tbuckley/cabot-search huggingface dataset:
THE ALLEGED INCREASE OF INSANITY.
Journal: JAMA (2006)

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
Interferon-stimulated gene 15 pathway is a novel mediator of endothelial dysfunction and aneurysms development in angiotensin II infused mice through increased oxidative stress
Authors: María González-Amor, Ana B García-Redondo, Inmaculada Jorge, Guillermo Zalba, Martina Becares, María J Ruiz-Rodríguez, Cristina Rodríguez, Hugo Bermeo, Raquel Rodrigues-Díez, Francisco J Rios, Augusto C Montezano, Jose Martínez-González, Jesús Vázquez, Juan Miguel Redondo, Rhian M Touyz, Susana Guerra, Mercedes Salaices, Ana M Briones
Journal: Cardiovascular Research (2021)

Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that induces a reversible post-translational modification (ISGylation) and can also be secreted as a free form. ISG15 plays an essential role as host-defence response to microbial infection; however, its contribution to vascular damage associated with hypertension is unknown.Bioinformatics identified ISG15 as a mediator of hypertension-associated vascular damage. ISG15 expression positively correlated with systolic and diastolic blood pressure and carotid intima-media thickness in human peripheral blood mononuclear cells. Consistently, Isg15 expression was enhanced in aorta from hypertension models and in angiotensin II (AngII)-treated vascular cells and macrophages. Proteomics revealed differential expression of proteins implicated in cardiovascular function, extracellular matrix and remodelling, and vascular redox state in aorta from AngII-infused ISG15-/- mice. Moreover, ISG15-/- mice were protected against AngII-induced hypertension, vascular stiffness, elastin remodelling, endothelial dysfunction, and expression of inflammatory and oxidative stress markers. Conversely, mice with excessive ISGylation (USP18C61A) show enhanced AngII-induced hypertension, vascular fibrosis, inflammation and reactive oxygen species (ROS) generation along with elastin breaks, aortic dilation, and rupture. Accordingly, human and murine abdominal aortic aneurysms showed augmented ISG15 expression. Mechanistically, ISG15 induces vascular ROS production, while antioxidant treatment prevented ISG15-induced endothelial dysfunction and vascular remodelling.ISG15 is a novel mediator of vascular damage in hypertension through oxidative stress and inflammation.
Association Between Systemic Inflammation and Individual Symptoms of Depression: A Pooled Analysis of 15 Population-Based Cohort Studies
Authors: Philipp Frank, Markus Jokela, G. David Batty, Dorina Cadar, Andrew Steptoe, Mika Kivimäki
Journal: American Journal of Psychiatry (2021)

Evidence from anti-inflammatory drug trials for the treatment of depression has been inconsistent. This may be ascribed to the differing symptom-specific effects of inflammation. Accordingly, the authors explored the associations between systemic inflammation and an array of individual symptoms of depression across multiple studies.This random-effects pooled analysis included 15 population-based cohorts and 56,351 individuals age 18 years and older. Serum or plasma concentrations of C-reactive protein (CRP) and interleukin-6 (IL-6) were measured at baseline. Using validated self-report measures, 24 depressive symptoms were ascertained in 15 cross-sectional studies, and, in seven cohorts, were also assessed at follow-up (mean follow-up period, 3.2 years).The prevalence of depressive symptoms ranged from 1.1% (suicidal ideation) to 21.5% (sleep problems). In cross-sectional analyses, higher concentrations of CRP were robustly associated with an increased risk of experiencing four physical symptoms (changes in appetite, felt everything was an effort, loss of energy, sleep problems) and one cognitive symptom (little interest in doing things). These associations remained after adjustment for sociodemographic variables, behavioral factors, and chronic conditions; in sex- and age-stratified analyses; in longitudinal analyses; when using IL-6 as the inflammatory marker of interest; in depressed individuals; and after excluding chronically ill individuals. For four exclusively emotional symptoms (bothered by things, hopelessness about the future, felt fearful, life had been a failure), the overall evidence was strongly against an association with inflammation.These findings suggest symptom-specific rather than generalized effects of systemic inflammation on depression. Future trials exploring anti-inflammatory treatment regimens for depression may benefit from targeting individuals presenting with symptom profiles characterized by distinct inflammation-related physical and cognitive symptoms.
Scan-based competing death risk model for re-evaluating lung cancer computed tomography screening eligibility
Authors: Anton Schreuder, Colin Jacobs, Nikolas Lessmann, Mireille J.M. Broeders, Mario Silva, Ivana Išgum, Pim A. de Jong, Michel M. van den Heuvel, Nicola Sverzellati, Mathias Prokop, Ugo Pastorino, Cornelia M. Schaefer-Prokop, Bram van Ginneken
Journal: European Respiratory Journal (2021)

