tbuckley/cabot-search huggingface dataset:
An orthogonal IL-2 and IL-2Rβ system drives persistence and activation of CAR T cells and clearance of bulky lymphoma
Authors: Paul-Joseph Aspuria, Sandro Vivona, Michele Bauer, Marie Semana, Navneet Ratti, Scott McCauley, Romina Riener, Rene de Waal Malefyt, Deepti Rokkam, Jan Emmerich, Rob A. Kastelein, Patrick J. Lupardus, Martin Oft
Journal: Science Translational Medicine (2021)

Chimeric antigen receptor (CAR) T cells induce durable responses in patients with refractory hematological tumors. However, low CAR T cell activity, poor engraftment, or short in-patient persistence can lead to tumor progression or relapse. Furthermore, excessive CAR T cell expansion and activation can result in life-threatening cytokine release syndrome (CRS). Thus, in-patient control of the CAR T cell population is essential. Interleukin-2 (IL-2) is a critical cytokine for T cell proliferation and effector function, but its clinical use is limited by immune-mediated toxicity. Here, we report on an orthogonal IL-2 receptor and ligand system that enables specific in vivo control of CAR T cell expansion and activation, wherein an orthogonal human IL-2 (STK-009) selectively pairs with an orthogonal human IL-2Rβ (hoRb) expressed on CAR T cells. STK-009 expands hoRb-expressing CAR T cells in the presence and absence of tumor antigen and maintains the presence of stem cell memory T cells (TSCM) and effector T cells. In preclinical models of human CAR-refractory lymphoma, STK-009 treatment resulted in systemic and intratumoral expansion and activation of hoRb-expressing anti–CD19-CD28ζ CAR T cells (SYNCAR). The orthogonal IL-2 receptor/ligand system delivers complete responses in large subcutaneous lymphomas, even with substantially reduced CAR T cell doses, by selectively expanding and activating CAR T cells in vivo. STK-009 withdrawal allowed normal CAR T cell contraction, thereby limiting CRS induced by tumor antigen–specific T cell activation. These data suggest that the orthogonal IL-2 receptor/ligand system provides the in vivo control necessary to maximize efficacy of CAR T therapies.
Abstract 12097: The Impact of a High-Performance Cardiopulmonary Resuscitation Protocol on Survival From Out-of-Hospital Cardiac Arrests Witnessed by Paramedics
Authors: Ziad Nehme, Jocasta Ball, Melanie Villani, Michael Stephenson, Tony Walker, Dion Stub, Karen L Smith
Journal: Circulation (2021)

Introduction: Some emergency medical services (EMS) have shown increases in survival from out-of-hospital cardiac arrest (OHCA) following the implementation of a high-performance cardiopulmonary resuscitation (CPR) protocol. Despite this, little is known about the effect of high-performance CPR on OHCA witnessed by EMS personnel. Methods: We performed a retrospective cohort study of adult, EMS-witnessed OHCA patients of medical etiology from a population-based registry in Victoria, Australia. Patients treated after the introduction of a high-performance CPR protocol and training program between February 2019 and January 2020 were compared to historical controls between January 2015 and January 2019. The effect of the intervention on survival to hospital discharge was examined using logistic regression models adjusted for temporal and arrest factors. Results: A total of 1,561 and 420 EMS-witnessed OHCA patients were treated in the control and intervention periods, respectively. Baseline characteristics were similar across control and intervention periods, including the median age of cases (69 vs. 69 years, p=0.97), male sex (65.2% vs. 60.5%, p=0.08) and initial shockable arrests (33.7% vs. 29.3%, p=0.09). Resuscitation interventions were similar across groups, except for the use of mechanical CPR which declined during the intervention period (17.0% vs. 10.7%, p&lt;0.001). Unadjusted survival to hospital discharge was similar across control and intervention periods for the overall population (29.4% vs. 32.1%, p=0.27), but significantly higher during the intervention period for initial shockable arrests (66.6% vs. 76.9%, p=0.03). After adjustment for confounders, cases in the intervention period were associated with a 43% increase (adjusted odds ratio [AOR] 1.43; 95% CI: 1.05, 1.94; p=0.02) in the risk-adjusted odds of survival to hospital discharge or a 79% increase (AOR 1.79, 95% CI: 1.09, 2.95; p=0.02) for initial shockable arrests. Conclusions: The implementation of a high-performance CPR quality improvement intervention was associated with significant improvement in survival from EMS witnessed OHCA. Efforts to monitor and improve CPR performance could yield further improvements in patient outcomes.
Autophagy enhanced by curcumin ameliorates inflammation in atherogenesis via the TFEB–P300–BRD4 axis
Authors: Xuesong Li, Ruigong Zhu, Hong Jiang, Quanwen Yin, Jiaming Gu, Jiajing Chen, Xian Ji, Xuan Wu, Haiping Fu, Hui Wang, Xin Tang, Yuanqing Gao, Bingjian Wang, Yong Ji, Hongshan Chen
Journal: Acta Pharmaceutica Sinica B (2021)

