tbuckley/cabot-search huggingface dataset:
Lost in Translation: Deciphering the Mechanism of Action of Anti-human CTLA-4
Authors: Sergio A. Quezada, Karl S. Peggs
Journal: Clinical Cancer Research (2018)

Despite a number of preclinical studies demonstrating that the activity of anti-CTLA-4 antibodies in murine models of cancer relies on effector T-cell activation and regulatory T cell depletion, the activity of the clinical antibodies remains controversial. To decipher such mechanisms is critical to the development of novel and more potent immunotherapies.See related article by Sharma et al., p. 1233.
Rapid Quantification Of Lung Inflation And Recruitment With Automatic Lung Segmentation Of Chest Computed Tomography In A Variable Lung Collapse Model
Authors: J. Graf, Arnoldo Santos, C. Silva, A. Salazar, P. Formenti, J. J. Marini
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rapid Quantification Of Lung Inflation And Recruitment With Automatic Lung Segmentation Of Chest Computed Tomography In A Variable Lung Collapse Model
γδ T cells amplify <i>Blomia tropicalis</i>‐induced allergic airway disease
Authors: Augustin Belkadi, Céline Dietrich, François Machavoine, Jefferson R. Victor, Maria Leite‐de‐Moraes
Journal: Allergy (2018)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Combined iron oxide nanoparticle ferumoxytol and gadolinium contrast enhanced MRI define glioblastoma pseudoprogression
Authors: Ramon F Barajas, Bronwyn E Hamilton, Daniel Schwartz, Heather L McConnell, David R Pettersson, Andrea Horvath, Laszlo Szidonya, Csanad G Varallyay, Jenny Firkins, Jerry J Jaboin, Charlotte D Kubicky, Ahmed M Raslan, Aclan Dogan, Justin S Cetas, Jeremy Ciporen, Seunggu J Han, Prakash Ambady, Leslie L Muldoon, Randy Woltjer, William D Rooney, Edward A Neuwelt
Journal: Neuro-Oncology (2018)

Noninvasively differentiating therapy-induced pseudoprogression from recurrent disease in patients with glioblastoma is prospectively difficult due to the current lack of a biologically specific imaging metric. Ferumoxytol iron oxide nanoparticle MRI contrast characterizes innate immunity mediated neuroinflammation; therefore, we hypothesized that combined ferumoxytol and gadolinium enhanced MRI could serve as a biomarker of glioblastoma pseudoprogression.In this institutional review board-approved, retrospective study, we analyzed ferumoxytol and gadolinium contrast enhanced T1-weighted 3T MRI in 45 patients with glioblastoma over multiple clinical timepoints. Isocitrate dehydrogenase 1 (IDH-1) mutational status was characterized by exome sequencing. Sum of products diameter measurements were calculated according to Response Assessment in Neuro-Oncology criteria from both gadolinium and ferumoxytol enhanced sequences. Enhancement mismatch was calculated as the natural log of the ferumoxytol to gadolinium sum of products diameter ratio. Analysis of variance and Student's t-test assessed differences in mismatch ratios. P-value <0.05 indicated statistical significance.With the development of pseudoprogression we observed a significantly elevated mismatch ratio compared with disease recurrence (P < 0.01) within IDH-1 wild type patients. Patients with IDH-1 mutation demonstrated significantly reduced mismatch ratio with the development of pseudoprogression compared with disease recurrence (P < 0.01). Receiver operator curve analysis demonstrated 100% sensitivity and specificity for the use of mismatch ratios as a diagnostic biomarker of pseudoprogression.Our study suggests that ferumoxytol to gadolinium contrast mismatch ratios are an MRI biomarker for the diagnosis of pseudoprogression in patients with glioblastoma. This may be due to the unique characterization of therapy-induced neuroinflammation.
Deceased Pediatric Donor Livers: How Current Policy Drives Allocation and Transplantation
Authors: Jin Ge, Evelyn K. Hsu, John Bucuvalas, Jennifer C. Lai
Journal: Hepatology (2018)