A baseline computed tomography (CT) scan for lung cancer (LC) screening may reveal information indicating that certain LC screening participants can be screened less, and instead require dedicated early cardiac and respiratory clinical input. We aimed to develop and validate competing death (CD) risk models using CT information to identify participants with a low LC risk and a high CD risk.Participant demographics and quantitative CT measures of LC, cardiovascular disease and chronic obstructive pulmonary disease were considered for deriving a logistic regression model for predicting 5-year CD risk using a sample from the National Lung Screening Trial (n=15 000). Multicentric Italian Lung Detection data were used to perform external validation (n=2287).Our final CD model outperformed an external pre-scan model (CD Risk Assessment Tool) in both the derivation (area under the curve (AUC) 0.744 (95% CI 0.727-0.761) and 0.677 (95% CI 0.658-0.695), respectively) and validation cohorts (AUC 0.744 (95% CI 0.652-0.835) and 0.725 (95% CI 0.633-0.816), respectively). By also taking LC incidence risk into consideration, we suggested a risk threshold where a subgroup (6258/23 096 (27%)) was identified with a number needed to screen to detect one LC of 216 (versus 23 in the remainder of the cohort) and ratio of 5.41 CDs per LC case (versus 0.88). The respective values in the validation cohort subgroup (774/2287 (34%)) were 129 (versus 29) and 1.67 (versus 0.43).Evaluating both LC and CD risks post-scan may improve the efficiency of LC screening and facilitate the initiation of multidisciplinary trajectories among certain participants.
An audit on the diagnosis of primary CNS lymphoma
Authors: Dorothy Joe, Lucia Yin, Shireen Kassam, Katia Cikurel, Jose-Pedro Lavrador, Francesco Vergani, Richard Gullan, Ranjeev Bhangoo, Keyoumars Ashkan, Gerald Finnerty
Journal: Neuro-Oncology (2021)

Abstract Aims Primary central nervous system lymphoma (PCNSL) is a rare form of non–Hodgkin lymphoma with exclusive manifestations in the central nervous system, leptomeninges and eyes. It forms around 5% of all primary brain tumours. It is an aggressive tumour which has a poor prognosis if left untreated. It is imperative that diagnosis is made timely so treatment can be started promptly. Therefore, we performed an audit looking into the speed of diagnostic process of PCNSL in our tertiary Neuro–oncology Unit. Method Single-centre retrospective review of PCNSL cases referred to a tertiary Neuro–Oncology Unit over a six month period from June to November 2020. Results A total of 1309 cases were discussed in the Neuro–oncology MDT meeting over the study period. Fourteen cases (6 male, 8 female; median age [range] 66 [59–83] years) were identified as highly likely PCNSL. Neuroimaging suggested PCNSL as the likely diagnosis in twelve patients. Twelve patients were started on steroids after CT or MRI brain scans. Nine patients had a surgical target and proceeded to have diagnostic brain biopsy. Two patients had different working diagnoses and three patients were deemed unsuitable for brain surgery. One patient required repeat brain biopsy. A tissue diagnosis was made in twelve patients. One patient deteriorated rapidly and one patient had a brain lesion that was deemed too high risk for surgery. The median time between neuroimaging and biopsy was 25 days. The median time taken from first investigation to the pathological confirmation of PCNSL was 36 days (range 6–86 days). Conclusion The chief reason for delay in diagnosis of PCNSL was that patients were started on steroids before diagnostic investigations were completed. Steroids caused the brain lesions to become smaller or disappear. Accordingly, time was needed to allow withdrawal of steroids before diagnostic investigations could be repeated. Diagnostic delays may have been exacerbated by logistical issues associated with COVID–19. We propose that there needs to be greater awareness of how early introduction of steroids can markedly delay the diagnosis of PCNSL.
Perspectives on the role of brown adipose tissue in human body temperature and metabolism
Authors: Camilla Scheele
Journal: Cell Reports Medicine (2021)

