69 vs. 0.70, p-value = 0.15). Both PCE and MESA scores had the best discriminative performance in whites and among individuals with top quintile SES relative to other racial and SES subgroups. In whites, MESA scores had better discriminative performance than PCE (c-statistic: 0.71 vs. 0.70, p-value = 0.005). PCE had higher discriminative performance for African Americans, Hispanics, and Asians but was not statistically significant. PCE and MESA scores had similar calibration metrics for whites but had differing degrees of calibration in African Americans (O to E: 0.79), Hispanics (O to E: 0.83), and Asians (O to E: 0.95) compared with MESA scores (O to E: African Americans: 1.17, Hispanics: 0.96, Asians: 1.51). Conclusion: While MESA and PCE have similar trends in discriminative performance across race/ethnicity and SES, they differed in calibration across minority groups. Clinicians should be cognizant of model performance differences across racial/ethnic and SES subgroups when using risk scores for determining preventive therapies such as statins.
CARDIOKIN1: Computational Assessment of Myocardial Metabolic Capability in Healthy Controls and Patients With Valve Diseases
Authors: Nikolaus Berndt, Johannes Eckstein, Iwona Wallach, Sarah Nordmeyer, Marcus Kelm, Marieluise Kirchner, Leonid Goubergrits, Marie Schafstedde, Anja Hennemuth, Milena Kraus, Tilman Grune, Philipp Mertins, Titus Kuehne, Hermann-Georg Holzhütter
Journal: Circulation (2021)

Background: Many heart diseases can result in reduced pumping capacity of the heart muscle. A mismatch between ATP demand and ATP production of cardiomyocytes is one of the possible causes. Assessment of the relation between myocardial ATP production (MV ATP ) and cardiac workload is important for better understanding disease development and choice of nutritional or pharmacologic treatment strategies. Because there is no method for measuring MV ATP in vivo, the use of physiology-based metabolic models in conjunction with protein abundance data is an attractive approach. METHOD: We developed a comprehensive kinetic model of cardiac energy metabolism (CARDIOKIN1) that recapitulates numerous experimental findings on cardiac metabolism obtained with isolated cardiomyocytes, perfused animal hearts, and in vivo studies with humans. We used the model to assess the energy status of the left ventricle of healthy participants and patients with aortic stenosis and mitral valve insufficiency. Maximal enzyme activities were individually scaled by means of protein abundances in left ventricle tissue samples. The energy status of the left ventricle was quantified by the ATP consumption at rest (MV ATP [rest]), at maximal workload (MV ATP [max]), and by the myocardial ATP production reserve, representing the span between MV ATP (rest) and MV ATP (max). Results: Compared with controls, in both groups of patients, MV ATP (rest) was increased and MV ATP (max) was decreased, resulting in a decreased myocardial ATP production reserve, although all patients had preserved ejection fraction. The variance of the energetic status was high, ranging from decreased to normal values. In both patient groups, the energetic status was tightly associated with mechanic energy demand. A decrease of MV ATP (max) was associated with a decrease of the cardiac output, indicating that cardiac functionality and energetic performance of the ventricle are closely coupled. Conclusions: Our analysis suggests that the ATP-producing capacity of the left ventricle of patients with valvular dysfunction is generally diminished and correlates positively with mechanical energy demand and cardiac output. However, large differences exist in the energetic state of the myocardium even in patients with similar clinical or image-based markers of hypertrophy and pump function. Registration: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT03172338 and NCT04068740.
Integrated Multiomic Profiling Identifies the Epigenetic Regulator PRC2 as a Therapeutic Target to Counteract Leukemia Immune Escape and Relapse
Authors: Valentina Gambacorta, Stefano Beretta, Martina Ciccimarra, Laura Zito, Kety Giannetti, Angela Andrisani, Daniela Gnani, Lucia Zanotti, Giacomo Oliveira, Matteo Giovanni Carrabba, Davide Cittaro, Ivan Merelli, Fabio Ciceri, Raffaella Di Micco, Luca Vago
Journal: Cancer Discovery (2022)

