tbuckley/cabot-search huggingface dataset:
Noninvasive Imaging of the Coronary Vasculature Using Ultrafast Ultrasound
Authors: David Maresca, Mafalda Correia, Olivier Villemain, Alain Bizé, Lucien Sambin, Mickael Tanter, Bijan Ghaleh, Mathieu Pernot
Journal: JACC. Cardiovascular imaging (2017)

The aim of this study was to investigate the potential of coronary ultrafast Doppler angiography (CUDA), a novel vascular imaging technique based on ultrafast ultrasound, to image noninvasively with high sensitivity the intramyocardial coronary vasculature and quantify the coronary blood flow dynamics. Noninvasive coronary imaging techniques are currently limited to the observation of the epicardial coronary arteries. However, many studies have highlighted the importance of the coronary microcirculation and microvascular disease. CUDA was performed in vivo in open-chest procedures in 9 swine. Ultrafast plane-wave imaging at 2,000 frames/s was combined to an adaptive spatiotemporal filtering to achieve ultrahigh-sensitive imaging of the coronary blood flows. Quantification of the flow change was performed during hyperemia after a 30-s left anterior descending (LAD) artery occlusion followed by reperfusion and was compared to gold standard measurements provided by a flowmeter probe placed at a proximal location on the LAD (n = 5). Coronary flow reserve was assessed during intravenous perfusion of adenosine. Vascular damages were evaluated during a second set of experiments in which the LAD was occluded for 90 min, followed by 150 min of reperfusion to induce myocardial infarction (n = 3). Finally, the transthoracic feasibility of CUDA was assessed on 2 adult and 2 pediatric volunteers. Ultrahigh-sensitive cine loops of venous and arterial intramyocardial blood flows were obtained within 1 cardiac cycle. Quantification of the coronary flow changes during hyperemia was in good agreement with gold standard measurements (r2 = 0.89), as well as the assessment of coronary flow reserve (2.35 ± 0.65 vs. 2.28 ± 0.84; p = NS). On the infarcted animals, CUDA images revealed the presence of strong hyperemia and the appearance of abnormal coronary vessel structures in the reperfused LAD territory. Finally, the feasibility of transthoracic coronary vasculature imaging was shown on 4 human volunteers. Ultrafast Doppler imaging can map the coronary vasculature with high sensitivity and quantify intramural coronary blood flow changes.
Transcriptional risk scores link GWAS to eQTLs and predict complications in Crohn's disease
Authors: Urko M Marigorta, Lee A Denson, Jeffrey S Hyams, Kajari Mondal, Jarod Prince, Thomas D Walters, Anne Griffiths, Joshua D Noe, Wallace V Crandall, Joel R Rosh, David R Mack, Richard Kellermayer, Melvin B Heyman, Susan S Baker, Michael C Stephens, Robert N Baldassano, James F Markowitz, Mi-Ok Kim, Marla C Dubinsky, Judy Cho, Bruce J Aronow, Subra Kugathasan, Greg Gibson
Journal: Nature Genetics (2017)
Abstract 5420: Dephosphorylation of the Cardiac Mitochondrial Voltage-Dependent Anion Channel Prevents Inhibition by Hexokinase
Authors: Qunli Cheng, Zeljko J Bosnjak, Wai-Meng Kwok
Journal: Circulation (2008)

