bluuebunny/crossref_metadata_2025_split huggingface dataset:
TMPRSS2 Is a Host Factor That Is Essential for Pneumotropism and Pathogenicity of H7N9 Influenza A Virus in Mice
Authors: Tarnow Carolin , Engels Géraldine , Arendt Annika , Schwalm Folker , Sediri Hanna , Preuss Annette , Nelson Peter S. , Garten Wolfgang , Klenk Hans-Dieter , Gabriel Gülsah , Böttcher-Friebertshäuser Eva 
Published: February 2014

ABSTRACT

Cleavage of the hemagglutinin (HA) by host proteases is essential for the infectivity of influenza viruses. Here, we analyzed the role of the serine protease TMPRSS2, which activates HA in the human respiratory tract, in pathogenesis in a mouse model. Replication of the human H7N9 isolate A/Anhui/1/13 and of human H1N1 and H3N2 viruses was compared in TMPRSS2 knockout (
TMPRSS2
−/−
) and wild-type (WT) mice. Knockout of TMPRSS2 expression inhibited H7N9 influenza virus replication in explants of murine tracheas, bronchi, and lungs. H1N1 virus replication was also strongly suppressed in airway explants of
TMPRSS2
−/−
mice, while H3N2 virus replication was only marginally affected. H7N9 and H1N1 viruses were apathogenic in
TMPRSS2
−/−
mice, whereas WT mice developed severe disease with mortality rates of 100% and 20%, respectively. In contrast, all H3N2 infected
TMPRSS2
−/−
and WT mice succumbed to lethal infection. Cleavage analysis showed that H7 and H1 are efficiently activated by TMPRSS2, whereas H3 is less susceptible to the protease. Our data demonstrate that TMPRSS2 is a host factor that is essential for pneumotropism and pathogenicity of H7N9 and H1N1 influenza virus in mice. In contrast, replication of H3N2 virus appears to depend on another, not yet identified protease, supporting the concept that human influenza viruses differ in protease specificity.

IMPORTANCE
Cleavage of the hemagglutinin (HA) by host proteases is essential for the infectivity of influenza virus, but little is known about its relevance for pathogenesis in mammals. Here, we show that knockout mice that do not express the HA-activating protease TMPRSS2 are resistant to pulmonary disease with lethal outcome when infected with influenza A viruses of subtypes H7N9 and H1N1, whereas they are not protected from lethal H3N2 virus infection. These findings demonstrate that human influenza viruses differ in protease specificity, and that expression of the appropriate protease in respiratory tissues is essential for pneumotropism and pathogenicity. Our observations also demonstrate that HA-activating proteases and in particular TMPRSS2 are promising targets for influenza therapy.
Substitutions near the Hemagglutinin Receptor-Binding Site Determine the Antigenic Evolution of Influenza A H3N2 Viruses in U.S. Swine
Authors: Lewis Nicola S. , Anderson Tavis K. , Kitikoon Pravina , Skepner Eugene , Burke David F. , Vincent Amy L. 
Published: February 2014

ABSTRACT
Swine influenza A virus is an endemic and economically important pathogen in pigs, with the potential to infect other host species. The hemagglutinin (HA) protein is the primary target of protective immune responses and the major component in swine influenza A vaccines. However, as a result of antigenic drift, vaccine strains must be regularly updated to reflect currently circulating strains. Characterizing the cross-reactivity between strains in pigs and seasonal influenza virus strains in humans is also important in assessing the relative risk of interspecies transmission of viruses from one host population to the other. Hemagglutination inhibition (HI) assay data for swine and human H3N2 viruses were used with antigenic cartography to quantify the antigenic differences among H3N2 viruses isolated from pigs in the United States from 1998 to 2013 and the relative cross-reactivity between these viruses and current human seasonal influenza A virus strains. Two primary antigenic clusters were found circulating in the pig population, but with enough diversity within and between the clusters to suggest updates in vaccine strains are needed. We identified single amino acid substitutions that are likely responsible for antigenic differences between the two primary antigenic clusters and between each antigenic cluster and outliers. The antigenic distance between current seasonal influenza virus H3 strains in humans and those endemic in swine suggests that population immunity may not prevent the introduction of human viruses into pigs, and possibly vice versa, reinforcing the need to monitor and prepare for potential incursions.

