bluuebunny/crossref_metadata_2025_split huggingface dataset:
Host Protein Moloney Leukemia Virus 10 (MOV10) Acts as a Restriction Factor of Influenza A Virus by Inhibiting the Nuclear Import of the Viral Nucleoprotein
Authors: Zhang Junsong , Huang Feng , Tan Likai , Bai Chuan , Chen Bing , Liu Jun , Liang Juanran , Liu Chao , Zhang Shaoying , Lu Gen , Chen Yuan , Zhang Hui 
Published: February 2016

ABSTRACT
The viral ribonucleoprotein (vRNP) complex of influenza A viruses (IAVs) contains an RNA-dependent RNA polymerase complex (RdRp) and nucleoprotein (NP) and is the functional unit for viral RNA transcription and replication. The vRNP complex is an important determinant of virus pathogenicity and host adaptation, implying that its function can be affected by host factors. In our study, we identified host protein Moloney leukemia virus 10 (MOV10) as an inhibitor of IAV replication, since depletion of MOV10 resulted in a significant increase in virus yield. MOV10 inhibited the polymerase activity in a minigenome system through RNA-mediated interaction with the NP subunit of vRNP complex. Importantly, we found that the interaction between MOV10 and NP prevented the binding of NP to importin-α, resulting in the retention of NP in the cytoplasm. Both the binding of MOV10 to NP and its inhibitory effect on polymerase activity were independent of its helicase activity. These results suggest that MOV10 acts as an anti-influenza virus factor through specifically inhibiting the nuclear transportation of NP and subsequently inhibiting the function of the vRNP complex.

IMPORTANCE
The interaction between the influenza virus vRNP complex and host factors is a major determinant of viral tropism and pathogenicity. Our study identified MOV10 as a novel host restriction factor for the influenza virus life cycle since it inhibited the viral growth rate. Conversely, importin-α has been shown as a determinant for influenza tropism and a positive regulator for viral polymerase activity in mammalian cells but not in avian cells. MOV10 disrupted the interaction between NP and importin-α, suggesting that MOV10 could also be an important host factor for influenza virus transmission and pathogenicity. Importantly, as an interferon (IFN)-inducible protein, MOV10 exerted a novel mechanism for IFNs to inhibit the replication of influenza viruses. Furthermore, our study potentially provides a new drug design strategy, the use of molecules that mimic the antiviral mechanism of MOV10.
Development of a Health Empowerment Programme to improve the health of working poor families: protocol for a prospective cohort study in Hong Kong
Authors: Fung Colman Siu Cheung , Yu Esther Yee Tak , Guo Vivian Yawei , Wong Carlos King Ho , Kung Kenny , Ho Sin Yi , Lam Lai Ying , Ip Patrick , Fong Daniel Yee Tak , Lam David Chi Leung , Wong William Chi Wai , Tsang Sandra Kit Man , Tiwari Agnes Fung Yee , Lam Cindy Lo Kuen 
Published: February 2016

IntroductionPeople from working poor families are at high risk of poor health partly due to limited healthcare access. Health empowerment, a process by which people can gain greater control over the decisions affecting their lives and health through education and motivation, can be an effective way to enhance health, health-related quality of life (HRQOL), health awareness and health-seeking behaviours of these people. A new cohort study will be launched to explore the potential for a Health Empowerment Programme to enable these families by enhancing their health status and modifying their attitudes towards health-related issues. If proven effective, similar empowerment programme models could be tested and further disseminated in collaborations with healthcare providers and policymakers.Method and analysisA prospective cohort study with 200 intervention families will be launched and followed up for 5 years. The following inclusion criteria will be used at the time of recruitment: (1) Having at least one working family member; (2) Having at least one child studying in grades 1–3; and (3) Having a monthly household income that is less than 75% of the median monthly household income of Hong Kong families. The Health Empowerment Programme that will be offered to intervention families will comprise four components: health assessment, health literacy, self-care enablement and health ambassador. Their health status, HRQOL, lifestyle and health service utilisation will be assessed and compared with 200 control families with matching characteristics but will not receive the health empowerment intervention.Ethics and disseminationThis project was approved by the University of Hong Kong—the Hospital Authority Hong Kong West Cluster IRB, Reference number: UW 12-517. The study findings will be disseminated through a series of peer-reviewed publications and conference presentations, as well as a yearly report to the philanthropic funding body–Kerry Group Kuok Foundation (Hong Kong) Limited.
Understanding and evaluating the effects of implementing an electronic paediatric prescribing system on care provision and hospital work in paediatric hospital ward settings: a qualitatively driven mixed-method study protocol
Authors: Farre Albert , Cummins Carole 
Published: February 2016

