tbuckley/cabot-search huggingface dataset:
FRI0312 The frequency and severity of patient-reported symptoms in giant cell arteritis
Authors: S Monti, A Leong, J Robson, A Craven, PA Merkel, R Watts, R Luqmani
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> A better understanding of the patients9 perspectives is pivotal in the development of patient-reported outcomes (PROs) in vasculitis. <h3>Objectives</h3> To assessed patients9 perspective of disease amongst cases with Giant Cell Arteritis (GCA) compared to comparator illnesses mimicking large vessel vasculitis (LVV) included in the Diagnostic and Classification Criteria in Vasculitis Study (DCVAS) database. <h3>Methods</h3> Patient Description of Illness (PDI) forms were circulated amongst Centres participating in the DCVAS study. The PDI form records up to 10 free-text severity ranked symptoms in descending order of severity, a body-map to localise the sites of pain and a free-text short summary of illness description. Free text was reorganized through content and thematic analysis. <h3>Results</h3> PDI forms from 89 patients with GCA and 28 comparators (COM) were analysed. There was no difference in age and sex distribution between groups (mean age 70±8 for GCA and 69±12 for COM). The symptoms description and frequency of the first most severe aspect of disease, including the patient9s own words, is presented in Table 1. The symptom regarded as the most severe by both groups was headache. While there were no differences in the frequency of sudden visual loss, visual symptoms were reported more commonly as the most severe feature by COM vs GCA (21% vs 8%, p=0.05). Arthralgia was more frequently reported by COM vs GCA (11% vs 1%, p=0.01). Headache was the most frequently reported symptom in both groups. Patients with GCA reported jaw claudication (37%) as the second most frequently reported symptom, while COM reported arthralgia/arthritis (32%). Shoulder/neck pain was the third most important symptom in GCA (33%), while fatigue was the third most common complaint among COM (21%). Fatigue was reported as the fourth most common feature by 30% of GCA patients. <h3>Conclusions</h3> Headache was the most frequent and most severe symptom reported by patients with GCA and comparators. However, the reported frequencies and severities of other symptoms were significantly different between the two groups. <h3>Disclosure of Interest</h3> None declared
Gastric Physiology in Relation to Gastric Cancer
Authors: A. C. Ivy
Journal: JNCI Journal of the National Cancer Institute (1945)

Journal Article Gastric Physiology in Relation to Gastric Cancer Get access A. C. Ivy A. C. Ivy Nathan Smith Davis Professor of Physiology Northwestern University, Medical School, Chicago Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 5, Issue 5, April 1945, Pages 313–337, https://doi.org/10.1093/jnci/5.5.313 Published: 01 April 1945
Hepatitis B surface antigen incorporated in dissolvable microneedle array patch is antigenic and thermostable
Authors: Danielle Poirier, Frédéric Renaud, Vincent Dewar, Laurent Strodiot, Florence Wauters, Jim Janimak, Toshio Shimada, Tatsuya Nomura, Koki Kabata, Koji Kuruma, Takayuki Kusano, Masaki Sakai, Hideo Nagasaki, Takayoshi Oyamada
Journal: Biomaterials (2017)

Alternatives to syringe-based administration are considered for vaccines. Intradermal vaccination with dissolvable microneedle arrays (MNA) appears promising in this respect, as an easy-to-use and painless method. In this work, we have developed an MNA patch (MNAP) made of hydroxyethyl starch (HES) and chondroitin sulphate (CS). In swines, hepatitis B surface antigen (HBsAg) formulated with the saponin QS-21 as adjuvant, both incorporated in HES-based MNAP, demonstrated the same level of immunogenicity as a commercially available aluminum-adjuvanted HBsAg vaccine, after two immunizations 28 days apart. MNAP application was associated with transient skin reactions (erythema, lump, scab), particularly evident when the antigen was delivered with the adjuvant. The thermostability of the adjuvanted antigen when incorporated in the HES-based matrix was also assessed by storing MNAP at 37, 45 or 50 °C for up to 6 months. We could demonstrate that antigenicity was retained at 37 and 45 °C and only a 10% loss was observed after 6 months at 50 °C. Our results are supportive of MNAP as an attractive alternative to classical syringe-based vaccination.
Posterior Vitreous Detachment and the Posterior Hyaloid Membrane
Authors: Gregory S. Fincham, Sean James, Carl Spickett, Michael Hollingshead, Christopher Thrasivoulou, Arabella V. Poulson, Annie McNinch, Allan Richards, David Snead, Gloria A. Limb, Martin P. Snead
Journal: Ophthalmology (2017)

