tbuckley/cabot-search huggingface dataset:
Radiation Delay Is Okay, but Where Is the Evidence?—Reply
Authors: Edward Christopher Dee, Anthony V. D’Amico, Vinayak Muralidhar
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Effects of dietary restriction on neuroinflammation in neurodegenerative diseases
Authors: Luigi Fontana, Laura Ghezzi, Anne H. Cross, Laura Piccio
Journal: The Journal of Experimental Medicine (2021)

Recent and accumulating work in experimental animal models and humans shows that diet has a much more pervasive and prominent role than previously thought in modulating neuroinflammatory and neurodegenerative mechanisms leading to some of the most common chronic central nervous system (CNS) diseases. Chronic or intermittent food restriction has profound effects in shaping brain and peripheral metabolism, immunity, and gut microbiome biology. Interactions among calorie intake, meal frequency, diet quality, and the gut microbiome modulate specific metabolic and molecular pathways that regulate cellular, tissue, and organ homeostasis as well as inflammation during normal brain aging and CNS neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, among others. This review discusses these findings and their potential application to the prevention and treatment of CNS neuroinflammatory diseases and the promotion of healthy brain aging.
SARS-CoV-2 antibody testing for estimating COVID-19 prevalence in the population
Authors: Thomas Vogl, Sigal Leviatan, Eran Segal
Journal: Cell Reports Medicine (2021)

Reliable antibody testing against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to uncover the population-wide spread of coronavirus disease 2019 (COVID-19), which is critical for making informed healthcare and economic decisions. Here we review different types of antibody tests available for SARS-CoV-2 and their application for population-scale testing. Biases because of varying test accuracy, results of ongoing large-scale serological studies, and use of antibody testing for monitoring development of herd immunity are summarized. Although current SARS-CoV-2 antibody testing efforts have generated valuable insights, the accuracy of serological tests and the selection criteria for the tested cohorts need to be evaluated carefully.
Intravascular Ultrasound Virtual Histology Derived Thin Cap Fibroatheroma: Now You See It, Now You Don't…⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Efthymios N. Deliargyris
Journal: Journal of the American College of Cardiology (2010)
Characterization of NT‐proBNP in a large cohort of COVID‐19 patients
Authors: Juan Caro‐Codón, Juan R. Rey, Antonio Buño, Angel M. Iniesta, Sandra O. Rosillo, Sergio Castrejon‐Castrejon, Laura Rodriguez‐Sotelo, Luis A. Martinez, Irene Marco, Carlos Merino, Lorena Martin‐Polo, Jose M. Garcia‐Veas, Marcel Martinez‐Cossiani, Luis Gonzalez‐Valle, Alicia Herrero, Esteban López‐de‐Sa, Jose L. Merino
Journal: European Journal of Heart Failure (2021)
Cholesterol alters mitophagy by impairing optineurin recruitment and lysosomal clearance in Alzheimer’s disease
Authors: Vicente Roca-Agujetas, Elisabet Barbero-Camps, Cristina de Dios, Petar Podlesniy, Xenia Abadin, Albert Morales, Montserrat Marí, Ramon Trullàs, Anna Colell
Journal: Molecular Neurodegeneration (2021)

