tbuckley/cabot-search huggingface dataset:
Sustained Impact of Real-time Continuous Glucose Monitoring in Adults With Type 1 Diabetes on Insulin Pump Therapy: Results After the 24-Month RESCUE Study
Authors: Sara Charleer, Christophe De Block, Frank Nobels, Régis P. Radermecker, Ine Lowyck, Annelies Mullens, Denis Scarnière, Katrien Spincemaille, Marie Strivay, Eric Weber, Youri Taes, Chris Vercammen, Bart Keymeulen, Chantal Mathieu, Pieter Gillard
Journal: Diabetes Care (2020)

OBJECTIVE In recent years, a growing number of people with type 1 diabetes gained access to real-time continuous glucose monitoring (rtCGM). Long-term benefits of rtCGM are unclear because of a lack of large studies of long duration. We evaluated whether real-world rtCGM use up to 24 months offered benefits, particularly in those living with impaired awareness of hypoglycemia (IAH). RESEARCH DESIGN AND METHODS This 24-month, prospective, observational cohort study followed 441 adults with insulin pumps receiving full reimbursement for rtCGM. Forty-two percent had IAH. The primary end point was evolution of HbA1c, with secondary end points change in acute hypoglycemia complications, diabetes-related work absenteeism, and quality of life scores. Additionally, we evaluated whether people could achieve glycemic consensus targets during follow-up. RESULTS After 24 months, HbA1c remained significantly lower compared with baseline (7.64% [60 mmol/mol] vs. 7.37% [57 mmol/mol], P &amp;lt; 0.0001). Sustained benefits were also observed for the score on the hypoglycemia fear survey and hypoglycemia-related acute complications irrespective of hypoglycemia awareness level. People with IAH had the strongest improvement, especially for severe hypoglycemia (862 events in the year before vs. 119 events per 100 patient-years in the 2nd year, P &amp;lt; 0.0001). Over 24 months, more people were able to meet hypoglycemia consensus targets at the expense of slightly fewer people achieving hyperglycemia consensus targets. Furthermore, the number of people with HbA1c &amp;lt;7% (&amp;lt;53 mmol/mol) without severe hypoglycemia events more than doubled (11.0% vs. 25.4%, P &amp;lt; 0.0001). CONCLUSIONS Use of rtCGM led to sustained improvements in hypoglycemia-related glucose control over 24 months. Lower fear of hypoglycemia, fewer acute hypoglycemia-related events, and fewer diabetes-related days off from work were observed, particularly in those with IAH.
In vivo education of CIK cells for anti tumor therapy
Authors: Mike Helms, Jennifer Prescher, Steve Thorne, Christopher Contag
Journal: Cancer Research (2008)

4641  Cytokine-induced killer (CIK) cells are broadly active tumoricidal immune cells, and are capable of recognizing and lysing a wide range of hematologic and solid tumors in vivo independent of MHC. These cells can be derived from human peripheral blood mononuclear cells after stimulation and expansion ex vivo. Autologous and allogeneic CIK cells have been tested in a number of clinical trials and demonstrated efficacy in patients with hepatoma, renal cell cancer, and hematological malignancies. Pre-clinical studies suggest they will also be effective in treating breast and ovarian cancer. For pre-clinical studies, CIK cells are derived from murine splenocytes that are similarly treated ex vivo with cytokines (IFNgamma, and IL2 or IL12) and α-CD3. The resulting activated cells possess phenotypic markers of both T cells (e.g., CD3) and NK cells (e.g., DX5 in mice and CD56 in humans) and functional NK cell proteins (NKG2D). In addition to their efficacy against primary tumors, CIK cells have been used to combat minimal residual disease (e.g., following a bone marrow transplant) in patients, highlighting their potential use in curbing metastases and preventing relapse from states of remission.  Despite the remarkable clinical promise of this immunotherapy, the requirement for a 12-14 day ex vivo education increases time and expense compromising their use in routine clinical applications. The most time consuming step in the education process is a 10 day long expansion at the end of the CIK culturing process which requires constant IL2 or IL12 stimulation. In this project we aim to overcome this problem by substantially shortening the ex vivo education procedure by delivery of IL12 after injection of CIK precursors in vivo. An additional advantage of this strategy is the strong anti-tumor effect of IL12. For the delivery of IL12 we are pursuing two strategies. In a first approach we deliver IL12 by intraperitoneal injections, in a second line of experiments we inject an IL12 expressing Adenovirus into the tumor.  We are studying the distribution and homing of CIK cells and their tumoricidal efficacy in response to IL12 by means of optical imaging in vivo. For this purpose we established a mouse model based on a Luciferase expressing FVB CIK cell donor mouse (“L2G85”) and Luciferase expressing FVB derived DB7 mouse mammary tumor cells. In different sets of experiments this enables us to track CIK cells and quantify tumor growth and regression in response to CIK treatment in vivo in an MHC matched model.  The FVB derived cells are allografted into T-cell deficient nude mice for optimal optical imaging conditions. Furthermore, the use of nude mice eliminates any IL12 dependent tumor regression which was shown to be T-cell dependent and lead to complete DB7 tumor regression in FVB mice making the described studies impossible.  The results of this study have the potential to eliminate one of the major problems in the clinical applications of CIK as a highly promising agent in cancer therapy.
66P High incidence of TP53 and epigenetic modifying oncogene mutations in a large cohort of patients enrolled in phase I clinical trials for R/R DLBCL
Authors: C. Quivoron, J-M. Michot, V. Camara-Clayette, A. Danu, J. Lazarovici, C. Sarkozy, D. Ghez, J. Rossignol, C. Baldini, P. Martin Romano, A. Varga, S. Cotteret, P. Dartigues, C. Massard, V. Ribrag
Journal: Annals of Oncology (2020)
A Fine Line
Authors: Eric L. Wald
Journal: JAMA (2020)