PurposeDespite posterior vitreous detachment being a common ocular event affecting most individuals in an aging population, there is little consensus regarding its precise anatomic definition. We investigated the morphologic appearance and molecular composition of the posterior hyaloid membrane to determine whether the structure clinically observed enveloping the posterior vitreous surface after posterior vitreous detachment is a true basement membrane and to postulate its origin. Understanding the relationship between the vitreous (in both its attached and detached state) and the internal limiting membrane of the retina is essential to understanding the cause of rhegmatogenous retinal detachment and vitreoretinal interface disorders, as well as potential future prophylactic and treatment strategies.DesignClinicohistologic correlation study.ParticipantsThirty-six human donor globes.MethodsVitreous bodies identified to have posterior vitreous detachment were examined with phase-contrast microscopy and confocal microscopy after immunohistochemically staining for collagen IV basement membrane markers, in addition to extracellular proteins that characterize the vitreoretinal junction (fibronectin, laminin) and vitreous gel (opticin) markers. The posterior retina similarly was stained to evaluate the internal limiting membrane. Findings were correlated to the clinical appearance of the posterior hyaloid membrane observed during slit-lamp biomicroscopy after posterior vitreous detachment and compared with previously published studies.Main Outcome MeasuresMorphologic appearance and molecular composition of the posterior hyaloid membrane.ResultsPhase-contrast microscopy consistently identified a creased and distinct glassy membranous sheet enveloping the posterior vitreous surface, correlating closely with the posterior hyaloid membrane observed during slit-lamp biomicroscopy in patients with posterior vitreous detachment. Immunofluorescent confocal micrographs demonstrated the enveloping membranous structure identified on phase-contrast microscopy to show positive stain results for type IV collagen. Immunofluorescence of the residual intact internal limiting membrane on the retinal surface also showed positive stain results for type IV collagen.ConclusionsThe results of this study provide immunohistochemical evidence that the posterior hyaloid membrane is a true basement membrane enveloping the posterior hyaloid surface. Because this membranous structure is observed only after posterior vitreous detachment, the results of this study indicate that it forms part of the internal limiting membrane when the vitreous is in its attached state.
Abstract 19830: Reduced Electromechanical Activity Related to the Functional Modification of Ion Channels in Hibernating Myocardium of Porcine Heart
Authors: Geru Wu, Yi Zheng, Xin Quan, Fred Baimbridge, Yutao Xi, Junping Sun, Shahrzad Abbasi, Guilherme V Silva, James T Willerson, Emerson C Perin, Jie Cheng
Journal: Circulation (2010)

Introduction: Chronic ischemia can lead to the development of hibernating myocardium, which is associated with an increased risk for cardiac sudden death. However, little is known of the changes in...
Hepatic peroxisome proliferator‐activated receptor γ coactivator 1β drives mitochondrial and anabolic signatures that contribute to hepatocellular carcinoma progression in mice
Authors: Elena Piccinin, Claudia Peres, Elena Bellafante, Simon Ducheix, Claudio Pinto, Gaetano Villani, Antonio Moschetta
Journal: Hepatology (2017)

The peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1β (PGC-1 β) is a master regulator of mitochondrial biogenesis and oxidative metabolism as well as of antioxidant defense. Specifically, in the liver, PGC-1β also promotes de novo lipogenesis, thus sustaining cellular anabolic processes. Given the relevant pathogenic role of mitochondrial and fatty acid metabolism in hepatocarcinoma (HCC), here we pointed to PGC-1β as a putative novel transcriptional player in the development and progression of HCC. For this purpose, we generated both hepatic-specific PGC-1β-overexpressing (LivPGC-1β) and PGC-1β knockout (LivPGC-1βKO) mice, and we challenged them with both chemical and genetic models of hepatic carcinogenesis. Our results demonstrate a pivotal role of PGC-1β in driving liver tumor development. Indeed, whereas mice overexpressing PGC-1β show greater tumor susceptibility, PGC-1β knockout mice are protected from carcinogenesis. High levels of PGC-1β are able to boost reactive oxygen species (ROS) scavenger expression, therefore limiting the detrimental ROS accumulation and, consequently, apoptosis. Moreover, it supports tumor anabolism, enhancing the expression of genes involved in fatty acid and triglyceride synthesis. Accordingly, the specific hepatic ablation of PGC-1β promotes the accumulation of ROS-driven macromolecule damage, finally limiting tumor growth.The present data elect hepatic PGC-1β as a transcriptional gatekeeper of mitochondrial function and redox status in HCC, orchestrating different metabolic programs that allow tumor progression. (Hepatology 2018;67:884-898).
Circular Noncoding RNA HIPK3 Mediates Retinal Vascular Dysfunction in Diabetes Mellitus
Authors: Kun Shan, Chang Liu, Bai-Hui Liu, Xue Chen, Rui Dong, Xin Liu, Yang-Yang Zhang, Ban Liu, Shu-Jie Zhang, Jia-Jian Wang, Sheng-Hai Zhang, Ji-Hong Wu, Chen Zhao, Biao Yan
Journal: Circulation (2017)