Abstract Background Emerging evidence indicates that impaired mitophagy-mediated clearance of defective mitochondria is a critical event in Alzheimer’s disease (AD) pathogenesis. Amyloid-beta (Aβ) metabolism and the microtubule-associated protein tau have been reported to regulate key components of the mitophagy machinery. However, the mechanisms that lead to mitophagy dysfunction in AD are not fully deciphered. We have previously shown that intraneuronal cholesterol accumulation can disrupt the autophagy flux, resulting in low Aβ clearance. In this study, we examine the impact of neuronal cholesterol changes on mitochondrial removal by autophagy. Methods Regulation of PINK1-parkin-mediated mitophagy was investigated in conditions of acute (in vitro) and chronic (in vivo) high cholesterol loading using cholesterol-enriched SH-SY5Y cells, cultured primary neurons from transgenic mice overexpressing active SREBF2 (sterol regulatory element binding factor 2), and mice of increasing age that express the amyloid precursor protein with the familial Alzheimer Swedish mutation (Mo/HuAPP695swe) and mutant presenilin 1 (PS1-dE9) together with active SREBF2. Results In cholesterol-enriched SH-SY5Y cells and cultured primary neurons, high intracellular cholesterol levels stimulated mitochondrial PINK1 accumulation and mitophagosomes formation triggered by Aβ while impairing lysosomal-mediated clearance. Antioxidant recovery of cholesterol-induced mitochondrial glutathione (GSH) depletion prevented mitophagosomes formation indicating mitochondrial ROS involvement. Interestingly, when brain cholesterol accumulated chronically in aged APP-PSEN1-SREBF2 mice the mitophagy flux was affected at the early steps of the pathway, with defective recruitment of the key autophagy receptor optineurin (OPTN). Sustained cholesterol-induced alterations in APP-PSEN1-SREBF2 mice promoted an age-dependent accumulation of OPTN into HDAC6-positive aggresomes, which disappeared after in vivo treatment with GSH ethyl ester (GSHee). The analyses in post-mortem brain tissues from individuals with AD confirmed these findings, showing OPTN in aggresome-like structures that correlated with high mitochondrial cholesterol levels in late AD stages. Conclusions Our data demonstrate that accumulation of intracellular cholesterol reduces the clearance of defective mitochondria and suggest recovery of the cholesterol homeostasis and the mitochondrial scavenging of ROS as potential therapeutic targets for AD.
Real-time monitoring shows substantial excess all-cause mortality during second wave of COVID-19 in Europe, October to December 2020
Authors: Sarah K. Nørgaard, Lasse S. Vestergaard, Jens Nielsen, Lukas Richter, Daniela Schmid, Natalia Bustos, Toon Braye, Maria Athanasiadou, Theodore Lytras, Gleb Denissov, Tatjana Veideman, Oskari Luomala, Teemu Möttönen, Anne Fouillet, Céline Caserio-Schönemann, Matthias an der Heiden, Helmut Uphoff, Kassiani Gkolfinopoulou, Janos Bobvos, Anna Paldy, Naama Rotem, Irene Kornilenko, Lisa Domegan, Joan O’Donnell, Francesca De Donato, Matteo Scortichini, Patrick Hoffmann, Telma Velez, Kathleen England, Neville Calleja, Liselotte van Asten, Lenny Stoeldraijer, Richard A White, Trine H Paulsen, Susana P da Silva, Ana P Rodrigues, Petra Klepac, Metka Zaletel, Mario Fafangel, Amparo Larrauri, Inmaculada León, Ahmed Farah, Ilias Galanis, Christoph Junker, Damir Perisa, Mary Sinnathamby, Nick Andrews, Mark G O'Doherty, David Irwin, Sharon Kennedy, Jim McMenamin, Cornelia Adlhoch, Nick Bundle, Pasi Penttinen, Jukka Pukkila, Richard Pebody, Tyra G Krause, Kåre Mølbak
Journal: Eurosurveillance (2021)

The European monitoring of excess mortality for public health action (EuroMOMO) network monitors weekly excess all-cause mortality in 27 European countries or subnational areas. During the first wave of the coronavirus disease (COVID-19) pandemic in Europe in spring 2020, several countries experienced extraordinarily high levels of excess mortality. Europe is currently seeing another upsurge in COVID-19 cases, and EuroMOMO is again witnessing a substantial excess all-cause mortality attributable to COVID-19.
Systematic analysis of enhancer regulatory circuit perturbation driven by copy number variations in malignant glioma
Authors: Jun Xiao, Xiaoyan Jin, Chunlong Zhang, Haozhe Zou, Zhenghong Chang, Nan Han, Xia Li, Yunpeng Zhang, Yongsheng Li
Journal: Theranostics (2021)

Background: Enhancers are emerging regulatory regions controlling gene expression in diverse cancer types. However, the functions of enhancer regulatory circuit perturbations driven by copy number variations (CNVs) in malignant glioma are unclear. Therefore, we aimed to investigate the comprehensive enhancer regulatory perturbation and identify potential biomarkers in glioma. Results: We performed a meta-analysis of the enhancer centered regulatory circuit perturbations in 683 gliomas by integrating CNVs, gene expression, and transcription factors (TFs) binding. We found widespread CNVs of enhancers during glioma progression, and CNVs were associated with the perturbations of enhancer activities. In particular, the degree of perturbations for amplified enhancers was much greater accompanied by the glioma malignant progression. In addition, CNVs and enhancers cooperatively regulated the expressions of cancer-related genes. Genome-wide TF binding profiles revealed that enhancers were pervasively regulated by TFs. A network-based analysis of TF-enhancer-gene regulatory circuits revealed a core TF-gene module (58 interactions including seven genes and 14 TFs) that was associated survival of patients with glioma (p < 0.001). Finally, we validated this prognosis-associated TF-gene regulatory module in an independent cohort. In summary, our analyses provided new molecular insights for enhancer-centered transcriptional perturbation in glioma therapy. Conclusion: Integrative analysis revealed enhancer regulatory perturbations in glioma and also identified a network module that was associated with patient survival, thereby providing novel insights into enhancer-centered cancer therapy.
NOD2 drives early IL-33–dependent expansion of group 2 innate lymphoid cells during Crohn’s disease–like ileitis
Authors: Carlo De Salvo, Kristine-Ann Buela, Brecht Creyns, Daniele Corridoni, Nitish Rana, Hannah L. Wargo, Chiara L. Cominelli, Peter G. Delaney, Alexander Rodriguez-Palacios, Fabio Cominelli, Séverine Vermeire, Theresa T. Pizarro
Journal: Journal of Clinical Investigation (2021)

