bluuebunny/crossref_metadata_2025_split huggingface dataset:
008 Revascularisation surgery for non-moyamoya symptomatic intracranial stenosis and occlusion
Authors: Stoodley Marcus , Rogers Jeffrey , Gunawardena Manuri , Morgan Michael 
Published: May 2018

IntroductionPrevious trials rejected a role of extracranial-to-intracranial bypass surgery for managing symptomatic atheromatous disease. However, haemodynamic insufficiency may still be a rationale for surgery, provided it can be performed with low morbidity and that patency is robust.MethodsConsecutive patients undergoing bypass surgery for non-moyamoya symptomatic intracranial arterial stenosis and occlusion were retrospectively identified. The clinical course and surgical outcomes of the cohort were evaluated at six-weeks, six-months, and annually thereafter.ResultsBetween 1992 and 2017, 112 patients underwent 127 bypasses. The angiographic abnormality was arterial occlusion in 80% and stenosis in 20%. Procedures were to prevent future stroke (76%) and stroke reversal (24%), with revascularisation using an arterial pedicle graft in 80% and venous interposition graft (VIG) in 20%. A poor outcome (bypass occlusion, new stroke, new neurological deficit, or worsening neurologic deficit) occurred in 8.9% of patients. The risk of poor outcome was significantly lower with arterial pedicle grafts (Odds ratio=0.15), bypass for prophylaxis against future stroke (Odds ratio=0.11), or anterior circulation bypass (Odds ratio=0.17). Over the first eight years following surgery there were no poor outcomes in the 66 cases exhibiting all three of these characteristics.ConclusionProphylactic arterial pedicle bypass surgery for anterior circulation ischemia is associated with high graft patency and low stroke and surgical complication rates. Higher risks are associated with acute procedures, typically for posterior circulation pathology and requiring VIGs. A carefully selected subset of individuals with haemodynamic insufficiency and ischaemic symptoms are likely to benefit from cerebral revascularisation surgery.
086 The rapid efficacy of natalizumab vs fingolimod in patients with active relapsing-remitting multiple sclerosis (RRMS): results from reveal, a randomised, head-to-head study
Authors: Butzkueven Helmut , Jeffery Douglas , Arnold Douglas L , Filippi Massimo , Geurts Jeroen JG , Dong Qunming , Campbell Nolan , Licata Stephanie , Ho Pei-Ran 
Published: May 2018

IntroductionREVEAL was designed as a 1 year, multicentre, randomised, rater- and sponsor-blinded, prospective study comparing natalizumab and fingolimod in patients with active RRMS. Although the study closed early (for non-safety/non-efficacy reasons), data permitted comparison of effects occurring shortly after treatment initiation. This analysis compares onset of efficacy with natalizumab and fingolimod in REVEAL.MethodsPatients were randomised to open-label intravenous natalizumab 300 mg every 4 weeks (n=54) or oral fingolimod 0.5 mg once daily (n=54). Magnetic resonance imaging was scheduled every 4 weeks for the first 24 weeks and at weeks 36 and 52. Analyses included Kaplan-Meier and Cox regression, negative binomial regression (annualised relapse rate [ARR] and number of T1 gadolinium-enhancing [Gd+] lesions) and a negative binomial generalised estimating equation (cumulative Gd +lesions over time).ResultsAs expected for a randomised study, patient characteristics and follow-up time (median 39 weeks) were generally similar between groups. Natalizumab patients were less likely than fingolimod patients to develop new Gd +lesions (for ≥1 lesion, cumulative probability 40.68% vs 57.99%; hazard ratio [HR]=1.678 [95% CI: 0.865 to 3.255]; p=0.1258; for ≥2 lesions, cumulative probability 11.54% vs 48.48%; HR=4.053 [95% CI: 1.474 to 11.144]; p=0.007). Natalizumab patients consistently had 63%–72% fewer Gd +lesions than fingolimod patients, with between-group differences apparent within 4 weeks and reaching significance by 12 weeks (p=0.030). ARR was 83% lower with natalizumab than with fingolimod (0.05 vs 0.29; p=0.023), and cumulative probability of relapse was 1.85% with natalizumab vs 22.28% with fingolimod (HR=12.184 [95% CI: 1.552 to 95.634]; p=0.017). Adverse events were consistent with known safety profiles.ConclusionThese results suggest that natalizumab reduces disease activity more rapidly and to a greater extent than fingolimod in patients with active RRMS. Given the early study closure, available data did not permit primary endpoint evaluation, and interpretation of these results requires caution.Study SupportBiogen.
009 The ambulance clinical triage-for acute stroke treatment (ACT-FAST) algorithmic pre-hospital triage tool for endovascular thrombectomy: ongoing paramedic validation
Authors: Zhao Henry , Pesavento Lauren , Rodrigues Edrich , Salvaris Patrick , Smith Karen , Bernard Stephen , Stephenson Michael , Parsons Mark , Yassi Nawaf , Davis Stephen M , Campbell Bruce CV 
Published: May 2018