In this Backstory, Camilla Scheele shares the journey of her group's research on human brown adipose tissue leading up to the study of winter swimmers' thermoregulation and energy expenditure (https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(21)00266-4) appearing in this issue of Cell Reports Medicine.
Reduced-Dose vs High-Dose Glucocorticoids Added to Rituximab and Remission Induction in ANCA-Associated Vasculitis
Authors: Zhijuan Kang, Zhihui Li
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
Dendritic cell based imminotherapy using BCG-cell wall skeleton in collaboration with chemotherapy: Unbelievably effective for acute myelocytic leukemia and small cell lung cancer
Authors: Akira Hayashi
Journal: Cancer Research (2007)

1855  It is well known that the use of conventional immuno-suppressive agents is incompatible with immunotherapy, and that immunotherapy should be performed with priority to the protection and maintenance of the patients9 immunity. Among many malignant tumors, acute myelocytic leukemia (AML) and small cell lung cancer (SCLC) are especially sensitive for chemotherapy. However their mortalities still remain very high.  Since the introduction of born marrow transplantation (BMT), the mortality of AML has been fairly improved, but BMT depends on various worrisome conditions, such as donor selection, clean room, age limit, high expense, etc.  As shown in the Table, the patients (cases 1 to 7) were treated with dendritic cell-based immunotherapy (DCI) using BCG-cell wall skeleton (BCG-CWS) alone (A. Hayashi, Immunology 2004, E718C6062, 365-368), after they were induced into the complete remission (CR) with chemotherapy. They are all alive in disease-free state, including case 1 who had DCI just after relapse, regardless of age limit (cases 3, 5, 6 and 7). Complete cure can be expected as in case 1 and 2. But the patients who had had multiple induction chemotherapies (cases 8 and 9) and had failed in BMTall died . So, DCI using BCG-CWS should be used as soon as possible just after CR induction before BMT.  As for SCLC, very close to AML, the patients were treated with DCI alone after they were induced into the complete response (CR) with chemotherapy. All 6 patients with limited disease (LD) are alive, of whom 2 more than 7 years. However, of 19 with extensive disease (ED), 17 patients in the relapsed or partial response (PR) state died in less than 2 years, but 2 patients in CR state were alive more than 4 years (one of them is still alive in disease-free state now).
Human stem cell-derived thymic epithelial cells enhance human T-cell development in a xenogeneic thymus
Authors: Rafael Gras-Peña, Nichole M. Danzl, Mohsen Khosravi-Maharlooei, Sean R. Campbell, Amanda E. Ruiz, Christopher A. Parks, William Meng Suen Savage, Markus A. Holzl, Debanjana Chatterjee, Megan Sykes
Journal: Journal of Allergy and Clinical Immunology (2021)
P45.04 Phase II Study of Brigatinib in ROS1 Positive Non-Small Cell Lung Cancer (NSCLC) Patients Previously Treated with Crizotinib: Barossa Cohort 2
Authors: J. Sakakibara-Konishi, S. Niho, H. Daga, H. Tanaka, Y. Goto, K. Ohashi, R. Toyozawa, M. Kodani, T. Takahashi, Y. Hattori, M. Morise, T. Ikeda, S. Matsumoto, K. Yoh, S. Nomura, K. Goto
Journal: Journal of Thoracic Oncology (2021)
OA12.01 Genomic and Immune Cell Landscape of Response to Chemo-Immunotherapy in Malignant Pleural Mesothelioma
Authors: N. Niknafs, P. Forde, M. Lanis, Z. Belcaid, K. Smith, Z. Sun, A. Balan, J. White, C. Cherry, A. Shivakumar, X. Shao, H. Kindler, T. Purcell, R. Santana-Davila, A. Dudek, H. Borghaei, P. Illei, V. Velculescu, R. Karchin, J. Brahmer, S. Ramalingam, V. Anagnostou
Journal: Journal of Thoracic Oncology (2021)
Abstract 16700: Mineralocorticoid Receptor Antagonist Utilization in Eligible Patients Post St-elevation Myocardial Infarction
Authors: Hamed Nazzari, Krishnan Ramanathan, Carolyn Taylor, Marc Deyell, Jasmine Grewal, Jonathan Tang, Wendy Largy, Michele Perry-Arnesen, Graham Wong, Mustafa Toma
Journal: Circulation (2015)

