tbuckley/cabot-search huggingface dataset:
Prime-boost vaccination targeting prostatic acid phosphatase (PAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) using Sipuleucel-T and a DNA vaccine
Authors: Ellen Wargowski, Laura E. Johnson, Jens C. Eickhoff, Lauren Delmastro, Mary Jane Staab, Glenn Liu, Douglas G. McNeel
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Prostatic acid phosphatase (PAP) is a prostate tumor antigen, and the target of the only FDA-approved anti-tumor vaccine, sipuleucel-T. We have previously reported in two clinical trials that a DNA vaccine encoding PAP (pTVG-HP) could elicit PAP-specific, Th1-biased T cells in patients with PSA-recurrent prostate cancer. In the current pilot trial we sought to evaluate whether this vaccine could augment PAP-specific immunity when used as a booster to immunization with sipuleucel-T in patients with metastatic, castration-resistant prostate cancer (mCRPC). <h3>Methods</h3> Eigthteen patients with mCRPC were randomized to receive sipuleucel-T alone or followed by intradermal immunization with pTVG-HP DNA vaccine. Patients were followed for time to progression, and immune monitoring was conducted at defined intervals. <h3>Results</h3> Overall, patients were followed for a median of 24&nbsp;months. 11/18 patients completed treatments as per protocol. No treatment-associated events &gt; grade 2 were observed. Th1-biased PAP-specific T-cell responses were detected in 11/18 individuals, and were not statistically different between study arms. Higher titer antibody responses to PAP were detectable in patients who received pTVG-HP booster immunizations. Median time to progression was less than 6&nbsp;months and not statistically different between study arms. The median overall survival for all patients was 28&nbsp;months. <h3>Conclusions</h3> These findings suggest that prime-boost vaccination can augment and diversify the type of immunity elicited with anti-tumor vaccination in terms of T-cell and humoral immunity. Future studies will explore DNA as priming immunization rather than a booster immunization. <h3>Trial registration</h3> NCT01706458.
Mini-Dose Glucagon as a Novel Approach to Prevent Exercise-Induced Hypoglycemia in Type 1 Diabetes
Authors: Michael R. Rickels, Stephanie N. DuBose, Elena Toschi, Roy W. Beck, Alandra S. Verdejo, Howard Wolpert, Martin J. Cummins, Brett Newswanger, Michael C. Riddell, Michael Rickels, Amy Peleckis, Margaret Evangelisti, Cornelia Dalton-Bakes, Carissa Fuller, Elena Toschi, Howard Wolpsert, Roeland Middelbeek, Louis Seow Cherng Jye, Jacqueline Shahar, Christine Slyne, Stephanie Edwards, Astrid Atakov Castillo, Stephanie N. DuBose, Roy W. Beck, Alandra S. Verdejo, Martin Cummins, Brett Newswanger, Steve Prestrelski
Journal: Diabetes Care (2018)

OBJECTIVE Patients with type 1 diabetes who do aerobic exercise often experience a drop in blood glucose concentration that can result in hypoglycemia. Current approaches to prevent exercise-induced hypoglycemia include reduction in insulin dose or ingestion of carbohydrates, but these strategies may still result in hypoglycemia or hyperglycemia. We sought to determine whether mini-dose glucagon (MDG) given subcutaneously before exercise could prevent subsequent glucose lowering and to compare the glycemic response to current approaches for mitigating exercise-associated hypoglycemia. RESEARCH DESIGN AND METHODS We conducted a four-session, randomized crossover trial involving 15 adults with type 1 diabetes treated with continuous subcutaneous insulin infusion who exercised fasting in the morning at ∼55% VO2max for 45 min under conditions of no intervention (control), 50% basal insulin reduction, 40-g oral glucose tablets, or 150-μg subcutaneous glucagon (MDG). RESULTS During exercise and early recovery from exercise, plasma glucose increased slightly with MDG compared with a decrease with control and insulin reduction and a greater increase with glucose tablets (P &amp;lt; 0.001). Insulin levels were not different among sessions, whereas glucagon increased with MDG administration (P &amp;lt; 0.001). Hypoglycemia (plasma glucose &amp;lt;70 mg/dL) was experienced by six subjects during control, five subjects during insulin reduction, and none with glucose tablets or MDG; five subjects experienced hyperglycemia (plasma glucose ≥250 mg/dL) with glucose tablets and one with MDG. CONCLUSIONS MDG may be more effective than insulin reduction for preventing exercise-induced hypoglycemia and may result in less postintervention hyperglycemia than ingestion of carbohydrate.
Image Gallery: Cutaneous findings in Hunter syndrome
Authors: E. Gómez Moyano, A. Vera-Casaño, M. Ayala-Blanca, L. Martinez-Pilar
Journal: British Journal of Dermatology (2018)