IntroductionThe ambulance clinical triage-for acute stroke treatment (ACT-FAST) algorithm is a severity based 3-step paramedic triage tool for pre-hospital recognition of large vessel occlusion (LVO), designed to improve specificity and paramedic assessment reliability compared to existing triage scales. ACT-FAST sequentially assesses 1. Unilateral arm fall to stretcher <10 s; 2a. Severe language disturbance (right arm weak), or 2b. Severe gaze deviation/hemi-neglect assessed by shoulder tap (left arm weak); 3. Clinical eligibility questions. We present the results of the ongoing Ambulance Victoria paramedic validation study.MethodsAmbulance Victoria paramedics assessed ACT-FAST in all suspected stroke patients pre-hospital in metropolitan Melbourne, Australia, and in the Royal Melbourne Hospital Emergency Department since July 2017. Algorithm results were validated against a comparator of ICA/M1 occlusion on CT-angiography with NIHSS ≥6 (Class 1 indications for endovascular thrombectomy).ResultsData were available from n=119 assessments (ED n=68, pre-hospital n=51). Patient diagnoses were LVO n=20 (15.6%), non-LVO infarcts n=45 (38.5%), ICH n=10 (8.3%) and no stroke on imaging n=44 (37.6%). ACT-FAST showed 85% sensitivity, 88.9% specificity, 60.7% (72% excluding ICH) positive predictive value and 96.7% negative predictive value for LVO. Of 10 false-positives, 4 received thrombectomy for non-Class 1 indications (basilar/M2 occlusions/cervical dissection), 3 were ICH, and 1 was tumour. Three false-negatives were LVO with milder syndromes.DiscussionThe ongoing ACT-FAST algorithm validation study shows high accuracy for clinical recognition of LVO. The streamlined algorithmic approach with just two examination items provides a more practical option for implementation in large emergency service networks. Accurate pre-hospital recognition of LVO will allow bypass to endovascular centres and early activation of neuro-intervention services to expedite endovascular thrombectomy.
Tau Mutations Serve as a Novel Risk Factor for Cancer
Authors: Rossi Giacomina , Redaelli Veronica , Contiero Paolo , Fabiano Sabrina , Tagliabue Giovanna , Perego Paola , Benussi Luisa , Bruni Amalia C. , Filippini Graziella , Farinotti Mariangela , Giaccone Giorgio , Buiatiotis Simona , Manzoni Claudia , Ferrari Raffaele , Tagliavini Fabrizio 
Published: May 2018

Abstract
In addition to its well-recognized role in neurodegeneration, tau participates in maintenance of genome stability and chromosome integrity. In particular, peripheral cells from patients affected by frontotemporal lobar degeneration carrying a mutation in tau gene (genetic tauopathies), as well as cells from animal models, show chromosome numerical and structural aberrations, chromatin anomalies, and a propensity toward abnormal recombination. As genome instability is tightly linked to cancer development, we hypothesized that mutated tau may be a susceptibility factor for cancer. Here we conducted a retrospective cohort study comparing cancer incidence in families affected by genetic tauopathies to control families. In addition, we carried out a bioinformatics analysis to highlight pathways associated with the tau protein interactome. We report that the risk of developing cancer is significantly higher in families affected by genetic tauopathies, and a high proportion of tau protein interactors are involved in cellular processes particularly relevant to cancer. These findings disclose a novel role of tau as a risk factor for cancer, providing new insights in the various pathologic roles of mutated tau.
Significance: This study reveals a novel role for tau as a risk factor for cancer, providing new insights beyond its role in neurodegeneration. Cancer Res; 78(13); 3731–9. ©2018 AACR.
Phase 0 Trial of AZD1775 in First-Recurrence Glioblastoma Patients
Authors: Sanai Nader , Li Jing , Boerner Julie , Stark Karri , Wu Jianmei , Kim Seongho , Derogatis Alanna , Mehta Shwetal , Dhruv Harshil D. , Heilbrun Lance K. , Berens Michael E. , LoRusso Patricia M. 
Published: May 2018

