tbuckley/cabot-search huggingface dataset:
Intratumoral virotherapy with 4-1BBL armed modified vaccinia Ankara eradicates solid tumors and promotes protective immune memory
Authors: Maria Hinterberger, Raphael Giessel, Giovanna Fiore, Fabienne Graebnitz, Barbara Bathke, Sonia Wennier, Paul Chaplin, Ignacio Melero, Mark Suter, Henning Lauterbach, Pedro Berraondo, Hubertus Hochrein, José Medina-Echeverz
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Human cancers are extraordinarily heterogeneous in terms of tumor antigen expression, immune infiltration and composition. A common feature, however, is the host's inability to mount potent immune responses that prevent tumor growth effectively. Often, naturally primed CD8+ T cells against solid tumors lack adequate stimulation and efficient tumor tissue penetration due to an immune hostile tumor microenvironment.Methods To address these shortcomings, we cloned tumor-associated antigens (TAA) and the immune-stimulatory ligand 4-1BBL into the genome of modified vaccinia Ankara (MVA) for intratumoral virotherapy.Results Local treatment with MVA-TAA-4-1BBL resulted in control of established tumors. Intratumoral injection of MVA localized mainly to the tumor with minimal leakage to the tumor-draining lymph node. In situ infection by MVA-TAA-4-1BBL triggered profound changes in the tumor microenvironment, including the induction of multiple proinflammatory molecules and immunogenic cell death. These changes led to the reactivation and expansion of antigen-experienced, tumor-specific cytotoxic CD8+ T cells that were essential for the therapeutic antitumor effect. Strikingly, we report the induction of a systemic antitumor immune response including tumor antigen spread by local MVA-TAA-4-1BBL treatment which controlled tumor growth at distant, untreated lesions and protected against local and systemic tumor rechallenge. In all cases, 4-1BBL adjuvanted MVA was superior to MVA.Conclusion Intratumoral 4-1BBL-armed MVA immunotherapy induced a profound reactivation and expansion of potent tumor-specific CD8+ T cells as well as favorable proinflammatory changes in the tumor microenvironment, leading to elimination of tumors and protective immunological memory.
Hugh W Simpson
Authors: Robin Simpson
Journal: BMJ (2021)

Hugh W Simpson was an explorer (recipient of Polar and Mungo Park medals), mountaineer, accomplished skier, photographer, pioneer of breast cancer research, and international lecturer.

On graduating he secured the role of medical officer for the Falkland Islands Dependency Survey, and a mountain is named after him (Simpson Nunatak, 3822 ft, Trinity Peninsula). During these lengthy sledging trips, he researched stress by measuring eosinophils as a …
Identifying patients at risk of post-discharge complications related to COVID-19 infection
Authors: Jocelin Hall, Katherine Myall, Jodie L Lam, Thomas Mason, Bhashkar Mukherjee, Alex West, Amy Dewar
Journal: Thorax (2021)

SARS-CoV-2 infection is a multisystem disease with post-discharge sequelae. We report early follow-up data from one UK hospital of the initial 200 hospital inpatients with slow recovery from the condition. At 4 weeks post-discharge, 321/957 survivors (34%) had persistent symptoms. A structured outpatient clinical assessment protocol was designed, and outcomes from the first 200 patients seen 4-6 weeks post-discharge are presented here. In 80/200 (40%), we identified at follow-up a cardiorespiratory cause of breathlessness, including persistent parenchymal abnormality (64 patients), pulmonary embolism (four patients) and cardiac complications (eight patients). These findings occurred both in patients who had intensive care unit (ICU) admissions and those who had been managed on the ward, although patients requiring ICU admissions were more likely to have a significant cardiorespiratory cause found for their breathlessness, risk ratio 2.8 (95% CI 1.5 to 5.1).
Role of Glucose Transporter 1 in Graft-Versus-Host Disease and Graft-Versus-Tumor Effect
Authors: Ying Huang, Yiqun Jiao, Peijie Shi, Xiaoli Nie, Wei Huang, Michael Choi, Andrew N Macintyre, Amanda Nichols, Nancie J. MacIver, Nelson J. Chao, Jeffrey Rathmell, Benny J. Chen
Journal: Blood (2017)
Racial bias in pulse oximetry: more statistical detail may help tackle the problem
Authors: Keir E J Philip, Robert Tidswell, Charles McFadyen
Journal: BMJ (2021)

We were glad to see a news article1 highlighting research by Sjoding and colleagues2 which identifies a racial bias in pulse oximetry, with hypoxaemia identified less frequently in black people compared with white. The research is valuable, identifying an important matter; however, further details would aid clinical application of the findings.

