tbuckley/cabot-search huggingface dataset:
Designer Extracellular Vesicles Modulate Pro‐Neuronal Cell Responses and Improve Intracranial Retention
Authors: Lilibeth Ortega‐Pineda, Alec Sunyecz, Ana I. Salazar‐Puerta, Maria Angelica Rincon‐Benavides, Diego Alzate‐Correa, Amrita Lakshmi Anaparthi, Elizabeth Guilfoyle, Louisa Mezache, Heather L. Struckman, Silvia Duarte‐Sanmiguel, Binbin Deng, David W. McComb, Daniel J. Dodd, William R. Lawrence, Jordan Moore, Jingjing Zhang, Eduardo Reátegui, Rengasayee Veeraraghavan, M. Tyler Nelson, Daniel Gallego‐Perez, Natalia Higuita‐Castro
Journal: Advanced Healthcare Materials (2022)

Abstract Gene/oligonucleotide therapies have emerged as a promising strategy for the treatment of different neurological conditions. However, current methodologies for the delivery of neurogenic/neurotrophic cargo to brain and nerve tissue are fraught with caveats, including reliance on viral vectors, potential toxicity, and immune/inflammatory responses. Moreover, delivery to the central nervous system is further compounded by the low permeability of the blood brain barrier. Extracellular vesicles (EVs) have emerged as promising delivery vehicles for neurogenic/neurotrophic therapies, overcoming many of the limitations mentioned above. However, the manufacturing processes used for therapeutic EVs remain poorly understood. Here, we conducted a detailed study of the manufacturing process of neurogenic EVs by characterizing the nature of cargo and surface decoration, as well as the transfer dynamics across donor cells, EVs, and recipient cells. Neurogenic EVs loaded with Ascl1 , Brn2 , and Myt1l ( ABM ) are found to show enhanced neuron‐specific tropism, modulate electrophysiological activity in neuronal cultures, and drive pro‐neurogenic conversions/reprogramming. Moreover, murine studies demonstrate that surface decoration with glutamate receptors appears to mediate enhanced EV delivery to the brain. Altogether, the results indicate that ABM‐ loaded designer EVs can be a promising platform nanotechnology to drive pro‐neuronal responses, and that surface functionalization with glutamate receptors can facilitate the deployment of EVs to the brain.
Dynamic changes of CSF sPDGFRβ during ageing and AD progression and associations with CSF ATN biomarkers
Authors: Jun Wang, Dong-Yu Fan, Hui-Yun Li, Chen-Yang He, Ying-Ying Shen, Gui-Hua Zeng, Dong-Wan Chen, Xu Yi, Ya-Hui Ma, Jin-Tai Yu, Yan-Jiang Wang
Journal: Molecular Neurodegeneration (2022)

Abstract Background Loss of brain capillary pericyte is involved in the pathologies and cognitive deficits in Alzheimer’s disease (AD). The role of pericyte in early stage of AD pathogenesis remains unclear. Methods We investigated the dynamic changes of soluble platelet-derived growth factor receptor β (sPDGFRβ) in cerebrospinal fluid (CSF), a marker of brain pericyte injury, in transition from normal ageing to early AD in a cognitively unimpaired population aged 20 to 90 years. Association between sPDGFRβ and ATN biomarkers were analyzed. Results In lifetime, CSF sPDGFRβ continually increased since age of 20 years, followed by the increases of phosphorylated tau-181 (P-tau181) and total tau (T-tau) at the age of 22.2 years and 31.7 years, respectively; CSF Aβ42 began to decline since the age of 39.6 years, indicating Aβ deposition. The natural trajectories of biomarkers suggest that pericyte injury is an early event during transition from normal status to AD, even earlier than Aβ deposition. In AD spectrum, CSF sPDGFRβ was elevated in preclinical stage 2 and participants with suspected non-AD pathophysiologies. Additionally, CSF sPDGFRβ was positively associated with P-tau181 and T-tau independently of Aβ42, and significantly strengthened the effects of Aβ42 on P-tau181, suggesting that pericyte injury accelerates Aβ-mediated tau hyperphosphorylation. Conclusions Our results suggest that pericyte injury contributes to AD progression in the early stage in an Aβ-independent pathway. Recovery of pericyte function would be a target for prevention and early intervention of AD.
A Phase II Study of Carfilzomib, Pegylated Liposomal Doxorubicin, and Dexamethasone for Relapsed or Refractory Multiple Myeloma
Authors: Mark A Fiala, Jesse Keller, Jeevan Sekhar, Connie Ceriotti, Camille N. Abboud, John F DiPersio, Michael H. Tomasson, Tanya M Wildes, Keith Stockerl-Goldstein, Ravi Vij
Journal: Blood (2016)
AUSTRIA
Journal: JAMA (1961)