IntroductionElectronic prescribing systems can improve the quality and safety of healthcare services, but their implementation is not straightforward and may create unexpected change. However, the added complexity of paediatric prescribing (eg, dose calculations, dilutions, manipulations) may pose additional challenges. This study will aim to (1) understand the complex organisational reality of a paediatric hospital in which a new electronic paediatric prescribing (ePP) system will be introduced; (2) describe ePP-related change, over time, in paediatric hospital ward settings; (3) explore staff perspectives in relation to currently established practices and processes; and (4) assess the impact of ePP on care provision and hospital work from the perspective of paediatricians, paediatric nurses and managers.Methods and analysisA qualitatively driven mixed-method approach will be adopted, including 3 inter-related substudies. The core component of the study will be qualitative (substudy 1): we will use ethnographic research methods, including non-participant observation in wards and informal conversational interviews with members of staff. In addition, the design will include 2 embedded supplementary components: a qualitative 1 (substudy 2) based on in-depth interviews and/or focus groups with paediatricians, paediatric nurses, paediatric pharmacists/pharmacy technicians and managers; and a quantitative 1 (substudy 3) in which a staff survey will be developed and administered before and after the ePP implementation. Analytic themes will be identified from ethnographic field notes and interview data. Survey data will be analysed using descriptive statistics and baseline and follow-up data compared to establish impact evaluation measures.Ethics and disseminationA favourable ethical opinion has been obtained from a National Health Service (NHS) Research Ethics Committee (15/SS/0157). NHS research governance approval has been obtained at the relevant hospital site. The results of the study will be disseminated through conferences and peer-reviewed journals, as well as fed back to those involved in clinical practice and policy development at the study site.
Calreticulin Expression in Human Non–Small Cell Lung Cancers Correlates with Increased Accumulation of Antitumor Immune Cells and Favorable Prognosis
Authors: Fucikova Jitka , Becht Etienne , Iribarren Kristina , Goc Jeremy , Remark Romain , Damotte Diane , Alifano Marco , Devi Priyanka , Biton Jerome , Germain Claire , Lupo Audrey , Fridman Wolf Herve , Dieu-Nosjean Marie-Caroline , Kroemer Guido , Sautès-Fridman Catherine , Cremer Isabelle 
Published: February 2016

Abstract
A high density of tumor-infiltrating mature dendritic cells (DC) and CD8+ T cells correlates with a positive prognosis in a majority of human cancers. The recruitment of activated lymphocytes to the tumor microenvironment, primed to recognize tumor-associated antigens, can occur in response to immunogenic cell death (ICD) of tumor cells. ICD is characterized by the preapoptotic translocation of calreticulin (CRT) from the endoplasmic reticulum (ER) to the cell surface as a result of an ER stress response accompanied by the phosphorylation of eukaryotic initiation factor 2α (eIF2α). We conducted a retrospective study on two independent cohorts of patients with non–small cell lung cancer (NSCLC) to investigate the prognostic potential of CRT. We report that the level of CRT expression on tumor cells, which correlated with eIF2α phosphorylation, positively influenced the clinical outcome of NSCLC. High CRT expression on tumor cells was associated with a higher density of infiltrating mature DC and effector memory T-cell subsets, suggesting that CRT triggers the activation of adaptive immune responses in the tumor microenvironment. Accordingly, patients with elevated CRT expression and dense intratumoral infiltration by DC or CD8+ T lymphocytes had the best prognosis. We conclude that CRT expression constitutes a new powerful prognostic biomarker that reflects enhanced local antitumor immune responses in the lung. Cancer Res; 76(7); 1746–56. ©2016 AACR.
Time to Colonoscopy after Positive Fecal Blood Test in Four U.S. Health Care Systems
Authors: Chubak Jessica , Garcia Michael P. , Burnett-Hartman Andrea N. , Zheng Yingye , Corley Douglas A. , Halm Ethan A. , Singal Amit G. , Klabunde Carrie N. , Doubeni Chyke A. , Kamineni Aruna , Levin Theodore R. , Schottinger Joanne E. , Green Beverly B. , Quinn Virginia P. , Rutter Carolyn M. 
Published: February 2016

