tbuckley/cabot-search huggingface dataset:
Highlights From the American College of Cardiology’s Scientific Sessions—New Heart Failure Management Guidelines, Alirocumab After a Myocardial Infarction, and Treating Mild Chronic Hypertension in Pregnancy
Authors: Jennifer Abbasi
Journal: JAMA (2022)

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Developing a shared sepsis data infrastructure: a systematic review and concept map to FHIR
Authors: Emily B. Brant, Jason N. Kennedy, Andrew J. King, Lawrence D. Gerstley, Pranita Mishra, David Schlessinger, James Shalaby, Gabriel J. Escobar, Derek C. Angus, Christopher W. Seymour, Vincent X. Liu
Journal: npj Digital Medicine (2022)

Abstract The development of a shared data infrastructure across health systems could improve research, clinical care, and health policy across a spectrum of diseases, including sepsis. Awareness of the potential value of such infrastructure has been heightened by COVID-19, as the lack of a real-time, interoperable data network impaired disease identification, mitigation, and eradication. The Sepsis on FHIR collaboration establishes a dynamic, federated, and interoperable system of sepsis data from 55 hospitals using 2 distinct inpatient electronic health record systems. Here we report on phase 1, a systematic review to identify clinical variables required to define sepsis and its subtypes to produce a concept mapping of elements onto Fast Healthcare Interoperability Resources (FHIR). Relevant papers described consensus sepsis definitions, provided criteria for sepsis, severe sepsis, septic shock, or detailed sepsis subtypes. Studies not written in English, published prior to 1970, or “grey” literature were prospectively excluded. We analyzed 55 manuscripts yielding 151 unique clinical variables. We then mapped variables to their corresponding US Core FHIR resources and specific code values. This work establishes the framework to develop a flexible infrastructure for sharing sepsis data, highlighting how FHIR could enable the extension of this approach to other important conditions relevant to public health.
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Journal: JAMA Network Open (2022)

Kiran J. Biddinger; Connor A. Emdin, MD, DPhil; Mary E. Haas, PhD; Minxian Wang, PhD; George Hindy, MD; Patrick T. Ellinor, MD, PhD; Sekar Kathiresan, MD; Amit V. Khera, MD, MSc; Krishna G. Aragam, MD, MS
von Willebrand factor as an indicator of endothelial injury in <scp>COVID</scp>‐19: comment on the article by Shi et al
Authors: Darryl E. Palmer‐Toy, Timothy M. Cotter, Hedyeh Shafi, Su‐Jau T. Yang, Alexander H. Cotter
Journal: Arthritis & Rheumatology (2022)

We read with great interest the article by Dr. Shi et al (1) on their efforts to “identify circulating factors contributing to endothelial cell activation and dysfunction in COVID-19.” Conspicuous by its absence in this otherwise thorough investigation was any mention of von Willebrand factor (vWF), a coagulation factor and early indicator of endothelial injury (2). Increases in circulating vWF antigen precede and directly promote thrombosis by mediating platelet adhesion and preventing clearance of coagulation factor VIII (3). Shi and colleagues postulated that antiphospholipid antibodies may activate endothelial cells in COVID-19, which others have shown to be mediated by vWF (4). Patients with COVID-19 commonly have increased levels of vWF antigen, and its presence is a marker that could be used to predict the risk of death and increased length of hospitalization in patients with COVID-19 (5-9). Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Tenascin-X Mediates Flow-Induced Suppression of EndMT and Atherosclerosis
Authors: Guozheng Liang, ShengPeng Wang, Jingchen Shao, Young-June Jin, Liran Xu, Yang Yan, Stefan Günther, Lei Wang, Stefan Offermanns
Journal: Circulation Research (2022)

