bluuebunny/crossref_metadata_2025_split huggingface dataset:
National mixed methods evaluation of the effects of removing legal barriers to full practice authority of Dutch nurse practitioners and physician assistants
Authors: De Bruijn-Geraets Daisy P , van Eijk-Hustings Yvonne J L , Bessems-Beks Monique C M , Essers Brigitte A B , Dirksen Carmen D , Vrijhoef Hubertus Johannes Maria 
Published: June 2018

ObjectiveTo evaluate the effects of granting legal full practice authority (FPA) to nurse practitioners (NP) and physician assistants (PA) regarding the performance of specified reserved medical procedures and to support governmental decision-making.DesignNationwide mixed methods design with triangulation of quantitative (Pre-post test design) and qualitative data (expert interviews and focus groups).MethodsSurveys focused on the performance of the procedures (monthly number, authorisation mode, consultations and procedural time) and legal cross-compliance requirements (adherence with protocols, competence). Interviews focused on competence, knowledge, skills, responsibilities, routine behaviour, NP/PA role, acceptance, organisational structure, collaboration, consultation, NP/PA positioning, adherence with protocols and resources. Data collection took place between 2011 and 2015.ResultsQuantitative data included 1251 NPs, 798 PAs and 504 physicians. Besides, expert interviews with 33 healthcare providers and 28 key stakeholders, and 5 focus groups (31 healthcare providers) were held.After obtaining FPA, the proportion of NPs and PAs performing reserved procedures increased from 77% to 85% and from 86% to 93%, respectively; the proportion of procedures performed on own authority increased from 63% to 76% for NPs and from 67% to 71% for PAs. The mean number of monthly contacts between NPs/PAs and physicians about procedures decreased (from 81 to 49 and from 107 to 54, respectively), as did the mean duration in minutes (from 9.9 to 8.6 and from 8.8 to 7.4, respectively). Utilisation of FPA was dependent on the setting, as scepticism of physicians and medical boards hampered full implementation. Legal cross-compliance requirements were mostly fulfilled.ConclusionsInformal practice was legalised. The opportunities to independently perform catheterisations, injections, prescribing, punctures and small surgical procedures were highly used. Care processes were organised more efficiently, services were performed by the most appropriate healthcare provider and conditions were met. This led to the recommendation to continue with FPA.
PREHAB study: a protocol for a prospective randomised clinical trial of exercise therapy for people living with frailty having cancer surgery
Authors: McIsaac Daniel I , Saunders Chelsey , Hladkowicz Emily , Bryson Gregory L , Forster Alan J , Gagne Sylvain , Huang Allen , Lalu Manoj , Lavallee Luke T , Moloo Husein , Nantel Julie , Power Barbara , Scheede-Bergdahl Celena , Taljaard Monica , van Walraven Carl , McCartney Colin J L 
Published: June 2018

IntroductionExercise prehabilitation may improve outcomes after surgery. Frailty is a key predictor of adverse postoperative outcomes in older people; the multidimensional nature of frailty makes this a population who may derive substantial benefit from exercise prehabilitation. The objective of this trial is to test the efficacy of exercise prehabilitation to improve postoperative functional outcomes for people living with frailty having cancer surgery with curative intent.Methods and analysisWe will conduct a single-centre, parallel-arm randomised controlled trial of home-based exercise prehabilitation versus standard care among consenting patients >60 years having elective cancer surgery (intra-abdominal and intrathoracic) and who are frail (Clinical Frailty Scale >4). The intervention consists of>3 weeks of exercise prehabilitation (strength, aerobic and stretching). The primary outcome is the 6 min walk test at the first postoperative clinic visit. Secondary outcomes include the short physical performance battery, health-related quality of life, disability-free survival, complications and health resource utilisation. The primary outcome will be analysed by intention to treat using analysis of covariance. Outcomes up to 1 year after surgery will be ascertained through linkage to administrative data.Ethics and disseminationEthical approval has been granted by our ethics review board (Protocol Approval #2016009–01H). Results will be disseminated through presentation at scientific conferences, through peer-reviewed publication, stakeholder organisations and engagement of social and traditional media.Trial registration numberNCT02934230; Pre-results.
Evaluation of an incidental cardiac finding in a patient with bronchitis
Authors: Bradley Andrew J , Lewis Jannet F , Choi Andrew D 
Published: June 2018