Disturbance of macrophage-associated lipid metabolism plays a key role in atherosclerosis. Crosstalk between autophagy deficiency and inflammation response in foam cells (FCs) through epigenetic regulation is still poorly understood. Here, we demonstrate that in macrophages, oxidized low-density lipoprotein (ox-LDL) leads to abnormal crosstalk between autophagy and inflammation, thereby causing aberrant lipid metabolism mediated through a dysfunctional transcription factor EB (TFEB)-P300-bromodomain-containing protein 4 (BRD4) axis. ox-LDL led to macrophage autophagy deficiency along with TFEB cytoplasmic accumulation and increased reactive oxygen species generation. This activated P300 promoted BRD4 binding on the promoter regions of inflammatory genes, consequently contributing to inflammation with atherogenesis. Particularly, ox-LDL activated BRD4-dependent super-enhancer associated with liquid-liquid phase separation (LLPS) on the regulatory regions of inflammatory genes. Curcumin (Cur) prominently restored FCs autophagy by promoting TFEB nuclear translocation, optimizing lipid catabolism, and reducing inflammation. The consequences of P300 and BRD4 on super-enhancer formation and inflammatory response in FCs could be prevented by Cur. Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific Brd4 overexpression or Tfeb knock-out in Apoe knock-out mice via bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.
Venetoclax Combined with FLAG-IDA Induction and Consolidation in Newly Diagnosed Acute Myeloid Leukemia
Authors: Curtis Lachowiez, Courtney D. DiNardo, Koichi Takahashi, Sanam Loghavi, Lian-Chun Xiao, Tapan M. Kadia, Naval Daver, Maria Adeoti, Nicholas J. Short, Koji Sasaki, Sa A Wang, Gautam Borthakur, Ghayas C. Issa, Abhishek Maiti, Yesid Alvarado, Naveen Pemmaraju, Guillermo Montalban-Bravo, Lucia Masarova, Musa Yilmaz, Nitin Jain, Michael Andreeff, Guillermo Garcia-Manero, Steven M. Kornblau, Farhad Ravandi, Elias J. Jabbour, Marina Konopleva, Hagop Kantarjian
Journal: Blood (2021)
Comments on Study About US Female Surgeons
Authors: Emily Oliver, Jocelyn Fitzgerald
Journal: JAMA Surgery (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Controlled Co-delivery of pPDGF-B and pBMP-2 from intraoperatively bioprinted bone constructs improves the repair of calvarial defects in rats
Authors: Kazim K. Moncal, R. Seda Tigli Aydın, Kevin P. Godzik, Timothy M. Acri, Dong N. Heo, Elias Rizk, Hwabok Wee, Gregory S. Lewis, Aliasger K. Salem, Ibrahim T. Ozbolat
Journal: Biomaterials (2021)
Mindfulness-Based Stress Reduction, Mediterranean Diet, and Fetal Growth
Authors: Margaret Bublitz, Methodius G. Tuuli
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2022 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
关于化脓性汗腺炎患者的感受, 我们了解多少?
Journal: British Journal of Dermatology (2021)

我们搜索了四个包含研究出版物的科学数据库。共筛查超过 5500 篇出版物, 发现 14 项有关 HS 感受的定性研究。我们总结了这些研究的主题, 并解读了研究结果。我们的结果证实, HS 患者的身心健康和社交状况面临诸多挑战, 影响了他们的生活。由于羞耻和尴尬, 患者会试图隐藏 HS。社会支持和心理接纳可以帮助患者应对这些挑战。本研究还提醒, 由于诊断延迟和患者在管理病情时感到不受支持, HS 患者并未得到医疗保健系统的有力保障。
Combining a CAR and a chimeric costimulatory receptor enhances T cell sensitivity to low antigen density and promotes persistence
Authors: Afroditi Katsarou, Maria Sjöstrand, Jyoti Naik, Jorge Mansilla-Soto, Dionysia Kefala, Georgios Kladis, Alexandros Nianias, Ruud Ruiter, Renée Poels, Irene Sarkar, Yash R. Patankar, Elena Merino, Rogier M. Reijmers, Kristine A. Frerichs, Huipin Yuan, Joost de Bruijn, Dina Stroopinsky, David Avigan, Niels W. C. J. van de Donk, Sonja Zweegman, Tuna Mutis, Michel Sadelain, Richard W. J. Groen, Maria Themeli
Journal: Science Translational Medicine (2021)