Each year, approximately 60 children, representing 12% of waitlist candidates, die awaiting liver transplantation. The current allocation algorithm for pediatric donor livers prioritizes local/regional adults over national children. We attempted to better understand the impact of the present algorithm on pediatric candidates. We analyzed pediatric donor liver offers from 2010 to 2014. Donors and recipients were classified based on age. We mapped allocation and acceptance patterns and used subgroup analyses to explore the significance of donor service areas (DSAs) with low pediatric transplant volumes. We used Cox proportional hazard regressions to evaluate posttransplantation outcomes: 3,318 pediatric donor livers were transplanted into 3,482 recipients, and 45% (1,569) were adults. Of the 1,569 adults, 25% (390) received a pediatric organ that was never offered to children; 52% (204) of these 390 pediatric organs originated in the 37 DSAs, with ≤25 pediatric liver transplantations; 278 children died or were delisted due to illness during the same time, with higher mortality rates in the 37 DSAs (10% versus 6%, P &lt; 0.01). Compared to adults, pediatric recipients aged &lt;12 years had lower risks of posttransplant mortality (hazard ratio, 0.62; 95% confidence interval, 0.46‐0.81; P &lt; 0.01). Conclusions: We found that 45% of pediatric donor livers were transplanted into adults: 390 adults were transplanted with pediatric organs never offered to children, while 278 children died or were delisted due to illness, which was more apparent in DSAs with low pediatric transplant volumes; we advocate for a change to allocation policies to allow pediatric organs to be offered to national children with status 1B or Model for End‐Stage Liver Disease/Pediatric End‐Stage Liver Disease &gt;15 before being offered to local/regional + circle non–status 1A adults.
Abstract 15575: Arterial Hyperoxia Exposure Time and Survival Among Resuscitated Patients With Out-of-hospital Cardiac Arrest, The Critical Study in Osaka, Japan
Authors: Takeyuki Kiguchi, Tetsuhisa Kitamura, Daisuke Kobayashi, Chika Nishiyama, Satoshi Fujimi, Takashi Kawamura, Taku Iwami
Journal: Circulation (2017)

Background: Hyperoxia is suggested to be a potential risk factor for mortality of post return of spontaneous circulation (ROSC) among patients with out-of-hospital cardiac arrest (OHCA). Objective:...
MEMBRAIN PROJECT: PROVISIONAL RESULTS OF UK NATIONAL, PROSPECTIVE AUDIT ON THE MANAGEMENT EVALUATION OF METASTASES IN THE BRAIN
Authors: Josephine Jung, Jignesh Tailor, Keyoumars Ashkan, Francesco Vergani
Journal: Neuro-Oncology (2018)

To determine if brain metastasis referrals to the neuro-oncology multidisciplinary team (MDT) in the UK & Ireland comply with current NICE guidelines and to understand how patients are being stratified based on recursive partitioning analysis (RPA) and/or graded prognostic assessment (GPA). Prospective multi-centre national audit on all adult patients referred to the local MDT with ≥ 1 cerebral metastasis. After a 2 months trial at King’s College Hospital, neurosurgical units were invited to recruit patients prospectively for a period of 4 months from November 2017. Anonymised data on patient age, type/status of primary malignancy, performance status, location/number of metastases, available imaging, treatment recommendations and length to decision making was entered into a secure online database. Follow-up data will be collected after 12 months. A total of 23/32 units participated. By end of February 2018 data on 579 patients (116% of initial target) had been submitted overall. Preliminary results from King’s College Hospital indicate a mean of 7 [range 3–13] referred cases per MDT. The median age of referred patients was 66 years [range 28–93 years] with 54.1% females and 45.9% males. Solitary metastases only comprised 44.6% of the referrals and specialist intervention (in the form of surgery or stereotactic radiosurgery) was only recommended in 48.0% of cases. The most common primary tumour was lung (33.8%) followed by melanoma (21.0%) and breast (21.0%); other comprised 24.4% (gastrointestinal 10.8%, renal 6.1%, cancer of unknown primary 4.1%, genito-urinary 3.4%). The national results will be presented at the SBNS meeting in autumn 2018. The preliminary prospective data is in keeping with our previous audit results. This audit will help to draw up a national picture of brain metastases referrals and inform NICE on current work load and MDT management.
Abstract 14078: Are You Safe to Ride a TESLA With an ICD? An in-vivo Study
Authors: Thein T Aung, Swe Zin Mar Win Htut Oo, Ronald Markert, Abdul Wase
Journal: Circulation (2017)

