tbuckley/cabot-search huggingface dataset:
Response by Pollack and Weisfeldt to Letter Regarding Article, “Impact of Bystander Automated External Defibrillator Use on Survival and Functional Outcomes in Shockable Observed Public Cardiac Arrests”
Authors: Ross A. Pollack, Myron L. Weisfeldt
Journal: Circulation (2018)

In Response:The letter by Karam and collaborators offers a number of appreciated compliments about this article 1 but offers a caution related to potential confounding from other efforts that bystanders may make to improve survival in patients aside from using an automatic external defibrillator (AED).As with any cohort study, there are always factors that cannot or are not measured.The authors of the letter are correct in stating that bystanders trained to apply an AED may have called an emergency medical service (EMS) with less delay and may have performed cardiopulmonary resuscitation with better quality than a bystander not using an AED.We are not currently able to determine quantitatively whether these concerns are valid.Although many studies report time intervals from the onset of arrest to call for EMS, these are at best retrospective statements from an understandably stressed bystander; these estimations have been shown to be unreliable. 2In addition, although the Resuscitation Outcomes Consortium network pioneered cardiopulmonary resuscitation quantitative assessment in many US and Canadian EMS systems, there has been only limited use of AEDs that monitor cardiopulmonary resuscitation quality measures.Thus, we must acknowledge these limitations.It might be noted that bystander AED application may also provide benefit in less delay for EMS to act because clothing is removed and leads are in place even if the rhythm is nonshockable.However, to be comprehensive, we should acknowledge that there are in fact many serious other unknowns in most resuscitation cohort studies that this study, we hope, minimized by concentrating on observed shockable arrests occurring in a public location.We reduced these unknowns by our exclusion of private or unobserved arrests, which are more likely to include arrests with noncardiac origin, 3 multiple comorbidities, 4 and a likely delayed time to 911 call.Because the arrest was observed, we propose that this led to a shorter and more uniform arrest-to-call time than in other locations where most cardiac arrests occur (in the home).These issues were the subject of a recent commentary in Circulation, written by the corresponding author, as related to entrance into randomized clinical trials. 5ur hope is that the present study in this ideal population, which demonstrated a nearly 3-fold increase in the rate of excellent functional outcome for those with a bystander AED shock compared with shock by EMS, will enhance efforts to bring the AED to the educated and willing bystander with greater frequency.In addition, these results should increase efforts to train the public in using AEDs, rapidly calling for EMS, and performing quality cardiopulmonary resuscitation.
A prospective observational safety study of patients with <scp> <i>BRAF</i> <sup>V</sup> </scp> <sup>600</sup> ‐mutated unresectable or metastatic melanoma treated with vemurafenib (Zelboraf Safety Study)
Authors: P.G. Corrie, P. Terheyden, A.J. Tije, R. Herbst, R. Jansen, M. Marples, D. Debus, R. Marconcini, M. Blasinska‐Morawiec, K. Freivogel, M.L.G. Munson, G.R. Goodman, J.J. Hsu, N. Sadetsky, D. Colburn, P. Rutkowski
Journal: British Journal of Dermatology (2018)
Apixaban to Prevent Venous Thromboembolism in Patients with Cancer
Authors: Marc Carrier, Karim Abou-Nassar, Ranjeeta Mallick, Vicky Tagalakis, Sudeep Shivakumar, Ariah Schattner, Philip Kuruvilla, Danny Hill, Silvana Spadafora, Katerine Marquis, Mateya Trinkaus, Anna Tomiak, Agnes Y.Y. Lee, Peter L. Gross, Alejandro Lazo-Langner, Robert El-Maraghi, Glenwood Goss, Gregoire Le Gal, David Stewart, Timothy Ramsay, Marc Rodger, Debra Witham, Philip S. Wells
Journal: New England Journal of Medicine (2018)

Patients with active cancer have an increased risk of venous thromboembolism, which results in substantial morbidity, mortality, and health care expenditures. The Khorana score (range, 0 to 6, with higher scores indicating a higher risk of venous thromboembolism) has been validated to identify patients with cancer at elevated risk for this complication and may help select those who could benefit from thromboprophylaxis.
Predicting Carfilzomib Resistance Mechanisms and Therapeutics Using Computational Modelling of Genomics and Proteomics
Authors: Andrej Besse, Christopher R. Cogle, Leylah M. Drusbosky, Shireen Vali, Taher Abbasi, Neeraj Kumar Singh, Neha G Gupta, Abha Kushwaha, Pallavi Kumari, Karthik Sundara Raju, Ganesh Naga, Sayani Basu, Christoph Driessen, Lenka Besse
Journal: Blood (2018)
iOS data app for supportive care in cancer.
Authors: Thomas Wayne Butler, Lucas Najera
Journal: Journal of Clinical Oncology (2018)