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
Abstracts cont.
Authors: Y ¨ner, S Okutan, E Artinyan, B Kocazeybek, R Yousefi Mashouf, J Hernandez, L Romero, C Velasco, L Martinez-Martinez, A Pascual, J Patzer, D Dzierzanowska, A Pawinska, P Turner, M El Gharbawy, M El Mofty, H Abd, El Hady, M El, A Moursi, A Ali, S Males, J Kitzis, R Nguyen Van, J Sanz, F Carlet
Journal: Clinical Microbiology and Infection (2005)
US Medical School Finances
Authors: Paul Jolly
Journal: JAMA (1987)

This review of the financial operations of US medical schools is intended to reflect trends in revenues and expenditures. The 28-year interval from 1958 to 1985 may be divided into two distinct periods, from 1958-1959 to 1978-1979 and from 1979-1980 to 1985-1986, the latest year for which financial data are available. The first period can be characterized by huge absolute and relative increases in all aspects of medical education. Some sense of the growth in the enterprise during the 21-year interval from 1958-1959 to 1978-1979 may be gleaned from an examination of a few of its dimensions shown in Table 1. The number of schools increased, the number of candidates for professional and academic doctorates doubled and tripled, respectively, and the population of postdoctoral students mushroomed. The seven-year period from 1979-1980 to 1985-1986, on the other hand, exhibits modest growth in the number of schools and the number of students,
Quantification of absolute perfusion reserve using 82Rb positron emission tomography defines greater extent of disease in three vessel coronary atherosclerosis Ratika Seth, Robert A. DeKemp, Terry D. Ruddy, Barbara Hart, Agis Kitsikis, May Aung, Natalie Levesque, Deborah Gauthier, Elizabeth Westerman, Robert S. Beanlands. University of Ottawa Heart Institute, Ottawa, ON, Canada
Journal: Journal of the American College of Cardiology (2001)
Medical Education, Registration and Hospital Service
Journal: JAMA (1924)

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
Incidental Uptake of 68Ga-DOTATATE Gastrointestinal Stromal Tumor of Duodenum
Authors: Gizem Köroğlu, Gözde Dağliöz Görür, Sevtap Doğan, Büşra Yaprak Bayrak, Hakan Demir
Journal: Clinical Nuclear Medicine (2022)

A 56-year-old man underwent 68Ga-DOTATATE PET/CT with suspicion of a pancreatic neuroendocrine tumor. However, in this imaging, a mass with 68Ga-DOTATATE uptake was observed not in pancreas but in the duodenojejunal junction. Abdominal tomography confirmed that the heterogeneously enhanced mass was originated from duodenum. The patient was operated, and the histopathology result was evaluated as low-risk gastrointestinal stromal tumor. Although there was low or no specific binding to gastrointestinal stromal tumor cells for all 68Ga-labeled DOTA peptides, uptake of 68Ga-DOTATATE was observed incidentally in this case.
RECORD OF PROCEEDINGS OF THE ANNUAL MEETING OF THE ASSOCIATION OF AMERICAN MEDICAL EDITORS IN CLEVELAND, JUNE 5, 1883.
Journal: JAMA (1883)