Combination of a CAR and a chimeric costimulatory receptor augments cytotoxicity and durability of T cells and elimination of antigen-low tumors.
JHEP at a glance (January 2022)
Authors: Sirt1 Cpt1, Natália Da, Silva Lima, Marcos Fondevila, Eva Nóvoa, Agueda Gonzalez-Rodriguez, Patricia Aspichueta, Ruben Nogueiras, Kathleen Corey, Rebecca Pitts, Michelle Lai, Robert Gerszten, Chinweike Ukomadu, Lori Jennings, Anne Cordes, Lilia Goudeva, Marc Lütgehetmann, Patrick Behrendt, Heiner Wedemeyer, Albert Heim, Chloé De Broucker, Aurélie Plessier, Isabelle Ollivier-Hourmand, Yazdan Yazdanpanah, Dominique Valla, Pierre-Emmanuel Rautou
Journal: Journal of Hepatology (2021)
How Yemen’s healthcare has been destroyed
Authors: Geetanjali Krishna, Sally Howard
Journal: BMJ (2021)

The Houthi assault on Marib, the last government stronghold in north Yemen, is the latest volley in a vicious seven year civil war that has left Yemen’s healthcare system in tatters and its population facing starvation, report <b>Geetanjali Krishna</b> and <b>Sally Howard</b>
Active vs Expectant Management of Persisting Pregnancy of Unknown Location
Authors: Jian-Rong He, Hui-Yun Xiao, Xiu Qiu
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Cost-effectiveness of chronic hepatitis C screening and treatment
Authors: Hye Won Lee, Hankil Lee, Beom Kyung Kim, Young Chang, Jae Young Jang, Do Young Kim
Journal: Clinical and Molecular Hepatology (2021)

Hepatitis C virus (HCV) infection is the second most common cause of chronic liver disease in South Korea, with a prevalence ranging from 0.6% to 0.8%, and HCV infection incidence increases with age. The anti-HCV antibody test, which is cheaper than the HCV RNA assay, is widely used to screen for HCV infections; however, the underdiagnosis of HCV is a major barrier to the elimination of HCV infections. Although several risk factors have been associated with HCV infections, including intravenous drug use, blood transfusions, and hemodialysis, most patients with HCV infections present with no identifiable risk factors. Universal screening for HCV in adults has been suggested to improve the detection of HCV infections. We reviewed the cost-effectiveness of HCV screening and the methodologies used to perform screening. Recent studies have suggested that universal HCV screening and treatment using direct-acting antivirals represent cost-effective approaches to the prevention and treatment of HCV infection. However, the optimal timing and frequency of HCV screening remain unclear, and further studies are necessary to determine the best approaches for the elimination of HCV infections.
COVID-19 vaccination and breakthrough infections in patients with cancer
Authors: A.L. Schmidt, C. Labaki, C.-Y. Hsu, Z. Bakouny, N. Balanchivadze, S.A. Berg, S. Blau, A. Daher, T. El Zarif, C.R. Friese, E.A. Griffiths, J.E. Hawley, B. Hayes-Lattin, V. Karivedu, T. Latif, B.H. Mavromatis, R.R. McKay, G. Nagaraj, R.H. Nguyen, O.A. Panagiotou, A.J. Portuguese, M. Puc, M. Santos Dutra, B.A. Schroeder, A. Thakkar, E.M. Wulff-Burchfield, S. Mishra, D. Farmakiotis, Yu Shyr, J.L. Warner, T.K. Choueiri, T.K. Choueiri, N. Duma, D. Farmakiotis, P. Grivas, G. de Lima Lopes, C.A. Painter, S. Peters, B.I. Rini, D.P. Shah, M.A. Thompson, J.L. Warner
Journal: Annals of Oncology (2021)

Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.
Intra-articular delivery of full-length antibodies through the use of an in situ forming depot
Authors: Alexis Fayd'herbe De Maudave, Wilhem Leconet, Karine Toupet, Michael Constantinides, Guillaume Bossis, Marion de Toledo, Jérôme Vialaret, Christophe Hirtz, Adolfo Lopez-Noriega, Christian Jorgensen, Daniele Noël, Pascale Louis-Plence, Sylvestre Grizot, Martin Villalba
Journal: Journal of Controlled Release (2021)
Abstract 10992: Machine Learning to Predict In-Hospital Cardiac Arrest in Patients Admitted from the Emergency Department with COVID-19 and Suspected Pneumonia
Authors: Tsung-Chien Lu, Eric H Chou, CHIH-HUNG WANG, Amir Mostafavi, Mario Tovar, John Garrett, Toral Bhakta, Chu-Lin Tsai, Matthew H Ma
Journal: Circulation (2021)