Background: Endothelial-to-mesenchymal transition (EndMT) has been identified as a critical driver of vascular inflammation and atherosclerosis, and TGF-β (transforming growth factor β) is a key mediator of EndMT. Both EndMT and atherosclerosis are promoted by disturbed flow, whereas unidirectional laminar flow limits EndMT and is atheroprotective. How EndMT and endothelial TGF-β signaling are regulated by different flow patterns is, however, still poorly understood. Methods: Flow chamber experiments in vitro and endothelium-specific knockout mice were used to study the role of tenascin-X in the regulation of EndMT and atherosclerosis as well as the underlying mechanisms. Results: In human endothelial cells as well as in human and mouse aortae, unidirectional laminar flow but not disturbed flow strongly increased endothelial expression of the extracellular matrix protein TN-X (tenascin-X) in a KLF4 (Krüppel-like factor 4) dependent manner. Mice with endothelium-specific loss of TN-X (EC-Tnxb-KO) showed increased endothelial TGF-β signaling as well as increased endothelial expression of EndMT and inflammatory marker genes. When EC-Tnxb-KO mice were subjected to partial carotid artery ligation, we observed increased vascular remodeling. EC-Tnxb-KO mice crossed to low-density lipoprotein receptor-deficient mice showed advanced atherosclerotic lesions after being fed a high-fat diet. Treatment of EC-Tnxb-KO mice with an anti-TGF-beta antibody or additional endothelial loss of TGF-beta receptors 1 and 2 normalized endothelial TGF-beta signaling and prevented EndMT. In in vitro studies, we found that TN-X through its fibrinogen-like domain directly interacts with TGF-β and thereby interferes with its binding to the TGF-β receptor. Conclusions: In summary, we show that TN-X is a central mediator of flow-induced inhibition of EndMT, endothelial inflammation and atherogenesis, which functions by binding to and by blocking the activity of TGF-β. Our data identify a novel mechanism of flow-dependent regulation of vascular TGF-β, which holds promise for generating new strategies to prevent vascular inflammation and atherosclerosis.
Table of Contents
Authors: John Dirks, Sandrine Florquin, Pierre Ronco, Charles Van Ypersele, Yves Pirson, Olivier Devuyst, Bilal Naved, Joseph Bonventre, Jeffrey Hubbell, Neil Hukriede, Benjamin Humphreys, Carl Kesselman, M Valerius, Andrew Mcmahon, Stuart Shankland, Jason Wertheim, Michael White, Mark De Caestecker, Iain Drummond, P Coates, Germaine Wong, Brad Rovin, Pierre Delanaye, Hans Pottel, Richard Glassock, Eric Olinger, Ian Wilson, John Sayer, Taisuke Ishii, Tetsuhiro Tanaka, Masaomi Nangaku, Wei Wang, Pamela Tran, Hiroshi Nishi, Menno Pruijm, Olivier Phan, Anne Zanchi, Sumoyee Basu, Anthony Dorling, Chia-Ling Wei, Ding-Jie Lee, Chia-Chao Wu, Tomasz Hołub, Marta Jagodzi Nska, Agnieszka Makówka, Kamila Ke ˛dzierska, Michał Open, Himabindu Yerneni, Miroslav Sekulic, Praveen Gundelly, Nagaraju Sarabu
Journal: Kidney International (2022)
Tissue-specific melt electrowritten polymeric scaffolds for coordinated regeneration of soft and hard periodontal tissues
Authors: Arwa Daghrery, Jessica A. Ferreira, Jinping Xu, Nasim Golafshan, Darnell Kaigler, Sarit B. Bhaduri, Jos Malda, Miguel Castilho, Marco C. Bottino
Journal: Bioactive Materials (2022)