Introduction: Electric vehicles (EV) are becoming ubiquitous. Effect of electromagnetic interference (EMI) from dedicated EV on ICD performance has not been studied in vivo. Hypothesis: There is no...
Abstract 19331: Assessments of Renal Perfusion in Patients With Congestive Heart Failure by Contrast Enhanced Ultrasonography
Authors: Kaoru Komuro, Kyo Shimazu, Yasuyuki Chiba, Midori Yukino, Shogo Imagawa, Teisuke Anzai, Kazuya Yonezawa
Journal: Circulation (2017)

Introduction: Renal congestion caused by elevation of central venous pressure decreases glomerular filtration in patients with congestive heart failure. Hypothesis: We sought to evaluate renal cong...
Abstract 18160: Cardiac Magnetic Resonance and Computational Fluid Dynamic Parameters Are Important Predictors of Adverse Events in the Fontan Almost 10 Years After Imaging
Authors: Mark A Fogel, Phillip Trusty, Alan Wei, Matthew Harris, Kevin Whitehead, Ajit Yoganathan
Journal: Circulation (2017)

Introduction: Single ventricle patients after Fontan can suffer significant adverse outcomes. There are few predictors based on cardiac magnetic resonance (CMR) or computational fluid dynamics (CFD...
Intratumoral injection of I-131 sodium iodide suppresses tumor growth in a rat breast cancer model
Authors: Franklin C. Wong, Andres Fonnegra, Yuetang Wang
Journal: Cancer Research (2005)

1470  Introduction: Locoregional applications of beta emitting radiopharmaceuticals are known to suppress tumor growth by nonspecific ablation of tumors. While the current clinical schemes involve intraarterial injection of particulate radiopharmaceuticals, direct intratumoral injection is an attractive alternative. This study is designed to investigate the intratumoral therapeutic application of I-131 NaI which is readily available to most nuclear medicine clinics. Methods: 2 triplicate groups of female Fisher rats inoculated with 13762 tumor cells (100,000) in the right thigh received 2 oral doses of non-radioactive iodine (Lugol solution) for thryoid blockade 1 day before and 1 hour before injection. Doses of 0.5 or 2 mCi of I-131 NaI in saline were injected into the tumor site. Serial whole-body scintigraphic images were acquired up to 19 hours using a Seimens M-CAM. Organ distribution of I-131 were evaluated and compared with reference standards. Time activity curves were constructed and tumor growth rates were recorded up to 3 months (to date). Results: Clearance of I-131 from the injection sites was mainly through the circulation with biologic half-life of approximately 1 hour. There is also fast clearance of I-131 from the body and transient visualization of the stomach. No thyroid was identified indicating effective thyroid blockade. The group treated with 0.5 mCi showed only slightly slower growth compared with the control group with no treatment and were euthanized at about day 25 after injection. In 2 of the 3 rats treated with 2mCi I-131 NaI prolonged tumor suppression (>3 months) was observed with no growth retardation. Conclusion: Despite relatively fast clearance, direct injection of I-131 NaI into the tumor site may serve as an effective means to suppress tumor. Thyroid blockade using non-radioactive iodine did not adversely affect the effectiveness of I-131 NaI. The approach may be further applied to other radionuclides. Discussion: This example illustrates the advantages of locoregional injection of therapeutic radionuclides: the initial maximal exposure, lower systemic toxicity because of dilution and the use of nonradioactive and nontoxic drugs to decrease systemic toxicit(ies). This direct intratumoral injection approach may further be aided by recent developments of image-guidance for tumor localization and accurate placement of the radionuclides.
PTU-026 The use of domperidone as a prokinetic in video capsule endoscopy
Authors: M Mcfarlane, B Liu, C Nwokolo
Journal: Gut (2017)

