tbuckley/cabot-search huggingface dataset:
Abstract 15035: Regional Variation in the Availability and Utilization of Cardiac Rehabilitation Services Among Eligible Medicare Fee-for-Service Beneficiaries: Where Are the Opportunities for Improvement?
Authors: Jessica McNeely, Matthew D Ritchey, Sha Maresh, Linda Schieb, Jennifer Lloyd, Tiffany Chang, Erica Taylor, Janet Wright
Journal: Circulation (2016)

Introduction:  Use of cardiac rehabilitation (CR) can save lives, improve health, and reduce health care costs, yet utilization remains low. The Million Hearts CR Collaborative aims to increase referrals to, participation in, and sustainability of CR programs. This study seeks to identify geographic variation in eligibility, access, and utilization of CR services among Medicare fee-for-service (FFS) beneficiaries.   Methods:  We used Medicare FFS administrative data from 2013-2014 to identify beneficiaries eligible for CR and sites billing for CR services, and to calculate CR utilization rates within 12 months of beneficiaries’ qualifying event, including by Census Division and hospital referral region (HRR). Analyses included all FFS beneficiaries who were continuously enrolled in 2013 and 2014, eligible for CR services in 2013, and alive for at least 30 days post-qualifying event.   Results:  Approximately 450,000 FFS beneficiaries had an event in 2013 that made them eligible for CR, with only 20% utilizing CR services. HRRs in the East South Central and West South Central divisions tended to have the greatest need for CR services (mean: 14.7 and 14.5 eligible beneficiaries per 1000 beneficiaries, resp.), but tended to have the least access to CR (mean: 5.9 and 6.0 CR sites per 1000 eligible beneficiaries, resp.) and the lowest utilization rates (mean: 14.3% and 15.3%, resp.) (Figure), suggesting areas for potential targeted intervention. Alternatively, HRRs in the West North Central division tended to have the most CR sites (mean: 16.8 CR sites per 1000 eligible beneficiaries) and the highest utilization rates (mean: 33.7%).   Conclusions:  Limited access to CR services may contribute to suboptimal uptake of CR among eligible Medicare FFS beneficiaries. This study provides foundational information confirming the widespread need for CR services and identifies geographic areas where the need for CR is incongruent with the number of sites providing these services.
Modulating allergic response by engineering the major Parietaria allergens
Authors: Angela Bonura, Daniela Di Blasi, Bianca Barletta, Cinzia Butteroni, Silvia Corinti, Francesco Gervasi, Mario Raphael Melis, Carina Uasuf, Maria Antonietta Ragusa, Cibella Fabio, Gabriella Di Felice, Paolo Colombo
Journal: Journal of Allergy and Clinical Immunology (2017)
British Association of Dermatologists’ guidelines for the management of pemphigus vulgaris 2017
Authors: K.E. Harman, D. Brown, L.S. Exton, R.W. Groves, P.J. Hampton, M.F. Mohd Mustapa, J.F. Setterfield, P.D. Yesudian, P.M. McHenry, K. Gibbon, D.A. Buckley, T.A. Leslie, E.C. Mallon, S. Wakelin, S. Ungureanu, R.Y.P. Hunasehally, M. Cork, G.A. Johnston, J. Natkunarajah, F.S. Worsnop, N. Chiang, C.E. Duarte Williamson, J. Donnelly, C. Saunders, A.G. Brain
Journal: British Journal of Dermatology (2017)

Plain language summary available online
Mesoporous Silica and Organosilica Nanoparticles: Physical Chemistry, Biosafety, Delivery Strategies, and Biomedical Applications
Authors: Jonas G. Croissant, Yevhen Fatieiev, Abdulaziz Almalik, Niveen M. Khashab
Journal: Advanced Healthcare Materials (2017)