Clinical introductionA 63-year-old man with HIV presented with 1 month of dyspnoea and productive cough without orthopnoea. He was afebrile with normal blood pressure, borderline tachycardia and mild pulmonary wheezing. He had exertional hypoxia requiring 4 L per minute of oxygen. No murmurs, jugular venous distention or lower extremity oedema was noted. Clinical evaluation included transthoracic echocardiography (TTE), which showed mild left ventricular hypertrophy with normal size and systolic function. The right ventricle was normal. There was mild aortic insufficiency; other valves were normal. An abnormality was incidentally seen at the aortic root.The patient was treated for bronchitis and chronic obstructive pulmonary disease exacerbation, while further evaluation of the incidental aortic root finding was performed with transoesophageal echocardiography (TEE) and cardiac MRI (CMR).QuestionWhat is the most likely diagnosis for this finding?Sinus of Valsalva aneurysm.Chronic aortic dissection.Left ventricular outflow tract (LVOT) pseudoaneurysm.Right coronary artery aneurysm.Aortic root abscess.
Sex ratios at birth among second-generation mothers of South Asian ethnicity in Ontario, Canada: a retrospective population-based cohort study
Authors: Wanigaratne Susitha , Uppal Pamela , Bhangoo Manvir , Januwalla Alia , Singal Deepa , Urquia Marcelo L 
Published: June 2018

BackgroundSon-biased sex ratios at birth (M:F), an extreme manifestation of son preference, are predominately found in East and South Asia. Studies have examined sex ratios among first-generation migrants from these regions, but few have examined second-generation descendants. Our objective was to determine whether son-biased sex ratios persist among second-generation mothers with South Asian ethnicity in Ontario, Canada.MethodologyA surname algorithm identified a population-based cohort of mothers with South Asian ethnicity who gave birth in Ontario between 1993 and 2014 (n=59 659). Linking to official immigration data identified births to first-generation mothers (ie, immigrants). Births not to immigrants were designated as being to second-generation mothers (ie, born in Canada) (n=10 273). Sex ratios and 95% CI were stratified by the sex of previous live births and by whether it was preceded by ≥1 abortion for both first-generation and second-generation mothers.ResultsAmong mothers with two previous daughters and at least one prior abortion since the second birth, both second-generation mothers and first-generation mothers had elevated sex ratios at the third birth (2.80 (95% CI 1.36 to 5.76) and 2.46 (95% CI 1.93 to 3.12), respectively). However, among mothers with no prior abortion, second-generation mothers had a normal sex ratio, while first-generation mothers gave birth to 142 boys for every 100 girls (95% CI 125 to 162 boys for every 100 girls).ConclusionSon preference persists among second-generation mothers of South Asian ethnicity. Culturally sensitive and community-driven gender equity interventions are needed.
Factors influencing the incidence and treatment of intracranial aneurysm and subarachnoid hemorrhage: time trends and socioeconomic disparities under an universal healthcare system
Authors: Lee Won Kyung , Oh Chang Wan , Lee Heeyoung , Lee Kun Sei , Park Hyeonseon 
Published: June 2018

BackgroundDespite increasing usage of endovascular treatments for intracranial aneurysms, few research studies have been conducted on the incidence of unruptured aneurysm (UA) and subarachnoid hemorrhage (SAH), and could not show a decrease in the incidence of SAH. Moreover, research on socioeconomic disparities with respect to the diagnosis and treatment of UA and SAH is lacking.MethodTrends in the incidences of newly detected UA and SAH and trends in the treatment modalities used were assessed from 2005 to 2015 using the nationwide database of the Korean National Health Insurance Service in South Korea. We also evaluated the influence of demographic characteristics including socioeconomic factors on the incidence and treatment of UA and SAH.ResultThe rates of newly detected UA and SAH were 28.3 and 13.7 per 100 000 of the general population, respectively, in 2015. The incidence of UA increased markedly over the 11-year study period, whereas that of SAH decreased slightly. UA patients were more likely to be female, older, employee-insured, and to have high incomes than SAH patients. In 2015, coiling was the most common treatment modality for both UA and SAH patients. Those who were female, employee-insured, or self-employed, with high income were likely to have a higher probability to be treated for UA and SAH.ConclusionThe marked increase in the detection and treatment of UA might have contributed to the decreasing incidence of SAH, though levels of contribution depend on socioeconomic status despite universal medical insurance coverage.
Clinical evaluation of volume of interest imaging combined with metal artifact reduction reconstruction techniques in coiling and stent assisted coiling during neurointerventional procedures
Authors: Zhang Qiang , Zhao Hao , Sun Qi , Han Jingfeng , Zhang Hao , Shan Tonghui , Pan Wenlong , Gu Chuanqi , Xu Ruxiang , Mao Gengsheng 
Published: June 2018