Introduction  Domperidone is thought to accelerate gastric emptying through its action on the D2 receptors at the gastro-oesophageal and gastro-duodenal junctions. It is currently listed in the BNF as a prokinetic anti-emetic and has been used for this purpose in clinical practice for several years. This belief led to its use during video capsule endoscopy (VCE), to accelerate capsule delivery to the small intestine and reduce the risk of an incomplete VCE. Here we audited VCEs performed in our department from 2011, when domperidone was given pre-VCE as standard practice, and 2012, when domperidone use was discontinued due to doubts as to its effectiveness.  Method  Thirty-one consecutive patients were pre-treated with domperidone 20 mg orally just before a VCE study. We then assessed a further 33 patients who underwent VCE without domperidone pre-treatment.  The VCE was done with the GIVEN capsule using the RAPID 6 software. Oro-pyloric transit time and oro-caecal transit time were calculated. If after 2 hours the capsule was still in the stomach a gastroscopy was performed to deliver it into the duodenum. Data was analysed using the Mann-Whitney test.  Results  There were 13 and 17 males in the untreated and domperidone groups respectively. The median age was 55 and 59 years in the untreated and domperidone groups respectively.  The median oro-pyloric transit time was 13 min (range 4–78 min) in the untreated group and increased to 30 min (2–120 min) (p=0.01) in the domperidone group. Median oro-caecal transit time was 242 min (76–457 min) in the untreated group and increased to 267 min (163–846 min) (p=0.02) in the domperidone group. There was no difference in pyloro-caecal transit in both groups (p=0.60).  6% (2/34) in the untreated group and 13% (4/31) of the domperidone group required gastroscopy assisted capsule delivery to the duodenum (p=0.65). VCE was completed in all untreated patients compared to 97% of the domperidone group. Clinically significant findings were reported in 9/33 of the untreated group and 5/31 of the domperidone group.  Conclusion  Unexpectedly we find that domperidone delays VCE transit through the stomach in humans. Although the oro-caecal time is also increased in patients pre-treated with domperidone this is almost entirely due to its effect on the foregut. Most studies into the prokinetic effects of domperidone have been on gastroparesis in diabetic patients. These have shown that whilst domperidone can achieve good symptomatic relief, it only improved gastric emptying in 27%–37% (1). Our study suggests that any anti-emetic effect of domperidone is not mediated through acceleration in gastric transit.  Reference  . Ahmad N, Keith-Ferris J, Gooden E, Abell T. Making a case for domperidone in the treatment of gastrointestinal motility disorders. Curr Opin Pharmacol. 2006Dec;6(6):571–6  Disclosure of Interest  None Declared
Mental health service made available to all doctors in England
Authors: Abi Rimmer
Journal: BMJ (2018)

The NHS Practitioner Health Programme will be rolled out to all doctors in England, Simon Steven has announced.

Speaking at a conference marking 10 years of the programme, the chief executive of NHS England said that there would be funding for the mental health and addiction service to cover all NHS doctors in England.

