tbuckley/cabot-search huggingface dataset:
Splenectomy for primary immune thrombocytopenia revisited in the era of thrombopoietin receptor agonists: New insights for an old treatment
Authors: Arthur Mageau, Louis Terriou, Mikael Ebbo, Odile Souchaud‐Debouverie, Corentin Orvain, Julie Graveleau, Jean‐Christophe Lega, Marc Ruivard, Jean‐François Viallard, Stéphane Cheze, Antoine Dossier, Bernard Bonnotte, Antoinette Perlat, Delphine Gobert, Nathalie Costedoat‐Chalumeau, Pierre‐Yves Jeandel, Amandine Dernoncourt, Marc Michel, Bertrand Godeau, Thibault Comont
Journal: American Journal of Hematology (2021)

Although splenectomy is still considered the most effective curative treatment for immune thrombocytopenia (ITP), its use has significantly declined in the last decade, especially since the approval of thrombopoietin receptor agonists (TPO-RAs). The main objective of the study was to determine whether splenectomy was still as effective nowadays, particularly for patients with failure to respond to TPO-RAs. Our secondary objective was to assess, among patients who relapsed after splenectomy, the pattern of response to treatments used before splenectomy. This multicenter retrospective study involved adults who underwent splenectomy for ITP in France from 2011 to 2020. Response status was defined according to international criteria. We included 185 patients, 100 (54.1%) and 135 (73.0%) patients had received TPO-RAs and/or rituximab before the splenectomy. The median follow-up after splenectomy was 39.2 months [16.5-63.0]. Overall, 144 (77.8%) patients had an initial response and 23 (12.4%) experienced relapse during follow-up, for an overall sustained response of 65.4%, similar to that observed in the pre-TPO-RA era. Among patients who received at least one TPO-RA or rituximab before splenectomy, 92/151 (60.9%) had a sustained response. Six of 13 (46%) patients with previous lack of response to both TPO-RAs and rituximab had a sustained response to splenectomy. Among patients with relapse after splenectomy, 13/21 (61.2%) patients responded to one TPO-RAs that failed before splenectomy. In conclusion, splenectomy is still a relevant option for treating adult primary ITP not responding to TPO-RAs and rituximab. Patients with lack of response or with relapse after splenectomy should be re-challenged with TPO-RAs.
T cell receptor–targeted immunotherapeutics drive selective in vivo HIV- and CMV-specific T cell expansion in humanized mice
Authors: Mengyan Li, Scott J. Garforth, Kaitlyn E. O’Connor, Hang Su, Danica M. Lee, Alev Celikgil, Rodolfo J. Chaparro, Ronald D. Seidel, R. Brad Jones, Ravit Arav-Boger, Steven C. Almo, Harris Goldstein
Journal: Journal of Clinical Investigation (2021)

To delineate the in vivo role of different costimulatory signals in activating and expanding highly functional virus-specific cytotoxic CD8+ T cells, we designed synTacs, infusible biologics that recapitulate antigen-specific T cell activation signals delivered by antigen-presenting cells. We constructed synTacs consisting of dimeric Fc-domain scaffolds linking CD28- or 4-1BB–specific ligands to HLA-A2 MHC molecules covalently tethered to HIV- or CMV-derived peptides. Treatment of HIV-infected donor PBMCs with synTacs bearing HIV- or CMV-derived peptides induced vigorous and selective ex vivo expansion of highly functional HIV- and/or CMV-specific CD8+ T cells, respectively, with potent antiviral activities. Intravenous injection of HIV- or CMV-specific synTacs into immunodeficient mice intrasplenically engrafted with donor PBMCs markedly and selectively expanded HIV-specific (32-fold) or CMV-specific (46-fold) human CD8+ T cells populating their spleens. Notably, these expanded HIV- or CMV-specific CD8+ T cells directed potent in vivo suppression of HIV or CMV infections in the humanized mice, providing strong rationale for consideration of synTac-based approaches as a therapeutic strategy to cure HIV and treat CMV and other viral infections. The synTac platform flexibility supports facile delineation of in vivo effects of different costimulatory signals on patient-derived virus-specific CD8+ T cells, enabling optimization of individualized therapies, including HIV cure strategies.
GPs overwhelmingly reject health secretary’s “rescue plan” for general practice
Authors: Elisabeth Mahase
Journal: BMJ (2021)

GPs have overwhelmingly rejected Sajid Javid’s rescue package for general practice, as 93% of those surveyed by the BMA said that it was an unacceptable response to the current crisis.