Innate lymphoid cells (ILCs) are enriched at barrier surfaces, including the gastrointestinal tract. While most studies have focused on the balance between pathogenic group 1 ILCs (ILC1s) and protective ILC3s in maintaining gut homeostasis and during chronic intestinal inflammation, such as Crohn's disease (CD), less is known regarding ILC2s. Using an established murine model of CD-like ileitis, i.e., the SAMP1/YitFc (SAMP) mouse strain, we showed that ILC2s, compared with ILC1s and ILC3s, were increased within draining mesenteric lymph nodes and ilea of SAMP versus AKR (parental control) mice early, during the onset of disease. Gut-derived ILC2s from CD patients versus healthy controls were also increased and expanded, similarly to ILC1s, in greater proportion compared with ILC3s. Importantly, we report that the intracellular bacteria–sensing protein, nucleotide-binding oligomerization domaining–containing protein 2, encoded by Nod2, the first and strongest susceptibility gene identified for CD, promoted ILC2 expansion, which was dramatically reduced in SAMP mice lacking NOD2 and in SAMP mice raised under germ-free conditions. Furthermore, these effects occurred through a mechanism involving the IL-33/ST2 ligand-receptor pair. Collectively, our results indicate a functional link between NOD2 and ILC2s, regulated by the IL-33/ST2 axis, that mechanistically may contribute to early events leading to CD pathogenesis.
Diagnostic and Predictive Role of DLL3 Expression in Gastroenteropancreatic Neuroendocrine Neoplasms
Authors: Chiara Liverani, Alberto Bongiovanni, Laura Mercatali, Federica Pieri, Chiara Spadazzi, Giacomo Miserocchi, Giandomenico Di Menna, Flavia Foca, Sara Ravaioli, Alessandro De Vita, Claudia Cocchi, Giulio Rossi, Federica Recine, Toni Ibrahim
Journal: Endocrine Pathology (2021)
Lenalidomide-Epoetin Alfa Versus Lenalidomide Monotherapy in Myelodysplastic Syndromes Refractory to Recombinant Erythropoietin
Authors: Alan F. List, Zhuoxin Sun, Amit Verma, John M. Bennett, Rami S. Komrokji, Kathy McGraw, Jaroslaw Maciejewski, Jessica K. Altman, Puneet S. Cheema, David F. Claxton, Selina M. Luger, Ryan J. Mattison, Timothy R. Wassenaar, Andrew S. Artz, Charles A. Schiffer, Mark R. Litzow, Martin S. Tallman
Journal: Journal of Clinical Oncology (2021)