Abstract
Purpose: AZD1775 is a first-in-class Wee1 inhibitor with dual function as a DNA damage sensitizer and cytotoxic agent. A phase I study of AZD1775 for solid tumors suggested activity against brain tumors, but a preclinical study indicated minimal blood–brain barrier penetration in mice. To resolve this controversy, we examined the pharmacokinetics and pharmacodynamics of AZD1775 in patients with first-recurrence, glioblastoma.
Patients and Methods: Twenty adult patients received a single dose of AZD1775 prior to tumor resection and enrolled in either a dose-escalation arm or a time-escalation arm. Sparse pharmacokinetic blood samples were collected, and contrast-enhancing tumor samples were collected intraoperatively. AZD1775 total and unbound concentrations were determined by a validated LC/MS-MS method. Population pharmacokinetic analysis was performed to characterize AZD1775 plasma pharmacokinetic profiles. Pharmacodynamic endpoints were compared to matched archival tissue.
Results: The AZD1775 plasma concentration–time profile following a single oral dose in patients with glioblastoma was well-described by a one-compartment model. Glomerular filtration rate was identified as a significant covariate on AZD1775 apparent clearance. AZD1775 showed good brain tumor penetration, with a median unbound tumor-to-plasma concentration ratio of 3.2, and achieved potential pharmacologically active tumor concentrations. Wee1 pathway suppression was inferred by abrogation of G2 arrest, intensified double-strand DNA breakage, and programmed cell death. No drug-related adverse events were associated with this study.
Conclusions: In contrast to recent preclinical data, our phase 0 study of AZD 1775 in recurrent glioblastoma indicates good human brain tumor penetration, provides the first evidence of clinical biological activity in human glioblastoma, and confirms the utility of phase 0 trials as part of an accelerated paradigm for drug development in patients with glioma. Clin Cancer Res; 24(16); 3820–8. ©2018 AACR.
See related commentary by Vogelbaum, p. 3790
Ad5NULL-A20: A Tropism-Modified, αvβ6 Integrin-Selective Oncolytic Adenovirus for Epithelial Ovarian Cancer Therapies
Authors: Uusi-Kerttula Hanni , Davies James A. , Thompson Jill M. , Wongthida Phonphimon , Evgin Laura , Shim Kevin G. , Bradshaw Angela , Baker Alexander T. , Rizkallah Pierre J. , Jones Rachel , Hanna Louise , Hudson Emma , Vile Richard G. , Chester John D. , Parker Alan L. 
Published: May 2018

Abstract
Purpose: Virotherapies are maturing in the clinical setting. Adenoviruses (Ad) are excellent vectors for the manipulability and tolerance of transgenes. Poor tumor selectivity, off-target sequestration, and immune inactivation hamper clinical efficacy. We sought to completely redesign Ad5 into a refined, tumor-selective virotherapy targeted to αvβ6 integrin, which is expressed in a range of aggressively transformed epithelial cancers but nondetectable in healthy tissues.
Experimental Design: Ad5NULL-A20 harbors mutations in each major capsid protein to preclude uptake via all native pathways. Tumor-tropism via αvβ6 targeting was achieved by genetic insertion of A20 peptide (NAVPNLRGDLQVLAQKVART) within the fiber knob protein. The vector's selectivity in vitro and in vivo was assessed.
Results: The tropism-ablating triple mutation completely blocked all native cell entry pathways of Ad5NULL-A20 via coxsackie and adenovirus receptor (CAR), αvβ3/5 integrins, and coagulation factor 10 (FX). Ad5NULL-A20 efficiently and selectively transduced αvβ6+ cell lines and primary clinical ascites-derived EOC ex vivo, including in the presence of preexisting anti-Ad5 immunity. In vivo biodistribution of Ad5NULL-A20 following systemic delivery in non–tumor-bearing mice was significantly reduced in all off-target organs, including a remarkable 107-fold reduced genome accumulation in the liver compared with Ad5. Tumor uptake, transgene expression, and efficacy were confirmed in a peritoneal SKOV3 xenograft model of human EOC, where oncolytic Ad5NULL-A20–treated animals demonstrated significantly improved survival compared with those treated with oncolytic Ad5.
Conclusions: Oncolytic Ad5NULL-A20 virotherapies represent an excellent vector for local and systemic targeting of αvβ6-overexpressing cancers and exciting platforms for tumor-selective overexpression of therapeutic anticancer modalities, including immune checkpoint inhibitors. Clin Cancer Res; 24(17); 4215–24. ©2018 AACR.
Genetic variation of bread wheat accessions in response to the cereal cyst nematode, Heterodera filipjevi
Authors: Moatamedi Marzieh , Bazgir Eidi , Esfahani Mehdi Nasr , Darvishnia Mostafa 
Published: May 2018