PurposeThree-dimensional (3D) scans with flat detector angiographic systems are widely used for neurointerventions by providing detailed vascular information. However, its associated radiation dose and streak metal artifact generated by implanted treatment devices remain issues. This work evaluates the feasibility and clinical value of volume of interest imaging combined with metal artifact reduction (VOI+MAR) to generate high quality 3D images with reduced radiation dose and metal artifacts.Material and methodsFull volume (FV) and VOI scans were acquired in 25 patients with intracranial aneurysms and treated with either endovascular coiling (n=9) or stent assisted coiling (n=16) procedures. FV and VOI scans were reconstructed with conventionalsyngoDynaCT and VOI +MAR prototype software, respectively.ResultsQuantitative evaluation results demonstrated that compared with standard FVsyngoDynaCT images, overall image quality was improved in the VOI+MAR reconstructed images, with streak metal artifacts considerably reduced or even removed; details of soft tissue in the vicinity of the metal devices was well preserved or recovered in the majority of cases. Radiation dose to patients calculated by dose area product was found to be significantly reduced using VOI scans.ConclusionThis study confirmed the feasibility of using VOI+MAR prototype software to achieve high image quality of a small volume of clinical interest and to reduce radiation dose. This technique has potential to improve patient safety and treatment outcomes.
Geological considerations of contemporary military tunnelling near Mosul, northern Iraq
Authors: Bulmer Mark H. 
Published: June 2018

Abstract
Members of the so-called Islamic State (IS) have used subterranea in Syria and Iraq as a core part of their control over territories and their military capability. Around Mosul they exploited existing natural sinkholes, caves and tunnels. The use of tunnels and the completion of new ones between 2014 and 2017 impacted the advance of Iraqi and Peshmerga forces in the battle for Mosul. IS created complex tunnel networks using hand tools, power tools and improvised tunnel-boring machines. To avoid detection, tunnels were started in buildings and spoil was hidden in rooms. The tunnels range from those large enough for one person to crouch in to those large enough for a vehicle. The most sophisticated tunnel complexes had dormitories, hospitals, armouries, kitchens, latrines, and command centres complete with CCTV, solar panels, computers, phones, electricity, respirators and ventilation facilitating underground occupation for long periods. IS tunnelled in almost all urban areas they controlled, demonstrating an enormous effort: moving from hand tools to tunnel-boring machines was a logical progression. The size of tunnel-boring machines and the amount of spoil generated defined the type of building they started in and the length of the tunnel they bored. Buildings with tunnels under them risk collapse.
Atglistatin ameliorates functional decline in heart failure via adipocyte-specific inhibition of adipose triglyceride lipase
Authors: Parajuli Nirmal , Takahara Shingo , Matsumura Nobutoshi , Kim Ty T. , Ferdaoussi Mourad , Migglautsch Anna K. , Zechner Rudolf , Breinbauer Rolf , Kershaw Erin E. , Dyck Jason R. B. 
Published: June 2018

Despite advancements in therapies for cardiovascular disease and heart failure (HF), the incidence and prevalence of HF are increasing. Previous work has suggested that inhibiting adipose triglyceride lipase (ATGL) in adipose tissue during HF development may assist in the treatment of HF. The ability to specifically target the adipocyte as a potential treatment for HF is a novel approach that could significantly influence the management of HF in the future. Our objectives were to assess the cardiac structural and functional effects of pharmacological inhibition of ATGL in mice with HF, to assess whether ATGL inhibition works in an adipocyte-autonomous manner, and to determine the role that adiposity and glucose homeostasis play in this HF treatment approach. Using a known ATGL inhibitor, atglistatin, as well as mice with germline deletion of adipocyte-specific ATGL, we tested the effectiveness of ATGL inhibition in mice with pressure overload-induced HF. Here, we show that atglistatin can prevent the functional decline in HF and provide evidence that specifically targeting ATGL in the adipocyte is sufficient to prevent worsening of HF. We further demonstrate that the benefit resulting from atglistatin in HF is not dependent on previously suggested improvements in glucose homeostasis, nor are the benefits derived from increased adiposity. Overall, the results of this study suggest that adipocyte-specific pharmacological inhibition of ATGL may represent a novel therapeutic option for HF. NEW & NOTEWORTHY This work shows for the first time that the adipose triglyceride lipase (ATGL)-specific inhibitor atglistatin can prevent worsening heart failure. Furthermore, using mice with adipocyte-specific ATGL ablation, this study demonstrates that ATGL inhibition works in an adipocyte-autonomous manner to ameliorate a functional decline in heart failure. Overall, this work demonstrates that specifically targeting the adipocyte to inhibit ATGL is a potential treatment for heart failure.
Long Noncoding RNA CRYBG3 Blocks Cytokinesis by Directly Binding G-Actin
Authors: Pei Hailong , Hu Wentao , Guo Ziyang , Chen Huaiyuan , Ma Ji , Mao Weidong , Li Bingyan , Wang Aiqing , Wan Jianmei , Zhang Jian , Nie Jing , Zhou Guangming , Hei Tom K. 
Published: June 2018