PURPOSE Impaired response to erythropoietin underlies ineffective erythropoiesis and anemia in myelodysplastic syndromes (MDS). We investigated whether treatment with lenalidomide (LEN), which augments erythropoietin receptor signaling in vitro, can restore and improve hemoglobin response to epoetin (EPO) alfa in patients with lower-risk, non-del(5q) MDS who have anemia that is refractory to or have low probability of benefit from treatment with recombinant erythropoietin. METHODS In a phase III, US intergroup trial, we randomly assigned patients to receive either LEN and EPO alfa or LEN alone following stratification by serum erythropoietin concentration and prior erythropoietin treatment. RESULTS A total of 195 evaluable patients were randomly assigned: 99 patients to the LEN-EPO alfa cohort and 96 to LEN alone. After four cycles of treatment, the primary end point of major erythroid response (MER) was significantly higher (28.3%) with the combination compared with LEN alone (11.5%) ( P = .004). Among 136 patients who completed 16 weeks of study treatment, 38.9% and 15.6% achieved MER, respectively ( P = .004). Additionally, minor erythroid response was achieved in 18.2% and 20.8% of patients, for an overall erythroid response rate of 46.5% versus 32.3%. Among LEN nonresponders, 38 crossed over to the addition of EPO alfa with 10 patients (26.3%) achieving a MER. Responses to the combined treatment were highly durable with a median MER duration of 23.8 months compared with 13 months with LEN alone. CONCLUSION LEN restores sensitivity to recombinant erythropoietin in growth factor–insensitive, lower-risk, non-del(5q) MDS, to yield a significantly higher rate and duration of MER compared with LEN alone (funded by the National Cancer Institute; E2905 ClinicalTrials.gov identifier: NCT02048813 ).
Functional impairment during post-acute COVID-19 phase: Preliminary finding in 56 patients
Authors: E. Zampogna, G.B. Migliori, R. Centis, F. Cherubino, C. Facchetti, D. Feci, G. Palmiotto, P. Pignatti, L. Saderi, G. Sotgiu, A. Spanevello, M. Zappa, D. Visca
Journal: Pulmonology (2021)
(Oligo)metastasis as a Spectrum of Disease
Authors: Stanley I. Gutiontov, Sean P. Pitroda, Phuoc T. Tran, Ralph R. Weichselbaum
Journal: Cancer Research (2021)

Abstract Cancer metastasis is the leading cause of cancer-related mortality, and most patients with metastases from solid tumors have historically been considered incurable. Here, we discuss the evolution of our understanding of the oligometastatic state with an emphasis on the view that cancer metastasis represents a spectrum of disease. We highlight several recently published prospective clinical trials demonstrating improvements in cancer-specific outcomes with the utilization of metastasis-directed local therapies. We discuss biological aspects of oligometastases, including genetic, epigenetic, and immune determinants of the metastatic spectrum. Finally, we propose future considerations regarding clinical trial design for patients with oligometastatic disease.
Abstract 14177: Saddle Pulmonary Embolism Treatment Patterns in the United States
Authors: Joshua B Goldberg, Ansab Haider, Aaqib H Malik, Syed Zaid
Journal: Circulation (2019)

Introduction: Saddle PE (SPE) refers to a large clot extending from the main pulmonary artery (PA) to the left and right PA and are often associated with hemodynamic instability. There is controver...
Cutaneous immune‐related adverse events in patients with melanoma treated with checkpoint inhibitors
Authors: A. Gault, A.E. Anderson, R. Plummer, C. Stewart, A.G. Pratt, N. Rajan
Journal: British Journal of Dermatology (2021)

Checkpoint inhibitor (CPI) therapy has vastly improved long-term outcomes in metastatic malignant melanoma (MMM). Therapy takes the form of monoclonal antibody infusions that target immune cell checkpoint proteins, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and programmed death 1/programmed death ligand 1 (PD1/PDL1). Cutaneous immune-related adverse effects (IrAEs) are frequent in patients with MMM treated with CPIs. Our aim was to review the clinical presentations of cutaneous IrAEs associated with CPI therapy in adult patients with MMM. We carried out a literature review of clinical trials, case series and case reports of patients with melanoma and those with other cancers treated with anti-CTLA4, anti-PD1/PDL1, or a combination of these therapies. Diverse clinical presentations of cutaneous IrAEs are recognized. Anti-CTLA4 therapy has a higher associated rate of cutaneous IrAEs than anti-PD1/PDL1 therapies. Low-grade cutaneous IrAEs are common and are usually managed supportively while continuing CPI therapy. Delayed presentations arising after established use of CPIs can make therapy-associated cutaneous IrAEs difficult to distinguish from coincidental dermatological disease. Vitiligo-like depigmentation is a good prognostic indicator of outcome in patients with melanoma. Life-threatening adverse events including toxic epidermal necrolysis are rare. The identification of predictive biomarkers that highlight patients at risk of life-threatening IrAEs remains an unmet need. The involvement of dermatologists in the multidisciplinary assessment of cutaneous IrAEs is increasingly pertinent in the management and care of CPI-treated patients with melanoma.
Exercise training in COPD: muscle O<sub>2</sub> transport plasticity
Authors: Ryan M. Broxterman, Peter D. Wagner, Russell S. Richardson
Journal: European Respiratory Journal (2021)