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
Endotoxin and severity of chronic heart failure Mathias Rauchhaus, Wolfram Doehner, Aidan Bolger, Rakesh Sharma, Hendrik Schmidt, Constantinos Davos, Michael Kemp, Andrew J. S. Coats, Stefan D. Anker. NHLI, Clinical Cardiology, London, United Kingdom, Martin-Luther-Universit�t Halle-Wittenberg, Klinik f�r Innere Medizin III, Halle/Saale, Germany
Journal: Journal of the American College of Cardiology (2001)
Table of Contents
Authors: Tobias Peikert, Krisztina Bogos, Zoltán Kiss, Gabriella Gálffy, Lilla Tamási, Gyula Ostoros, Veronika Müller, László Urbán, Nóra Bittner, Veronika Sárosi, Aladár Vastag, Zoltán Polányi, Zsófia Nagy-Erdei, Zoltán Vokó, Balázs Nagy, Krisztián Horváth, György Rokszin, Zsolt Abonyi-Tóth, Zsófia Barcza, Judit Moldvay, Sufang Tian, Weidong Hu, Li Niu, Huan Liu, Haibo Xu, Shu-Yuan Xiao, Graham Warren, Anthony Alberg, K Cummings, Carolyn Dresler, William Travis, Sanja Dacic, Ignacio Wistuba, Lynette Sholl, Prasad Adusumilli, Lukas Bubendorf, Paul Bunn, Tina Cascone, Jamie Chaft, Gang Chen, Teh-Ying Chou, Wendy Cooper, Jeremy Erasmus, Carlos Ferreira, Jin-Mo Goo, John Heymach, Fred Hirsch, Hidehito Horinouchi, Keith Kerr, Mark Kris, Deepali Jain, Young Kim, Fernando Lopez-Rios, Shun Lu, Philippe Jamme, Marie Fernandes, Marie-Christine Copin, Clotilde Descarpentries, Fabienne Escande, Angela Morabito, Valérie Grégoire, Matthieu Jamme, Simon Baldacci, David Tulasne, Zoulika Kherrouche, Alexis Cortot
Journal: Journal of Thoracic Oncology (2020)
Abstract P262: Association of Weight History With Risk of Diabetes
Authors: Molly Jung, Casey M Rebholz, June Stevens, Josef Coresh, Chiadi Ndumele
Journal: Circulation (2018)

Introduction: Weight gain during early adulthood may contribute to diabetes risk above and beyond a single measure in midlife. Nonetheless, most epidemiologic studies have focused on the risks associated with a one body mass index (BMI) value in midlife. Hypothesis: Accounting for change in BMI from early to mid-adulthood would add prognostic value for estimating risk of diabetes compared to using a single value. Methods: We included 9,857 participants from the Atherosclerosis Risk in Communities (ARIC) Study without diabetes and with BMI ≥18.5 kg/m 2 in 1996-1998 (visit 4). Participants were followed through 2015 for incident diagnosed diabetes. Current BMI was defined as calculated BMI using measured height and weight at visit 4. Early adulthood BMI was calculated from current height and self-reported weight at age 25. We classified current and early adulthood BMI into three categories (18.5-&lt;25, 25-&lt;30, and ≥30 kg/m 2 ) and we examined the associations of changes in BMI category with diabetes risk using Cox proportional hazards models. Results: Overall, 64% (6,205 of 9,857) of the participants moved from a lower to higher BMI category between age 25 and visit 4 (mean age, 63), 35% (3,446 of 9,857) remained stable, and 2% (206 of 9,857) moved from a higher to lower BMI category. Adding BMI at age 25 to a model with current BMI significantly improved model fit. In analyses using BMI change categories between age 25 and visit 4, relative to persons with normal BMI at age 25 and visit 4, persons who moved from a lower to higher BMI category and those who maintained a high BMI had a higher risk for diabetes ( Table ). Conclusions: Current weight is associated with diabetes risk. Past weight gain from early adulthood did not appear to add information above and beyond current weight. Our findings highlight the importance of weight management at all ages for optimal diabetes prevention.
Tubercular Spondylitis
Authors: Amit Bohil, Nagabhushan Seshadri, Nitika Rathi, Rashika Fernando, Sobhan Vinjamuri
Journal: Clinical Nuclear Medicine (2022)