Immune escape represents a major driver of acute myeloid leukemia (AML) reemergence after allogeneic hematopoietic cell transplantation (allo-HCT), with up to 40% of relapses prompted by nongenomic loss of HLA class II expression in leukemia cells. By integrative analysis of gene expression, DNA methylation, and chromatin accessibility in paired diagnosis/relapse primary samples and in the respective patient-derived xenografts (PDX), we identify the polycomb repressive complex 2 (PRC2) as a key epigenetic driver of this immune escape modality. We report that loss of expression of HLA class II molecules is accompanied by a PRC2-dependent reduction in chromatin accessibility. Pharmacologic inhibition of PRC2 subunits rescues HLA class II expression in AML relapses in vitro and in vivo, with consequent recovery of leukemia recognition by CD4+ T cells. Our results uncover a novel link between epigenetics and leukemia immune escape, which may rapidly translate into innovative strategies to cure or prevent AML posttransplantation relapse. Loss of HLA class II expression represents a frequent mechanism of leukemia posttransplantation relapse. Here we identify PRC2 as the main epigenetic driver of this immune escape modality and show that its chemical inhibition can reinstate a proficient graft-versus-leukemia effect, providing an innovative rationale for personalized epigenetic immunotherapies. See related commentary by Köhler and Zeiser, p. 1410. This article is highlighted in the In This Issue feature, p. 1397.
Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant
Authors: Nick Andrews, Julia Stowe, Freja Kirsebom, Samuel Toffa, Tim Rickeard, Eileen Gallagher, Charlotte Gower, Meaghan Kall, Natalie Groves, Anne-Marie O’Connell, David Simons, Paula B. Blomquist, Asad Zaidi, Sophie Nash, Nurin Iwani Binti Abdul Aziz, Simon Thelwall, Gavin Dabrera, Richard Myers, Gayatri Amirthalingam, Saheer Gharbia, Jeffrey C. Barrett, Richard Elson, Shamez N. Ladhani, Neil Ferguson, Maria Zambon, Colin N.J. Campbell, Kevin Brown, Susan Hopkins, Meera Chand, Mary Ramsay, Jamie Lopez Bernal
Journal: New England Journal of Medicine (2022)

A rapid increase in coronavirus disease 2019 (Covid-19) cases due to the omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 in highly vaccinated populations has aroused concerns about the effectiveness of current vaccines.
Overcoming PD-1 Blockade Resistance with CpG-A Toll-Like Receptor 9 Agonist Vidutolimod in Patients with Metastatic Melanoma
Authors: Antoni Ribas, Theresa Medina, John M. Kirkwood, Yousef Zakharia, Rene Gonzalez, Diwakar Davar, Bartosz Chmielowski, Katie M. Campbell, Riyue Bao, Heather Kelley, Aaron Morris, David Mauro, James E. Wooldridge, Jason J. Luke, George J. Weiner, Arthur M. Krieg, Mohammed M. Milhem
Journal: Cancer Discovery (2021)