Currently, GPs in England can access support from the programme through the GP Health Service. Mental health support for hospital doctors has previously been the responsibility of NHS trusts or clinical commissioning groups, …
Toxicity Related to Radiotherapy Dose and Targeting Strategy: A Pooled Analysis of Cooperative Group Trials of Combined Modality Therapy for Locally Advanced Non–Small Cell Lung Cancer
Authors: Steven E. Schild, Wen Fan, Thomas E. Stinchcombe, Everett E. Vokes, Suresh S. Ramalingam, Jeffrey D. Bradley, Karen Kelly, Herbert H. Pang, Xiaofei Wang
Journal: Journal of Thoracic Oncology (2018)
Abstract 19317: Real-Time Visualization of Endogenous Titin Dynamics in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Adrian G Cadar, Tromondae K Feaster, Kevin R Bersell, Lili Wang, Dan M Roden, Bjorn C Knollmann, Charles C Hong, Chee C Lim
Journal: Circulation (2016)

Introduction: The giant myofilament protein titin is a critical determinant of myofibril elasticity and sarcomere structure in striated muscle. Although significant advances have been made in our understanding of the biophysical and mechanical properties of titin, the mechanisms governing sarcomeric titin turnover are poorly understood. Our goal is to establish a cardiomyocyte cell culture model that would enable visualization of sarcomeric titin turnover, in real-time. Methods and Results: To directly visualize titin incorporation and turnover in cardiac sarcomeres, we used CRISPR/Cas9 genome editing in human induced pluripotent stem cells (hiPSC) to knock-in a photoconvertible fluorescent protein, mEos3.2, into the C-terminus of titin to produce hiPSC-derived cardiomyocytes (hiPSC-CM) that express endogenous sarcomeric titin-mEos3.2 fusion proteins. Cardiomyocyte induction of the titin-mEos3.2 hiPSC line demonstrated that the titin-mEos3.2 fusion protein is expressed in the sarcomeres in the expected st...
Abstract 20128: Addressing a Prominent Old Problem With an Innovative Approach to Reduce Care-seeking Delays in Patients With Acute Myocardial Infarction: A Study Protocol and Feasibility Report
Authors: Polly Wai-chi Li, Doris Sau-fung Yu
Journal: Circulation (2017)

Introduction: Prolonged delay by patients in making care-seeking decision remains the most significant limiting factor for effective management of acute myocardial infarction (AMI) despite decades ...
Impact of caveolin-1 in microglial/macrophages and glioblastoma within a tumour environment
Authors: Ms Catia Neto, Prof Geoff Pilkington, Prof Mark Gumbleton
Journal: Neuro-Oncology (2018)

Glioblastoma multiform (GBM) is a highly lethal brain tumour composed by many distinct types of cells that are closely connected and dependent on their surrounding environment. Microglia and macrophages are highly abundant in GBM and create an inflammatory microenvironment that promotes tumour progression. Caveolin-1 (Cav1) is the most important protein of caveolae and is involved in cell signalling activity, regulating the cell proliferation, differentiation and migration. Its role within GBM and microglia/macrophages is poorly understood, so the aim of our project is to investigate how Cav1 status in GBM and microglia/macrophages may modulate the cell-cell communications and the cell invasion. Three human GBM cell lines (U87MG, UP007 and UP029) and a human microglia cell line (CHME3) were used. Cav1 was knockout (KO) using CRISPR-Cas9 approach. The invasive ability of GBM cells was accessed by 3D spheroid invasion assay. The standard microglial activation was performed with M1 (IFN-ɣ and LPS) and M2 (IL-4 and IL-13), for 48 hours. Microglia was co-cultured (CC) for 48 hours with GBM cells using Transwell systems. The activation status was accessed by qPCR and WB. Cav1 KO in GBM prevented the overall spheroid invasion in all GBM cell lines tested. Microglia overexpressed the phosphorylated levels of STAT1 and STAT6 after M1 or M2 polarization, respectively, even when the Cav1 levels were KO. CHME3 Cav1 KO cells seem to be less reactive to M1 and M2 stimulus, decreasing the expression of M1-related markers and some of M2-related markers, compared to Cav1 non-target (NT) cells. The CC of CHME3 Cav1 NT with GBM cells lead to an immunosuppressive environment with a decrease of all M1-related markers and to an up-regulation of TGF-β M2-related marker by the microglial cells.
PHLI-seq: constructing and visualizing cancer genomic maps in 3D by phenotype-based high-throughput laser-aided isolation and sequencing
Authors: Sungsik Kim, Amos Chungwon Lee, Han-Byoel Lee, Jinhyun Kim, Yushin Jung, Han Suk Ryu, Yongju Lee, Sangwook Bae, Minju Lee, Kyungmin Lee, Ryong Nam Kim, Woong-Yang Park, Wonshik Han, Sunghoon Kwon
Journal: Genome biology (2018)