Useful, additional, commonly used metrics absent from the paper include bias, precision, limits of agreement, and accuracy value. A …
Japan should aim to eliminate covid -19
Authors: Kazuki Shimizu, Yasuharu Tokuda, Kenji Shibuya
Journal: BMJ (2021)

Compared with other G7 countries, Japan has been relatively successful in mitigating the spread of covid-19. 1However, Japan has the second worst record in the Western Pacific region, with over 40 deaths per million population over the course of the crisis. 1 Japan entered a second state of emergency in January 2021 2 following an exponential rise in confirmed cases of covid-19. 1A clear, consistent exit strategy is now critical.Despite shortcomings in its early covid-19 response, 3 4 Japan failed to reflect sufficiently on lessons from the first wave, sticking instead to notions of exceptionalism.Unlike several countries in the region, Japan initially followed a hybrid of mitigation and suppression strategies, primarily focusing on symptomatic patients, controlling clusters, and seeking to find a way of living with the virus rather than eliminating it.However, a hasty resumption of social and economic activity after the first wave brought a resurgence of covid-19.
Impact of Type 1 Diabetes in the Developing Brain in Children: A Longitudinal Study
Authors: Nelly Mauras, Bruce Buckingham, Neil H. White, Eva Tsalikian, Stuart A. Weinzimer, Booil Jo, Allison Cato, Larry A. Fox, Tandy Aye, Ana Maria Arbelaez, Tamara Hershey, Michael Tansey, William Tamborlane, Lara C. Foland-Ross, Hanyang Shen, Kimberly Englert, Paul Mazaika, Matthew Marzelli, Allan L. Reiss
Journal: Diabetes Care (2021)

OBJECTIVE To assess whether previously observed brain and cognitive differences between children with type 1 diabetes and control subjects without diabetes persist, worsen, or improve as children grow into puberty and whether differences are associated with hyperglycemia. RESEARCH DESIGN AND METHODS One hundred forty-four children with type 1 diabetes and 72 age-matched control subjects without diabetes (mean ± SD age at baseline 7.0 ± 1.7 years, 46% female) had unsedated MRI and cognitive testing up to four times over 6.4 ± 0.4 (range 5.3–7.8) years; HbA1c and continuous glucose monitoring were done quarterly. FreeSurfer-derived brain volumes and cognitive metrics assessed longitudinally were compared between groups using mixed-effects models at 6, 8, 10, and 12 years. Correlations with glycemia were performed. RESULTS Total brain, gray, and white matter volumes and full-scale and verbal intelligence quotients (IQs) were lower in the diabetes group at 6, 8, 10, and 12 years, with estimated group differences in full-scale IQ of −4.15, −3.81, −3.46, and −3.11, respectively (P &amp;lt; 0.05), and total brain volume differences of −15,410, −21,159, −25,548, and −28,577 mm3 at 6, 8, 10, and 12 years, respectively (P &amp;lt; 0.05). Differences at baseline persisted or increased over time, and brain volumes and cognitive scores negatively correlated with a life-long HbA1c index and higher sensor glucose in diabetes. CONCLUSIONS Detectable changes in brain volumes and cognitive scores persist over time in children with early-onset type 1 diabetes followed longitudinally; these differences are associated with metrics of hyperglycemia. Whether these changes can be reversed with scrupulous diabetes control requires further study. These longitudinal data support the hypothesis that the brain is a target of diabetes complications in young children.
プログラヌリンはヒトアテローム性動脈硬化症性プラークに存在し,平滑筋細胞,内皮細胞,およびマクロファージからのIL-8分泌を減少する
Authors: Kojima Yoji, Ono Koh, Inoue Katsumi, Yoshida Yoshinori, Nakashima Yasuhiro, Nobuyoshi Masakiyo, Kita Toru, Kimura Takeshi, Tanaka Makoto
Journal: Circulation (2010)
Ubiquitin-Specific Protease 6 Functions as a Tumor Suppressor in Ewing Sarcoma through Immune Activation
Authors: Ian C. Henrich, Kanika Jain, Robert Young, Laura Quick, Jarrett M. Lindsay, Daniel H. Park, Andre M. Oliveira, Gerd A. Blobel, Margaret M. Chou
Journal: Cancer Research (2021)