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
Cytosolic pH regulates proliferation and tumour growth by promoting expression of cyclin D1
Authors: Lisa Maria Koch, Eivind Salmorin Birkeland, Stefania Battaglioni, Xiao Helle, Mayura Meerang, Stefanie Hiltbrunner, Alfredo J. Ibáñez, Matthias Peter, Alessandra Curioni-Fontecedro, Isabelle Opitz, Reinhard Dechant
Journal: Nature Metabolism (2020)
Tissue engineered autologous cartilage-bone grafts for temporomandibular joint regeneration
Authors: David Chen, Josephine Y. Wu, Kelsey M. Kennedy, Keith Yeager, Jonathan C. Bernhard, Johnathan J. Ng, Brandon K. Zimmerman, Samuel Robinson, Krista M. Durney, Courtney Shaeffer, Olaia F. Vila, Catherine Takawira, Jeffrey M. Gimble, X. Edward Guo, Gerard A. Ateshian, Mandi J. Lopez, Sidney B. Eisig, Gordana Vunjak-Novakovic
Journal: Science Translational Medicine (2020)

Bioengineered autologous cartilage-bone ramus-condyle grafts enable temporomandibular joint regeneration in a clinically sized porcine model.
tPA Mobilizes Immune Cells That Exacerbate Hemorrhagic Transformation in Stroke
Authors: Kaibin Shi, Ming Zou, Dong-Mei Jia, Samuel Shi, Xiaoxia Yang, Qiang Liu, Jing-fei Dong, Kevin N. Sheth, Xiaoying Wang, Fu-Dong Shi
Journal: Circulation Research (2020)