Spatial mapping of genomic data to tissue context in a high-throughput and high-resolution manner has been challenging due to technical limitations. Here, we describe PHLI-seq, a novel approach that enables high-throughput isolation and genome-wide sequence analysis of single cells or small numbers of cells to construct genomic maps within cancer tissue in relation to the images or phenotypes of the cells. By applying PHLI-seq, we reveal the heterogeneity of breast cancer tissues at a high resolution and map the genomic landscape of the cells to their corresponding spatial locations and phenotypes in the 3D tumor mass.
Excess deaths: government review should include the use of occupied bed space
Authors: Sunku Guptha
Journal: BMJ (2018)

The UK government’s review into excess deaths is essential to improving patient safety and care.1 Inclement weather and flu alone cannot explain the rise in death rate; rising age, social isolation, and lack of adequate social care support for vulnerable adults have been speculated as contributing factors.

Recognising that the provision of …
Abstract 11651: Effect of Combination Lipid Therapy on Incident Atrial Fibrillation or its Electrocardiographic Surrogate in the Action to Control Cardiovascular Risk in Diabetes Lipid (ACCORD Lipid) Trial
Authors: Lin Y Chen, Haiying Chen, Thomas Bigger, Kathleen T Hickey, David C Goff, Heather Lochnan, Abraham Thomas, Michael E Miller, Elizabeth R Seaquist, Elsayed Z Soliman
Journal: Circulation (2015)

Introduction: Atrial fibrillation (AF) is associated with increased cardiovascular disease (CVD) risk in patients with type 2 diabetes (DM). Observational studies have suggested that higher HDL and lower triglycerides are associated with lower AF risk. Hypothesis: We hypothesized that raising HDL and lowering triglycerides will reduce AF incidence in patients with DM. As such, we compared combination lipid therapy with simvastatin and fenofibrate vs. simvastatin alone in relation to incidence of AF or its established ECG surrogate, P-wave indices (PWI), in patients with DM. Methods: We analyzed data from the Action to Control Cardiovascular Risk in Diabetes Lipid (ACCORD Lipid) trial (Jan 2001-June 2009), a randomized controlled blinded trial of patients with DM and who were aged 40–79 years with CVD or aged 55–79 years with subclinical CVD or &gt;2 CVD risk factors. Patients were randomized to receive simvastatin plus placebo vs. simvastatin plus fenofibrate. Dosing of simvastatin and fenofibrate was based on trial protocol. The primary outcome was a composite of incident AF (ascertained from study ECGs) or PWI (P wave duration in lead II ≥120 ms, P’ (negative) amplitude in V1 ≥100 μV, or P-terminal force in V1 &gt;-4000 μV.ms). Results: Data from 5518 participants (mean age, 62.3 years; women, 30.7%; non-white, 34.5%) were analyzed. The Table shows the results after a mean follow-up of 4.7 years. Conclusions: Compared with simvastatin alone, combination lipid therapy with simvastatin and fenofibrate did not reduce the incidence of AF or its ECG surrogate in patients with DM at high CVD risk. Further research is needed to elucidate the role of dyslipidemia in the etiology of AF and to discover effective prevention strategies for AF in patients with DM.