Ewing sarcoma is the second most common pediatric bone cancer, with a 5-year survival rate for metastatic disease of only 20%. Recent work indicates that survival is strongly correlated with high levels of tumor-infiltrating lymphocytes (TIL), whose abundance is associated with IFN-inducible chemokines CXCL10 and CCL5. However, the tumor-intrinsic factors that drive chemokine production and TIL recruitment have not been fully elucidated. We previously showed that ubiquitin-specific protease 6 (USP6) directly deubiquitinates and stabilizes Jak1, thereby inducing an IFN signature in Ewing sarcoma cells. Here, we show that this gene set comprises chemokines associated with immunostimulatory, antitumorigenic functions, including CXCL10 and CCL5. USP6 synergistically enhanced chemokine production in response to exogenous IFN by inducing surface upregulation of IFNAR1 and IFNGR1. USP6-expressing Ewing sarcoma cells stimulated migration of primary human monocytes and T lymphocytes and triggered activation of natural killer (NK) cells in vitro. USP6 inhibited Ewing sarcoma xenograft growth in nude but not NSG mice and was accompanied by increased intratumoral chemokine production and infiltration and activation of NK cells, dendritic cells, and macrophages, consistent with a requirement for innate immune cells in mediating the antitumorigenic effects of USP6. High USP6 expression in patients with Ewing sarcoma was associated with chemokine production, immune infiltration, and improved survival. This work reveals a previously unrecognized tumor-suppressive function for USP6, which engenders an immunostimulatory microenvironment through pleiotropic effects on multiple immune lineages. This further raises the possibility that USP6 activity may be harnessed to create a "hot" tumor microenvironment in immunotherapy. SIGNIFICANCE: This study reveals a novel tumor-suppressive function for USP6 by inducing an immunostimulatory microenvironment, suggesting that USP6 activity may be exploited to enhance immunotherapy regimens.
Yolk sac, but not hematopoietic stem cell–derived progenitors, sustain erythropoiesis throughout murine embryonic life
Authors: Francisca Soares-da-Silva, Laina Freyer, Ramy Elsaid, Odile Burlen-Defranoux, Lorea Iturri, Odile Sismeiro, Perpétua Pinto-do-Ó, Elisa Gomez-Perdiguero, Ana Cumano
Journal: The Journal of Experimental Medicine (2021)

In the embryo, the first hematopoietic cells derive from the yolk sac and are thought to be rapidly replaced by the progeny of hematopoietic stem cells. We used three lineage-tracing mouse models to show that, contrary to what was previously assumed, hematopoietic stem cells do not contribute significantly to erythrocyte production up until birth. Lineage tracing of yolk sac erythromyeloid progenitors, which generate tissue resident macrophages, identified highly proliferative erythroid progenitors that rapidly differentiate after intra-embryonic injection, persisting as the major contributors to the embryonic erythroid compartment. We show that erythrocyte progenitors of yolk sac origin require 10-fold lower concentrations of erythropoietin than their hematopoietic stem cell-derived counterparts for efficient erythrocyte production. We propose that, in a low erythropoietin environment in the fetal liver, yolk sac-derived erythrocyte progenitors efficiently outcompete hematopoietic stem cell progeny, which fails to generate megakaryocyte and erythrocyte progenitors.
Cytosolic Phospholipase A2 (PLA2G4A) Polymorphisms Associated with Acute Urticaria/angioedema Induced by Nonsteroidal Anti-inflammatory Drugs
Authors: Raquel Jurado Escobar, Jose Triano-Cornejo, Inmaculada Doña, Natalia Pérez Sánchez, Gador Bogas Herrera, Joan Bartra, Jose Laguna, Maria Torres JaÃ©n, Jose Cornejo-Garcia
Journal: Journal of Allergy and Clinical Immunology (2021)
Follicular Papules in a Linear Distribution on a Child’s Face
Authors: Carolina Carvajal-Zuñiga, Javiera Jerez, Eduardo Rozas-Muñoz
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Human neurons from Christianson syndrome iPSCs reveal mutation-specific responses to rescue strategies
Authors: Sofia B. Lizarraga, Li Ma, Abbie M. Maguire, Laura I. van Dyck, Qing Wu, Qing Ouyang, Brian C. Kavanaugh, Dipal Nagda, Liane L. Livi, Matthew F. Pescosolido, Michael Schmidt, Shanique Alabi, Mara H. Cowen, Paul Brito-Vargas, Diane Hoffman-Kim, Ece D. Gamsiz Uzun, Avner Schlessinger, Richard N. Jones, Eric M. Morrow
Journal: Science Translational Medicine (2021)