Patients with advanced melanoma that is resistant to PD-1 blockade therapy have limited treatment options. Vidutolimod (formerly CMP-001), a virus-like particle containing a CpG-A Toll-like receptor 9 (TLR9) agonist, may reverse PD-1 blockade resistance by triggering a strong IFN response to induce and attract antitumor T cells. In the dose-escalation part of this phase Ib study, vidutolimod was administered intratumorally at escalating doses with intravenous pembrolizumab to 44 patients with advanced melanoma who had progressive disease or stable disease on prior anti-PD-1 therapy. The combination of vidutolimod and pembrolizumab had a manageable safety profile, and durable responses were observed in 25% of patients, with tumor regression in both injected and noninjected lesions, including visceral lesions. Patients who responded to vidutolimod and pembrolizumab had noninflamed tumors at baseline and induction of an IFNγ gene signature following treatment, as well as increased systemic expression of the IFN-inducible chemokine CXCL10. In this phase Ib study in patients with advanced melanoma, intratumoral TLR9 agonist vidutolimod in combination with pembrolizumab had a manageable safety profile and showed promising clinical activity, supporting the further clinical development of vidutolimod to overcome PD-1 blockade resistance through induction of an IFN response. See related commentary by Sullivan, p. 2960. This article is highlighted in the In This Issue feature, p. 2945.
Pulmonary Hypertension in Children Part 1: Causes and Symptoms
Authors: Natalie Villafranco, Nidhy Varghese, Marianna Sockrider, Erin Ely, Elizabeth Neptune
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Pulmonary Hypertension in Children Part 1: Causes and Symptoms." American Journal of Respiratory and Critical Care Medicine, 204(10), pp. P17–P18
Positive Multifocal PSMA PET/CT in a Patient With Prostate Cancer and Follicular Lymphoma
Authors: Katharina Dendl, Andreas Merkel, Clemens Kratochwil, Peter L. Choyke, Christian Kleist, Jens Cardinale, Uwe Haberkorn, Frederik L. Giesel
Journal: Clinical Nuclear Medicine (2021)

Abstract Prostate-specific membrane antigen (PSMA) PET/CT is a highly reliable nuclear tracer for diagnostic imaging of prostate cancer. However, PSMA is also expressed by some nonprostatic tissues such as benign tumors, inflammatory processes, and malignant neoplasms. This case presents a patient with prostate cancer and follicular lymphoma undergoing PSMA PET/CT. Remarkably, both tumor entities were clearly detected in the scan. Yet, the 2 malignancies demonstrated rather different ranges in terms of SUV max uptake values and therefore still enabled precise and accurate discrimination of prostate cancer and follicular lymphoma.
Abstract P129: Qanadli Index And SPESI Score Correlation With Echocardiographic Indexes In Patients With Submassive Pulmonary Embolism
Authors: Scott R Jafarian Kerman, Shokoufeh Hajsadeghi, Ali Shamsadini
Journal: Circulation (2022)

Introduction: While management and risk stratification of pulmonary embolism (PE) are still unclear, early understanding of the severity of the diseases can help both physician and the patient to set up better milestones. Clinical and obstruction scoring indexes have been utilized as a semi-quantitative measure in numerous settings; however, there has not been a direct comparison reporting mortality and morbidity rates in patients with submissive PE. Here, we mainly focus on the relationship between Qanadli and sPESI indexes with echocardiographic findings in patients with pulmonary emboli. Methods: A total of 200 adult patients who were admitted with diagnosis of PE between January 2014 and March 2019, were retrospectively included in this cross-sectional study. Patients were assessed for Qanadli index, ECG and echocardiographic findings, mortality, and morbidity, and sPESI score. Descriptive, regression and receiver operation characteristic (ROC) analyses were performed. Results: The relationship between total Qanadli score and right ventricle enlargement (p=0.004), McConnel sign (p=0.037), pulmonary artery hypertension (p=0.008), Tricuspid regurgitation severity (p=0.009), pulmonary artery pressure (p=0.006), 4-month follow up Ejection fraction (p=0.006) and systolic blood pressure (p=0.019) were significant. Qanadli score’s performance as a predictor of death with ROC curve (AUC) was found to be %70.11. There was no correlation between Qanadli and sPESI scores. Conclusion: While there were significant relationships between Qanadli score and few of the indicators, the relationship between total Qanadli score and sPESI score and mortality was not significant. Therefore, it might not be a good predictor for mortality and morbidity.
Candesartan prevents arteriopathy progression in cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy model
Authors: Taisuke Kato, Ri-ichiroh Manabe, Hironaka Igarashi, Fuyuki Kametani, Sachiko Hirokawa, Yumi Sekine, Natsumi Fujita, Satoshi Saito, Yusuke Kawashima, Yuya Hatano, Shoichiro Ando, Hiroaki Nozaki, Akihiro Sugai, Masahiro Uemura, Masaki Fukunaga, Toshiya Sato, Akihide Koyama, Rie Saito, Atsushi Sugie, Yasuko Toyoshima, Hirotoshi Kawata, Shigeo Murayama, Masaki Matsumoto, Akiyoshi Kakita, Masato Hasegawa, Masafumi Ihara, Masato Kanazawa, Masatoyo Nishizawa, Shoji Tsuji, Osamu Onodera
Journal: Journal of Clinical Investigation (2021)