AbstractThe dynamic interchange between monomeric globular actin (G-actin) and polymeric filamentous actin filaments (F-actin) is fundamental and essential to many cellular processes, including cytokinesis and maintenance of genomic stability. Here, we report that the long noncoding RNA LNC CRYBG3 directly binds G-actin to inhibit its polymerization and formation of contractile rings, resulting in M-phase cell arrest. Knockdown of LNC CRYBG3 in tumor cells enhanced their malignant phenotypes. Nucleotide sequence 228-237 of the full-length LNC CRYBG3 and the ser14 domain of β-actin is essential for their interaction, and mutation of either of these sites abrogated binding of LNC CRYBG3 to G-actin. Binding of LNC CRYBG3 to G-actin blocked nuclear localization of MAL, which consequently kept serum response factor (SRF) away from the promoter region of several immediate early genes, including JUNB and Arp3, which are necessary for cellular proliferation, tumor growth, adhesion, movement, and metastasis. These findings reveal a novel lncRNA-actin-MAL-SRF pathway and highlight LNC CRYBG3 as a means to block cytokinesis and to treat cancer by targeting the actin cytoskeleton.Significance: Identification of the long noncoding RNA LNC CRYBG3 as a mediator of microfilament disorganization marks it as a novel therapeutic antitumor strategy. Cancer Res; 78(16); 4563–72. ©2018 AACR.
Recombinant MDA-7/IL24 Suppresses Prostate Cancer Bone Metastasis through Downregulation of the Akt/Mcl-1 Pathway
Authors: Pradhan Anjan K. , Bhoopathi Praveen , Talukdar Sarmistha , Shen Xue-Ning , Emdad Luni , Das Swadesh K. , Sarkar Devanand , Fisher Paul B. 
Published: June 2018

Abstract
Prostate cancer is a principal cause of cancer-associated morbidity in men. Although 5-year survival of patients with localized prostate cancer approaches 100%, survival decreases precipitously after metastasis. Bone is the preferred site for disseminated prostate cancer cell colonization, altering the equilibrium of bone homeostasis resulting in weak and fragile bones. Currently, no curative options are available for prostate cancer bone metastasis. Melanoma differentiation associated gene-7 (MDA-7)/IL24 is a well-studied cytokine established as a therapeutic in a wide array of cancers upon delivery as a gene therapy. In this study, we explored the potential anticancer properties of MDA-7/IL24 delivered as a recombinant protein. Using bone metastasis experimental models, animals treated with recombinant MDA-7/IL24 had significantly less metastatic lesions in their femurs as compared with controls. The inhibitory effects of MDA-7/IL24 on bone metastasis resulted from prostate cancer–selective killing and inhibition of osteoclast differentiation, which is necessary for bone resorption. Gain- and loss-of-function genetic approaches document that prosurvival Akt and Mcl-1 pathways are critically important in the antibone metastatic activity of MDA-7/IL24. Our previous findings showed that MDA-7/IL24 gene therapy plus Mcl-1 inhibitors cooperate synergistically. Similarly, an Mcl-1 small-molecule inhibitor synergized with MDA-7/IL24 and induced robust antibone metastatic activity. These results expand the potential applications of MDA-7/IL24 as an anticancer molecule and demonstrate that purified recombinant protein is nontoxic in preclinical animal models and has profound inhibitory effects on bone metastasis, which can be enhanced further when combined with an Mcl-1 inhibitory small molecule. Mol Cancer Ther; 17(9); 1951–60. ©2018 AACR.
Induction of Thioredoxin-Interacting Protein by a Histone Deacetylase Inhibitor, Entinostat, Is Associated with DNA Damage and Apoptosis in Esophageal Adenocarcinoma
Authors: Feingold Paul L. , Surman Deborah R. , Brown Kate , Xu Yuan , McDuffie Lucas A. , Shukla Vivek , Reardon Emily S. , Crooks Daniel R. , Trepel Jane B. , Lee Sunmin , Lee Min-Jung , Gao Shaojian , Xi Sichuan , McLoughlin Kaitlin C. , Diggs Laurence P. , Beer David G. , Nancarrow Derek J. , Neckers Leonard M. , Davis Jeremy L. , Hoang Chuong D. , Hernandez Jonathan M. , Schrump David S. , Ripley R. Taylor 
Published: June 2018