The mitochondrial permeability transition pore (mPTP) has been implicated as the end effector in ischemic and pharmacological preconditioning. Though the molecular composition of the mPTP is thought to consist of cyclophilin D located in the mitochondrial matrix, adenine nucleotide translocase on the inner mitochondrial membrane, and the voltage-dependent anion channel (VDAC) on the outer mitochondrial membrane, recent studies have raised the possibility that VDAC may be a regulatory, rather than a major, component of mPTP. Nevertheless, VDAC is likely to be a critical component of the preconditioning signaling pathway since it is the main conduit for metabolite diffusion across the mitochondrial outer membrane. Yet, the direct measurements of cardiac VDAC activity and modulation have been limited. In the present study, we purified VDAC from rat hearts using standard procedure and investigated its modulation by phosphatase and hexokinase. VDAC was incorporated into planar lipid bilayer for measurements of channel activities. The channel exhibited the reported voltage-dependent gating. Several conductance states were identified, with the most prevalent between 1.5 to 2 nS in 0.5 M NaCl. Koenig’s polyanion, a VDAC blocker, triggered channel flickering and decreased the mean current by 78±6%. In the presence of phosphatase (1 unit/ml), the mean conductance significantly increased from 1.81±0.03 to 3.68±0.61 nS (n=9; mean±SEM). However, the addition of a recombinant hexokinase (5 units/ml; GenWay Biotech) had no significant effect on the phosphatase-enhanced VDAC current (n=4). In contrast, recombinant hexokinase alone significantly decreased the mean conductance from 1.75±0.05 to 0.79±0.19 nS (n=4). The addition of phosphatase reversed the inhibitory effect of hexokinase and further enhanced VDAC activity, increasing the mean conductance to 2.69±0.19 nS (n=4). Our results suggest that the dephosphorylation of VDAC prevents the inhibitory effects of hexokinase. Furthermore, VDAC activity suppressed by hexokinase can be reversed by dephosphorylation of the channel. In conclusion, we have reported on a novel observation at the functional level that basal phosphorylation of the cardiac VDAC may be required for its modulation by hexokinase.
A phase I trial of AT9283 (a selective inhibitor of Aurora kinases) given for 72 hours every 21 days via intravenous infusion in children and adolescents with relapsed and refractory solid tumours.
Authors: Darren R Hargrave, Andrew DJ Pearson, Lucas Moreno, Bruce Morland, Martin Elliott, Guy Makin, Quentin Campbell-Hewson, Peter J. Wyld, Sarah E. R. Halford, Victoria Lock, John F. Lyons, Alan V. Boddy, Murray Yule
Journal: Journal of Clinical Oncology (2012)

9542 Background: AT9283, is a multi-targeted inhibitor, against Aurora A and B, JAK &amp; ABL kinases. Aurora kinases are potential therapeutic targets in paediatric solid cancers. Methods: A phase I dose escalation study was performed using a 72 hour intravenous infusion repeated 3 weekly using a rolling 6 design for patients aged &gt;2 to &lt;19 years with relapsed/ refractory solid tumours. Results: Eighteen patients treated with a median age of 10 (range 3 to 16) years. Four dose cohorts of 7, 9, 11.5 and 14.5 mg/m 2 /day. The diagnoses included; 5 high grade glioma, 4 rhabdoid tumours, 3 neuroblastomas, 3 sarcomas &amp; 3 others. There has been only one dose limiting toxicity; Grade 3 febrile neutropenia at 11.5 mg/m 2 /day. The majority of adverse events (AEs) have been grade 1/2 &amp; considered unrelated/ unlikely related to study drug. Two patients have experienced Grade 3 or 4 AEs considered at least possibly related to study drug: Grade 3 haemoglobin and Grade 4 neutrophils in a patient treated at 9 mg/m 2 /day &amp; Grade 3 lymphopenia, neutrophils, infection with normal neutrophil count and aspartate transaminase in a patient treated at 11.5 mg/m 2 /day. Pharmacokinetics of AT9283 in this population are largely in keeping with those seen in adult patients at similar doses (Arkenau et al., 2011) although there may be greater variability. Pharmacodynamic evidence of aurora B inhibition, as manifested by a reduction in histone H3 phosphorylation in normal skin biopsies pre &amp; post infusion, has been documented at all dose levels tested. Stable disease (up to 6 cycles) has been observed in 3 patients. Conclusions: This paediatric phase I study has demonstrated AT9283 administered as a 72 hour continuous infusion can be given at a dose level of 11.5 mg/m 2 /day which is higher than the maximum tolerated dose observed in adult patients (9 mg/m 2 /day) with advanced solid tumours. Myelosuppresion is the main toxicity but the regimen is well tolerated with preliminary anticancer activity seen in heavily pre-treated paediatric patients. [Table: see text]
Measuring the symptom burden of head and neck cancer patients undergoing concurrent chemotherapy and radiation therapy using area under the curve
Authors: T. Mendoza, D. Rosenthal, X. Wang, G. Mobley, C. Cleeland
Journal: Journal of Clinical Oncology (2009)