BCGosis is a rare complication of intravesical BCG immunotherapy as adjuvant therapy for urinary bladder cancer manifesting in the form of disseminated tuberculosis or organ-specific tuberculosis, rarely involving the vertebra. PSMA is overexpressed in prostate cancer but also expressed in a variety of benign and malignant conditions. We present a patient with incidental detection of abnormal uptake in a vertebral lesion during assessment of prostate cancer with 18F-PSMA PET/CT, subsequently proven to be vertebral osteitis, likely due to BCG immunotherapy. The case highlights the role of interdisciplinary patient assessment to confirm nature of abnormal foci on 18F-PSMA PET/CT.
The Referendum on Alcohol
Journal: JAMA (2022)

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
ERJ July Podcast: Nontuberculous mycobacteria
Journal: European Respiratory Journal (2019)

As part of the July issue, the European Respiratory Journal presents the latest in its series of podcasts. Deputy Chief Editor James Chalmers interviews Michael Loebinger (Royal Brompton Hospital and Imperial College London, UK) and Jakko van Ingen (Radboud University Medical Center, Nijmegen, the Netherlands) about five articles on the subject on nontuberculous mycobacteria published in this issue.
Effect of an Exercise Intervention on Functional Decline in Very Old Patients During Acute Hospitalizations
Authors: Nicolás Martínez-Velilla, Pedro Abizanda, Javier Gómez-Pavón, Fabricio Zambom-Ferraresi, Mikel L. Sáez de Asteasu, Maria Fiatarone Singh, Mikel Izquierdo
Journal: JAMA Internal Medicine (2022)

This randomized clinical trial examines the effectiveness and generalizability of implementing a multicomponent exercise program for treating functional decline associated with acute hospitalization in very old patients.
High-risk gene expression in colorectal liver metastasis: Potential for novel therapies.
Authors: Caroline Medin, Michael K. Turgeon, Jessica M. Keilson, Bhakti Dwivedi, Cameron Herting, Shishir K. Maithel, Gregory B. Lesinski
Journal: Journal of Clinical Oncology (2022)

147 Background: Over half of patients with colorectal cancer (CRC) develop liver metastases. While immunotherapy is an emerging treatment of solid tumors, its use among CRC patients is limited. Furthermore, gene expression patterns of liver-specific CRC metastases remain unclear. The purpose of this study was to identify a high-risk gene expression profile for patients with colorectal liver metastasis (CRLM) to better inform prognosis and development of novel targeted therapies. Methods: Fifty-three FFPE CRLM samples from patients who underwent complete metastatectomy from 2009-2017 were examined. Expression profiling of extracted RNA was performed using NanoString Immuno-Oncology (IO360) 750-gene panel. Statistical analyses using cutoffs of absolute log 2-fold change≥1.5 and p-value≤0.05 were performed. Patients were analyzed by extremes of outcomes: survival time in the lowest quartile compared to those still alive at last follow-up. Results: Eight differentially expressed genes were associated with poor survival. Overexpressed genes included IL6R, CXCL2, C7, MGMT, PCK2, CSF1 and LILRB4 (Table). PLA2G2A was under-expressed. Conclusions: This study demonstrates differential gene expression associated with poor survival among patients with CRLM. Specific genes of interest include IL6R, MGMT, CSF1 and LILRB4. IL6R is a known effector in tumor proliferation via IL-6 signaling from tumor-associated macrophages, myeloid-derived suppressor cells (MDSCs) and T-cells. MGMT repairs alkylating DNA damage and is implicated in carcinogenesis and response to chemotherapy. CSF1 promotes macrophage differentiation to M2 phenotype, suppressing inflammation and anti-tumor defense mechanisms. LILRB4 activation via MDSCs leads to T-cell inhibition. These overall suggest a myeloid-dominant tumor immune microenvironment and represent important potential therapeutic targets. Next steps include performing immunohistochemistry to validate findings at the protein level and investigate the tumor intrinsic role using human cell lines.[Table: see text]
Galantamine slows functional decline in Alzheimer's disease
Journal: BMJ (2000)