Abstract Predetermining the physico‐chemical properties, biosafety, and stimuli‐responsiveness of nanomaterials in biological environments is essential for safe and effective biomedical applications. At the forefront of biomedical research, mesoporous silica nanoparticles and mesoporous organosilica nanoparticles are increasingly investigated to predict their biological outcome by materials design. In this review, it is first chronicled that how the nanomaterial design of pure silica, partially hybridized organosilica, and fully hybridized organosilica (periodic mesoporous organosilicas) governs not only the physico‐chemical properties but also the biosafety of the nanoparticles. The impact of the hybridization on the biocompatibility, protein corona, biodistribution, biodegradability, and clearance of the silica‐based particles is described. Then, the influence of the surface engineering, the framework hybridization, as well as the morphology of the particles, on the ability to load and controllably deliver drugs under internal biological stimuli (e.g., pH, redox, enzymes) and external noninvasive stimuli (e.g., light, magnetic, ultrasound) are presented. To conclude, trends in the biomedical applications of silica and organosilica nanovectors are delineated, such as unconventional bioimaging techniques, large cargo delivery, combination therapy, gaseous molecule delivery, antimicrobial protection, and Alzheimer's disease therapy.
Abstract 61: Overcoming acquired resistance to PI3K inhibitors in head and neck squamous cell carcinoma with combination treatment
Authors: Aviram Mizrachi, Lara Dunn, Alan Ho, Maurizio Scaltriti
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Activating mutations in PIK3CA, the gene coding for the catalytic subunit of phosphoinositide-3-kinase (PI3K), are prevalent in both HPV+ and HPV- head and neck squamous cell carcinoma (HNSCC). These mutations are therapeutic targets and selection for PIK3CA mutations leads to superior activity of PI3K inhibitors. However, early clinical trials have been disappointing, mainly because the durability of activity of these drugs is limited. Recent preclinical data suggest that acquired resistance to PI3K inhibition is a result of activation of alternative pathways such as mTORC1 and the Cyclin D1 complex. Experimental Design: We challenged two different mechanisms by which PIK3CA-mutated tumors develop resistance to PI3K inhibitors by combining PI3K inhibitors with either mTORC1 inhibitor or CDK 4/6 inhibitor. Using patient-derived xenograft models of HNSCC, we tested whether these therapeutic strategies can overcome drug resistance and result in durable response. Results: Administration of the PI3K inhibitor BYL719 together with the mTORC inhibitor RAD001 delayed tumor growth in comparison with either of these drugs alone. Similarly, treatment with another PI3K inhibitor GDC-0032 and the CDK4/6 inhibitor abemaciclib was superior to single-agent treatments. Conclusions: Co-suppression of PI3K and either mTORC1 or CDK4/6 is effective in preclinical models of HNSCC. These results may provide the rationale to test these therapeutic strategies in the clinic. Citation Format: Aviram Mizrachi, Lara Dunn, Alan Ho, Maurizio Scaltriti. Overcoming acquired resistance to PI3K inhibitors in head and neck squamous cell carcinoma with combination treatment [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 61.
Abstract 20150: High Intensity Aerobic Training Stimulus Over Two Years Improves Left Ventricular Stiffness
Authors: Satyam Sarma, Erin J Howden, Mitchel Samels, Braden Everding, Sheryl Livingston, Michael D Palmer, Benjamin D Levine
Journal: Circulation (2016)

Background:  Low fitness is a risk factor for heart failure, particularly heart failure with preserved ejection fraction (HFpEF). This risk may be mediated via increased cardiac stiffness which is also linked to low fitness. Prior studies of aerobic exercise in seniors failed to show a decrease in stiffness. We hypothesized a high volume and intensity aerobic training stimulus over two years in previously sedentary middle aged adults would improve left ventricular stiffness.   Methods:  We recruited 61 (48% male) healthy but sedentary normotensive middle aged subjects (53 ± 5 yrs). Subjects were randomized to either aerobic exercise (Ex; n=34) or attention control/yoga (Yg; n=27). Fitness (peak VO 2 ) and left ventricular stiffness from invasive hemodynamic construction of end-diastolic pressure volume relationship (EDPVR) was measured at baseline and 2 years after training. LV stiffness was calculated by curve fit of the diastolic portion of the pressure-volume curve using pulmonary capillary wedge pressure as end diastolic pressure and 3D echocardiography to measure LV end diastolic volume (LVEDV). Eight subjects withdrew over the course of the study.   Results:  Adherence to prescribed exercise sessions was greater than 90% in the aerobic study arm. Baseline fitness was similar between groups (Ex: 29.0 ± 5.1; Yg: 29.5 ± 5.1 ml/kg/min). After 2 years, fitness improved by 18% in the aerobic group (Ex: 34.3 ± 6.5; Yg: 28.7 ± 5.4 p   Conclusions:  In sedentary healthy middle age adults, 2 years of high aerobic stimulus improved fitness and decreased cardiac stiffness. Decreases in stiffness tracked improvements in LVEDV. Regular aerobic exercise may mediate protection against future risk of HFpEF by decreasing cardiac stiffness.
Clinical Firsts — Christiaan Barnard’s Heart Transplantations
Authors: Shelley McKellar
Journal: New England Journal of Medicine (2017)