DEAR EDITOR, A 6-year-old boy presented with multiple asymptomatic ivory-white papules with a 'cobblestone' appearance on his back and upper arms (a), which had appeared 3 years earlier.His past medical history included intellectual disability, delayed tooth eruption, persistent mucoid nasal discharge and respiratory infections.Physical examination revealed macrocephaly, coarse facies, short neck, hoarse voice, hepatosplenomegaly and claw hands.Persistent and extensive Mongolian spots were noted on his back (b).Histological examination of a papule on the arm showed mucin deposition between separated collagen bundles in the dermis (c).
Evidence of Signaling and Adhesion Roles for β-Catenin in the Sponge Ephydatia muelleri
Authors: Klaske J Schippers, Scott A Nichols
Journal: Molecular Biology and Evolution (2018)

β-Catenin acts as a transcriptional coactivator in the Wnt/β-catenin signaling pathway and a cytoplasmic effector in cadherin-based cell adhesion. These functions are ancient within animals, but the earliest steps in β-catenin evolution remain unresolved due to limited data from key lineages—sponges, ctenophores, and placozoans. Previous studies in sponges have characterized β-catenin expression dynamics and used GSK3B antagonists to ectopically activate the Wnt/β-catenin pathway; both approaches rely upon untested assumptions about the conservation of β-catenin function and regulation in sponges. Here, we test these assumptions using an antibody raised against β-catenin from the sponge Ephydatia muelleri. We find that cadherin-complex genes coprecipitate with endogenous Em β-catenin from cell lysates, but that Wnt pathway components do not. However, through immunostaining we detect both cell boundary and nuclear populations, and we find evidence that Em β-catenin is a conserved substrate of GSK3B. Collectively, these data support conserved roles for Em β-catenin in both cell adhesion and Wnt signaling. Additionally, we find evidence for an Em β-catenin population associated with the distal ends of F-actin stress fibers in apparent cell–substrate adhesion structures that resemble focal adhesions. This finding suggests a fundamental difference in the adhesion properties of sponge tissues relative to other animals, in which the adhesion functions of β-catenin are typically restricted to cell–cell adhesions.
Lifetime Smoking History and Risk of Lung Cancer: Results From the Framingham Heart Study
Authors: Hilary A Tindle, Meredith Stevenson Duncan, Robert A Greevy, Ramachandran S Vasan, Suman Kundu, Pierre P Massion, Matthew S Freiberg
Journal: JNCI Journal of the National Cancer Institute (2018)

The relative risk of lung cancer decreases with years since quitting (YSQ) smoking, but risk beyond 25 YSQ remains unclear. Current lung cancer screening guidelines, which exclude smokers with more than 15 YSQ, may not detect lung cancers in this population. We analyzed data from Framingham Heart Study Original (n = 3905) and Offspring cohort (n = 5002) participants for lifetime smoking and lung cancer incidence from 1954 to 1958 (Exam 4) and 1971 to 1975 (Exam 1), respectively, through 2013. We used multivariable-adjusted Cox proportional hazards regression models to compare current, former, and never smokers and lung cancer risk. Smoking status and covariates were time-updated every two years (Original) or four years (Offspring). Primary analyses were restricted to heavy ever smokers with more than 21.3 pack-years; additional analyses included all ever smokers. On follow-up (median = 28.7 years), 284 lung cancers were detected: incidence rates/1000 person-years in current, former, and never smokers were 1.97 (95% confidence interval [CI] = 1.66 to 2.33), 1.61 (95% CI = 1.34 to 1.93), and 0.26 (95% CI = 0.17 to 0.39), respectively. Heavy former (vs never) smokers had elevated lung cancer risk at all YSQ (<5: hazard ratio [HR] = 12.12, 95% CI = 6.94 to 21.17; 5–9: HR = 11.77, 95% CI = 6.78 to 20.45; 10–14: HR = 7.81, 95% CI = 3.98 to 15.33; 15–24: HR = 5.88, 95% CI = 3.19–10.83; ≥25: HR = 3.85, 95% CI = 1.80 to 8.26). Heavy former (vs current) smokers had 39.1% lower lung cancer risk within five YSQ. Among all former smokers, 40.8% of lung cancers occurred after more than 15 YSQ. Among heavy former smokers, lung cancer risk drops within five YSQ relative to continuing smokers, yet it remains more than threefold higher than never smokers after 25 YSQ. Four of ten lung cancers occurred in former smokers with more 15 YSQ, beyond the screening window of the current guideline.
Implications of Screening for Brain Metastases in Patients With Breast Cancer and Non–Small Cell Lung Cancer
Authors: Daniel N. Cagney, Allison M. Martin, Paul J. Catalano, Paul D. Brown, Brian M. Alexander, Nancy U. Lin, Ayal A. Aizer
Journal: JAMA Oncology (2018)