6067 Background: Patients with head and neck cancer (HNC) experience a significant treatment-related symptom burden during therapy that presents management challenges for both patients and treatment staff. Typical symptom measurement approaches have failed to capture the extent of this symptom burden over the course of therapy. We evaluated frequent symptom measurement summarized as area under the curve (AUC) as a way of portraying treatment related symptom burden in HNC patients, and explored this method for comparing symptoms produced by treatments that were expected to produce different levels of symptom impact. Methods: The M. D. Anderson Symptom Inventory - Head and Neck module - was administered at baseline and weekly for 10 weeks following the start of treatment to patients undergoing radiation therapy (XRT) as a single modality therapy (N = 49) and a second group receiving chemoradiotherapy CXRT (N = 53). We expected that treatment-related symptom burden would be greater for those patients receiving CXRT. A single value (AUC) was calculated based on the core symptoms reported by both groups of patients. Results: AUC comparisons for mean symptom severity for core symptom items demonstrated the expected greater symptom burden associated with CXRT (170.6 vs 120.9, p &lt; 0.008). The AUC for symptom interference, as measured by the MDASI-HN, was also greater for the CXRT group (p &lt; 0.002). AUCs for individual symptoms, such as fatigue (p &lt; 0.002), sleep disturbance (p &lt; 0.05) and lack of appetite (p &lt; 0.02), were also significantly larger for the CXRT group. Conclusions: The AUC of individual and combined symptoms during cancer therapy present a useful summary of treatment related symptoms that can be used to compare treatment-related symptom burden between different treatment strategies used for the same disease. No significant financial relationships to disclose.
ヘパリン不使用冠動脈造影にても冠動脈内血栓が惹起された抗ヘパリン‐抗PF4複合体抗体(HIT抗体)陽性の一例
Authors: 大西衛, 植田充典, 堤千佳子, 澁谷真彦, 廣本憲司, 小田成彦, 高橋敬子
Journal: Circulation (2006)
CDC Grand Rounds: Newborn Screening for Hearing Loss and Critical Congenital Heart Disease
Authors: Scott D. Grosse, Tiffany Riehle-Colarusso, Marcus Gaffney, Craig A. Mason, Stuart K. Shapira, Marci K. Sontag, Kim Van Naarden Braun, John Iskander
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Newborn screening is a public health program that benefits 4 million U.S. infants every year by enabling early detection of serious conditions, thus affording the opportunity for timely intervention to optimize outcomes (1). States and other U.S. jurisdictions decide whether and how to regulate newborn screening practices. Most newborn screening is done through laboratory analyses of dried bloodspot specimens collected from newborns. Point-of-care newborn screening is typically performed before discharge from the birthing facility. The Recommended Uniform Screening Panel includes two point-of-care conditions for newborn screening: hearing loss and critical congenital heart disease (CCHD). The objectives of point-of-care screening for these two conditions are early identification and intervention to improve neurodevelopment, most notably language and related skills among infants with permanent hearing loss, and to prevent death or severe disability resulting from delayed diagnosis of CCHD. Universal screening for hearing loss using otoacoustic emissions or automated auditory brainstem response was endorsed by the Joint Committee on Infant Hearing in 2000 and 2007* and was incorporated in the first Recommended Uniform Screening Panel in 2005. Screening for CCHD using pulse oximetry was recommended by the Advisory Committee on Heritable Disorders in Newborns and Children in 2010 based on an evidence review† and was added to the Recommended Uniform Screening Panel in 2011.§.
Abstract 14958: Role of Gata4 in Reduction of Fibrosis After Myocardial Infarction
Authors: Megumi Mathison, Vivek Singh, Deepthi Sanagasetti, Lina Yang, Vivekkumar Patel, Jianchang Yang, Todd Rosengart
Journal: Circulation (2016)

Background: A variety of cardio-differentiating transcription factors, including Gata4, Mef2c andTbx5 (GMT) have been shown to reprogram cardiac fibroblasts into induced cardiomyocyte-like cells (i...
Local Immunotherapy of Cancer: Innovative Approaches to Harnessing Tumor-Specific Immune Responses
Authors: Vivek Murthy, Janna Minehart, Daniel H Sterman
Journal: JNCI Journal of the National Cancer Institute (2017)

Modern cancer immunotherapies represent a major shift in paradigm with respect to how we understand innate and adaptive responses to malignancy. Successful tumors co-opt normal immunosurveillance mechanisms by potent interactions between the tumor and local draining lymph nodes. Tumor cells mediate a complex and dynamic immunoediting procedure that results in increased vascular efflux into the draining lymphatics, an immunosuppressive microenvironment rich in regulatory T-lymphocytes, dysfunctional antigen presentation, and downregulation of normal effector lymphocyte responses. Our current approach to reversing this process for antitumor effect involves mainly systemic administration of immunotherapeutic agents, many of which have become standard of care in the management of a variety of cancers. Despite this, we are still learning how best to administer these drugs alone and in combination to maximize efficacy while minimizing adverse events. Increasing evidence suggests that comparable efficacy may be achieved by local administration of immunotherapies in the tumor or tumor-draining lymph nodes with substantially lower doses and better tolerability, even with combination therapy. Herein, we review the literature on intratumoral and intranodal immunotherapies in preclinical models and early-phase studies, with particular emphasis on approaches potentially suitable for translation to larger-scale clinical trials.
Coronary Artery Disease in Patients With Out-of-Hospital Refractory Ventricular Fibrillation Cardiac Arrest
Authors: Demetris Yannopoulos, Jason A. Bartos, Ganesh Raveendran, Marc Conterato, Ralph J. Frascone, Alexander Trembley, Ranjit John, John Connett, David G. Benditt, Keith G. Lurie, Robert F. Wilson, Tom P. Aufderheide
Journal: Journal of the American College of Cardiology (2017)
Risk of Serous Endometrial Carcinoma in Women With Pathogenic BRCA1/2 Variant After Risk-Reducing Salpingo-Oophorectomy
Authors: Claire Saule, Emmanuelle Mouret-Fourme, Adrien Briaux, Véronique Becette, Roman Rouzier, Claude Houdayer, Dominique Stoppa-Lyonnet
Journal: JNCI Journal of the National Cancer Institute (2017)