SummaryBread wheat,Triticum aestivum, produces large edible grains and is consumed by 75% of the world’s populations. Cereal cyst nematodes have a global distribution and cause significant economic yield losses in many countries. Therefore, there is an urgent need to identify new resistance sources. In this study, the genetic diversity of 43 wheat accessions in response to cereal cyst nematode,Heterodera filipjeviIsfahan pathotype, was assessed using a simple sequence repeat (SSR) marker. Seven primers were used, out of which five primers showed polymorphisms. Alleles per primer varied from one to three per locus (mean 2.85). The highest and lowest polymorphic information content of 0.81 and 0.44 (mean 0.66) were related to Xgwm 3012DL and Xgwm147, respectively. Genetic similarity was 29-88% between accessions. SSR analysis divided the accessions into five main groups. Resistant cultivars ‘Bam’ and ‘Behrang’ possessed bothCre1 andCre8 resistant genes. TheCre3 andCatgenes were partially sequenced in five cultivars of different responses toH. filipjevi. The nucleotide sequences were compared toCre3 andCathomologues, indicating 93-100% and 86-92% homology, respectively. The MEGA program showed highest similarity ofCre3 andCatgenes amplified with the resistance gene analogues (RGA14) in the wheat andCat3-A1 gene in ‘Carnamah’. This research showed that SRR markers could efficiently verify genetic diversity between wheat accessions, and the known resistance genes (Cregenes) against the cereal cyst nematodes could not control theH. filipjeviIsfahan pathotype populations, except theCre1 gene.
Impact of Collaborative Shared Medical Appointments on Diabetes Outcomes in a Family Medicine Clinic
Authors: Hartzler Melody L. , Shenk McKenzie , Williams Julie , Schoen James , Dunn Thomas , Anderson Douglas 
Published: May 2018

Purpose The purpose of this study is to evaluate the impact of a collaborative diabetes shared medical appointment on patient outcomes in an urban family medicine practice. Methods Fifty-nine patients were enrolled to participate in multiple shared medical appointments (SMAs) over 12 months. Baseline data included hemoglobin (A1C), lipids, systolic blood pressure (SBP), weight, adherence to American Diabetes Association (ADA) guidelines, and surveys, including the Problem Areas in Diabetes (PAID-2) scale and the Spoken Knowledge in Low Literacy in Diabetes Scale (SKILLD). A1C and SBP were evaluated at each visit. Lipid control was assessed at baseline and at 6 and 12 months. Adherence to ADA guidelines, SKILLD and PAID-2 survey scores, and number of antihyperglycemic and antihypertensive medications were also evaluated at 12 months. Results Thirty-eight patients completed the study. Compared with baseline, A1C and low-density lipoprotein cholesterol (LDL-C) levels decreased significantly over 12 months ( P < .001 and P = .004, respectively). More patients became compliant with the ADA guidelines throughout the course of the study. Specifically, more patients achieved the LDL-C goal of ≤100 mg/dL (2.59 mmol/L; P < .001), were prescribed appropriate antihypertensive medications ( P < .001) and aspirin ( P < .001), and received the pneumonia vaccine ( P < .001). PAID-2 and SKILLD survey scores also significantly improved over the course of the study ( P ≤ .001 and P = .003, respectively). Conclusion Short-term interdisciplinary SMAs decreased A1C and LDL-C, improved patient adherence to ADA guidelines, improved emotional distress related to diabetes, and increased knowledge of diabetes.
Safranin-O removal from aqueous solutions using lignin nanoparticle-g-polyacrylic acid adsorbent: Synthesis, properties, and application
Authors: Azimvand J , Didehban Kh , Mirshokraie SA 
Published: May 2018