IMPORTANCE
Influenza A virus (IAV) is an important pathogen in pigs and humans. The hemagglutinin (HA) protein is the primary target of protective immune responses and the major target of vaccines. However, vaccine strains must be updated to reflect current strains. Characterizing the differences between seasonal IAV in humans and swine IAV is important in assessing the relative risk of interspecies transmission of viruses. We found two primary antigenic clusters of H3N2 in the U.S. pig population, with enough diversity to suggest updates in swine vaccine strains are needed. We identified changes in the HA protein that are likely responsible for these differences and that may be useful in predicting when vaccines need to be updated. The difference between human H3N2 viruses and those in swine is enough that population immunity is unlikely to prevent new introductions of human IAV into pigs or vice versa, reinforcing the need to monitor and prepare for potential introductions.
Linked health data for pharmacovigilance in children: perceived legal and ethical issues for stakeholders and data guardians
Authors: Hopf Yvonne Marina , Bond Christine B , Francis Jill J , Haughney John , Helms Peter J 
Published: February 2014

ObjectiveThe inclusion of the Community Health Index in the recording of National Health Service (NHS) contacts in Scotland facilitates national linkage of data such as prescribing and healthcare utilisation. This linkage could be the basis for identification of adverse drug reactions. The aim of this article is to report the views of healthcare professionals on data sharing, ownership and the legal and other applicable frameworks relevant to linkage of routinely collected paediatric healthcare data.DesignQualitative study using semistructured face-to-face interviews addressing the study aims.ParticipantsPurposive sample of professional stakeholders (n=25) including experts on ethics, data protection, pharmacovigilance, data linkage, legal issues and prescribing. Interviews were audio-recorded, transcribed and thematically analysed using a framework approach.ResultsParticipants identified existing data sharing systems in the UK. Access to healthcare data should be approved by the data owners. The definition of data ownership and associated legal responsibilities for linked healthcare data were seen as important factors to ensure accountability for the use of linked data. Yet data owners were seen as facilitators of the proposed data linkage. Twelve frameworks (legal, regulatory and governance) applicable to the linkage of healthcare data were identified.ConclusionsA large number of potentially relevant legal and regulatory frameworks were identified. Ownership of the linked data was seen as an extension of responsibility for, or guardianship of, the source datasets. The consensus emerging from the present study was that clarity is required on the definition of data sharing, data ownership and responsibilities of data owners.
A systematic review of barriers to early presentation and diagnosis with breast cancer among black women
Authors: Jones Claire EL , Maben Jill , Jack Ruth H , Davies Elizabeth A , Forbes Lindsay JL , Lucas Grace , Ream Emma 
Published: February 2014

ObjectiveTo explore barriers to early presentation and diagnosis with breast cancer among black women.DesignSystematic review.MethodsWe searched multiple bibliographic databases (January 1991–February 2013) for primary research, published in English, conducted in developed countries and investigating barriers to early presentation and diagnosis with symptomatic breast cancer among black women (≥18 years). Studies were excluded if they did not report separate findings by ethnic group or gender, only reported differences in time to presentation/diagnosis, or reported on interventions and barriers to cancer screening. We followed Cochrane and PRISMA guidance to identify relevant research. Findings were integrated through thematic synthesis. Designs of quantitative studies made meta-analysis impossible.ResultsWe identified 18 studies (6183 participants). Delay was multifactorial, individual and complex. Factors contributing to delay included: poor symptom and risk factor knowledge; fear of detecting breast abnormality; fear of cancer treatments; fear of partner abandonment; embarrassment disclosing symptoms to healthcare professionals; taboo and stigmatism. Presentation appears quicker following disclosure. Influence of fatalism and religiosity on delay is unclear from evidence in these studies. We compared older studies (≥10 years) with newer ones (<10 years) to determine changes over time. In older studies, delaying factors included: inaccessibility of healthcare services; competing priorities and concerns about partner abandonment. Partner abandonment was studied in older studies but not in newer ones. Comparisons of healthy women and cancer populations revealed differences between how people perceive they would behave, and actually behave, on finding breast abnormality.ConclusionsStrategies to improve early presentation and diagnosis with breast cancer among black women need to address symptom recognition and interpretation of risk, as well as fears of the consequences of cancer. The review is limited by the paucity of studies conducted outside the USA and limited detail reported by published studies preventing comparison between ethnic groups.
More than a score: a qualitative study of ancillary benefits of performance measurement
Authors: Powell Adam A , White Katie M , Partin Melissa R , Halek Krysten , Hysong Sylvia J , Zarling Edwin , Kirsh Susan R , Bloomfield Hanna E 
Published: February 2014