Vaccines may have non-specific effects in developing countriesAlthough studies have found that vaccination against measles may have a non-specific beneficial effect in developing countries, the effect of other routine immunisations has not been assessed.On p 1435 Kristensen et al examined the mortality in vaccinated and unvaccinated children in rural Guinea-Bissau.Both BCG and measles vaccines were associated with reductions in mortality that could not be explained by the prevention of measles or tuberculosis.Polio and diphtheria, tetanus, and pertussis vaccines were associated with higher mortality.Since different vaccines were associated with opposite tendencies, selection biases are unlikely to explain these associations fully.The authors conclude that non-specific effects may occur with many routine vaccinations in areas with high mortality and should be considered when planning immunisation programmes.
Integration of best practice into multidisciplinary care for heart failure in the elderly: New benefits realised John M. Cahill, Ken McDonald, Mark Ledwidge, Peter Quigley, Brian Maurer, Mary Ryder, Bronagh Travers. ST. VINCENT'S CARDIOMYOPATHY RESEARCH CENTRE, DUBLIN, Ireland, Laboratories Servier (Ireland) Ltd., DUBLIN, Ireland
Journal: Journal of the American College of Cardiology (2001)
Systemic high-dose dexamethasone treatment may modulate the efficacy of intratumoral viral oncolytic immunotherapy in glioblastoma models
Authors: Marilin S Koch, Mykola Zdioruk, Michal O Nowicki, Alec M Griffith, Estuardo Aguilar, Laura K Aguilar, Brian W Guzik, Francesca Barone, Paul P Tak, Ghazaleh Tabatabai, James A Lederer, E Antonio Chiocca, Sean Lawler
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Intratumoral viral oncolytic immunotherapy is a promising new approach for the treatment of a variety of solid cancers. CAN-2409 is a replication-deficient adenovirus that delivers herpes simplex virus thymidine kinase to cancer cells, resulting in local conversion of ganciclovir or valacyclovir into a toxic metabolite. This leads to highly immunogenic cell death, followed by a local immune response against a variety of cancer neoantigens and, next, a systemic immune response against the injected tumor and uninjected distant metastases. CAN-2409 treatment has shown promising results in clinical studies in glioblastoma (GBM). Patients with GBM are usually given the corticosteroid dexamethasone to manage edema. Previous work has suggested that concurrent dexamethasone therapy may have a negative effect in patients treated with immune checkpoint inhibitors in patients with GBM. However, the effects of dexamethasone on the efficacy of CAN-2409 treatment have not been explored. Methods In vitro experiments included cell viability and neurosphere T-cell killing assays. Effects of dexamethasone on CAN-2409 in vivo were examined using a syngeneic murine GBM model; survival was assessed according to Kaplan-Meier; analyses of tumor-infiltrating lymphocytes were performed with mass cytometry (CyTOF - cytometry by time-of-flight). Data were analyzed using a general linear model, with one-way analysis of variance followed by Dunnett’s multiple comparison test, Kruskal-Wallis test, Dunn’s multiple comparison test or statistical significance analysis of microarrays. Results In a mouse model of GBM, we found that high doses of dexamethasone combined with CAN-2409 led to significantly reduced median survival (29.0 days) compared with CAN-2409 treatment alone (39.5 days). CyTOF analyses of tumor-infiltrating immune cells demonstrated potent immune stimulation induced by CAN-2409 treatment. These effects were diminished when high-dose dexamethasone was used. Functional immune cell characterization suggested increased immune cell exhaustion and tumor promoting profiles after dexamethasone treatment. Conclusion Our data suggest that concurrent high-dose dexamethasone treatment may impair the efficacy of oncolytic viral immunotherapy of GBM, supporting the notion that dexamethasone use should be balanced between symptom control and impact on the therapeutic outcome.