Neurons from patient-derived iPSCs demonstrate mutation-specific responses to potential therapeutic strategies for Christianson syndrome.
Impact of immunization with pneumococcal conjugated vaccines on the aplicability of the diagnostic criteria for specific pneumococcal antibody deficiency
Authors: Daniela Navarrete-Cortés, David Rodriguez-Cabezas, María Cristina Mayol, Antonia Sánchez, Aileen Ferran, Nicole Silva, Constanza Silva, Teresa Quiroga, Katia Abarca, Rodrigo Hoyos
Journal: Journal of Allergy and Clinical Immunology (2021)
CNS fibroblasts form a fibrotic scar in response to immune cell infiltration
Authors: Cayce E. Dorrier, Dvir Aran, Ezekiel A. Haenelt, Ryan N. Sheehy, Kimberly K. Hoi, Lucija Pintarić, Yanan Chen, Carlos O. Lizama, Kelly M. Cautivo, Geoffrey A. Weiner, Brian Popko, Stephen P. J. Fancy, Thomas D. Arnold, Richard Daneman
Journal: Nature Neuroscience (2021)
COVID-19 Vaccination in Pregnant and Lactating Women
Authors: Emily H. Adhikari, Catherine Y. Spong
Journal: JAMA (2021)

Sivan Haia Perl, MD; Atara Uzan-Yulzari, MSc; Hodaya Klainer, BSc; Liron Asiskovich, MSc; Michal Youngster, MD; Ehud Rinott, BSc; Ilan Youngster, MD, MMSc
Abstract 15462: Anti-Arrhythmic Potential of Transendocardial CD34+ Cell Therapy in Patients With Chronic Heart Failure
Authors: Gregor Poglajen, Gregor Zemljic, Andraž Cerar, Martina Jaklic, Sabina Frljak, Bojan Vrtovec
Journal: Circulation (2018)

Background: Data from preclinial models suggest that cell therapy may be associated with antiarrythmic effects due to improved cell-to-cell coupling. Hypothesis: We sought to investigate potential ...
From organic and inorganic phosphates to valvular and vascular calcifications
Authors: Magnus Bäck, Jean-Baptiste Michel
Journal: Cardiovascular Research (2021)

Calcification of the arterial wall and valves is an important part of the pathophysiological process of peripheral and coronary atherosclerosis, aortic stenosis, ageing, diabetes, and chronic kidney disease. This review aims to better understand how extracellular phosphates and their ability to be retained as calcium phosphates on the extracellular matrix initiate the mineralization process of arteries and valves. In this context, the physiological process of bone mineralization remains a human model for pathological soft tissue mineralization. Soluble (ionized) calcium precipitation occurs on extracellular phosphates; either with inorganic or on exposed organic phosphates. Organic phosphates are classified as either structural (phospholipids, nucleic acids) or energetic (corresponding to phosphoryl transfer activities). Extracellular phosphates promote a phenotypic shift in vascular smooth muscle and valvular interstitial cells towards an osteoblast gene expression pattern, which provokes the active phase of mineralization. A line of defense systems protects arterial and valvular tissue calcifications. Given the major roles of phosphate in soft tissue calcification, phosphate mimetics, and/or prevention of phosphate dissipation represent novel potential therapeutic approaches for arterial and valvular calcification.
Cancer Care Under the Biden Administration
Authors: Stacie B. Dusetzina
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
Government to reverse Lansley reforms in major NHS shake up
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Key elements of the Health and Social Care Act 2012 are to be reversed in the biggest legislative shake up of the English health service in a decade.