Abstract
Background: To reduce colorectal cancer mortality, positive fecal blood tests must be followed by colonoscopy.
Methods: We identified 62,384 individuals ages 50 to 89 years with a positive fecal blood test between January 1, 2011 and December 31, 2012 in four health care systems within the Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. We estimated the probability of follow-up colonoscopy and 95% confidence intervals (CI) using the Kaplan–Meier method. Overall differences in cumulative incidence of follow-up across health care systems were assessed with the log-rank test. HRs and 95% CIs were estimated from multivariate Cox proportional hazards models.
Results: Most patients who received a colonoscopy did so within 6 months of their positive fecal blood test, although follow-up rates varied across health care systems (P &lt;0.001). Median days to colonoscopy ranged from 41 (95% CI, 40–41) to 174 (95% CI, 123–343); percent followed-up by 12 months ranged from 58.1% (95% CI, 51.6%–63.7%) to 83.8% (95% CI, 83.4%–84.3%) and differences across health care systems were also observed at 1, 2, 3, and 6 months. Increasing age and comorbidity score were associated with lower follow-up rates.
Conclusion: Individual characteristics and health care system were associated with colonoscopy after positive fecal blood tests. Patterns were consistent across health care systems, but proportions of patients receiving follow-up varied. These findings suggest that there is room to improve follow-up of positive colorectal cancer screening tests.
Impact: Understanding the timing of colonoscopy after positive fecal blood tests and characteristics associated with lack of follow-up may inform future efforts to improve follow-up. Cancer Epidemiol Biomarkers Prev; 25(2); 344–50. ©2016 AACR.
The Role of Neoadjuvant Trials in Drug Development for Solid Tumors
Authors: Funt Samuel A. , Chapman Paul B. 
Published: February 2016

Abstract
The relatively low success rate of phase II oncology trials in predicting success of novel drugs in phase III trials and in gaining regulatory approval may be due to reliance on the endpoint of response rate defined by the RECIST. The neoadjuvant treatment paradigm allows the antitumor activity of a novel therapy to be determined on a pathologic basis at the time of surgery instead of by RECIST, which was not developed to guide clinical decision making or correlate with long-term outcomes. Indeed, the FDA endorsed pathologic complete response (pCR) as a surrogate for overall survival (OS) in early-stage breast cancer and granted accelerated approval to pertuzumab based on this endpoint. We propose that pCR is a biologically rational method of determining treatment effect that may be more likely to predict OS. We discuss some advantages of the neoadjuvant trial design, review the use of neoadjuvant therapy as standards of care, and consider the neoadjuvant platform as a method for drug development. Clin Cancer Res; 22(10); 2323–8. ©2016 AACR.
Using Quantitative Seroproteomics to Identify Antibody Biomarkers in Pancreatic Cancer
Authors: Jhaveri Darshil T. , Kim Min-Sik , Thompson Elizabeth D. , Huang Lanqing , Sharma Rajni , Klein Alison P. , Zheng Lei , Le Dung T. , Laheru Daniel A. , Pandey Akhilesh , Jaffee Elizabeth M. , Anders Robert A. 
Published: February 2016

Abstract
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. Less than 6% of patients survive beyond the fifth year due to inadequate early diagnostics and ineffective treatment options. Our laboratory has developed an allogeneic, granulocyte-macrophage colony-stimulating factor (GM-CSF)–secreting pancreatic cancer vaccine (GVAX) that has been tested in phase II clinical trials. Here, we employed a serum antibodies–based SILAC immunoprecipitation (SASI) approach to identify proteins that elicit an antibody response after vaccination. The SASI approach uses immunoprecipitation with patient-derived antibodies that is coupled to quantitative stable isotope–labeled amino acids in cell culture (SILAC). Using mass spectrometric analysis, we identified more than 150 different proteins that induce an antibody response after vaccination. The regulatory subunit 12A of protein phosphatase 1 (MYPT1 or PPP1R12A), regulatory subunit 8 of the 26S proteasome (PSMC5), and the transferrin receptor (TFRC) were shown to be pancreatic cancer–associated antigens recognized by postvaccination antibodies in the sera of patients with favorable disease-free survival after GVAX therapy. We further interrogated these proteins in over 80 GVAX-treated patients' pancreases and uniformly found a significant increase in the expression of MYPT1, PSMC5, and TFRC in neoplastic compared with non-neoplastic pancreatic ductal epithelium. We show that the novel SASI approach can identify antibody targets specifically expressed in patients with improved disease-free survival after cancer vaccine therapy. These targets need further validation to be considered as possible pancreatic cancer biomarkers. Cancer Immunol Res; 4(3); 225–33. ©2016 AACR.
Spanish Consensus Guidelines on prophylaxis with bypassing agents in patients with haemophilia and inhibitors
Authors: Roca Carmen Altisent , Álvarez-Román Maria Teresa , Canaro Hirnyk Mariana Isabel , Mingot-Castellano Maria Eva , Jiménez-Yuste Víctor , Cid Haro Ana Rosa , Pérez-Garrido Rosario , Sedano Balbas Carmen , López-Fernández Maria Fernanda 
Published: February 2016