Abstract
In 2017, an estimated 17,000 individuals were diagnosed with esophageal adenocarcinoma (EAC), and less than 20% will survive 5 years. Positron emission tomography avidity is indicative of high glucose utilization and is nearly universal in EAC. TXNIP blocks glucose uptake and exhibits proapoptotic functions. Higher expression in EAC has been associated with improved disease-specific survival, lack of lymph node involvement, reduced perineural invasion, and increased tumor differentiation. We hypothesized that TXNIP may act as a tumor suppressor that sensitizes EAC cells to standard chemotherapeutics. EAC cell lines and a Barrett epithelial cell line were used. qRT-PCR, immunoblot, and immunofluorescence techniques evaluated gene expression. TXNIP was stably overexpressed or knocked down using lentiviral RNA transduction techniques. Murine xenograft methods examined growth following overexpression of TXNIP. Apoptosis and DNA damage were measured by annexin V and γH2AX assays. Activation of the intrinsic apoptosis was quantitated with green fluorescence protein-caspase 3 reporter assay. In cultured cells and an esophageal tissue array, TXNIP expression was higher in Barrett epithelia and normal tissue compared with EAC. Constitutive overexpression of TXNIP decreased proliferation, clonogenicity, and tumor xenograft growth. TXNIP overexpression increased, whereas knockdown abrogated, DNA damage and apoptosis following cisplatin treatment. An HDAC inhibitor, entinostat (currently in clinical trials), upregulated TXNIP and synergistically increased cisplatin-mediated DNA damage and apoptosis. TXNIP is a tumor suppressor that is downregulated in EACC. Its reexpression dramatically sensitizes these cells to cisplatin. Our findings support phase I/II evaluation of “priming” strategies to enhance the efficacy of conventional chemotherapeutics in EAC. Mol Cancer Ther; 17(9); 2013–23. ©2018 AACR.
Hypoxia Promotes Resistance to EGFR Inhibition in NSCLC Cells via the Histone Demethylases, LSD1 and PLU-1
Authors: Lu Yuhong , Liu Yanfeng , Oeck Sebastian , Glazer Peter M. 
Published: June 2018

Abstract
The development of small-molecule tyrosine kinase inhibitors (TKI) specific for epidermal growth factor receptors (EGFR) with activating mutations has led to a new paradigm in the treatment of non–small cell lung cancer (NSCLC) patients. However, most patients eventually develop resistance. Hypoxia is a key microenvironmental stress in solid tumors that is associated with poor prognosis due, in part, to acquired resistance to conventional therapy. This study documents that long-term, moderate hypoxia promotes resistance to the EGFR TKI, gefitinib, in the NSCLC cell line HCC827, which harbors an activating EGFR mutation. Following hypoxic growth conditions, HCC827 cells treated with gefitinib upregulated N-cadherin, fibronectin, and vimentin expression and downregulated E-cadherin, characteristic of an epithelial-mesenchymal transition (EMT), which prior studies have linked to EGFR TKI resistance. Mechanistically, knockdown of the histone demethylases, LSD1 and PLU-1, prevented and reversed hypoxia-induced gefitinib resistance, with inhibition of the associated EMT, suggesting that LSD1 and PLU-1 play key roles in hypoxia-induced gefitinib resistance and EMT. Moreover, hypoxia-treated HCC827 cells demonstrated more aggressive tumor growth in vivo compared with cells grown in normoxia, but inhibition of LSD1 function by shRNA-mediated knockdown or by the small-molecular inhibitor SP2509 suppressed tumor growth and enhanced gefitinib response in vivo. These results suggest that hypoxia is a driving force for acquired resistance to EGFR TKIs through epigenetic change and coordination of EMT in NSCLC. This study suggests that combination of therapy with EGFR TKIs and LSD1 inhibitors may offer an attractive therapeutic strategy for NSCLCs. Mol Cancer Res; 16(10); 1458–69. ©2018 AACR.