Almost 3500 GPs in England took part in the poll, and the BMA described the findings as the “clearest articulation yet” that GPs do not believe that the plan will go any way towards tackling the growing pressures on general practice staff and patients.

Javid, England’s secretary for health and social care, announced his plan …
P52.03 Efficacy of Sotorasib in KRAS p.G12C-Mutated NSCLC with Stable Brain Metastases: A Post-Hoc Analysis of CodeBreaK 100
Authors: S. Ramalingam, F. Skoulidis, R. Govindan, V. Velcheti, B. Li, B. Besse, G. Dy, D. Kim, M. Schuler, M. Vincent, F. Wilson, J. Park, J. Gutierrez, Q. Tran, S. Jones, J. Wolf
Journal: Journal of Thoracic Oncology (2021)
The prevalence and clinical associations of ultrasound measures of congestion in patients at risk of developing heart failure
Authors: Joseph J. Cuthbert, Pierpaolo Pellicori, Rachel Flockton, Anna Kallvikbacka‐Bennett, Javed Khan, Alan S. Rigby, Nicolas Girerd, Faiez Zannad, John G.F. Cleland, Andrew L. Clark
Journal: European Journal of Heart Failure (2021)
Spatially resolved analysis of the T cell immune contexture in lung cancer-associated brain metastases
Authors: Benjamin Y Lu, Richa Gupta, Adam Aguirre-Ducler, Nicole Gianino, Hailey Wyatt, Matthew Ribeiro, Veronica L Chiang, Joseph N Contessa, Adebowale J Adeniran, Lucia B Jilaveanu, Harriet M Kluger, Kurt A Schalper, Sarah B Goldberg
Journal: Journal for ImmunoTherapy of Cancer (2021)

Despite unique genetic alterations within brain metastases (BrMs) and an immunologically distinct surrounding microenvironment, the composition and functional properties of tumor-infiltrating lymphocytes within BrM remain largely unexplored. In particular, the expression of coinhibitory receptors, such as programmed cell death 1 (PD-1), T cell immunoglobulin mucin receptor 3 (TIM-3), and lymphocyte activation gene 3 (LAG-3), within BrMs is unknown. Using multiplexed quantitative immunofluorescence (QIF), this study evaluates the localized expression of PD-L1, level and functional profile of major T cell subsets, and coinhibitory receptors within lung cancer-associated BrMs and primary lung tumors. Clinicopathologically annotated samples from 95 patients with lung cancer between 2002 and 2015 were represented in a tissue microarray format. Spatially resolved and multiplexed QIF was used to evaluate PD-L1 protein, phenotype markers for major T cell subsets (CD3, CD4, CD8, and FOXP3), cell-localized activation and proliferation markers (granzyme B and Ki67), and coinhibitory receptors (PD-1, LAG-3, and TIM-3). The signal for each marker was measured in marker-selected tissue compartments, and associations between marker levels, tumor location, and major clinicopathological variables were studied. In total, 41 primary lung tumors and 65 BrMs were analyzed, including paired samples from 11 patients. Levels of tumor PD-L1 expression were comparable between BrMs and primary lung tumors. BrMs had significantly lower levels of all T cell subsets relative to primary lung tumors, and T cells in BrMs displayed lower levels of granzyme B than primary lesions. PD-1, TIM-3, and LAG-3 levels in CD3 + T-cells were also significantly lower in BrMs. Marker expression in patients with paired samples from BrMs and primary lung tumors showed comparable results. High CD3 + T-cells, as well as high levels of TIM-3 and LAG-3 in CD3 + T-cells, were associated with longer overall survival in BrMs but not primary lung tumors. Lung cancer-associated BrMs display lower T cell infiltration, markers of cytolytic function, and immune regulatory signals than primary lung tumors. Despite these differences, high TIM-3 and high LAG-3 expressions in CD3 + T-cells were associated with longer survival. These features are accompanied by comparable levels of PD-L1 protein expression compared with primary lung tumors. These results highlight unique aspects of the tumor immune microenvironment within the brain and provide further support for intracranially focused therapies.
Implantable vs Prolonged External Electrocardiographic Monitoring for Atrial Fibrillation Detection in Patients With Ischemic Stroke—Reply
Authors: Brian H. Buck, Michael D. Hill, Derek V. Exner
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
Real-world Cardiovascular Outcomes Associated With Degarelix vs Leuprolide for Prostate Cancer Treatment
Authors: Joshua D. Wallach, Yihong Deng, Rozalina G. McCoy, Sanket S. Dhruva, Jeph Herrin, Alyssa Berkowitz, Eric C. Polley, Kenneth Quinto, Charu Gandotra, William Crown, Peter Noseworthy, Xiaoxi Yao, Nilay D. Shah, Joseph S. Ross, Timothy D. Lyon
Journal: JAMA Network Open (2021)