Introduction: There are only scarce models developed for stratifying the risk of cardiac arrest from COVID-19 patients presenting to the ED with suspected pneumonia. By using the machine learning (ML) approach, we aimed to develop and validate the ML models to predict in-hospital cardiac arrest (IHCA) in patients admitted from the ED. Hypothesis: We hypothesized that ML approach can serve as a valuable tool in identifying patients at risk of IHCA in a timely fashion. Methods: We included the COVID-19 patients admitted from the EDs of five hospitals in Texas between March and November 2020. All adult (≥ 18 years) patients were included if they had positive RT-PCR for SARS-CoV-2 and also received CXR examination for suspected pneumonia. Patients’ demographic, past medical history, vital signs at ED triage, CXR findings, and laboratory results were retrieved from the EMR system. The primary outcome (IHCA) was identified via a resuscitation code. Patients presented as OHCA or without any blood testing were excluded. Nonrandom splitting strategy based on different location was used to divide the dataset into the training (one urban and two suburban hospitals) and testing cohort (one urban and one suburban hospital) at around 2-to-1 ratio. Three supervised ML models were trained and performances were evaluated and compared with the National Early Warning Score (NEWS) by the area under the receiver operating characteristic curve (AUC). Results: We included 1,485 records for analysis. Of them, 190 (12.8%) developed IHCA. Of the constructed ML models, Random Forest outperformed the others with the best AUC result (0.930, 95% CI: 0.896-0.958), followed by Gradient Boosting (0.929, 95% CI: 0.891-0.959) and Extra Trees classifier (0.909, 95% CI: 0.875-0.943). All constructed ML models performed significantly better than by using the NEWS scoring system (AUC: 0.787, 95% CI: 0.725-0.840). The top six important features selected were age, oxygen saturation at triage, and lab data of APTT, lactic acid, and LDH. Conclusions: The ML approach showed excellent discriminatory performance to identify IHCA for patients with COVID-19 and suspected pneumonia. It has the potential to save more life or provide end-of-life decision making if successfully implemented in the EMR system.
Identifying and addressing health inequalities in asthma care
Authors: Dermot Ryan, Ian Sabroe
Journal: European Respiratory Journal (2021)

In this issue of the European Respiratory Journal , Håkansson et al. [1] describe the existence of inequalities affecting asthma care in the Danish healthcare system, demonstrating the persistence of the inverse care law of health first described by Hart [2] 50 years ago. This states that resources and opportunities to receive care are concentrated most in those areas that need them least. Their findings are striking because of the widespread perceptions that Scandinavian-style tax and spend systems generate high investment in social support, healthcare and wellbeing, and yet significant health inequalities still exist here. Whilst increasing levels of disease severity should prompt more referrals to specialist care, Håkansson et al. [1] show that referral for expert asthma support still happens far too infrequently, and that the chances of referral are affected by four main domains of age, gender, employment status and educational attainment, as well as proximity to major centres of care, confirming that even when financial barriers to care are minimised, inverse care persists [3]. Socioeconomic factors are also important to consider in the diagnosis and assessment of asthma and prejudice referral to specialist care <https://bit.ly/2UvzNPZ>
In ACS, de-escalation of DAPT reduces bleeding and does not increase ischemic events vs. other DAPT strategies
Authors: Ameenathul M. Fawzy, Gregory Y.H. Lip
Journal: Annals of Internal Medicine (2021)

ACP Journal ClubDecember 2021In ACS, de-escalation of DAPT reduces bleeding and does not increase ischemic events vs. other DAPT strategiesAmeenathul M. Fawzy, MB, Gregory Y.H. Lip, MDAmeenathul M. Fawzy, MBLiverpool Heart & Chest Hospital, Liverpool, England, UK (A.M.F., G.Y.L.)Search for more papers by this author, Gregory Y.H. Lip, MDLiverpool Heart & Chest Hospital, Liverpool, England, UK (A.M.F., G.Y.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ202112210-138 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationShoji S, Kuno T, Fujisaki T, et al. De-escalation of dual antiplatelet therapy in patients with acute coronary syndromes. J Am Coll Cardiol. 2021;78:763-77. https://pubmed.ncbi.nlm.nih.gov/34275697Clinical Impact RatingsGIM/FP/GP: Cardiology: Reference1. Kim HS, Kang J, Hwang D, et al. Prasugrel-based de-escalation of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (HOST-REDUCE-POLYTECH-ACS): an open-label, multicentre, non-inferiority randomised trial. Lancet. 2020;396:1079-89. [PMID: 32882163] Google Scholar Author, Article, and Disclosure InformationAffiliations: Liverpool Heart & Chest Hospital, Liverpool, England, UK (A.M.F., G.Y.L.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-7323.This article was published at Annals.org on 7 December 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics December 2021Volume 174, Issue 12Page: JC138 ePublished: 7 December 2021 Issue Published: December 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...