Cerebral small vessel disease (CSVD) causes dementia and gait disturbance due to arteriopathy. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a hereditary form of CSVD caused by loss of high-temperature requirement A1 (HTRA1) serine protease activity. In CARASIL, arteriopathy causes intimal thickening, smooth muscle cell (SMC) degeneration, elastic lamina splitting, and vasodilation. The molecular mechanisms were proposed to involve the accumulation of matrisome proteins as substrates or abnormalities in transforming growth factor β (TGF-β) signaling. Here, we show that HTRA1-/- mice exhibited features of CARASIL-associated arteriopathy: intimal thickening, abnormal elastic lamina, and vasodilation. In addition, the mice exhibited reduced distensibility of the cerebral arteries and blood flow in the cerebral cortex. In the thickened intima, matrisome proteins, including the hub protein fibronectin (FN) and latent TGF-β binding protein 4 (LTBP-4), which are substrates of HTRA1, accumulated. Candesartan treatment alleviated matrisome protein accumulation and normalized the vascular distensibility and cerebral blood flow. Furthermore, candesartan reduced the mRNA expression of Fn1, Ltbp-4, and Adamtsl2, which are involved in forming the extracellular matrix network. Our results indicate that these accumulated matrisome proteins may be potential therapeutic targets for arteriopathy in CARASIL.
Abstract 11462: A Surprising Role of TNIK in Regulating Endothelial Interferon Signaling and Activation
Authors: Abishai Dominic, Jun-ichi Abe, Nhat-Tu Le
Journal: Circulation (2021)

Background: Endothelial cells (ECs) predominantly govern vascular tone and homeostasis. Activation of ECs is the central pathophysiological process in the initiation of atherosclerosis (AS). Interferon signaling (IFN Type I and II) is activated in ECs under inflammatory conditions such as systemic lupus erythematosus and is implicated in EC activation. Yet, the underlying mechanisms are still unknown. Through RNA sequencing and pathway analysis we have identified, TNIK, a Ste20 family of MAP kinases (MAP4K) to regulate IFN signaling in ECs. Our study is the first to report the role and function of TNIK in IFN and EC activation. Hypothesis: TNIK regulates IFNs through focal adhesion kinase (FAK) mediated STAT signaling in EC activation (Fig 1A). Methods: Cultured human aortic endothelial cells (HAECs) were treated with control or TNIK-targeted siRNA. Later cells were subjected to static, laminar or disturbed flow conditions. Total RNA was isolated and then RNA-sequencing was performed. The differential expression data were analyzed using CLC genomics and Ingenuity Pathway Analysis (IPA). Western blotting and qRT-PCR were performed to validate STAT activation and interferon-stimulated genes (ISGs) Results: We found &gt;450 genes differentially expressed in siTNIK vs siCTRL treated ECs (fold change&gt;2, FDR&lt;0.05). IPA revealed that under static (ST) and disturbed flow (DF) conditions TNIK depletion led to inhibition IFN (-log P-value &gt;11) and upregulation of eukaryotic transcription elongation factor signaling (eIF2, -log P-value &gt;7) (Fig 1B, C). In addition, under DF, TNIK depletion led to downregulation of hypercytokinemia/hyperchemokinemia (-log P-value &gt;8, Fig 1B). Validation through western blotting and qRT-PCR (Fig 1D, E) confirmed that TNIK regulates FAK and STAT phosphorylation and IFN stimulated gene targets. Conclusions: Our study elucidates the unique role of TNIK in regulating FAK-STAT mediated IFN signaling and subsequently EC activation.