Background: Mineralocorticoid receptor antagonists (MRAs) have been shown to reduce the morbidity and mortality in patients with reduced left ventricular ejection fraction (LVEF) post myocardial infarction (MI). Canadian guidelines recommend a MRA in patients post MI with an LVEF of ≤40% and documented heart failure or diabetes before hospital discharge, in the absence of any contraindications. We sought to examine if discrepancies between guideline-based therapy and actual prescribing rates exists in the use of MRAs in acute ST-elevation myocardial infarction (STEMI) patients. Methods: Retrospective analysis of utilization rates of MRAs in eligible patients enrolled in the Vancouver Coastal Health Authority STEMI database between October 2007 and October 2014. Inclusion criteria were based on the EPHESUS trial, which included an LVEF &lt;40% and documented heart failure or history of diabetes. Patients on dialysis or with a serum Cr &gt;221 were excluded. Results: 2583 patients had a STEMI during the study period. 192 (7.4%) patients were determined to be eligible for MRA prescription at discharge, 32 were excluded due missing discharge prescription information. Of the remaining 160 patients, the mean age was 67.9, 71.3% were male, 72.5% had an anterior MI and the mean LVEF was 30.4%. During hospitalization 51.6% had clinical evidence of HF and 21.3% were diagnosed with cardiogenic shock. PCI was performed in 75.6% of those eligible and 11.3% underwent CABG, 11.9% were medically managed and 1.25% underwent thrombolysis as a final revascularization strategy. On discharge 98% were on ASA, 81.3% on a second anti-platelet agent, 96% were on a beta-blocker, 75.6% were on an ACEi, 15.6% were on an ARB, 99.4% were on a statin. Only 22 (13.8%) of eligible patients were discharged on an MRA. No significant clinical difference existed amongst those that received an MRA compared to those that did not. Conclusions: Despite a Class IA recommendation for the use of MRAs in this patient population, our study demonstrates that the majority of patients are not prescribed an MRA after STEMI. This demonstrates a large care gap between evidence based guidelines and clinical practice. The reasons for this discrepancy in practice patterns are unclear and will be the focus of further study.
Alanine aminotransferase during treatment predicts long-term survival in patients with autoimmune hepatitis type 1
Authors: Maaike Biewenga, Xavier Verhelst, Martine Baven-Pronk, Hein Putter, Aad P. Van den Berg, Isabelle Colle, Jeoffrey Schouten, Filip Sermon, Christophe Van Steenkiste, Hans Van Vlierberghe, Adriaan J. Van der Meer, Bart Van Hoek
Journal: Hepatology (2020)
84TiP Predictive value of exosomes for therapy response in resectable/borderline resectable pancreatic cancer patients
Authors: I.M. Cazacu, V.M. Croitoru, D. Paul, E. Popa, I. Matei, C. Gheorghe, V. Herlea, M. Diculescu, D. Bogdan, I. Sandra, I-M. Gramaticu, N.I. Luca, I.M. Dinu, S. Alexandrescu, A. Sorop, A.E. Croitoru, S. Dima, I. Popescu, D. Lyden
Journal: Annals of Oncology (2021)
P64.02 EMERGE 402 Phase 4 Observational Study: Safety and Outcomes in Patients With SCLC Receiving Treatment With Lurbinectedin
Authors: R. Hanvesakul, A. Boccuti, J. Meyer, B. Rengarajan, A. Wu, D. Chakrabarti, W. Li
Journal: Journal of Thoracic Oncology (2021)
Enhanced IL-2 in early life limits the development of TFH and protective antiviral immunity
Authors: Chloe J. Pyle, Lucia Labeur-Iurman, Helen T. Groves, Franz Puttur, Clare M. Lloyd, John S. Tregoning, James A. Harker
Journal: The Journal of Experimental Medicine (2021)