SummaryProphylaxis with the blood clotting factor, factor VIII (FVIII) is ineffective for individuals with haemophilia A and high-titre inhibitors to FVIII. Prophylaxis with the FVIII bypassing agents activated prothrombin complex concentrates (aPCC; FEIBA® Baxalta) or recombinant activated factor VII (rFVIIa; Novo-Seven®, Novo Nordisk) may be an effective alternative. It was our aim to develop evidence -and expert opinion- based guidelines for prophylactic therapy for patients with high-titre inhibitors to FVIII. A panel of nine Spanish haematologists undertook a systematic review of the literature to develop consensusbased guidance. Particular consideration was given to prophylaxis in patients prior to undergoing immune tolerance induction (ITI) (a process of continued exposure to FVIII that can restore sensitivity for some patients), during the ITI period and for those not undergoing ITI or for whom ITI had failed. These guidelines offer guidance for clinicians in deciding which patients might benefit from prophylaxis with FVIII bypassing agents, the most appropriate agents in various clinical settings related to ITI, doses and dosing regimens and how best to monitor the efficacy of prophylaxis. The paper includes recommendations on when to interrupt or stop prophylaxis and special safety concerns during prophylaxis. These consensus guidelines offer the most comprehensive evaluation of the clinical evidence base to date and should be of considerable benefit to clinicians facing the challenge of managing patients with severe haemophilia A with high-titre FVIII inhibitors.
High mortality in patients presenting with acute pulmonary embolism and elevated INR not on anticoagulant therapy
Authors: Wong Christopher , Lau Jerrett , Chow Vincent , Chen Vivien , Yong Andy , Sindone Andrew , Marwick Thomas , Kritharides Leonard , Ng Austin , Ng Arnold 
Published: February 2016

SummaryThe prognostic significance of patients presenting with pulmonary embolism (PE) and elevated International Normalised Ratio (INR) not on anticoagulant therapy has not been described. We investigated whether these patients had higher mortality compared to patients with normal INR. A retrospective study of patients admitted to a tertiary hospital with acute PE from 2000 to 2012 was undertaken, with study outcomes tracked using a state-wide death registry. Patients were excluded if they were taking anticoagulants or had inadequate documentation of their INR and medication status. Of the 1,039 patients identified, 94 (9 %) had an elevated INR (> 1.2) in the absence of anticoagulant use. These patients had higher mortality at six months follow-up (26 % vs 6 %, p< 0.001) compared to controls (INR ≤ 1.2). An INR > 1.2 at diagnosis was an independent predictor of death at six months post-PE (hazard ratio [HR] 2.9, 95 % confidence interval [CI] 1.8–4.7, p< 0.001). The addition of INR to a multivariable model that included the simplified pulmonary embolism severity index (sPESI), chest pain, and serum sodium led to a significant net reclassification improvement estimated at 8.1 %. The final model’s C statistic increased significantly by 0.04 (95 % CI 0.01–0.08, p=0.03) to 0.83 compared to sPESI alone (0.79). In summary, patients presenting with acute PE and elevated INR while not on anticoagulant therapy appear to be at high risk of death. Future validation studies in independent cohorts will clarify if this novel finding can be usefully incorporated into clinical decision making in patients with acute PE.
Oral anticoagulation, stroke and thromboembolism in patients with atrial fibrillation and valve bioprosthesis
Authors: Philippart Raphael , Brunet-Bernard Anne , Clementy Nicolas , Bourguignon Thierry , Mirza Alain , Angoulvant Denis , Babuty Dominique , Lip Gregory Y. H. , Fauchier Laurent 
Published: February 2016