The vascular complications of diabetes mellitus are the major causes of morbidity and mortality among people with diabetes. Circular RNAs are a class of endogenous noncoding RNAs that regulate gene expression in eukaryotes. In this study, we investigated the role of circular RNA in retinal vascular dysfunction induced by diabetes mellitus.Quantitative polymerase chain reactions, Sanger sequencing, and Northern blots were conducted to detect circular HIPK3 (circHIPK3) expression pattern on diabetes mellitus-related stresses. MTT (3-[4,5-dimethythiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assays, EdU (5-ethynyl-2'-deoxyuridine) incorporation assays, Transwell migration assays, and Matrigel assays were conducted to detect the role of circHIPK3 in retinal endothelial cell function in vitro. Retinal trypsin digestion, vascular permeability assays, and ELISA assays were conducted to detect the role of circHIPK3 in retinal vascular dysfunction in vivo. Bioinformatics analysis, luciferase activity assays, RNA pull-down assays, and in vitro studies were conducted to reveal the mechanism of circHIPK3-mediated retinal vascular dysfunction.circHIPK3 expression was significantly upregulated in diabetic retinas and retinal endothelial cells following stressors related to diabetes mellitus. circHIPK3 silencing or overexpressing circHIPK3 changed retinal endothelial cell viability, proliferation, migration, and tube formation in vitro. circHIPK3 silencing in vivo alleviated retinal vascular dysfunction, as shown by decreased retinal acellular capillaries, vascular leakage, and inflammation. circHIPK3 acted as an endogenous miR-30a-3p sponge to sequester and inhibit miR-30a-3p activity, which led to increased vascular endothelial growth factor-C, FZD4, and WNT2 expression. Ectopic expression of miR-30a-3p mimicked the effect of circHIPK3 silencing on vascular endothelial phenotypes in vivo and in vitro.The circular RNA circHIPK3 plays a role in diabetic retinopathy by blocking miR-30a function, leading to increased endothelial proliferation and vascular dysfunction. These data suggest that circular RNA is a potential target to control diabetic proliferative retinopathy.
Deciphering antitumour response and resistance with intratumour heterogeneity (DARWIN II).
Authors: Crispin T. Hiley, Tanya Ahmad, Mariam Jamal-Hanjani, Christopher Abbosh, Yenting Ngai, Alan Hackshaw, Paul Patterson, Shobhit Baijal, Marianne Nicolson, Jason Francis Lester, Matthew Krebs, Christian H.H Ottensmeier, Dean Anthony Fennell, Peter Schmid, Muthuveni Ezhil, Sarah Danson, Nicola L. Steele, Gary William Middleton, Caroline Dive, Charles Swanton
Journal: Journal of Clinical Oncology (2017)

TPS9099 Background: The importance of intratumour heterogeneity (ITH) is increasingly recognised as a driver of cancer progression and survival outcome. However understanding how tumour clonal heterogeneity impacts upon therapeutic outcome is still an area of unmet clinical and scientific need. The TRACERx trial (NCT01888601), a prospective study of patients with radically resected primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through genetic analysis of multi-region and longitudinal tumour sampling. DARWIN II is an investigator initiated study for patients who are enrolled within the TRACERx trial, or who have multi-region sequencing of their primary disease, but subsequently relapse with metastatic disease. This study will examine the role of intra-tumour heterogeneity and predicted neo-antigens on the anti-tumour activity of anti-PDL1 immunotherapy. Methods: This multicentre non-randomised phase II molecularly stratified umbrella study will examine how clonal dominance and ITH influence outcomes after treatment, offering a unique opportunity to decipher mechanisms of resistance to immunotherapy with anti-PDL1. These data will help improve future study design by developing greater understanding of patient selection for immunotherapies in patients with NSCLC. The relationship between ITH and cfDNA/CTCs will also be explored in DARWIN II. The study arms: Arm 1: Patients either -1) without an actionable mutation and PDL1 positive or 2) without an actionable mutation and PDL1 negative following first line cytotoxic chemotherapy - Atezolizumab. Arm 2: BRAFV600 - Vemurafenib. Arm 3: ALK/RET gene rearrangement - Alectinib. Arm 4: Her2 Amplification - Trastuzumab Emtansine. Primary Outcome Measures: Progression free survival (PFS), defined as the period between the date of registration to the date of subsequent progression or death will be assessed according to: Neo-antigen burden, mutational burden, ITH as assessed using an ITH ratio index and genomic instability as assessed using a weighted genome instability index (wGII). Trial Sponsor: University College London. Clinical trial information: NCT02314481.
Diagnostic Accuracy of Novel and Traditional Rapid Tests for Influenza Infection Compared With Reverse Transcriptase Polymerase Chain Reaction
Authors: Joanna Merckx, Rehab Wali, Ian Schiller, Chelsea Caya, Genevieve C. Gore, Caroline Chartrand, Nandini Dendukuri, Jesse Papenburg
Journal: Annals of Internal Medicine (2017)