148 Background: Providers in oncology must optimize time to serve as many patients as possible daily with the caveat that patient outcomes and satisfaction is paramount. However, a paucity of tools are available to evaluate efficiency. An objective analysis of productivity and patient flow would optimize staff utilization, resulting in an increase in quality and economics of patient care. Methods: Patient flow in a supportive care clinic was recorded manually to delineate patient flow and staff productivity. This method provided baseline data for analysis. An iOS app was then created which can be adjusted to gather data and measure the flow in the clinic prompting patients to complete a questionnaire in the waiting room. The application stores the weather and driving distances to determine how these possibly correlate with efficiency. Additional data points were identified to trend staffing schedules and patient flow. Data inputs include diseases, characteristics, family dynamics and other clinical demographics for analysis and deliverables received. Results: The application generates reports for any variable collected, with a predefined daily report to compute the total relative value units (RVU) of the visit, the total cost and RVUs distribution by provider and/or staff. A percent profit or loss illustrates “value” created by individual objects and staff. The application interprets changes in efficiency over time. In the preliminary results we found direct intervention with the patient and record taking to be the primary deterrent to efficiency and having adequate oncology nursing staffing was most conducive with physician wait times varying significantly with changes in oncology staffing. Conclusions: This tool is unique in producing a cost-effective tool to evaluate daily patient flow and staff utilization. It has future applicability in dynamic analysis of how symptom burden and barriers to care in cancer patients effects the economics of a supportive care clinic. This production of real time information will provide data to improve efficiency, outcomes of care. We plan a pilot study in the supportive care clinic to further evaluate this tool and its benefit to optimizing flow, and enhance cost-effective, patient-centered allocation of resources in supportive care.
Prediction of final infarct volume from native CT perfusion and treatment parameters using deep learning
Authors: David Robben, Anna M.M. Boers, Henk A. Marquering, Lucianne L.C.M. Langezaal, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Wim H. van Zwam, Diederik W.J. Dippel, Charles B.L.M. Majoie, Aad van der Lugt, Robin Lemmens, Paul Suetens
Journal: Medical Image Analysis (2019)
A Phase 2 Randomized, Sham-Controlled Trial of Internal Carotid Artery Infusion of Autologous Bone Marrow–Derived ALD-401 Cells in Patients With Recent Stable Ischemic Stroke (RECOVER-Stroke)
Authors: Sean I. Savitz, Dileep Yavagal, George Rappard, William Likosky, Neal Rutledge, Carmelo Graffagnino, Yazan Alderazi, Jennifer A. Elder, Peng R. Chen, Ronald F. Budzik, Ronald Tarrel, David Y. Huang, James M. Hinson
Journal: Circulation (2019)