SummaryVitamin K antagonists are currently recommended in patients with ‘valvular’ atrial fibrillation (AF), e. g. those having mitral stenosis or artificial heart valves. We compared thromboembolic risk in patients with ‘non valvular’ AF and in those with AF and biological valve replacement (valve bioprosthesis). Among 8962 AF patients seen between 2000 and 2010, a diagnosis of ‘non-valvular AF’ was found in 8053 (94 %). Among patients with ‘valvular’ AF, 549 (6 %) had a biological prosthesis. The patients with bioprosthesis were older and had a higher CHA2DS2-VASc score than those with non valvular AF. After a follow-up of 876 é 1048 days (median 400 days, interquartile range 12–1483), the occurrence of thromboembolic events was similar in AF patients with bioprosthesis compared to those with ‘non valvular’ AF (hazard ratio [HR] 1.10 95 % confidence interval [CI] 0.83–1.45, p=0.52, adjusted HR 0.93, 95 %CI 0.68–1.25, p=0.61). Factors independently associated with increased risk of stroke/TE events were older age (HR 1.25, 95 %CI 1.16–1.34 per 10-year increase, p> 0.0001) and higher CHA2DS2-VASc score (HR 1.35, 95 %CI 1.24–1.46, p> 0.0001) whilst female gender (HR 0.75, 95 %CI 0.62–0.90, p=0.002), use of vitamin K antagonist (HR 0.83, 95 %CI 0.71–0.98, p=0.03) were independently associated with a lower risk of stroke/TE. Neither the presence of bioprosthesis nor the location of bioprosthesis was independent predictor for TE events. In conclusion, AF patients with bioprosthesis had a non-significantly higher risk of stroke/TE events compared to patients with non-valvular AF. Second, the CHA2DS2-VASc score was independently associated with an increased risk of TE events, and was a valuable determinant of TE risk both in AF patients with non-valvular AF as well as those with bioprosthesis, whether treated or not treated with OAC.Note: The review process for this paper was fully handled by Christian Weber, Editor in Chief.
Contribution to the knowledge of Turkish stoneflies with annotated catalogue (Insecta: Plecoptera)
Authors: DARILMAZ MUSTAFA CEMAL , SALUR ALİ , Murányi DáVID , VINÇON GILLES 
Published: February 2016

The stoneflies of Turkey are reviewed providing all known distributions and including new records. Additionally, ecological and biogeographical notes are given. The genus Taeniopteryx Pictet 1841 is reported from Turkey for the first time and 12 species new for the Turkish fauna: Leuctra joosti Braasch 1970, L. kopetdaghi Zhiltzova 1972, Protonemura rauschi Theischinger 1975, P. strandschaensis Braasch & Joost 1972, Nemoura asceta Murányi 2007, N. cambrica Stephens 1836, N. uncinata Despax 1934, Taeniopteryx caucasica Zhiltzova 1981, Brachyptera risi (Morton 1896), Pontoperla katherinae (Balinsky 1950), Siphonoperla neglecta (Rostock 1881), and Bulgaroperla mirabilis nigrita Zwick 1978. Protonemura bithynica Aubert 1964 and Nemoura turcica Zwick 1972 are recognized as full species. The previously unknown female of Leuctra marilouae Vinçon & Sivec 2001 is described. The type locality is also given for each species located in Turkey. The distributions of several rare endemic species are augmented by additional new records (Leuctra aculeata Zwick 1982, L. brachyptera Kazancı 1985, L. karcali Vinçon & Sivec 2001, L. kurui Kazancı 1983, L. marilouae Vinçon & Sivec 2001, L. sipahilerae Vinçon & Sivec 2001, L. theischingeri Vinçon & Sivec 2001, Protonemura bacurianica bacurianica Zhiltzova 1957, P. oreas Martynov 1928, P. spinulata Martynov 1928 (first confirmed records from Anatolia), P. triangulata Martynov 1928, Nemoura dromokeryx Theischinger 1976, N. martynovia Claassen 1936, and Brachyptera berkii Kazancı 2001. Several species previously reported only from females are excluded from the Turkish fauna: Leuctra minuta minuta Zhiltzova 1960, L. svanetica Zhiltzova 1960, P. dilatata Martynov 1928. Other species are also excluded from the Turkish fauna: L. fusca fusca (Linnaeus 1758), N. carpathica Illies 1963, Siphonoperla burmeisteri (Pictet 1841), and S. libanica Alouf, 1992. According to literature and our new faunistic data, 117 stonefly taxa representing 7 families and 24 genera are known from Turkey. Among them, 44 are endemic species from Anatolia.
Competition, Openness and Inequality of Firm Size in the Indian Manufacturing
Authors: Govinda Hariprasad 
Published: February 2016

This article is an attempt to study the impacts of trade openness and competition on inequality of firm size in the Indian manufacturing during 1990–2010. A number of empirical studies have observed a positive skewness in the size distribution of firms (log-normal distribution) and an increasing concern over raising inequality of firm sizes in the industry. I have attempted to study the direction of the causation between export openness and inequality of firm size distribution (FSD), which is not often studied so far, despite it being purely empirical. The empirical results clearly show that export openness is statistically significant (1 per cent) throughout all the models and has negative effects on inequality. This is one interesting and robust empirical finding that export openness has the capability to reduce inter-firm performance differences, and hence, reducing inequality in FSD.