Periodontitis is a chronic inflammatory condition that often causes serious damage to tooth-supporting tissues. The limited successful outcomes of clinically available approaches underscore the need for therapeutics that cannot only provide structural guidance to cells but can also modulate the local immune response. Here, three-dimensional melt electrowritten (
Author Correction: The Molecular Tumor Board Portal supports clinical decisions and automated reporting for precision oncology
Authors: David Tamborero, Rodrigo Dienstmann, Maan Haj Rachid, Jorrit Boekel, Adria Lopez-Fernandez, Markus Jonsson, Ali Razzak, Irene Braña, Luigi De Petris, Jeffrey Yachnin, Richard D. Baird, Yohann Loriot, Christophe Massard, Patricia Martin-Romano, Frans Opdam, Richard F. Schlenk, Claudio Vernieri, Michele Masucci, Xenia Villalobos, Elena Chavarria, Shubha Anand, Danny Baars, Svetlana Bajalica-Lagercrantz, Richard Baird, Mariska Bierkens, Lennart Blomqvist, Costanza Bono, Luigi De Petris, Gary J. Doherty, Arnauld Forest, Valentina Fornerone, Paola Gabaldi, Felix Haglund, Johan Hartman, Peter Horak, Tanja Jutzi, Mary Kasanicki, Simon Kreutzfeldt, Lucian Le Cornet, Rolf Lewensohn, Johan Lindberg, Carlos Lopez, Andreas Lundqvist, Jose-Ezequiel Martin, Gerrit Meijer, Susana Muñoz, Maud Ngo Camus, Claudio Nicotra, Paolo Nuciforo, Petra Oberrauch, Päivi Östling, Laura Pelz, Alejandro Piris-Gimenez, Elena Provenzano, Etienne Rouleau, John Rowell, Omar Saavedra, Giovanni Scoazec, Kenneth Seamon, Marc Tischkowitz, Lizet van der Kolk, Ruud van der Noll, Maria Vieito, Daniel Vis, Ana Vivancos, Christina von Gertten, Anders Wennborg, Lodewyk Wessels, Valtteri Wirta, Judith Balmaña, Giovanni Apolone, Carlos Caldas, Jonas Bergh, Ingemar Ernberg, Stefan Fröhling, Elena Garralda, Claes Karlsson, Josep Tabernero, Emile Voest, Jordi Rodon, Janne Lehtiö
Journal: Nature Cancer (2022)
Calorie Restriction with or without Time-Restricted Eating in Weight Loss
Authors: Deying Liu, Yan Huang, Chensihan Huang, Shunyu Yang, Xueyun Wei, Peizhen Zhang, Dan Guo, Jiayang Lin, Bingyan Xu, Changwei Li, Hua He, Jiang He, Shiqun Liu, Linna Shi, Yaoming Xue, Huijie Zhang
Journal: New England Journal of Medicine (2022)

We randomly assigned 139 patients with obesity to time-restricted eating (eating only between 8:00 a.m. and 4:00 p.m.) with calorie restriction or daily calorie restriction alone. For 12 months, all the participants were instructed to follow a calorie-restricted diet that consisted of 1500 to 1800 kcal per day for men and 1200 to 1500 kcal per day for women. The primary outcome was the difference between the two groups in the change from baseline in body weight; secondary outcomes included changes in waist circumference, body-mass index (BMI), amount of body fat, and measures of metabolic risk factors.
In utero exposure to maternal anti–aquaporin-4 antibodies alters brain vasculature and neural dynamics in male mouse offspring
Authors: Simone Mader, Lior Brimberg, An Vo, Joshua J. Strohl, James M. Crawford, Alexandre Bonnin, Joseph Carrión, Delcora Campbell, Tomás S. Huerta, Andrea La Bella, Roseann Berlin, Stephen L. Dewey, Matthew Hellman, David Eidelberg, Irena Dujmovic, Jelena Drulovic, Jeffrey L. Bennett, Bruce T. Volpe, Patricio T. Huerta, Betty Diamond
Journal: Science Translational Medicine (2022)