This study analyzes the value of magnetic resonance imaging of the brain for patients with cancers that frequently metastasize to the brain.
Sickness absence rates across the NHS
Authors: Tom Moberly
Journal: BMJ (2018)

Sickness absence rates across the NHSSickness rates among doctors were less than a third of rates across the NHS as a whole in 2016/17, data released by NHS Digital show Tom MoberlyThe BMJ On average, hospital doctors were absent because of sickness on 1.3% of the days on which they were scheduled to work in 2016/17.Doctors in training had an average annual sickness rate of 1.1%, and the average rate among consultants was 1.2%.This compares with an average annual sickness absence rate of 4.2% for all NHS hospital staff, 4.5% for nurses, and 5.5% for ambulance workers.
PD-1 axis expression in musculoskeletal tumors and antitumor effect of nivolumab in osteosarcoma model of humanized mouse
Authors: Bingxin Zheng, Tingting Ren, Yi Huang, Kunkun Sun, Shidong Wang, Xing Bao, Kuisheng Liu, Wei Guo
Journal: Journal of Hematology & Oncology (2018)

Immune checkpoint inhibitors have led to a breakthrough in solid tumor immunotherapy, but related studies on musculoskeletal tumors are few, especially for PD-L2. We examined expression of three molecular effectors of the PD-1 axis in 234 patients with musculoskeletal tumors, including osteosarcoma, chondrosarcoma, synovial sarcoma, and giant cell tumor. Survival analyses and potential mechanisms were investigated in osteosarcoma per the Gene Expression Omnibus (GEO) and immunohistochemistry analyses. In vivo, humanized mice were used to evaluate the effect of nivolumab on osteosarcoma. PD-L1, PD-L2, and PD-1 expression levels were significantly different between the histologic types of the musculoskeletal tumors. For osteosarcoma, PD-L1 was negatively correlated with prognosis, while PD-1 had a negative correlation tendency with overall survival (OS). Meanwhile, PD-L2 had a positive correlation trend with OS. Nivolumab inhibited osteosarcoma metastasis in humanized mice by increasing CD4+ and CD8+ lymphocytes and the cytolytic activity of CD8 lymphocytes in the lung but did not affect primary osteosarcoma growth. We systematically detected the expression patterns of PD-L1, PD-L2, and PD-1 in musculoskeletal tumors for the first time and demonstrated the prognostic roles and underlying mechanisms of PD-1 axis in osteosarcoma. Furthermore, PD-1 blockade could effectively control osteosarcoma pulmonary metastasis in vivo. Therefore, the PD-1 axis may be a potential immunotherapeutic target for metastatic osteosarcoma.
Abstract 14264: The Target Value Of Low Density Lipoprotein Cholesterol And Preventive Effect Of Statins Were Different Between Elderly Patients And Younger Patients
Authors: Akihiro Endo, Taiji Okada, Shimpei Ito, Nobuhide Watanabe, Takeshi Ouch, Nobuyuki Takahashi, Hiroyuki Yoshitomi, Kazuaki Tanabe
Journal: Circulation (2016)

Introduction: With an aging society, elderly patients with cardiac ischemia are increasing. However, there is little information regarding predictors in secondary prevention of Japanese elderly pat...
Reduced neural gating of respiratory sensations is associated with increased dyspnoea perception
Authors: Michaela Herzog, Josef Sucec, Ilse Van Diest, Omer Van den Bergh, Pei-Ying Sarah Chan, Paul Davenport, Andreas von Leupoldt
Journal: European Respiratory Journal (2018)