<h3>Importance</h3> With a growing interest in the use of real-world evidence for regulatory decision-making, it is important to understand whether real-world data can be used to emulate the results of randomized clinical trials. <h3>Objective</h3> To use electronic health record and administrative claims data to emulate the ongoing PRONOUNCE trial (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease). <h3>Design, Setting, and Participants</h3> This retrospective, propensity-matched cohort study included adult men with a diagnosis of prostate cancer and cardiovascular disease who initiated either degarelix or leuprolide between December 24, 2008, and June 30, 2019. Participants were commercially insured individuals and Medicare Advantage beneficiaries included in a large US administrative claims database. <h3>Exposures</h3> Degarelix or leuprolide. <h3>Main Outcomes and Measures</h3> The primary end point was time to first occurrence of a major adverse cardiovascular event (MACE), defined as death due to any cause, myocardial infarction, or stroke, analogous to the PRONOUNCE trial. Secondary end points were time to death due to any cause, myocardial infarction, stroke, and angina. Cox proportional hazards regression was used to evaluate primary and secondary end points. <h3>Results</h3> A total of 32 172 men initiated degarelix or leuprolide for prostate cancer; of them, 9490 (29.5%) had cardiovascular disease, and 7800 (24.2%) met the PRONOUNCE trial eligibility criteria and were included in this study. Overall, 165 participants (2.1%) were Asian, 1390 (17.8%) were Black, 663 (8.5%) were Hispanic, and 5258 (67.4%) were White. The mean (SD) age was 74.4 (7.4) years. Among 2226 propensity score–matched patients, no significant difference was observed in the risk of MACE for patients taking degarelix vs those taking leuprolide (10.18 vs 8.60 events per 100 person-years; hazard ratio [HR], 1.18; 95% CI, 0.86-1.61). Degarelix was associated with a higher risk of death from any cause (HR, 1.48; 95% CI, 1.01-2.18) but not of myocardial infarction (HR, 1.16; 95% CI, 0.60-2.25), stroke (HR, 0.92; 95% CI, 0.45-1.85), or angina (HR, 1.36; 95% CI, 0.43-4.27). <h3>Conclusions and Relevance</h3> In this emulation of a clinical trial of men with cardiovascular disease undergoing treatment for prostate cancer, degarelix was not associated with a lower risk of cardiovascular events than leuprolide. Comparison of these data with PRONOUNCE trial results, when published, will help enhance our understanding of the appropriate role of using real-world data to emulate clinical trials.
Evaluation and Treatment of Febrile Ulceronecrotic Mucha-Habermann Disease With Ruxolitinib and Tocilizumab as Guided by Cytokine Profile
Authors: Richard Wu, Ashley DiLorenzo, Michael Lotke, Kaiane Habeshian, Joel Brooks, Michael D. Keller, A. Yasmine Kirkorian
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
Ordered assembly of the cytosolic RNA-sensing MDA5-MAVS signaling complex via binding to unanchored K63-linked poly-ubiquitin chains
Authors: Bin Song, Yun Chen, Xin Liu, Fei Yuan, Eddie Yong Jun Tan, Yixuan Lei, Ning Song, Yinqi Han, Bruce D Pascal, Patrick R Griffin, Cheng Luo, Bin Wu, Dahai Luo, Jie Zheng
Journal: Immunity (2021)
Abstract 892: The Forkhead Transcription Factor, FOXO3a, is a Negative Regulator of Angiogenic Immediate Early Gene, CYR61, Leading to Inhibition of Vascular Smooth Muscle Cells Proliferation and Neointimal Hyperplasia
Authors: Hae-young Lee, Seock-Won Youn, Hyun-Jae Kang, Joo-hee Zo, Myung-A Kim, Dong-Ju Choi, Cheol-Ho Kim, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Journal: Circulation (2006)