The fetal brain is constantly exposed to maternal IgG before the formation of an effective blood-brain barrier (BBB). Here, we studied the consequences of fetal brain exposure to an antibody to the astrocytic protein aquaporin-4 (AQP4-IgG) in mice. AQP4-IgG was cloned from a patient with neuromyelitis optica spectrum disorder (NMOSD), an autoimmune disease that can affect women of childbearing age. We found that embryonic radial glia cells in neocortex express AQP4. These cells are critical for blood vessel and BBB formation through modulation of the WNT signaling pathway. Male fetuses exposed to AQP4-IgG had abnormal cortical vasculature and lower expression of WNT signaling molecules
Orteronel for Metastatic Hormone-Sensitive Prostate Cancer: A Multicenter, Randomized, Open-Label Phase III Trial (SWOG-1216)
Authors: Neeraj Agarwal, Catherine M. Tangen, Maha H.A. Hussain, Shilpa Gupta, Melissa Plets, Primo N. Lara, Andrea L. Harzstark, Przemyslaw W. Twardowski, Channing J. Paller, Dylan Zylla, Matthew R. Zibelman, Ellis Levine, Bruce J. Roth, Amir Goldkorn, Daniel A. Vaena, Manish Kohli, Tony Crispino, Nicholas J. Vogelzang, Ian M. Thompson, David I. Quinn
Journal: Journal of Clinical Oncology (2022)

Orteronel (TAK-700) is a nonsteroidal 17,20-lyase inhibitor suppressing androgen synthesis. We evaluated the clinical benefit of orteronel when added to androgen deprivation therapy (ADT) in patients with newly diagnosed metastatic hormone-sensitive prostate cancer.In this open-label randomized phase III study, patients with metastatic hormone-sensitive prostate cancer were randomly assigned 1:1 to ADT with orteronel (300 mg oral twice daily; experimental arm) or ADT with bicalutamide (50 mg oral once daily; control arm). The primary objective was the comparison of overall survival (OS), targeting a 33% improvement in median survival. A stratified log-rank test with a one-sided P ≤ .022 would indicate statistical significance. Secondary end points were progression-free survival (PFS), prostate-specific antigen (PSA) level at 7 months (≤ 0.2 v 0.2 to ≤ 4 v > 4 ng/mL), and adverse event profile.Among 1,279 patients included in the analysis, 638 were randomly assigned to the ADT plus orteronel arm and 641 to the control arm. The median age was 68 years; 49% had extensive disease. After a median follow-up of 4.9 years, there was a significant improvement in PFS (median 47.6 v 23.0 months, hazard ratio 0.58; 95% CI, 0.51 to 0.67; P < .0001) and PSA response at 7 months (P < .0001), but not in OS (median 81.1 v 70.2 months, hazard ratio 0.86; 95% CI, 0.72 to 1.02; P = .040, one-sided). More grade 3/4 adverse events occurred in the experimental versus the control arms (43% v 14%). Postprotocol life-prolonging therapy was received by 77.4% of patients in the control arm and 61.3% of patients in the orteronel arm.The study did not meet the primary end point of improved OS with orteronel. The lack of correlation of PFS and PSA response with OS raises concerns over assumption of their consistent surrogacy for OS in the context of extensive postprotocol therapy in this setting.
GM-CSF disruption in CART cells modulates T cell activation and enhances CART cell anti-tumor activity
Authors: Michelle J. Cox, Claudia Manriquez Roman, Erin E. Tapper, Elizabeth L. Siegler, Dale Chappell, Cameron Durrant, Omar Ahmed, Sutapa Sinha, Raphael Mwangi, Nancy S. Scott, Mehrdad Hefazi, Kendall J. Schick, Paulina Horvei, Michael W. Ruff, Ismail Can, Mohamad Adada, Evandro Bezerra, Lionel Aurelien Kankeu Fonkoua, Sameer A. Parikh, Neil E. Kay, Reona Sakemura, Saad S. Kenderian
Journal: Leukemia (2022)
A randomized-controlled trial comparing 20% albumin to plasmalyte in patients with cirrhosis and sepsis-induced hypotension [ALPS trial]
Authors: Rakhi Maiwall, Abhinav Kumar, Samba Siva Rao Pasupuleti, Ashini Kumar Hidam, Harshvardhan Tevethia, Guresh Kumar, Amrish Sahney, Lalita Gouri Mitra, Shiv Kumar Sarin
Journal: Journal of Hepatology (2022)
SARS-CoV-2 epitope–specific CD4 <sup>+</sup> memory T cell responses across COVID-19 disease severity and antibody durability
Authors: Ryan W. Nelson, Yuezhou Chen, Olivia L. Venezia, Richard M. Majerus, Daniel S. Shin, Mary N. Carrington, Xu G. Yu, Duane R. Wesemann, James J. Moon, Andrew D. Luster
Journal: Science Immunology (2022)