BackgroundPrior research has examined clinical effects of performance measurement systems. To the extent that non-clinical effects have been researched, the focus has been on negative unintended consequences. Yet, these same systems may also have ancillary benefits for patients and providers—that is, benefits that extend beyond improvements on clinical measures. The purpose of this study is to identify and describe potential ancillary benefits of performance measures as perceived by primary care staff and facility leaders in a large US healthcare system.MethodsIn-person individual semistructured interviews were conducted with 59 primary care staff and facility leaders at four Veterans Health Administration facilities. Transcribed interviews were coded and organised into thematic categories.ResultsInterviewed staff observed that local performance measurement implementation practices can result in increased patient knowledge and motivation. These effects on patients can lead to improved performance scores and additional ancillary benefits. Performance measurement implementation can also directly result in ancillary benefits for the patients and providers. Patients may experience greater satisfaction with care and psychosocial benefits associated with increased provider–patient communication. Ancillary benefits of performance measurement for providers include increased pride in individual or organisational performance and greater confidence that one's practice is grounded in evidence-based medicine.ConclusionsA comprehensive understanding of the effects of performance measurement systems needs to incorporate ancillary benefits as well as effects on clinical performance scores and negative unintended consequences. Although clinical performance has been the focus of most evaluations of performance measurement to date, both patient care and provider satisfaction may improve more rapidly if all three categories of effects are considered when designing and evaluating performance measurement systems.
LncRNA profile study reveals a three-lncRNA signature associated with the survival of patients with oesophageal squamous cell carcinoma
Authors: Li Jiagen , Chen Zhaoli , Tian Liqing , Zhou Chengcheng , He Max Yifan , Gao Yibo , Wang Suya , Zhou Fang , Shi Susheng , Feng Xiaoli , Sun Nan , Liu Ziyuan , Skogerboe Geir , Dong Jingsi , Yao Ran , Zhao Yuda , Sun Jian , Zhang Baihua , Yu Yue , Shi Xuejiao , Luo Mei , Shao Kang , Li Ning , Qiu Bin , Tan Fengwei , Chen Runsheng , He Jie 
Published: February 2014

BackgroundOesophageal cancer is one of the most deadly forms of cancer worldwide. Long non-coding RNAs (lncRNAs) are often found to have important regulatory roles.ObjectiveTo assess the lncRNA expression profile of oesophageal squamous cell carcinoma (OSCC) and identify prognosis-related lncRNAs.MethodLncRNA expression profiles were studied by microarray in paired tumour and normal tissues from 119 patients with OSCC and validated by qRT-PCR. The 119 patients were divided randomly into training (n=60) and test (n=59) groups. A prognostic signature was developed from the training group using a random Forest supervised classification algorithm and a nearest shrunken centroid algorithm, then validated in a test group and further, in an independent cohort (n=60). The independence of the signature in survival prediction was evaluated by multivariable Cox regression analysis.ResultsLncRNAs showed significantly altered expression in OSCC tissues. From the training group, we identified a three-lncRNA signature (including the lncRNAs ENST00000435885.1, XLOC_013014 and ENST00000547963.1) which classified the patients into two groups with significantly different overall survival (median survival 19.2 months vs >60 months, p<0.0001). The signature was applied to the test group (median survival 21.5 months vs >60 months, p=0.0030) and independent cohort (median survival 25.8 months vs >48 months, p=0.0187) and showed similar prognostic values in both. Multivariable Cox regression analysis showed that the signature was an independent prognostic factor for patients with OSCC. Stratified analysis suggested that the signature was prognostic within clinical stages.ConclusionsOur results suggest that the three-lncRNA signature is a new biomarker for the prognosis of patients with OSCC, enabling more accurate prediction of survival.
Pre-procedural fasting for coronary interventions: is it time to change practice?
Authors: Hamid Tahir , Aleem Qaiser , Lau Yeecheng , Singh Ravi , McDonald John , Macdonald John E , Sastry Sanjay , Arya Sanjay , Bainbridge Anthony , Mudawi Telal , Balachandran Kanarath 
Published: February 2014