Rationale: Hemorrhagic complications represent a major limitation of intravenous thrombolysis using tPA (tissue-type plasminogen activator) in patients with ischemic stroke. The expression of tPA receptors on immune cells raises the question of what effects tPA exerts on these cells and whether these effects contribute to thrombolysis-related hemorrhagic transformation. Objective: We aim to determine the impact of tPA on immune cells and investigate the association between observed immune alteration with hemorrhagic transformation in ischemic stroke patients and in a rat model of embolic stroke. Methods and Results: Paired blood samples were collected before and 1 hour after tPA infusion from 71 patients with ischemic stroke. Control blood samples were collected from 27 ischemic stroke patients without tPA treatment. A rat embolic middle cerebral artery occlusion model was adopted to investigate the underlying mechanisms of hemorrhagic transformation. We report that tPA induces a swift surge of circulating neutrophils and T cells with profoundly altered molecular features in ischemic stroke patients and a rat model of focal embolic stroke. tPA exacerbates endothelial injury, increases adhesion and migration of neutrophils and T cells, which are associated with brain hemorrhage in rats subjected to embolic stroke. Genetic ablation of annexin A2 in neutrophils and T cells diminishes the effect of tPA on these cells. Decoupling the interaction between mobilized neutrophils/T cells and the neurovascular unit, achieved via a S1PR (sphingosine-1-phosphate receptor) 1 modulator RP101075 and a CCL2 (C-C motif chemokine ligand 2) synthesis inhibitor bindarit, which block lymphocyte egress and myeloid cell recruitment, respectively, attenuates hemorrhagic transformation and improves neurological function after tPA thrombolysis. Conclusions: Our findings suggest that immune invasion of the neurovascular unit represents a previously unrecognized mechanism underlying tPA-mediated brain hemorrhage, which can be overcome by precise immune modulation during thrombolytic therapy.
Environmental risk factors, protective factors, and peripheral biomarkers for ADHD: an umbrella review
Authors: Jae Han Kim, Jong Yeob Kim, Jinhee Lee, Gwang Hun Jeong, Eun Lee, San Lee, Keum Hwa Lee, Andreas Kronbichler, Brendon Stubbs, Marco Solmi, Ai Koyanagi, Sung Hwi Hong, Elena Dragioti, Louis Jacob, Andre R Brunoni, Andre F Carvalho, Joaquim Radua, Trevor Thompson, Lee Smith, Hans Oh, Lin Yang, Igor Grabovac, Felipe Schuch, Michele Fornaro, Andrew Stickley, Theodor B Rais, Gonzalo Salazar de Pablo, Jae Il Shin, Paolo Fusar-Poli
Journal: The Lancet Psychiatry (2020)
Raine Roberts: founder of the UK’s first sexual assault referral centre
Authors: Joanna Lyall
Journal: BMJ (2020)

Photo credit: PA

Raine Roberts, who has died aged 88, was the police surgeon who founded the UK’s first sexual assault referral centre, at St Mary’s Hospital, Manchester, in December 1986. Jointly funded by Greater Manchester Police and the NHS, the centre was the result of years of campaigning on Roberts’s part. “Raine was a battler and always being criticised, but stalwart and absolutely determined to do the right thing,” said Albert Yates, former detective chief superintendent of Greater Manchester Police, who worked on the establishment of the centre, now one of 50 across the UK. “At the time, women were being examined in grubby police stations, often with the suspect next door. It was a terrible experience for women to have to go through.” Initially staffed with five counsellors and eight doctors, the team now includes 25 forensic physicians, working on a sessional basis.

Roberts was born in Lancashire, where her father, John Birchall, was a farmer, …
We don’t need bad doctors, but we don’t need bad appraisals and revalidations either
Authors: Terry Kemple
Journal: BMJ (2020)

Whistleblowing on the flawed structure and process of NHS appraisal and General Medical Council revalidation is both a professional duty and overdue.1 When NHS appraisals started in 2002, a general practitioner I knew said: “I don’t see the need for this—when I look around I don’t see any bad doctors.” At that moment I realised the truism: “If I look around and can’t see …
GSH-responsive SN38 dimer-loaded shape-transformable nanoparticles with iRGD for enhancing chemo-photodynamic therapy
Authors: Congcong Lin, Fan Tong, Rui Liu, Rou Xie, Ting Lei, Yuxiu Chen, Zhihang Yang, Huile Gao, Xiangrong Yu
Journal: Acta Pharmaceutica Sinica B (2020)

Accurate tumor targeting, deep penetration and superb retention are still the main pursuit of developing excellent nanomedicine. To achieve these requirements, a stepwise stimuli-responsive strategy was developed through co-administration tumor penetration peptide iRGD with shape-transformable and GSH-responsive SN38-dimer (d-SN38)-loaded nanoparticles ([email protected]/iRGD). Upon intravenous injection, [email protected] with high drug loading efficiency (33.92 ± 1.33%) could effectively accumulate and penetrate into the deep region of tumor sites with the assistance of iRGD. The gathered nanoparticles simultaneously transformed into nanofibers upon 650 nm laser irradiation at tumor sites so as to promote their retention in the tumor and burst release of reactive oxygen species for photodynamic therapy. The loaded d-SN38 with disulfide bond responded to the high level of GSH in tumor cytoplasm, which consequently resulted in SN38 release and excellent chemo-photodynamic effect on tumor. In vitro, co-administering iRGD with [email protected]+laser showed higher cellular uptake, apoptosis ratio and multicellular spheroid penetration. In vivo, [email protected]/iRGD+laser displayed advanced penetration and accumulation in tumor, leading to 60.89% of tumor suppression in 4T1 tumor-bearing mouse model with a favorable toxicity profile. Our new strategy combining iRGD with structural transformable nanoparticles greatly improves tumor targeting, penetrating and retention, and empowers anticancer efficacy.
Population-based estimates of survival among elderly patients with brain metastases
Authors: Nayan Lamba, Rachel Brigell Kearney, Paul J Catalano, Michael J Hassett, Patrick Y Wen, Daphne A Haas-Kogan, Ayal A Aizer
Journal: Neuro-Oncology (2020)