CD4 + T cells are central to long-term immunity against viruses through the functions of T helper 1 (T H 1) and T follicular helper (T FH ) cell subsets. To better understand the role of these subsets in coronavirus disease 2019 (COVID-19) immunity, we conducted a longitudinal study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific CD4 + T cell and antibody responses in convalescent individuals who seroconverted during the first wave of the pandemic in Boston, MA, USA, across a range of COVID-19 disease severities. Analyses of spike (S) and nucleocapsid (N) epitope–specific CD4 + T cells using peptide and major histocompatibility complex class II (pMHCII) tetramers demonstrated expanded populations of T cells recognizing the different SARS-CoV-2 epitopes in most individuals compared with prepandemic controls. Individuals who experienced a milder disease course not requiring hospitalization had a greater percentage of circulating T FH (cT FH ) and T H 1 cells among SARS-CoV-2–specific cells. Analysis of SARS-CoV-2–specific CD4 + T cells responses in a subset of individuals with sustained anti-S antibody responses after viral clearance also revealed an increased proportion of memory cT FH cells. Our findings indicate that efficient early disease control also predicts favorable long-term adaptive immunity.
Risk factors for severe reactions in food allergy: Rapid evidence review with meta‐analysis
Authors: Paul J. Turner, Stefania Arasi, Barbara Ballmer‐Weber, Alessia Baseggio Conrado, Antoine Deschildre, Jennifer Gerdts, Susanne Halken, Antonella Muraro, Nandinee Patel, Ronald Van Ree, Debra de Silva, Margitta Worm, Torsten Zuberbier, Graham Roberts
Journal: Allergy (2022)

This rapid review summarizes the most up to date evidence about the risk factors for severe food-induced allergic reactions. We searched three bibliographic databases for studies published between January 2010 and August 2021. We included 88 studies and synthesized the evidence narratively, undertaking meta-analysis where appropriate. Significant uncertainties remain with respect to the prediction of severe reactions, both anaphylaxis and/or severe anaphylaxis refractory to treatment. Prior anaphylaxis, an asthma diagnosis, IgE sensitization or basophil activation tests are not good predictors. Some molecular allergology markers may be helpful. Hospital presentations for anaphylaxis are highest in young children, yet this age group appears at lower risk of severe outcomes. Risk of severe outcomes is greatest in adolescence and young adulthood, but the contribution of risk taking behaviour in contributing to severe outcomes is unclear. Evidence for an impact of cofactors on severity is lacking, although food-dependent exercise-induced anaphylaxis may be an exception. Some medications such as beta-blockers or ACE inhibitors may increase severity, but appear less important than age as a factor in life-threatening reactions. The relationship between dose of exposure and severity is unclear. Delays in symptom recognition and anaphylaxis treatment have been associated with more severe outcomes. An absence of prior anaphylaxis does not exclude its future risk.
Echocardiography findings in COVID-19 patients admitted to intensive care units: a multi-national observational study (the ECHO-COVID study)
Authors: Stephen Huang, Philippe Vignon, Armand Mekontso-Dessap, Ségolène Tran, Gwenael Prat, Michelle Chew, Martin Balik, Filippo Sanfilippo, Gisele Banauch, Fernando Clau-Terre, Andrea Morelli, Daniel De Backer, Bernard Cholley, Michel Slama, Cyril Charron, Marine Goudelin, Francois Bagate, Pierre Bailly, Patrick-Johansson Blixt, Paul Masi, Bruno Evrard, Sam Orde, Paul Mayo, Anthony S. McLean, Antoine Vieillard-Baron, Anne-Marie Welsh, H. Didriksson, Yoann Zerbib, Clément Brault, Laetitia Bodénes, Nicolas Ferrière, S. Clavier, I. Ma, Luigi La Via, Veronica Dezio, J. B. Rius, J. R. Palomares, Fernando Piscioneri, S. Giglioli, S. Banauch-Mayer, Bruno François, Anne-Laure Fedoux, Thomas Daix
Journal: Intensive Care Medicine (2022)
Estimated Health Outcomes and Costs of COVID-19 Prophylaxis With Monoclonal Antibodies Among Unvaccinated Household Contacts in the US
Authors: Abraham D. Flaxman, Rodal Issema, Ruanne V. Barnabas, Jennifer M. Ross
Journal: JAMA Network Open (2022)