It has recently been shown that the risk of a rare subtype of endometrial carcinoma (serous type) in women carrying a germline BRCA1/2 pathogenic variant is increased. We assessed the incidence of serous endometrial carcinoma in an independent prospective cohort study of 369 BRCA1/2 women (1779 woman-years of follow-up) who underwent risk-reducing salpingo-oophorectomy by laparoscopy. This occurrence in two BRCA1 carriers led us to estimate that BRCA1/2 carriers present a higher risk than the control population (standardized incidence ratio = 32.2, 95% confidence interval = 11.5 to 116.4, P < .001, two-sided chi-square test, 1 degree of freedom). In addition, in both tumors, the wild-type BRCA1 allele was lost, indicating the inactivation of the BRCA1 gene and arguing for a link with endometrial carcinogenesis. Prophylactic hysterectomy could be discussed with informed women through a shared decision-making process although the estimated 3% life-long risk is moderate. Additional studies are required to establish future prophylactic surgery guidelines.
OP0009-HPR The effect of an 8-week water exercise program on anaerobic exercise capacity in children with juvenile idiopathic arthritis
Authors: D Bayraktar, S Savci, O Altug-Gucenmez, E Manci, B Makay, N Ilcin, SE Unsal
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Anaerobic exercise capacity was reported to be lower in children with juvenile idiopathic arthritis (JIA) than healthy children. However, to our knowledge, there is no study focusing on improving anaerobic exercise capacity in JIA. <h3>Objectives</h3> To investigate the effect of an 8-week water exercise program, which was performed at the weekends, on anaerobic exercise capacity in children with JIA. <h3>Methods</h3> Forty-two children with JIA were divided into two groups as exercise and control. Prior to the study, anaerobic exercise capacity was measured performing a 30-second Wingate test. Deep water running was employed as the progressive water exercise program for the exercise group. Control group did not receive any additional treatment other than their usual care. Weekends were chosen for the exercise sessions considering the educational program of the children. Exercise intensity was set as moderate. Exercise intensity was determined with a wearable heart rate tracking system during the exercises. All children were reassessed regarding to anaerobic exercise capacity two months after the first assessment. <h3>Results</h3> All children completed the study without any adverse effects. Twenty-one children were in the exercise group, others were assessed as controls. No significant differences were determined between groups prior the study regarding to age, disease duration, height, weight, body-mass index, and anaerobic exercise capacity related parameters (p&lt;0.05). While all anaerobic exercise capacity parameters improved in the exercise group, no improvement were seen in the control group. The in-group comparisons were shown at Table 1. The comparison of the changes between groups after 8 weeks were demonstrated at Table 2. <h3>Conclusions</h3> The present study is the first study focusing on improving anaerobic capacity in children with JIA. According to our results, an 8-week water exercise program which is performed at the weekends might be beneficial to improve anaerobic exercise capacity in children with JIA. <h3>Disclosure of Interest</h3> None declared
Identification of a transitional fibroblast function in very early rheumatoid arthritis
Authors: Andrew Filer, Lewis S C Ward, Samuel Kemble, Christopher S Davies, Hafsa Munir, Rebekah Rogers, Karim Raza, Christopher Dominic Buckley, Gerard B Nash, Helen M McGettrick
Journal: Annals of the Rheumatic Diseases (2017)