Abstract Background Prognostic estimates for patients with brain metastases (BM) stem from younger, healthier patients enrolled in clinical trials or databases from academic centers. We characterized population-level prognosis in elderly patients with BM. Methods Using Surveillance, Epidemiology, and End Results (SEER)–Medicare data, we identified 9882 patients ≥65 years old with BM secondary to lung, breast, skin, kidney, esophageal, colorectal, and ovarian primaries between 2014 and 2016. Survival was assessed by primary site and evaluated with Cox regression. Results In total, 2765 versus 7117 patients were diagnosed with BM at primary cancer diagnosis (synchronous BM, median survival = 2.9 mo) versus thereafter (metachronous BM, median survival = 3.4 mo), respectively. Median survival for all primary sites was ≤4 months, except ovarian cancer (7.5 mo). Patients with non-small-cell lung cancer (NSCLC) receiving epidermal growth factor receptor (EGFR)– or anaplastic lymphoma kinase (ALK)–based therapy for synchronous BM displayed notably better median survival at 12.5 and 20.1 months, respectively, versus 2.8 months exhibited by other patients with NSCLC; survival estimates in melanoma patients based on receipt of BRAF/MEK therapy versus not were 6.7 and 2.8 months, respectively. On multivariable regression, older age, greater comorbidity, and type of managing hospital were associated with poorer survival; female sex, higher median household income, and use of brain-directed stereotactic radiation, neurosurgical resection, or systemic therapy (versus brain-directed non-stereotactic radiation) were associated with improved survival (all P &amp;lt; 0.05). Conclusions Elderly patients with BM have a poorer prognosis than suggested by prior algorithms. If prognosis is driven by systemic and not intracranial disease, brain-directed therapy with potential for significant toxicity should be utilized cautiously.
Interferons and viruses induce a novel truncated ACE2 isoform and not the full-length SARS-CoV-2 receptor
Authors: Olusegun O. Onabajo, A. Rouf Banday, Megan L. Stanifer, Wusheng Yan, Adeola Obajemu, Deanna M. Santer, Oscar Florez-Vargas, Helen Piontkivska, Joselin M. Vargas, Timothy J. Ring, Carmon Kee, Patricio Doldan, D. Lorne Tyrrell, Juan L. Mendoza, Steeve Boulant, Ludmila Prokunina-Olsson
Journal: Nature Genetics (2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, utilizes angiotensin-converting enzyme 2 (ACE2) for entry into target cells. ACE2 has been proposed as an interferon-stimulated gene (ISG). Thus, interferon-induced variability in ACE2 expression levels could be important for susceptibility to COVID-19 or its outcomes. Here, we report the discovery of a novel, transcriptionally independent truncated isoform of ACE2, which we designate as deltaACE2 (dACE2). We demonstrate that dACE2, but not ACE2, is an ISG. In The Cancer Genome Atlas, the expression of dACE2 was enriched in squamous tumors of the respiratory, gastrointestinal and urogenital tracts. In vitro, dACE2, which lacks 356 amino-terminal amino acids, was non-functional in binding the SARS-CoV-2 spike protein and as a carboxypeptidase. Our results suggest that the ISG-type induction of dACE2 in IFN-high conditions created by treatments, an inflammatory tumor microenvironment or viral co-infections is unlikely to increase the cellular entry of SARS-CoV-2 and promote infection. dACE2 is a newly identified isoform of ACE2 that is unable to bind the SARS-CoV-2 spike protein. Truncated dACE2, but not full-length ACE2, is induced by interferons and viruses, thus suggesting that such conditions are unlikely to increase cellular entry of SARS-CoV-2.
Effects of Braiding Parameters on Tissue Engineered Vascular Graft Development
Authors: Jacob C. Zbinden, Kevin M. Blum, Alycia G. Berman, Abhay B. Ramachandra, Jason M. Szafron, Katherine E. Kerr, Jennifer L. Anderson, Gurneet S. Sangha, Conner C. Earl, Noah R. Nigh, Gabriel J. M. Mirhaidari, James W. Reinhardt, Yu‐Chun Chang, Tai Yi, Ryan Smalley, Peter D. Gabriele, Jeremy J. Harris, Jay D. Humphrey, Craig J. Goergen, Christopher K. Breuer
Journal: Advanced Healthcare Materials (2020)