Background: Ischemic stroke has no approved treatments to enhance recovery. ALD-401 is an enriched population of aldehyde dehydrogenase-bright stem cells, capable of reducing neurological deficits in animal models. The primary objective of this trial was to determine the safety of internal carotid artery, intra-arterially delivered autologous bone marrow–derived ALD-401 in patients with disabling middle cerebral artery stroke in comparison with sham harvest with sham infusion. Secondary objectives were to determine feasibility and efficacy. Methods: This was a prospective phase 2, industry-funded, randomized, sham-controlled, parallel-group, multicenter study with blinded assessments. One hundred subjects were planned, aged 30 to 83 years, with confirmed first-time middle cerebral artery ischemic stroke with modified Rankin scale ≥3. Study patients were randomly assigned 3:2 to bone marrow harvest at 11 to 17 days after stroke followed 2 days later by intracarotid infusion of ALD-401 versus sham harvest and then sham infusion in the same timeframe. The primary study outcome was safety based on the incidence of a 4-point National Institutes of Health Stroke Scale worsening and the proportion of serious adverse events. Efficacy was based on modified Rankin scale change at 90 days. Other secondary outcomes were the proportions of patients experiencing adverse events, disability by Barthel Index, quality of life using EQ-5D, rehabilitation utilization, disability at 1 year, and MRI evidence of complications. Results: There were no infusional or allergic reactions and no difference in treatment emergent adverse events. Four patients had small areas of asymptomatic restricted diffusion on MRI in the treatment group. There was no significant difference between the ALD-401 and placebo groups on the modified Rankin scale for the intent-to-treat population at day 90 (mean difference, 0.3; 95% CI, –0.3 to 0.8; P =0.330). There were no significant differences between the groups on any of the secondary efficacy measures. Conclusions: Intracarotid infusion of ALD-401 does not lead to clinical adverse events in patients with subacute ischemic stroke, although there was a higher incidence of small lesions on MRI in the treatment group. There was no difference in the primary efficacy end point between the groups. The study provides a framework for the design and conduct of future intra-arterial cell therapy trials in stroke. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01273337.
Trivalent RING Assembly on Retroviral Capsids Activates TRIM5 Ubiquitination and Innate Immune Signaling
Authors: Adam J. Fletcher, Marina Vaysburd, Sarah Maslen, Jingwei Zeng, J. Mark Skehel, Greg J. Towers, Leo C. James
Journal: Cell Host & Microbe (2018)

TRIM5 is a RING domain E3 ubiquitin ligase with potent antiretroviral function. TRIM5 assembles into a hexagonal lattice on retroviral capsids, causing envelopment of the infectious core. Concomitantly, TRIM5 initiates innate immune signaling and orchestrates disassembly of the viral particle, yet how these antiviral responses are regulated by capsid recognition is unclear. We show that hexagonal assembly triggers N-terminal polyubiquitination of TRIM5 that collectively drives antiviral responses. In uninfected cells, N-terminal monoubiquitination triggers non-productive TRIM5 turnover. Upon TRIM5 assembly on virus, a trivalent RING arrangement allows elongation of N-terminally anchored K63-linked ubiquitin chains (N-K63-Ub). N-K63-Ub drives TRIM5 innate immune stimulation and proteasomal degradation. Inducing ubiquitination before TRIM5 assembly triggers premature degradation and ablates antiviral restriction. Conversely, driving N-K63 ubiquitination after TRIM5 assembly enhances innate immune signaling. Thus, the hexagonal geometry of TRIM5's antiviral lattice converts a capsid-binding protein into a multifunctional antiviral platform.
Nanoparticles targeting extra domain B of fibronectin-specific to the atherosclerotic lesion types III, IV, and V-enhance plaque detection and cargo delivery
Authors: Mikyung Yu, Carleena A. Ortega, Kevin Si, Roberto Molinaro, Frederick J. Schoen, Renata F. C. Leitao, Xiaoding Xu, Morteza Mahmoudi, Suyeon Ahn, Jerry Liu, Phei Er Saw, In-Hyun Lee, Mirna M. B. Brayner, Azita Lotfi, Jinjun Shi, Peter Libby, Sangyong Jon, Omid C. Farokhzad
Journal: Theranostics (2018)