Synovial fibroblasts actively regulate the inflammatory infiltrate by communicating with neighbouring endothelial cells (EC). Surprisingly, little is known about how the development of rheumatoid arthritis (RA) alters these immunomodulatory properties. We examined the effects of phase of RA and disease outcome (resolving vs persistence) on fibroblast crosstalk with EC and regulation of lymphocyte recruitment.Fibroblasts were isolated from patients without synovitis, with resolving arthritis, very early RA (VeRA; symptom ≤12 weeks) and established RA undergoing joint replacement (JRep) surgery. Endothelial-fibroblast cocultures were formed on opposite sides of porous filters. Lymphocyte adhesion from flow, secretion of soluble mediators and interleukin 6 (IL-6) signalling were assessed.Fibroblasts from non-inflamed and resolving arthritis were immunosuppressive, inhibiting lymphocyte recruitment to cytokine-treated endothelium. This effect was lost very early in the development of RA, such that fibroblasts no longer suppressed recruitment. Changes in IL-6 and transforming growth factor beta 1 (TGF-β1) signalling appeared critical for the loss of the immunosuppressive phenotype. In the absence of exogenous cytokines, JRep, but not VeRA, fibroblasts activated endothelium to support lymphocyte.In RA, fibroblasts undergo two distinct changes in function: first a loss of immunosuppressive responses early in disease development, followed by the later acquisition of a stimulatory phenotype. Fibroblasts exhibit a transitional functional phenotype during the first 3 months of symptoms that contributes to the accumulation of persistent infiltrates. Finally, the role of IL-6 and TGF-β1 changes from immunosuppressive in resolving arthritis to stimulatory very early in the development of RA. Early interventions targeting 'pathogenic' fibroblasts may be required in order to restore protective regulatory processes.
OC-014 A regional frozen faecal transplant service for the treatment of chronic recurrent clostridium difficile infection: a review
Authors: K Bicknell, C Fogg, A Fowell, R Porter, O Bannister, A Flatt
Journal: Gut (2017)

Introduction  In July 2015, the Wessex Faecal Microbiota Bank was funded to provide frozen faecal microbiota transplant (FMT) service to patients with recurrent Clostridium difficile infection (CDI). FMTs have a reported cure rate of 94% (1), but barriers to widespread use include logistics, patient perception and a lack of local expert clinical advice (2). Frozen FMT shows non-inferiority to fresh in a randomised controlled trial (3). The frozen Wessex FMT service was designed to overcome these issues and provide an accessible, timely, widespread service.  The aims of the service evaluation are to describe the demographics of FMT patients, establish whether the clinical outcomes are comparable to those described in the literature, evaluate patient’s acceptance of FMT and determine if an FMT bank can provide a regional service.  Method  The service has been evaluated using clinical outcomes, patient satisfaction surveys, and quality of life (EuroQol Group EQ-5D) surveys. Data is collected pre-procedure, immediately post-procedure, and at 6 weeks and 6 months post procedure.  Results  50 patients have been treated to date; 23 of who have completed 6 month follow up, 27 are not yet 6 months post procedure and remain in follow up. Preliminary data shows the demographics of patients receiving FMT are similar to those with chronic CDI (mean age 69, Charlson comorbidity index 4 M:F ratio 1:1). Outcomes are similar to those reported in the literature; 80% of patients resolving symptoms following first FMT, 95% cure rate after a second FMT. Patient feedback is reassuring; with perceived quality of life increasing significantly (mean 20 point increase on EuroQol Group EQ-5D). Information and the procedure have received primarily positive feedback. FMT uptake in Wessex; All regional hospitals perform FMTs locally.  Conclusion  The service is achieving promising clinical and quality of life outcomes, patients are positive about FMTs and the uptake shows a regional bank is a desirable resource.  References  Van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor faeces for recurrent Clostridium difficile. N Engl J Med2013;368:407–15.  Porter RJet al. Faecal microbiota transplantation for Clostridium difficile infection in the United Kingdom. Clin Microbiol Infect. 2016;6:578–582  Lee CHet al. Frozen vs Fresh Faecal Microbiota Transplantation and Clinical Resolution of Diarrhoea in Patients with Recurrent Clostridium difficile Infection. A Randomised Control Trial. JAMA 149-142: (2) 315:2016  Disclosure of Interest  None Declared
An Erysipeloid Cutaneous Eruption in a Woman With Advanced Breast Cancer
Authors: Christina E. Alexander, Melody Maarouf, Drew J. B. Kurtzman
Journal: JAMA Oncology (2017)

A woman in her 60s with a history of metastatic breast cancer presented with a 3-month history of a progressive, asymptomatic cutaneous eruption of nontender discrete erysipeloid plaques on her chest and back. What is your diagnosis?
Sweet’s Syndrome in a Patient with Rheumatoid Arthritis
Authors: Zheng-Hao Huang, Hsiang-Cheng Chen
Journal: New England Journal of Medicine (2017)

A 52-year-old woman who was taking immunosuppressive therapy for rheumatoid arthritis presented with a 1-month history of painful plaques on both palms. Biopsy findings were consistent with Sweet’s syndrome.