Rapid and accurate influenza diagnostics can improve patient care.To summarize and compare accuracy of traditional rapid influenza diagnostic tests (RIDTs), digital immunoassays (DIAs), and rapid nucleic acid amplification tests (NAATs) in children and adults with suspected influenza.6 databases from their inception through May 2017.Studies in English, French, or Spanish comparing commercialized rapid tests (that is, providing results in <30 minutes) with reverse transcriptase polymerase chain reaction reference standard for influenza diagnosis.Data were extracted using a standardized form; quality was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) criteria.162 studies were included (130 of RIDTs, 19 of DIAs, and 13 of NAATs). Pooled sensitivities for detecting influenza A from Bayesian bivariate random-effects models were 54.4% (95% credible interval [CrI], 48.9% to 59.8%) for RIDTs, 80.0% (CrI, 73.4% to 85.6%) for DIAs, and 91.6% (CrI, 84.9% to 95.9%) for NAATs. Those for detecting influenza B were 53.2% (CrI, 41.7% to 64.4%) for RIDTs, 76.8% (CrI, 65.4% to 85.4%) for DIAs, and 95.4% (CrI, 87.3% to 98.7%) for NAATs. Pooled specificities were uniformly high (>98%). Forty-six influenza A and 24 influenza B studies presented pediatric-specific data; 35 influenza A and 16 influenza B studies presented adult-specific data. Pooled sensitivities were higher in children by 12.1 to 31.8 percentage points, except for influenza A by rapid NAATs (2.7 percentage points). Pooled sensitivities favored industry-sponsored studies by 6.2 to 34.0 percentage points. Incomplete reporting frequently led to unclear risk of bias.Underreporting of clinical variables limited exploration of heterogeneity. Few NAAT studies reported adult-specific data, and none evaluated point-of-care testing. Many studies had unclear risk of bias.Novel DIAs and rapid NAATs had markedly higher sensitivities for influenza A and B in both children and adults than did traditional RIDTs, with equally high specificities.Québec Health Research Fund and BD Diagnostic Systems.
Clinical characteristics of patients with chronic hepatitis B who developed genotypic resistance to entecavir: Real-life experience
Authors: Hong Joo Kim, Yong Kyun Cho, Woo Kyu Jeon, Byung Ik Kim
Journal: Clinical and Molecular Hepatology (2017)

Clinical characteristics of patients with chronic hepatitis B (CHB) who developed genotypic resistance to entecavir (ETV) were compared to those without resistance.Two hundred fifty eight CHB patients who underwent ETV treatment in our institution from July 2007 to May 2013 were included.Eight (3.1%) patients developed genotypic resistance to ETV during the follow-up period. The patterns of genotypic resistance to ETV were as follows: L180M + M204V + S202G (n=3); M204I + V173M (n=1); I169V + V173M (n=1); L180M + M204V + V173L (n=1); L180M + M204V + V173L + M250V (n=1); M204I + V214A + P237H (n=1). The cumulative occurrence rates of genotypic resistance to ETV were not significantly different between CHB patients with prior nucleos(t)tide analogues (NA) exposure (NA experienced, n=56) and NA naïve patients (n=202, P=0.823 by log rank comparison). Older age, higher baseline log10hepatitis B virus-deoxynucleic acid (log10HBV-DNA), higher log10HBV-DNA at 3, 6, 12 and 24 months after baseline, and complete virologic response (CVR, undetectable serum HBV-DNA by polymerase chain reaction 6 months after ETV treatment) were significant contributors to the development of genotypic resistance to ETV. Multivariate analyses showed higher log10HBV-DNA 6 months after baseline and absence of CVR were independent and significant contributors to the development of ETV resistance.Clinical characteristics of patients who developed ETV resistance were higher log10HBV-DNA 6 months after baseline and absence of CVR during the ETV treatment.
Remodeling the blood–brain barrier microenvironment by natural products for brain tumor therapy
Authors: Xiao Zhao, Rujing Chen, Mei Liu, Jianfang Feng, Jun Chen, Kaili Hu
Journal: Acta Pharmaceutica Sinica B (2017)