T follicular helper cell (TFH)-dependent antibody responses are critical for long-term immunity. Antibody responses are diminished in early life, limiting long-term protective immunity and allowing prolonged or recurrent infection, which may be important for viral lung infections that are highly prevalent in infancy. In a murine model using respiratory syncytial virus (RSV), we show that TFH and the high-affinity antibody production they promote are vital for preventing disease on RSV reinfection. Following a secondary RSV infection, TFH-deficient mice had significantly exacerbated disease characterized by delayed viral clearance, increased weight loss, and immunopathology. TFH generation in early life was compromised by heightened IL-2 and STAT5 signaling in differentiating naive T cells. Neutralization of IL-2 during early-life RSV infection resulted in a TFH-dependent increase in antibody-mediated immunity and was sufficient to limit disease severity upon reinfection. These data demonstrate the importance of TFH in protection against recurrent RSV infection and highlight a mechanism by which this is suppressed in early life.
Core Cross‐Linked Polymeric Micelles for Specific Iron Delivery: Inducing Sterile Inflammation in Macrophages (Adv. Healthcare Mater. 19/2021)
Authors: Tobias A. Bauer, Natalie K. Horvat, Oriana Marques, Sara Chocarro, Christina Mertens, Silvia Colucci, Sascha Schmitt, Luca M. Carrella, Svenja Morsbach, Kaloian Koynov, Federico Fenaroli, Peter Blümler, Michaela Jung, Rocio Sotillo, Matthias W. Hentze, Martina U. Muckenthaler, Matthias Barz
Journal: Advanced Healthcare Materials (2021)

Iron Metabolism In article number 2100385 by Matthias W. Hentze, Martina U. Muckenthaler, Matthias Barz, and co-workers, core cross-linked micelles based on polypept(o)ides are designed for specific delivery of iron to macrophages that trigger sterile inflammation. Iron recognition leads to feedback mechanisms for preferred cell uptake, inducing macrophage activation. The approach abolishes undesired immune tolerance unleashing the potential of iron as a therapeutic agent.
P47.03 Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met+ Advanced Non-Small Cell Lung Cancer: Stage 2
Authors: J. Goldman, F. Moiseenko, I. Cicin, H. Horinouchi, E. Filippova, J. Bar, S. Lu, P. Tomasini, C. Ocampo, D. Sullivan, D. Maag, M. Motwani, J. Jin, D.R. Camidge
Journal: Journal of Thoracic Oncology (2021)
The SARS-CoV-2 main protease Mpro causes microvascular brain pathology by cleaving NEMO in brain endothelial cells
Authors: Jan Wenzel, Josephine Lampe, Helge Müller-Fielitz, Raphael Schuster, Marietta Zille, Kristin Müller, Markus Krohn, Jakob Körbelin, Linlin Zhang, Ümit Özorhan, Vanessa Neve, Julian U. G. Wagner, Denisa Bojkova, Mariana Shumliakivska, Yun Jiang, Anke Fähnrich, Fabian Ott, Valentin Sencio, Cyril Robil, Susanne Pfefferle, Florent Sauve, Caio Fernando Ferreira Coêlho, Jonas Franz, Frauke Spiecker, Beate Lembrich, Sonja Binder, Nina Feller, Peter König, Hauke Busch, Ludovic Collin, Roberto Villaseñor, Olaf Jöhren, Hermann C. Altmeppen, Manolis Pasparakis, Stefanie Dimmeler, Jindrich Cinatl, Klaus Püschel, Matija Zelic, Dimitry Ofengeim, Christine Stadelmann, François Trottein, Ruben Nogueiras, Rolf Hilgenfeld, Markus Glatzel, Vincent Prevot, Markus Schwaninger
Journal: Nature Neuroscience (2021)

Abstract Coronavirus disease 2019 (COVID-19) can damage cerebral small vessels and cause neurological symptoms. Here we describe structural changes in cerebral small vessels of patients with COVID-19 and elucidate potential mechanisms underlying the vascular pathology. In brains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals and animal models, we found an increased number of empty basement membrane tubes, so-called string vessels representing remnants of lost capillaries. We obtained evidence that brain endothelial cells are infected and that the main protease of SARS-CoV-2 (M pro ) cleaves NEMO, the essential modulator of nuclear factor-κB. By ablating NEMO, M pro induces the death of human brain endothelial cells and the occurrence of string vessels in mice. Deletion of receptor-interacting protein kinase (RIPK) 3, a mediator of regulated cell death, blocks the vessel rarefaction and disruption of the blood–brain barrier due to NEMO ablation. Importantly, a pharmacological inhibitor of RIPK signaling prevented the M pro -induced microvascular pathology. Our data suggest RIPK as a potential therapeutic target to treat the neuropathology of COVID-19.