The COVID-19 pandemic has led to more than 900 000 deaths in the US and continues to disrupt lives even as effective vaccines are available.
Phase Ib Study of Navicixizumab Plus Paclitaxel in Patients With Platinum-Resistant Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
Authors: Siqing Fu, Bradley R. Corr, Kerry Culm-Merdek, Colleen Mockbee, Hagop Youssoufian, Robert Stagg, R. Wendel Naumann, Robert M. Wenham, Rafael D. Rosengarten, Laura Benjamin, Erika Paige Hamilton, Kathleen N. Moore
Journal: Journal of Clinical Oncology (2022)

This phase Ib study evaluated the safety and efficacy of paclitaxel plus navicixizumab, a bispecific antiangiogenic antibody to vascular endothelial growth factor and delta-like ligand 4, against platinum-resistant ovarian cancer.This open-label, nonrandomized, dose-escalation and -expansion study included 44 patients with previously treated, recurrent, platinum-resistant grade 2/3 ovarian cancer. Treatment was intravenous navicixizumab (3 mg/kg or 4 mg/kg once every 2 weeks) plus paclitaxel (80 mg/m2 intravenously on days 0, 7, and 14 of 28-day cycles). The primary and secondary objectives were to evaluate the safety and efficacy of navicixizumab plus paclitaxel. An RNA-based diagnostic panel was retrospectively used to test the hypothesis that tumors with high angiogenesis or immune-suppressed tumor microenvironment (TME) subtypes (biomarker-positive) are more likely to respond to navicixizumab than those with immune-active/-desert TME subtypes (biomarker-negative). RNA expression was analyzed in available pretreatment tumor tissue to classify 33 patients' TME subtypes, and TME panel findings were correlated with tumor response.The dose-escalation cohorts enrolled patients at navicixizumab doses of 3 mg/kg once every 2 weeks (n = 3) and 4 mg/kg once every 2 weeks (n = 2); 3 mg/kg was selected for expansion (n = 39). No dose-limiting toxicities occurred. The most common grade 3/4 treatment-related adverse events were hypertension (40.9%), neutropenia (6.8%), and thrombocytopenia (4.5%). Pulmonary hypertension occurred in 18.2% (grade 1-2). The overall objective response rate was 43.2% (95% CI, 28.3 to 59.0): 33.3% (95% CI, 17.3 to 52.8) in patients previously treated with bevacizumab, 64.3% (95% CI, 35.1 to 87.2) in bevacizumab-naive patients, and 62% (95% CI, 31.6 to 86.1) in biomarker-positive patients. The median duration of response was 6 months (95% CI, 5.4 months to not estimable).Navicixizumab plus paclitaxel demonstrated promising clinical activity in bevacizumab-treated and -naive patients with platinum-resistant ovarian cancer, with manageable toxicity.