Brain tumor incidence shows an upward trend in recent years; brain tumors account for 5% of adult tumors, while in children, this figure has increased to 70%. Moreover, 20%–30% of malignant tumors will eventually metastasize into the brain. Both benign and malignant tumors can cause an increase in intracranial pressure and brain tissue compression, leading to central nervous system (CNS) damage which endangers the patients' lives. Despite the many approaches to treating brain tumors and the progress that has been made, only modest gains in survival time of brain tumor patients have been achieved. At present, chemotherapy is the treatment of choice for many cancers, but the special structure of the blood–brain barrier (BBB) limits most chemotherapeutic agents from passing through the BBB and penetrating into tumors in the brain. The BBB microenvironment contains numerous cell types, including endothelial cells, astrocytes, peripheral cells and microglia, and extracellular matrix (ECM). Many chemical components of natural products are reported to regulate the BBB microenvironment near brain tumors and assist in their treatment. This review focuses on the composition and function of the BBB microenvironment under both physiological and pathological conditions, and the current research progress in regulating the BBB microenvironment by natural products to promote the treatment of brain tumors.
THU0409 Not just a swollen big toe: increasing all-cause hospitalizations in patients with gout in the united states: 1993–2014
Authors: G Singh, A Mithal, A Mithal
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Gout is a disorder of uric acid metabolism and often presents as acute severe joint pain. However, several recent studies have highlighted systemic complications of associated hyperuricemia in patients with gout, including possible increased risk of renal and cardiovascular comorbidities. <h3>Objectives</h3> To study all-cause hospitalizations in patients with gout in the United States (US) from 1993 to 2014. <h3>Methods</h3> The Nationwide Inpatient Sample (NIS) is a stratified random sample of all US community hospitals. It is the only US national hospital database with information on all patients, regardless of payer, including persons covered by Medicare, Medicaid, private insurance, and the uninsured. We examined all inpatient hospitalizations in NIS from 1993 to 2014 with a primary or secondary diagnosis of gout, and compared them to total all-cause US hospitalizations during the same period. US population estimates and projections for the resident US population were obtained from the US Census Bureau. <h3>Results</h3> There were 789.8 million all-cause hospitalizations in 6.4 billion person-years of observation from 1993 to 2014 (123.4 hospitalizations per 1,000 person-years). During this time-period, 9,741,598 hospitalizations occurred in patients with gout (152.2 per 100,000 person-years). All-cause US hospitalizations increased from 33.7 million in 1993 to 35.4 million in 2014, an increase of 4.8% over 22 years (Figure, dotted blue line). All-cause hospitalizations in gout patients have increased from 167,441 in 1993 (64.2 per 100,000 person-year) to 854,475 in 2014 (267.9 per 100,000 person-years, a dramatic increase of over 410% (p&lt;0.0001, Figure solid red line). In 2014, hospitalizations in gout patients accounted for over 4.6 million hospital days at a total national cost of over US $42.6 billion. <h3>Conclusions</h3> All-cause hospitalizations in patients with gout in the US have significantly increased by 410% in the last 22 years, almost hundred-fold of the 4.8% increase in US population all-cause hospitalization rate in the same time-period. This calls for an increase need for identification and management of serious co-morbid conditions in patients with gout. <h3>Disclosure of Interest</h3> G. Singh Grant/research support from: Horizon Pharmaceuticals, A. Mithal: None declared, A. Mithal: None declared
State educated children do better medical school
Authors: Adrian O’Dowd
Journal: BMJ (2017)

Medical students from state funded schools do better when attending medical school than their counterparts from independent schools, research published in BMJ Open has shown.1

UK researchers found that, while students from independent schools tended to enter medical training scoring slightly higher in entry tests, students from state schools were around twice as likely to graduate in the top 10% of their class.

Evidence suggests that the make up of medical students has become increasingly diverse in terms of gender, ethnicity, and age, but that progress has not been replicated by a …