Abstract Tissue engineered vascular grafts (TEVGs) using scaffolds fabricated from braided poly(glycolic acid) (PGA) fibers coated with poly(glycerol sebacate) (PGS) are developed. The approach relies on in vivo tissue engineering by which neotissue forms solely within the body after a scaffold has been implanted. Herein, the impact of altering scaffold braid design and scaffold coating on neotissue formation is investigated. Several combinations of braiding parameters are manufactured and evaluated in a Beige mouse model in the infrarenal abdominal aorta. Animals are followed with 4D ultrasound analysis, and 12 week explanted vessels are evaluated for biaxial mechanical properties as well as histological composition. Results show that scaffold parameters (i.e., braiding angle, braiding density, and presence of a PGS coating) have interdependent effects on the resulting graft performance, namely, alteration of these parameters influences levels of inflammation, extracellular matrix production, graft dilation, neovessel distensibility, and overall survival. Coupling carefully designed in vivo experimentation with regression analysis, critical relationships between the scaffold design and the resulting neotissue that enable induction of favorable cellular and extracellular composition in a controlled manner are uncovered. Such an approach provides a potential for fabricating scaffolds with a broad range of features and the potential to manufacture optimized TEVGs.
Esophageal Temperature Measurement
Authors: Mathieu Pasquier, Peter Paal, Sylweriusz Kosinski, Douglas Brown, Pawel Podsiadlo, Tomasz Darocha
Journal: New England Journal of Medicine (2020)

Hypothermia as encountered in clinical practice may be due to accidental exposure or intentional medical therapy. This video reviews the indications and contraindications for esophageal temperature measurement as well as the equipment and techniques required to perform the procedure in adults.
SAT0231 Hindrances in effecting insurances among dutch ankylosing spondylitis (as) patients
Authors: A Van Tubergen, A Boonen, S Van der Linden
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To evaluate whether AS patients encounter hindrances in effecting different types of insurances after the diagnosis of AS. <h3>Methods</h3> In January 2000, a questionnaire was sent to 129 Dutch AS patients inquiring about three different types of insurances: health insurance, additional work-disability insurance (for non-covered loss of income due to illness) and life insurance. We identified patients who had effected one or more insurances after the diagnosis of AS, and had encountered hindrances. Hindrances were defined as obligation to supply medical information, obligation to undergo medical examination, or restrictions in the insurance contract, such as higher premium, no restitution for AS-related problems etc. As a control group served those patients who also effected the above insurances, but before the diagnosis of AS. <h3>Results</h3> After diagnosis of AS 15 out of 129 patients had effected a health insurance. Four of them were obliged to supply medical information versus 0 from the control group (n = 114) (p &lt; 0.001); 1 patient had to undergo a medical examination versus 3 from the controls (p = 0.96); and for 2 patients restrictions in the contract were imposed versus 0 from the controls (p = 0.005). 19 out of 38 patients effected an additional work-disability insurance after the diagnosis of AS. Six of them were obliged to supply medical information versus 0 from the control group (n = 19) (p = 0.027); 2 patients had to undergo a medical examination versus 0 from the controls (p = 0.47); for 2 patients restrictions in the contract were imposed versus 0 from the controls (p = 0.47). 25 out of 57 patients effected a life insurance after the diagnosis of AS. Seventeen patients were obliged to supply medical information versus 2 from the control group (n = 32) (p &lt; 0.001); 6 patients had to undergo a medical examination versus 3 from the controls (p = 0.26); for 7 patients restrictions in the contract were imposed versus 1 from the controls (p = 0.02). <h3>Conclusion</h3> In The Netherlands, AS patients encounter substantial hindrances in effecting insurances. Especially in effecting a health or life insurance medical information is often requested, which may lead to restrictions in the insurance contract.