In this study, alkali lignin modified by ethylene glycol and lignin nanoparticles was prepared through acid precipitation technology. Lignin nanoparticle-g-polyacrylic acid adsorbent was prepared using copolymerization reactions between lignin nanoparticle and polyacrylic acid in the presence of potassium persulfate as the radical initiator. Then, lignin nanoparticle-g-polyacrylic acid adsorbent was used to remove Safranin-O from an aqueous environment. The adsorbent structures and morphologies of lignin nanoparticle and lignin nanoparticle-g-polyacrylic acid adsorbent were investigated using scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. Nanoparticle sizes were assessed using dynamic light scattering. Equilibrium isotherms were compared using the Langmuir, Freundlich, and Temkin adsorption models. Both adsorbent lignin nanoparticle and lignin nanoparticle-g-polyacrylic acid adsorbent showed good agreement with the Langmuir isotherm. The maximum adsorption capacities of lignin nanoparticle and lignin nanoparticle-g-polyacrylic acid adsorbent reached 99 and 138.88 mg g−1 using model-like, pseudo-second-order, and intraparticle diffusion, respectively. Experimental results showed that adsorbent lignin nanoparticle and lignin nanoparticle-g-polyacrylic acid adsorbent followed the pseudo-second order kinetic model.
Effects of TGF-β Overexpression via rAAV Gene Transfer on the Early Repair Processes in an Osteochondral Defect Model in Minipigs
Authors: Cucchiarini Magali , Asen Ann-Kathrin , Goebel Lars , Venkatesan Jagadeesh K. , Schmitt Gertrud , Zurakowski David , Menger Michael D. , Laschke Matthias W. , Madry Henning 
Published: May 2018

Background: Application of the chondrogenic transforming growth factor beta (TGF-β) is an attractive approach to enhance the intrinsic biological activities in damaged articular cartilage, especially when using direct gene transfer strategies based on the clinically relevant recombinant adeno-associated viral (rAAV) vectors. Purpose: To evaluate the ability of an rAAV–TGF-β construct to modulate the early repair processes in sites of focal cartilage injury in minipigs in vivo relative to control (reporter lacZ gene) vector treatment. Study Design: Controlled laboratory study. Methods: Direct administration of the candidate rAAV–human TGF-β (hTGF-β) vector was performed in osteochondral defects created in the knee joint of adult minipigs for macroscopic, histological, immunohistochemical, histomorphometric, and micro–computed tomography analyses after 4 weeks relative to control (rAAV- lacZ) gene transfer. Results: Successful overexpression of TGF-β via rAAV at this time point and in the conditions applied here triggered the cellular and metabolic activities within the lesions relative to lacZ gene transfer but, at the same time, led to a noticeable production of type I and X collagen without further buildup on the subchondral bone. Conclusion: Gene therapy via direct, local rAAV–hTGF-β injection stimulates the early reparative activities in focal cartilage lesions in vivo. Clinical Relevance: Local delivery of therapeutic (TGF-β) rAAV vectors in focal defects may provide new, off-the-shelf treatments for cartilage repair in patients in the near future.
Ethical values of academic nurses: A pilot study
Authors: Denat Yıldız , Dikmen Yurdanur , Arslan Gülşah Gürol 
Published: May 2018

Background: While academics contribute to the development of society through all the subjects that they work on, they also have other important tasks to fulfill, such as being role models for their students and society. Therefore, the place of academic ethical values is a significant topic for academic nurses. Objective: The main objective of this research was to examine the attitudes of academic nurses toward academic ethics. Research design: This descriptive and cross-sectional research study was conducted between March and June 2017 in three different public universities in Turkey. The research sample consisted of 132 nurses in different professional positions at different universities who volunteered to participate in the study. The data were collected with an Information Form and an Academic Ethical Values Scale developed in Turkey. Ethical considerations: Ethical approval was granted by the institutions involved, and all participants provided informed verbal consent. Findings: The attitudes of academics participating in the research on academic ethical values were found to be highly positive. When the sub-dimensions of the scale were examined, the dimension with the highest average attitudinal score is found to be “values regarding the teaching process” and the dimension with the lowest average attitude score is found to be “values regarding society.” Depending on the participants’ academic position, it was determined that the total average score for the Academic Ethical Values Scale and the average scores of the “values regarding scientific research” and “values regarding the teaching process” sub-dimensions differed significantly (p < 0.05). Conclusion: It was found that academic nurses had highly positive attitudes of toward academic ethical values. It can be argued that academics act more responsibly with regard to the ethical values of the teaching process than other areas. In addition, academics who are professors are most sensitive in their perception of academic ethical values.