On December 3, 1967, South African cardiac surgeon Christiaan Barnard transplanted a healthy heart into 55-year-old Louis Washkansky, expanding organ-replacement therapy beyond corneas, sex glands, kidneys, lungs, pancreas, and liver in the quest to treat heart failure.
Remote Patient Management After Discharge of Hospitalized Heart Failure Patients: The Better Effectiveness After Transition - Heart Failure Study
Authors: Michael K Ong, Patrick S Romano, Sarah Edgington, Andrew D Auerbach, Harriet U Aronow, Jeanne T Black, Teresa De Marco, Jose J Escarce, Lorraine Evangelista, Theodore G Ganiats, Barry Greenberg, Sheldon Greenfield, Sherrie H Kaplan, Asher Kimchi, Honghu Liu, Dawn Lombardo, Carol M Mangione, Majid Sarrafzadeh, Kathleen Tong, Gregg C Fonarow, Beat-Hf Rsch Grp
Journal: Circulation (2015)

Author(s): Ong, Michael K; Romano, Patrick S; Edgington, Sarah; Auerbach, Andrew D; Aronow, Harriet U; Black, Jeanne T; De Marco, Teresa; Escarce, Jose J; Evangelista, Lorraine; Ganiats, Theodore G; Greenberg, Barry; Greenfield, Sheldon; Kaplan, Sherrie H; Kimchi, Asher; Liu, Honghu; Lombardo, Dawn; Mangione, Carol M; Sarrafzadeh, Majid; Tong, Kathleen; Fonarow, Gregg C; Grp, BEAT-HF Rsch
Abstract 18971: Anti-Tachycardia Pacing After Continuous Flow Left Ventricular Assist Device Implantation is Associated With Reduced Mortality Compared to Defibrillation
Authors: Brian D Greet, Deep Pujara, Haren Patel, Michael Shieh, Ryle Przybylowicz, Justin Arunthamakun, David Burkland, Masahiro Ono, Jeffrey Morgan, Jie Cheng, Nilesh Mathuria
Journal: Circulation (2017)

Introduction: Despite a high incidence of ventricular arrhythmia (VA) after continuous flow left ventricular assist device (CFLVAD) implantation, the benefit of implantable cardioverter defibrillat...
Margaret McCartney: Scottish GP contract—responsibility without power?
Authors: Margaret McCartney
Journal: BMJ (2017)

The proposed Scottish GP contract is clearly intended to shore up GPs and support primary care, and there’s much in it to like. It effectively underwrites premises so that younger GPs won’t be dissuaded from joining a practice that owns its buildings. It includes a minimum income expectation for 40 hour full time GP equivalents, some 20% of whom in Scotland earn less than the proposed minimum of £80 000.

It contains impressive statements on the link between workforce morale and patient experience and says that not all patients need a doctor’s expertise to be treated. And help is promised through pharmacists and physiotherapists stepping …
Immune cells involved in tumor regression in syngeneic rat and mouse models of glioma
Authors: James F. Curtin, Gwendalyn D. King, Weidong Xiong, Chunyan Liu, Phillip Ng, Pedro R. Lowenstein, Maria G. Castro
Journal: Cancer Research (2005)