IntroductionTraditionally, patients are kept nil-per-os/nil-by-mouth (NPO/NBM) prior to invasive cardiac procedures, yet there exists neither evidence nor clear guidance about the benefits of this practice.ObjectivesTo demonstrate that percutaneous cardiac catheterisation does not require prior fasting.MethodsThe data source is a retrospective analysis of data registry of consecutive patients who underwent percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and stable angina at two district general hospitals in the UK with no on-site cardiac surgery services.ResultsA total of 1916 PCI procedures were performed over a 3-year period. None of the patients were kept NPO/NBM prior to their coronary procedures. The mean age was 67±16 years. 1349 (70%) were men; 38.5% (738/1916) had chronic stable angina, while the rest had ACS. 21% (398/1916) were diabetics while 53% (1017/1916) were hypertensive. PCI was technically successful in 95% (1821/1916) patients. 88.5% (1697/1916) had transradial approach. 77% (570/738) of elective PCI patients were discharged within 6 h postprocedure. No patients required emergency endotracheal intubation and there were no occurrences of intraprocedural or postprocedural aspiration pneumonia.ConclusionsOur observational study demonstrates that patients undergoing PCI do not need to be fasted prior to their procedures.
Attitudes towards cytology and human papillomavirus self-sample collection for cervical screening among Hindu women in London, UK: a mixed methods study
Authors: Cadman Louise , Ashdown-Barr Lesley , Waller Jo , Szarewski Anne 
Published: February 2014

ObjectivesTo explore the attitudes, views and understanding of women attending a Hindu temple in London, UK towards cervical screening, human papillomavirus (HPV) testing and two HPV self-sample collection devices: the Dacron swab and Evalyn®brush.MethodsA mixed methods design comprising a survey and four focus groups was adopted. Focus group discussions were recorded and transcribed verbatim and explored using thematic framework analysis.ResultsA total of 185 Hindu women completed surveys and 23 attended focus groups. Of the respondents 75% aged 25–64 years reported having cervical screening within the last 5 years; 85% had attended college or university. Familiar barriers to attendance for screening were identified: fear of pain and the test result, embarrassment, screener's attitude, inconvenient appointment times and difficulty with child care. Additional barriers cited included age and country of birth, with older and Indian-born women thought to be less likely to attend for screening. Self-collected sampling had a mixed reception. Women were not confident that their sample would be as good as a clinician sample and expressed concern about the impact that a positive HPV result might have on their relationships.ConclusionsScreening attendance in this highly educated group of Hindu women was slightly lower than in the general population (75% of women aged 25–64 years had been screened in the last 5 years compared with 79% in England as a whole). Familiar barriers to screening were identified. Women felt able to collect their own sample for HPV testing with a Dacron swab but lacked confidence that it would be as good as that obtained by a clinician.
Structure of a multiprocessor using microprogrammable building blocks
Authors: Davis R. L. , Zucker S. 
Published: February 2014

This paper describes a general purpose, microprogrammable, hardware building block called an Interpreter, an LSI-multiprocessing system in which the Interpreter is used, and a machine structure, implemented via firmware on the Interpreter.
The Interpreter consists of five types of functional modules, each partitioned for eventual implementation with LSI arrays of 450-750 gates and less than 126 signal pins. One of these functional units is the writable microprogram memory, whose contents define the function of the Interpreter. The flexibility of the Interpreter is typified by its present use as a device controller, a stand-alone emulator of other machines, and as a multiprocessor.
The Interpreter's main design concept allows functions formerly performed by software alone to be now performed by the emulating hardware. In this presentation an instruction set, which includes those software functions frequently and consistently used in operating systems, is emulated. The order code will allow for easy table and list manipulation or handling since much of scheduling and resource handling is confined to such operations.
The ability to write code independent of the data to be processed is provided by accessing information through descriptions. These descriptions can locate the requested information, describe its structure, impose controls on the use of the information and provide signals to the operating system for special functions.
Intrinsic Subtypes from the PAM50 Gene Expression Assay in a Population-Based Breast Cancer Survivor Cohort: Prognostication of Short- and Long-term Outcomes
Authors: Caan Bette J. , Sweeney Carol , Habel Laurel A. , Kwan Marilyn L. , Kroenke Candyce H. , Weltzien Erin K. , Quesenberry Charles P. , Castillo Adrienne , Factor Rachel E. , Kushi Lawrence H. , Bernard Philip S. 
Published: February 2014