According to the neural gating model of respiratory sensations, breathing occurs under normal conditions automatically without reaching consciousness (gating-out). This neural filter mechanism prevents the brain from being flooded with irrelevant respiratory sensations leaving sufficient neural processing capacities for everyday activities [1, 2]. However, in some circumstances, breathing can become conscious either voluntarily ( e.g. attention, meditation) or due to increased respiratory demand ( e.g. exacerbations, respiratory disease). In such cases, respiratory information is no longer filtered out but transmitted to higher brain centres which leads to the allocation of attentional resources towards the breathing sensation and brings it to conscious awareness (gating-in) [1, 2]. Similar to the neural gating in other modalities, such as auditory/visual/somatosensory gating [3, 4], this respiratory gating mechanism is, therefore, the neural basis for monitoring respiratory functioning and a pre-requisite for subsequent adaptive behaviour, such as medication intake or physician visits. Anxiety, which is prevalent in patients with dyspnoea [1, 5], has been shown to be associated with reduced neural gating of respiratory sensations, suggesting gating deficits to be a potential mechanism for the documented over-perception of dyspnoea in anxious individuals [6, 7]. The neural gating model of respiratory sensations implies that decreased neural gating of respiratory sensations is associated with increasing dyspnoea [4]. However, this implication has never been tested and was investigated in the present study by using respiratory-related evoked potentials (RREP) in the electroencephalogram (EEG) while additionally exploring potential effects of anxiety. Reduced respiratory neural gating is associated with increased dyspnoea, particularly in high anxious individuals <http://ow.ly/xW4B30k34KR> We thank Thierry Troosters for his valuable and critical evaluation of the present findings and previous versions of this manuscript.
Response by Oldgren and Sundström to Letter Regarding Article, “Low-Dose Aspirin Discontinuation and Risk of Cardiovascular Events: A Swedish Nationwide, Population-Based Cohort Study”
Authors: Jonas Oldgren, Johan Sundström
Journal: Circulation (2018)

In Response:We thank Dr Yi-tong for the interest in our paper. 1First, observational studies seldom answer questions about mechanisms.Platelet function returns to normal within a week from cessation of aspirin, thus leaving the patient without protection for new cardiovascular events because of the underlying cardiovascular disease that indicated antiplatelet treatment.An enhancement or rebound in the platelet function after cessation of aspirin has been suggested, but study results are conflicting. 2,3econd, there is little evidence supporting long-term treatment with low molecular weight heparins to prevent cardiovascular events, and this therapy is cumbersome for patients and expensive.Thus, all efforts should be made to inform patients to increase treatment persistence and to avoid unnecessary interruption of aspirin treatment.Third, the effect of discontinuation of P2Y 12 inhibitors was not evaluated in our study.However, there is little reason to believe that the results would be different when interrupting treatment with P2Y 12 inhibitors. 4Warfarin was also not in the scope of the present study.
Intraoperative monitoring of neuromuscular function with soft, skin-mounted wireless devices
Authors: Yuhao Liu, Limei Tian, Milan S. Raj, Matthew Cotton, Yinji Ma, Siyi Ma, Bryan McGrane, Arjun V. Pendharkar, Nader Dahaleh, Lloyd Olson, Haiwen Luan, Orin Block, Brandon Suleski, Yadong Zhou, Chandrasekaran Jayaraman, Tyler Koski, A. J. Aranyosi, John A. Wright, Arun Jayaraman, Yonggang Huang, Roozbeh Ghaffari, Michel Kliot, John A. Rogers
Journal: npj Digital Medicine (2018)

Peripheral nerves are often vulnerable to damage during surgeries, with risks of significant pain, loss of motor function, and reduced quality of life for the patient. Intraoperative methods for monitoring nerve activity are effective, but conventional systems rely on bench-top data acquisition tools with hard-wired connections to electrode leads that must be placed percutaneously inside target muscle tissue. These approaches are time and skill intensive and therefore costly to an extent that precludes their use in many important scenarios. Here we report a soft, skin-mounted monitoring system that measures, stores, and wirelessly transmits electrical signals and physical movement associated with muscle activity, continuously and in real-time during neurosurgical procedures on the peripheral, spinal, and cranial nerves. Surface electromyography and motion measurements can be performed non-invasively in this manner on nearly any muscle location, thereby offering many important advantages in usability and cost, with signal fidelity that matches that of the current clinical standard of care for decision making. These results could significantly improve accessibility of intraoperative monitoring across a broad range of neurosurgical procedures, with associated enhancements in patient outcomes.
CMR-Based and Time-Shift Corrected Pressure Gradients Provide Good Agreement to Invasive Measurements in Aortic Coarctation
Authors: Joao Filipe Fernandes, Rita Alves, Tiago Ferreira da Silva, Sarah Nordmeyer, Florian Hellmeier, Leonid Goubergrits, Anja Hennemuth, Felix Berger, Stephen Schubert, Titus Kuehne, Marcus Kelm
Journal: JACC. Cardiovascular imaging (2018)
Abstract 15916: EGF-Like Ligands Contribute to Neointimal Formation via Nox1-Mediated SMC Growth
Authors: Nader M Makki, Eric G Heller, Wassef Y Karrowni, Shuxia Jiang, Maysam Takapoo, Brandon M Schickling, Bojana Stanic, Frances Johnson, Francis J Miller
Journal: Circulation (2013)