Extra domain B of fibronectin (FN-EDB) is upregulated in the extracellular matrix during tissue remodeling and has been postulated as a potential biomarker for atherosclerosis, yet no systematic test for FN-EDB in plaques has been reported.We hypothesized that FN-EDB expression would intensify in advanced plaques.Furthermore, engineering of FN-EDB-targeted nanoparticles (NPs) could enable imaging/diagnosis and local delivery of payloads to plaques.Methods: The amount of FN-EDB in human atherosclerotic and normal arteries (ages: 40 to 85 years) was assessed by histological staining and quantification using an FN-EDB-specific aptide (APT FN-EDB ).FN-EDB-specific NPs that could serve as MRI beacons were constructed by immobilizing APT FN-EDB on the NP surface containing DTPA [Gd].MRI visualized APT FN-EDB -[Gd]NPs administered to atherosclerotic apolipoprotein E-deficient mice in the brachiocephalic arteries.Analysis of the ascending-to-descending thoracic aortas and the aortic roots of the mice permitted quantitation of Gd, FN-EDB, and APT FN-EDB -[Gd]NPs.Cyanine, a model small molecule drug, was used to study the biodistribution and pharmacokinetics of APT FN-EDB -NPs to evaluate their utility for drug delivery.Results: Atherosclerotic tissues had significantly greater FN-EDB-positive areas than normal arteries (P < 0.001).This signal pertained particularly to Type III (P < 0.01), IV (P < 0.01), and V lesions (P < 0.001) rather than Type I and II lesions (AHA classification).FN-EDB expression was positively correlated with macrophage accumulation and neoangiogenesis.Quantitative analysis of T1-weighted images of atherosclerotic mice revealed substantial APT FN-EDB -[Gd]NPs accumulation in plaques compared to control NPs, conventional MRI contrast agent (Gd-DTPA) or accumulation in wild-type C57BL/6J mice.Additionally, the APT FN-EDB -NPs significantly prolonged the blood-circulation time (t 1/2 : ~ 6 h) of a model drug and increased its accumulation in plaques (6.9-fold higher accumulation vs. free drug).Conclusions: Our findings demonstrate augmented FN-EDB expression in Type III, IV, and V atheromata and that APT FN-EDB -NPs could serve as a platform for identifying and/or delivering agents locally to a subset of atherosclerotic plaques.
General and Abdominal Obesity and Incident Distal Sensorimotor Polyneuropathy: Insights Into Inflammatory Biomarkers as Potential Mediators in the KORA F4/FF4 Cohort
Authors: Sabrina Schlesinger, Christian Herder, Julia M. Kannenberg, Cornelia Huth, Maren Carstensen-Kirberg, Wolfgang Rathmann, Gidon J. Bönhof, Wolfgang Koenig, Margit Heier, Annette Peters, Christa Meisinger, Michael Roden, Barbara Thorand, Dan Ziegler
Journal: Diabetes Care (2018)

OBJECTIVE To investigate the associations between different anthropometric measurements and development of distal sensorimotor polyneuropathy (DSPN) considering interaction effects with prediabetes/diabetes and to evaluate subclinical inflammation as a potential mediator. RESEARCH DESIGN AND METHODS This study was conducted among 513 participants from the Cooperative Health Research in the Region of Augsburg (KORA) F4/FF4 cohort (aged 62–81 years). Anthropometry was measured at baseline. Incident DSPN was defined by neuropathic impairments using the Michigan Neuropathy Screening Instrument at baseline and follow-up. Associations between anthropometric measurements and DSPN were estimated by multivariable logistic regression. Potential differences by diabetes status were assessed using interaction terms. Mediation analysis was conducted to determine the mediation effect of subclinical inflammation in these associations. RESULTS After a mean follow-up of 6.5 years, 127 cases with incident DSPN were detected. Both general and abdominal obesity were associated with development of DSPN. The odds ratios (95% CI) of DSPN were 3.06 (1.57; 5.97) for overweight, 3.47 (1.72; 7.00) for obesity (reference: normal BMI), and 1.22 (1.07; 1.38) for 5-cm differences in waist circumference, respectively. Interaction analyses did not indicate any differences by diabetes status. Two chemokines (C-C motif chemokine ligand 7 [CCL7] and C-X-C motif chemokine ligand 10 [CXCL10]) and one neuron-specific marker (Delta/Notch-like epidermal growth factor–related receptor [DNER]) were identified as potential mediators, which explained a proportion of the total effect up to 11% per biomarker. CONCLUSIONS General and abdominal obesity were associated with incident DSPN among individuals with and without diabetes, and this association was partly mediated by inflammatory markers. However, further mechanisms and biomarkers should be investigated as additional mediators to explain the remainder of this association.
Vaccine Prevents Active Tuberculosis
Authors: Anita Slomski
Journal: JAMA (2018)

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Caregiver training for a therapeutic alliance in palliative home care.
Authors: Diego Lopane, Carlotta Pavesi, Concetta Arcanà, Beatrice Bonelli, Stefano Ferrari, Diego Lopane, Santina Giuffrè, Chiara Poggio, Annalisa Saetta, Lorenza Rimassa, Armando Santoro
Journal: Journal of Clinical Oncology (2018)