Objective: Cysteine-rich angiogenic protein 61 (CYR61, CCN1) is an immediate early gene expressed in vascular smooth muscle cells (VSMCs) on growth factor stimulation and its expression has been as...
Modular Evolution of the <i>Drosophila</i> Metabolome
Authors: Benjamin R Harrison, Jessica M Hoffman, Ariana Samuelson, Daniel Raftery, Daniel E L Promislow
Journal: Molecular Biology and Evolution (2021)

Abstract Comparative phylogenetic studies offer a powerful approach to study the evolution of complex traits. Although much effort has been devoted to the evolution of the genome and to organismal phenotypes, until now relatively little work has been done on the evolution of the metabolome, despite the fact that it is composed of the basic structural and functional building blocks of all organisms. Here we explore variation in metabolite levels across 50 My of evolution in the genus Drosophila, employing a common garden design to measure the metabolome within and among 11 species of Drosophila. We find that both sex and age have dramatic and evolutionarily conserved effects on the metabolome. We also find substantial evidence that many metabolite pairs covary after phylogenetic correction, and that such metabolome coevolution is modular. Some of these modules are enriched for specific biochemical pathways and show different evolutionary trajectories, with some showing signs of stabilizing selection. Both observations suggest that functional relationships may ultimately cause such modularity. These coevolutionary patterns also differ between sexes and are affected by age. We explore the relevance of modular evolution to fitness by associating modules with lifespan variation measured in the same common garden. We find several modules associated with lifespan, particularly in the metabolome of older flies. Oxaloacetate levels in older females appear to coevolve with lifespan, and a lifespan-associated module in older females suggests that metabolic associations could underlie 50 My of lifespan evolution.
Indications for medical antibiotic prophylaxis and potential targets for antimicrobial stewardship intervention: a narrative review
Authors: Petros Ioannou, Stamatis Karakonstantis, Jeroen Schouten, Tomislav Kostyanev, Esmita Charani, Vera Vlahovic-Palcevski, Diamantis P. Kofteridis
Journal: Clinical Microbiology and Infection (2021)
NHS must eliminate waste to build greener health system, say medical colleges
Authors: Bryan Christie
Journal: BMJ (2021)

Action is needed to eliminate waste in the health system if the NHS is to make its contribution to global efforts to combat climate change, say health professionals in Scotland.

The Academy of Medical Royal Colleges and Faculties in Scotland called for greater efforts to build a greener health system, in a statement published in advance of the COP26 United Nations climate change conference opening in Glasgow on 31 October.1 …
DNA methylation-calling tools for Oxford Nanopore sequencing: a survey and human epigenome-wide evaluation
Authors: Yang Liu, Wojciech Rosikiewicz, Ziwei Pan, Nathaniel Jillette, Ping Wang, Aziz Taghbalout, Jonathan Foox, Christopher Mason, Martin Carroll, Albert Cheng, Sheng Li
Journal: Genome biology (2021)

Nanopore long-read sequencing technology greatly expands the capacity of long-range, single-molecule DNA-modification detection. A growing number of analytical tools have been developed to detect DNA methylation from nanopore sequencing reads. Here, we assess the performance of different methylation-calling tools to provide a systematic evaluation to guide researchers performing human epigenome-wide studies.We compare seven analytic tools for detecting DNA methylation from nanopore long-read sequencing data generated from human natural DNA at a whole-genome scale. We evaluate the per-read and per-site performance of CpG methylation prediction across different genomic contexts, CpG site coverage, and computational resources consumed by each tool. The seven tools exhibit different performances across the evaluation criteria. We show that the methylation prediction at regions with discordant DNA methylation patterns, intergenic regions, low CG density regions, and repetitive regions show room for improvement across all tools. Furthermore, we demonstrate that 5hmC levels at least partly contribute to the discrepancy between bisulfite and nanopore sequencing. Lastly, we provide an online DNA methylation database ( https://nanome.jax.org ) to display the DNA methylation levels detected by nanopore sequencing and bisulfite sequencing data across different genomic contexts.Our study is the first systematic benchmark of computational methods for detection of mammalian whole-genome DNA modifications in nanopore sequencing. We provide a broad foundation for cross-platform standardization and an evaluation of analytical tools designed for genome-scale modified base detection using nanopore sequencing.
P48.02 Real-World Data of Dacomitinib in EGFR TKI-Naïve Patients With Advanced Epidermal Growth Factor Receptor-positive Non-small Cell Lung Cancer
Authors: J. Zhang, Y. Wang, Y. Yao, X. Li, Z. Liu, X. Hou, X. Hao, Y. Liu, L. Wang, L. Liang, X. Li, P. Xing, J. Li
Journal: Journal of Thoracic Oncology (2021)
Longitudinal Connectome Analyses following Low-Grade Glioma Neurosurgery: Implications for Cognitive Rehabilitation
Authors: Anujan Poologaindran, Mike Hart, Tom Santarius, Stephen Price, Rohit Sinha, Mike Sughrue, Yaara Erez, Rafael Romero-Garcia, John Suckling
Journal: Neuro-Oncology (2021)