Abstract
Background: The PAM50, a gene expression assay to categorize breast tumors into intrinsic subtypes, has not been previously used to examine short- and long-term prognostication in a population-based cohort where treatment patterns and time of initial follow-up vary.
Methods: In a stratified case–cohort design of 1,691 women from the LACE and Pathways breast cancer survivor cohorts, we used PAM50 to categorize tumors into Luminal A (LumA), Luminal B (LumB), HER2-enriched (HER2-E), Basal-like and Normal-like, and to examine risk of early and late recurrence and mortality by Cox proportional hazards regression.
Results: Compared with LumA, cumulative risk of recurrence and breast cancer death was higher for LumB, HER2-E, and Basal-like tumors at 2, 5, and 10 years. However, HR of breast cancer death varied over time [&lt;5 years (early) vs. &gt; 5 years (late)] for both Basal-like (HR, 6.23 early vs. HR, 0.63 late) and HER2-E tumors (HR, 2.97 early vs. HR, 0.73 late) but not for LumB tumors where risk was elevated consistently (HR, 2.67 early vs. HR, 1.47 late). The contrast between LumB, HER2-E, and Basal-like compared with LumA on early recurrence was stronger when subtype was defined by PAM50 than by immunohistochemistry (IHC) markers.
Conclusions: The PAM50 categorized intrinsic subtypes in a manner that more accurately predicts recurrence and survival, especially for luminal tumors, compared with commonly used methods that rely on traditional IHC clinical markers.
Impact: The PAM50 is robust for use in epidemiologic studies and should be considered when archived tumor tissues are available. Cancer Epidemiol Biomarkers Prev; 23(5); 725–34. ©2014 AACR.
Genetic Variants and Multiple Myeloma Risk: IMMEnSE Validation of the Best Reported Associations—An Extensive Replication of the Associations from the Candidate Gene Era
Authors: Martino Alessandro , Campa Daniele , Jurczyszyn Artur , Martínez-López Joaquín , Moreno María José , Varkonyi Judit , Dumontet Charles , García-Sanz Ramón , Gemignani Federica , Jamroziak Krzysztof , Stępień Anna , Jacobsen Svend E. Hove , Andersen Vibeke , Jurado Manuel , Landi Stefano , Rossi Anna Maria , Lesueur Fabienne , Marques Herlander , Dudziński Marek , Wątek Marzena , Moreno Victor , Orciuolo Enrico , Petrini Mario , Reis Rui Manuel , Ríos Rafael , Sainz Juan , Vogel Ulla , Buda Gabriele , Vangsted Annette Juul , Canzian Federico 
Published: February 2014

Abstract
Background: Genetic background plays a role in multiple myeloma susceptibility. Several single-nucleotide polymorphisms (SNP) associated with genetic susceptibility to multiple myeloma were identified in the last years, but only a few of them were validated in independent studies.
Methods: With the aim to conclusively validate the strongest associations so far reported, we selected the polymorphisms rs2227667 (SERPINE1), rs17501108 (HGF), rs3136685 (CCR7), rs16944 (IL1B), rs12147254 (TRAF3), rs1805087 (MTR), rs1800629 (TNF-α), rs7516435 (CASP9), rs1042265 (BAX), rs2234922 (mEH), and rs1801133 (MTHFR). We genotyped them in 1,498 multiple myeloma cases and 1,934 controls ascertained in the context of the International Multiple Myeloma rESEarch (IMMEnSE) consortium, and meta-analyzed our results with previously published ones.
Results: None of the selected SNPs were significantly associated with multiple myeloma risk (P value range, 0.055–0.981), possibly with the exception of the SNP rs2227667 (SERPINE1) in women.
Conclusions: We can exclude that the selected polymorphisms are major multiple myeloma risk factors.
Impact: Independent validation studies are crucial to identify true genetic risk factors. Our large-scale study clarifies the role of previously published polymorphisms in multiple myeloma risk. Cancer Epidemiol Biomarkers Prev; 23(4); 670–4. ©2014 AACR.