Chronic inflammation is associated with extracellular oxidative stress and accelerated vascular disease. We have reported that a more oxidized extracellular redox state promotes epidermal growth factor (EGF)-like ligand shedding, resulting in EGFR-mediated increase in expression of Nox1 NADPH oxidase and proliferation of smooth muscle cells (SMC). Furthermore, we observed increased plasma levels of EGF-like ligands, particularly HB-EGF, in a non-human primate model of atherosclerosis. We hypothesized that EGF-like ligands contribute to the development of vascular disease by promoting Nox1-mediated SMC growth. In cultured SMCs, treatment with HB-EGF increased Nox1 transcription and SMC proliferation. Expression of siRNA to Nox1, but not Nox4, prevented HB-EGF-induced cell growth. The mitochondria-targeted antioxidant MitoTEMPO inhibited HB-EGF-mediated Nox1 expression and SMC proliferation. Furthermore, overexpression of Nox1 restored HB-EGF-mediated proliferation in the presence of MitoTEMPO. We next implanted osmotic minipumps containing HB-EGF into 16-wk old hypercholesterolemic mice and 2d later performed carotid ligation as a model of vascular injury. Two weeks following ligation, mice receiving HB-EGF demonstrated a 60% increase in plasma HB-EGF, 65% increase in aortic expression of Nox1, and a 55% increase in carotid intimal area (I/M ratio 0.52±0.01 vs. 0.91±0.01, p 50%) were divided into two groups based on the severity of allograft vasculopathy as determined by angiography. HB-EGF levels positively correlated with disease severity, with circulating concentrations 1.9-fold higher in patients with moderate to severe coronary disease as compared to patients with absent to mild disease (n=9/group; p
Quiet Moment on Night Call
Authors: Rebekka DePew
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 16655: Bone Marrow Cell Therapy in Patients With Ischemic Heart Disease: A Meta-analysis of Randomized Controlled Trials Using Cardiac MRI
Authors: Muhammad R Afzal, Anweshan Samanta, Briha Ansari, Vinodh Jeevanantham, Buddhadeb Dawn
Journal: Circulation (2015)

Introduction: The results from clinical trials of bone marrow cell (BMC) therapy in ischemic heart disease (IHD) have been discordant with regard to left ventricular (LV) functional improvement. This discrepancy has been attributed, in part, to the use of dissimilar cardiac imaging modalities. MRI is the gold standard for assessment of cardiac structure/function. Hypothesis: We hypothesized that BMC therapy will improve LV parameters in patients with IHD when assessed by cardiac MRI. Methods: We performed a systematic review and meta-analysis of data from randomized controlled trials (RCTs) of BMC therapy in patients with IHD that used cardiac MRI. Database searches through May 30, 2015 identified 27 eligible RCTs (enrolling 1826 patients). The MRI data on LV ejection fraction (EF), infarct size, LV end-systolic volume (LVESV), and LV end-diastolic volume (LVEDV) were analyzed with random-effects meta-analysis. Clinical outcomes were analyzed using Peto odds ratio (OR). Results: Compared with standard therapy, BMC therapy improved LVEF (1.62%; 95% confidence interval [CI]: 0.49 to 2.75; P=0.005) and reduced LVESV (-2.00 ml; 95% CI: -3.19 to -0.82; P=0.0009). The improvement in LVEF was similar in patients with acute myocardial infarction (MI) and chronic IHD. Perhaps more importantly, BMC therapy was associated with reduced incidence of recurrent MI (OR: 0.39; 95% CI: 0.20 to 0.78; P=0.007) along with substantial improvement in other outcome parameters, including mortality (Table). However, these changes did not reach statistical significance perhaps due to smaller patient numbers. Conclusions: These results from meta-analysis of RCTs using cardiac MRI indicate that BMC therapy improves LV function and outcomes in patients with IHD. These data may help resolve the controversy regarding whether the reported benefits of BMC therapy are dependent on the selection of imaging modalities.