Both convective oxygen (O2) transport to, and diffusive transport within, skeletal muscle are markedly diminished in patients with COPD. However, it is unknown how these determinants of peak muscle O2 uptake (V'mO2peak) respond to exercise training in patients with COPD. Therefore, the purpose of this study was to assess the plasticity of skeletal muscle O2 transport determinants of V'mO2peak in patients with COPD.Adaptations to 8 weeks of single-leg knee-extensor exercise training were measured in eight patients with severe COPD (mean±sem forced expiratory volume in 1 s (FEV1) 0.9±0.1 L) and eight healthy, well-matched controls. Femoral arterial and venous blood samples, and thermodilution-assessed leg blood flow were used to determine muscle O2 transport and utilisation at maximal exercise pre- and post-training.Training increased V'mO2peak in both COPD (by ∼26% from 271±29 to 342±35 mL·min-1) and controls (by ∼32% from 418±37 to 553±41 mL·min-1), restoring V'mO2peak in COPD to only ∼80% of pre-training control V'mO2peak Muscle diffusive O2 transport increased similarly in both COPD (by ∼38% from 6.6±0.9 to 9.1±0.9 mL·min-1·mmHg-1) and controls (by ∼36% from 10.4±0.7 to 14.1±0.8 mL·min-1·mmHg-1), with the patients reaching ∼90% of pre-training control values. In contrast, muscle convective O2 transport increased significantly only in controls (by ∼26% from 688±57 to 865±69 mL·min-1), leaving patients with COPD (438±45 versus 491±51 mL·min-1) at ∼70% of pre-training control values.While muscle diffusive O2 transport in COPD was largely restored by exercise training, V'mO2peak remained constrained by limited plasticity in muscle convective O2 transport.
Abstract 16969: Improved Cardiac Function in Gravin Knockout Mice Following Acute Beta-Adrenergic Stimulation
Authors: Ashley N Guillory, Cori S Wijaya, Andrea C Diaz Diaz, Xing Yin, Bradley K McConnell
Journal: Circulation (2012)

Gravin is an A kinase anchoring protein that facilitates the action of protein kinase A (PKA) by targeting the kinase as well as other signaling molecules to the β2-adrenergic receptor (β2-AR). PKA...
Evaluation of Patient Willingness to Adopt Remote Digital Monitoring for Diabetes Management
Authors: Theodora Oikonomidi, Philippe Ravaud, Emmanuel Cosson, Victor Montori, Viet Thi Tran
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Patients will decide whether to adopt remote digital monitoring (RDM) for diabetes by weighing its health benefits against the inconvenience it may cause. <h3>Objective</h3> To identify the minimum effectiveness patients report they require to adopt 36 different RDM scenarios. <h3>Design, Setting, and Participants</h3> This survey study was conducted among adults with type 1 or type 2 diabetes living in 30 countries from February to July 2019. <h3>Exposures</h3> Survey participants assessed 3 randomly selected scenarios from a total of 36. Scenarios described different combinations of digital monitoring tools (glucose, physical activity, food monitoring), duration and feedback loops (feedback in consultation vs real-time telefeedback by a health care professional or by artificial intelligence), and data handling modalities (by a public vs private company), reflecting different degrees of RDM intrusiveness in patients' personal lives. <h3>Main Outcomes and Measures</h3> Participants assessed the minimum effectiveness for 2 diabetes-related outcomes (reducing hypoglycemic episodes and preventing ophthalmologic complications) for which they would adopt each RDM (from much less effective to much more effective than their current monitoring). <h3>Results</h3> Of 1577 individuals who consented to participate, 1010 (64%; 572 [57%] women, median [interquartile range] age, 51 [37-63] years, 524 [52%] with type 1 diabetes) assessed at least 1 vignette. Overall, 2860 vignette assessments were collected. In 1025 vignette assessments (36%), participants would adopt RDM only if it was much more effective at reducing hypoglycemic episodes compared with their current monitoring; in 1835 assessments (65%), participants would adopt RDM if was just as or somewhat more effective. The main factors associated with required effectiveness were food monitoring (β = 0.32; SE, 0.12;<i>P</i> = .009), real-time telefeedback by a health care professional (β = 0.49; SE, 0.15;<i>P</i> = .001), and perceived intrusiveness (β = 0.36; SE, 0.06;<i>P</i> &lt; .001). Minimum required effectiveness varied among participants; 34 of 36 RDM scenarios (94%) were simultaneously required to be just as or less effective by at least 25% of participants and much more effective by at least 25% of participants. Results were similar for participant assessments of scenarios regarding the prevention of ophthalmologic complications. <h3>Conclusions and Relevance</h3> The findings of this study suggest that patients require greater health benefits to adopt more intrusive RDM modalities, food monitoring, and real-time feedback by a health care professional. Patient monitoring devices should be designed to be minimally intrusive. The variability in patients' requirements points to a need for shared decision-making.