Abstract Aims Low-grade gliomas (LGG) slowly grow and infiltrate the brain's network architecture (the connectome). Unlike strokes that acutely damage the connectome, LGGs intricately remodel it, leading to varying deficits in executive function (i.e. attention, concentration, working memory). By longitudinally mapping the “mesoscale” architecture of the connectome, we may begin to systematically accelerate domain-general cognitive rehabilitation in LGG patients. In this study, we pursued the following aims: 1) track cognitive and connectome trajectories following LGG surgery, 2) determine optimal time period for cognitive rehabilitation, and 3) distinguish patients with perioperative predictors of long-term cognitive deficits (&amp;gt;1 year). Method With MRI and cognitive data from n=629 individuals across the lifespan, we first validated the structural, functional, and topological relevance of the multiple demand (MD) system for higher-order cognition. Next, in n=17 patients undergoing glioma surgery, we longitudinally acquired connectome and cognitive data: pre-surgery, post-surgery Day 1, Month 3, &amp; 12. We assessed how glioma infiltration, surgery, and rehabilitation affected MD system trajectories at the single-subject level. Deploying transcriptomic and graph theoretical analyses, we tested if perioperative connectome modularity can accurately distinguish long-term cognitive trajectories. Results Controlling for age and sex, the MD system’s multi-scale architecture in health was positively associated with higher-order cognition (Catell’s fluid intelligence). Pre-operative glioma infiltration into the MD system was negatively associated with the number of long-term cognitive deficits (OCS-Bridge cognitive battery), suggesting its functional reorganisation. Mixed-effects modelling demonstrated the resilience of the MD system to infiltration and resection, while the early post-operative period was critical for effective neurorehabilitation. Graph analyses revealed perioperative modularity can distinguish patients with long-term cognitive deficits at one-year follow-up. Transcriptomic analyses of inter-module connector hubs revealed increased gene expression for mitochondrial metabolism and synaptic plasticity. Conclusion This is the first serial functional mapping of LGG patient trajectories for domain-general cognition. By assessing the mesoscale architecture, we demonstrate how connectomics can help overcome the intrinsic heterogeneity in LGG patients and predict long-term rehabilitation trajectories. We discuss how to identify neurobiologically-grounded personalised targets for 'interventional neurorehabilitation' following LGG surgery.
OA19.01 Prospective Study of Lung Cancer Screening Criteria: USPSTF2013 vs PLCOm2012 – International Lung Screening Trial (ILST) Results
Authors: M. Tammemagi, R. Myers, M. Ruparel, A. Tremblay, S. Atkar-Khattra, H. Marshall, F. Brims, A. Mcwilliams, P. Fogarty, E. Stone, R. Manser, K. Canfell, K.P. Lim, A. Rosell, M. Weber, J. Yee, J. Mayo, C. Berg, D. Lam, S. Janes, K. Fong, S. Lam
Journal: Journal of Thoracic Oncology (2021)
Maternal Metabolic Disease and Offspring Neurodevelopment—An Evolving Public Health Crisis
Authors: Andrea G. Edlow
Journal: JAMA Network Open (2021)

Raquel Nogueira Avelar e Silva, PhD; Yongfu Yu, PhD; Zeyan Liew, PhD; Anne Vested, PhD; Henrik Toft Sørensen, MD, DMSc; Jiong Li, PhD