A draft white paper,1 leaked to the website Health Policy Insight, outlines proposals to reverse major parts of former health secretary Andrew Lansley’s controversial reorganisation, including formally abolishing requirements to do with competition and competitive tendering in the NHS, and shifting control and decision making power back to Whitehall.

As The BMJ reported in December 2020,2 clinical commissioning groups, created in 2012, will be replaced by new larger statutory “integrated care …
Isobel Hilary Grant
Authors: Alison Grant, Myint Oo, Peter Morrell
Journal: BMJ (2021)

Isobel Hilary Grant (“Hilary”) was born in Edinburgh, the third child of two general practitioners in Carlisle. After education at Red Gables School in Carlisle and Malvern Girls’ College, she trained in medicine at Newnham College, Cambridge, (1945-8) and University College Hospital London (1948-51). She held house officer posts in Doncaster, Manchester, Southampton, and Elizabeth Garrett Anderson Hospital, London, then was a registrar in paediatrics in Manchester and King’s College Hospital, London. Between 1962 and 1966 she worked at University College Hospital, Ibadan, Nigeria, first as a senior registrar and then consultant in paediatrics.

On returning from Nigeria in 1966 Hilary was appointed consultant paediatrician in Teesside, one …
Androgen Receptor Splice Variant 7 Predicts Shorter Response in Patients with Metastatic Hormone-sensitive Prostate Cancer Receiving Androgen Deprivation Therapy
Authors: Heng Li, Yucong Zhang, Dong Li, Xin Ma, Kai Xu, Beichen Ding, Hongzhao Li, Zhize Wang, Wei Ouyang, Gongwei Long, Jin Zeng, Haoran Liu, Libin Yan, Yangjun Zhang, Zheng Liu, Wei Guan, Zhiquan Hu, Cong Liu, Jie Wan, Guoping Wang, Xiaoyong Pu, Minghui Zhang, Linlang Guo, Ruihua An, Jiping Qi, Aitao Guo, Zhangqun Ye, Jiumin Liu, Xu Zhang, Hua Xu
Journal: European Urology (2021)
Personal exposure to air pollution and respiratory health of COPD patients in London
Authors: Dimitris Evangelopoulos, Lia Chatzidiakou, Heather Walton, Klea Katsouyanni, Frank J. Kelly, Jennifer K. Quint, Roderic L. Jones, Benjamin Barratt
Journal: European Respiratory Journal (2021)

Previous studies have investigated the effects of air pollution on chronic obstructive pulmonary disease (COPD) patients using either fixed-site measurements or a limited number of personal measurements, usually for one pollutant and a short time period. These limitations may introduce bias and distort the epidemiological associations as they do not account for all the potential sources or the temporal variability of pollution.We used detailed information on individuals' exposure to various pollutants measured at fine spatiotemporal scale to obtain more reliable effect estimates. A panel of 115 patients was followed up for an average continuous period of 128 days carrying a personal monitor specifically designed for this project that measured temperature, nitrogen dioxide (NO2), ozone (O3), nitric oxide (NO), carbon monoxide (CO), and particulate matter with aerodynamic diameter <2.5 and <10 μm at 1-min time resolution. Each patient recorded daily information on respiratory symptoms and measured peak expiratory flow (PEF). A pulmonologist combined related data to define a binary variable denoting an "exacerbation". The exposure-response associations were assessed with mixed effects models.We found that gaseous pollutants were associated with a deterioration in patients' health. We observed an increase of 16.4% (95% CI 8.6-24.6%), 9.4% (95% CI 5.4-13.6%) and 7.6% (95% CI 3.0-12.4%) in the odds of exacerbation for an interquartile range increase in NO2, NO and CO, respectively. Similar results were obtained for cough and sputum. O3 was found to have adverse associations with PEF and breathlessness. No association was observed between particulate matter and any outcome.Our findings suggest that, when considering total personal exposure to air pollutants, mainly the gaseous pollutants affect COPD patients' health.