6026  Malignant glioma is a highly invasive and neurologically destructive tumor frequently resulting in death within nine months after diagnosis. While treatments utilizing gene therapeutic vectors expressing HSV1-thymidine kinase (HSV1-TK) in combination with the pro-drug ganciclovir (GCV) are 100% efficient in many preclinical glioma models, phase 1 and 2 clinical trials in human patients have not shown such dramatic results. We have developed a macroscopic preclinical model of glioma in rats and have shown that all single cytokine and cytotoxic gene therapies fail. Furthermore, combined treatments with HSV1-TK and various immuno-modulatory agents were also unsuccessful for improving survival. Only combined treatment with HSV1-TK and the potent cytokine for stimulation of dendritic cells, human soluble Fms like tyrosine kinase 3 ligand (hsFlt3L), provided 80% survival in this syngeneic model of glioma. This model is a more faithful reflection of the clinical results obtained utilizing single gene therapies in human patients suffering from glioma. In the present study a detailed FACS based analysis of immune cells present in naive and glioma bearing animals was conducted after treatment with HSV1-TK and hsFlt3L alone or in combination. We found that when adenoviral vectors expressing HSV1-TK and hsFlt3L are injected into naive brains, large increases in B, NK-T, NK and plasmacytoid dendritic cell (pDC) populations were observed. NK and NK-T cells are important mediators of antigen-independent anti-tumor cytotoxicity. pDC’s may improve antigen presentation and prime an efficient adaptive immune response against the tumor. ELISA and ICC were used to assess long-term expression of both HSV1-TK and hsFlt3L transgenes. In summary, our results indicate that the combined anti-tumor effect of HSV-1TK and hsFlt3L enhances both innate and adaptive branches of the immune system and improves survival in a syngeneic macroscopic glioma model.
Abstract 20109: Midterm Outcome of Valve-Sparing Aortic Root Replacement in Loeys-Dietz Syndrome
Authors: Haruo Yamauchi, Kan Nawata, Norifumi Takeda, Daishi Fujita, Masao Daimon, Osamu Kinoshita, Yasutaka Hirata, Minoru Ono
Journal: Circulation (2017)

Introduction: Loeys-Dietz syndrome (LDS) is characterized as an aggressive aortic disease with transforming growth factor-beta receptor (TGFBR) mutations. The outcome for patients undergoing valve-...
Epigenetic biomarkers in gastrointestinal cancers: The current state and clinical perspectives
Authors: Hege Marie Vedeld, Ajay Goel, Guro E. Lind
Journal: Seminars in Cancer Biology (2017)

Each year, almost 4.1 million people are diagnosed with gastrointestinal (GI) cancers. Due to late detection of this disease, the mortality is high, causing approximately 3 million cancer-related deaths annually, worldwide. Although the incidence and survival differs according to organ site, earlier detection and improved prognostication have the potential to reduce overall mortality burden from these cancers. Epigenetic changes, including aberrant promoter DNA methylation, are common events in both cancer initiation and progression. Furthermore, such changes may be identified non-invasively with the use of PCR based methods, in bodily fluids of cancer patients. These features make aberrant DNA methylation a promising substrate for the development of disease biomarkers for early detection, prognosis and for predicting response to therapy. In this article, we will provide an update and current clinical perspectives for DNA methylation alterations in patients with colorectal, gastric, pancreatic, liver and esophageal cancers, and discuss their potential role as cancer biomarkers.
Abstract 17882: A Method for Real-time CPR Detection From the Thoracic Impedance Signal
Authors: Heemun Kwok, Jason Coult, Lawrence Sherman, Jennifer Blackwood, Peter Kudenchuk, Thomas Rea
Journal: Circulation (2015)

Introduction: Accurate detection of chest compressions is a means to improve CPR through real-time feedback or post-event review. Accelerometer technology is the gold standard to detect compressions but is not universally available and requires additional equipment. Hypothesis: An algorithm derived from the transthoracic impedance signal could achieve high sensitivity and specificity for compression detection and accurately measure the CPR fraction. Methods: Defibrillator recordings from cardiac arrest cases were used to develop (N=20) and validate (N=62) the compression detection algorithm. Accelerometer data were used to define the presence or absence of compressions at 1-second intervals throughout entire cases, up to 10 minutes per case. The impedance-based algorithm cross-correlates the impedance signal with a series of wavelets and then integrates sequential outputs with a hidden Markov model. Using accelerometer classification as the gold standard, the sensitivity and specificity of the impedance-based algorithm for compression detection were estimated by a multilevel model to account for clustering of classifications within cases. The difference in CPR fractions was calculated for each case by subtracting the accelerometer-derived CPR fraction from the impedance-derived CPR fraction, and their median and 95% CI were estimated by the Wilcoxon signed-rank test. Results: The validation set included a median 535 seconds per case. The impedance-derived algorithm had mean sensitivity 0.95 (95% CI 0.93, 0.96) and mean specificity 0.91 (95% CI 0.90, 0.93). Median CPR fraction was 0.74 (IQR 0.65, 0.79) based on the accelerometer assessment. The impedance-derived CPR fraction was 0.71 (95% CI 0.64, 0.77), for a difference of -0.01 (95% CI -0.03, 0.00). Conclusion: A method that identifies CPR from the impedance signal alone had high mean sensitivity and high mean specificity but slightly underestimated the CPR fraction.
Oncolytic virotherapy as an immunotherapeutic strategy for multiple myeloma
Authors: Daniel E. Meyers, Satbir Thakur, Chandini M. Thirukkumaran, Don G. Morris
Journal: Blood Cancer Journal (2017)