15 Background: Caregiver (CG) presence and efficiency are crucial in providing a palliative home care (PC) program. The Aims of this study were: 1. to investigate educational needs expressed by caregivers (CGs) of advanced cancer patients (pts) in home care service (HCS) of our Institution; 2. to develop a guide to support PC team; 3. to evaluate the impact of this tool on CGs skills. Methods: Based on published data, we identified 3 areas of interest (therapy administration (TA), care, symptoms management) and 17 specific topics: mobilization, hygiene, skin/mouth care, dysphagia, xerostomia, bowel function, diuresis/urinary catheter care, feeding, and some symptoms. We then prepared a guide with clear information regarding each topic. We mainly focused on symptoms, in particular on pain. We elaborated instructions on TA and administration routes (techniques for subcutaneous (SC) injection/infusion with elastomeric pump). Use of short tips, images, pictures, and cartoons made the guide very accessible. From July to September 2017 the guide was provided to 24 CGs, 8 (33%) men, 16 (66%) women. 12 CGs (50%) were pts’ partners, 10 (41.6%) son/daughter, 1 relative (4.1%), 1 formal CG (4.1%). Several educational interventions (EI) were adopted to reinforce learning according to the pt conditions and CGs’ needs. The effectiveness of EI was retrospectively assessed from clinical records. Results: We offered 218 EI to 24 CGs, with an average of 9 per CG, and within a range of 6-13 per CG. Topics most frequently addressed were: SC injection technique (100%), skin care (21 CGs, 87.5%), pain care (21 CGs, 87.5%), feeding (20 CGs, 83.3%), mobilization techniques (17 CGs, 70.8%). We also performed 16 EI repetitions on 11 CGs (45.8%) on ≥1 topics: 4 for mobilization, 2 for pain, dysphagia, SC injection, feeding, bowel function, 2 for other topics.Assessment of EI effectiveness showed great CG receptivity, with 93% of interventions followed by a change in CG behaviour thereafter. Conclusions: The proposed intervention, the use of a simple guide to reinforce EI, is feasible, well accepted and appears to improve CG’s ability in providing home PC. Based on these results, we added a section dedicated to EI for CGs into the new electronic record of our HCS, introduced since January 2018.
Stigma and its impact on the families of former soldiers of the German Armed Forces: an exploratory study
Authors: Katrin Schuy, Simone Dors, Loni Brants, Marie Horzetzky, Gerd Willmund, Andreas Ströhle, Peter Zimmermann, Heinrich Rau, Stefan Siegel
Journal: Military Medical Research (2018)

Military families who have a family member with a mental illness see themselves confronted with many demands. Stigmatization is one of these challenges. Stigmatization affects not only the individual who suffers from a mental illness but also other family members via stigma by association and vicarious stigma. Stigma by association occurs when mental illness stigma spills over to individuals associated with an individual with a mental illness. Vicarious stigma describes the suffering of family members when they note the impact of stigma on their relative with mental illness. As a societal phenomenon, stigma plays out in social interactions and might therefore influence the social networks of families. It is also associated with healthcare utilization.Narrative interviews were conducted with 15 family members (partners, spouses, parents and children) of former soldiers of the German Armed Forces with a service-induced mental illness. The transcribed interview data were analyzed using a thematic analysis approach, in which codes were formed and emerging themes were systemized. Relationships between stigma, the families' reactions to it, its effects on their social relationships and its interference with their healthcare utilization were analyzed.This study provides a detailed description of how relatives of former German soldiers with mental health problems experience stigma by association and vicarious stigma. Their perceptions are shown in a model that describes stigma-related attitudes, reactions to them and their effects on the social relationships of former soldiers' families. These families felt stigmatized because of the former soldiers' mental illness (mental illness stigma) and the military context in which it occurred (former soldier stigma). They reacted with nondisclosure, anger, acceptance and self-blame. Stigma was associated with smaller and weaker social networks that were characterized by social exclusion, self-segregation and conflicts with extended family, friends and colleagues. Stigma also affected the families' healthcare utilization.Urgently needed anti-stigma campaigns, particularly in the civilian context, should address the stigmatization of both mental illness and the military participation of the families affected. They should consider the needs of both former soldiers with a mental illness and their families.
Abstract 15313: Long Non-Coding RNA MIAT Regulates Smooth Muscle Cell Plasticity and Macrophage Activity in Advanced Atherosclerosis Lesions
Authors: Yuhuang Li, Hong Jin, Ljubica Perisic, Ekaterina Chernogubova, Göran K Hansson, Ulf Hedin, Claes Bergmark, Lars Maegdefessel
Journal: Circulation (2017)

Background: Long noncoding RNAs (lncRNAs) have recently received great attention as epigenetic regulators in disease processes. Aim of the current study was to identify and functionally assess the ...