Abstract Multiple Myeloma (MM), a clonal malignancy of antibody-producing plasma cells, is the second most common hematologic malignancy and results in significant patient morbidity and mortality. The high degree of immune dysregulation in MM, including T cell imbalances and up-regulation of immunosuppressive checkpoint proteins and myeloid derived suppressor cells, allows this malignancy to escape from host immune control. Despite advances in the therapeutic landscape of MM over the last decade, including the introduction of immunomodulatory drugs, the prognosis for this disease is poor, with less than 50% of patients surviving 5 years. Thus, novel treatment strategies are required. Oncolytic viruses (OV) are a promising new class of therapeutics that rely on tumour specific oncolysis and the generation of a potent adaptive anti-tumour immune response for efficacy. To date, a number of OV have shown efficacy in pre-clinical studies of MM with three reaching early phase clinical trials. OVs represent a rational therapeutic strategy for MM based on (1) their tumour tropism, (2) their ability to potentiate anti-tumour immunity and (3) their ability to be rationally combined with other immunotherapeutic agents to achieve a more robust clinical response.
Abstract 15142: Disagreement Among Echocardiographic Parameters of Mitral Regurgitant Severity is Associated With Discordance Between MRI and Echocardiography
Authors: Seth Uretsky, Leo Marcoff, Konstantinos Koulogiannis, Lillian Aldaia, Edgar Argulian, Mark Rosenthal, Linda Gillam, Steven Wolff
Journal: Circulation (2016)

Introduction:  Echocardiographic (Echo) parameters to determine the severity of mitral regurgitation (MR) may disagree. To this date, no study has determined the rate of disagreement of Echo parameters in patients with MR. Furthermore, no study has determined whether disagreement among Echo parameters is associated with discordance between Echo and MRI in assessing the severity of MR.   Hypothesis:  Disagreement of Echo parameters will be associated with discordance between Echo and MRI assessment of MR.   Methods:  This study included 115 patients (62 ± 14yrs, male 55%) enrolled in a prospective multicenter study of patients with MR who underwent Echo and MRI. Severity of MR by MRI was determined by regurgitant volume (mild    Results:  All nine Echo parameters agreed in 6 (5%) patients. There was agreement of 78-89% of parameters in 54 (47%) patients and 56-67% in 55 (48%) patients. There was a significantly lower agreement among Echo parameters in patients in whom there was a 2 grade difference between Echo and MRI compared to patients in whom Echo and MRI agreed (figure).   Conclusions:  There was significant disagreement among Echo parameters in almost half the patients with complete agreement among Echo parameters in only 5% of patients. Disagreement among Echo parameters was associated with discordance between Echo and MRI in the quantification of MR.
β2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer
Authors: Bernhard W. Renz, Ryota Takahashi, Takayuki Tanaka, Marina Macchini, Yoku Hayakawa, Zahra Dantes, H. Carlo Maurer, Xiaowei Chen, Zhengyu Jiang, C. Benedikt Westphalen, Matthias Ilmer, Giovanni Valenti, Sarajo K. Mohanta, Andreas J.R. Habenicht, Moritz Middelhoff, Timothy Chu, Karan Nagar, Yagnesh Tailor, Riccardo Casadei, Mariacristina Di Marco, Axel Kleespies, Richard A. Friedman, Helen Remotti, Maximilian Reichert, Daniel L. Worthley, Jens Neumann, Jens Werner, Alina C. Iuga, Kenneth P. Olive, Timothy C. Wang
Journal: Cancer Cell (2017)