bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Lysine Residues within the Human Ribosomal Protein S17 Sequence Naturally Inserted into the Viral Nonstructural Protein of a Unique Strain of Hepatitis E Virus Are Important for Enhanced Virus Replication
Authors: Kenney Scott P. , Meng Xiang-Jin 
Published: January 2015

ABSTRACT
Hepatitis E virus (HEV) is an important but extremely understudied human pathogen. Due largely to the lack of an efficient cell culture system for HEV, the molecular mechanisms of HEV replication and pathogenesis are poorly understood. Recently, a unique genotype 3 strain of HEV recovered from a chronically infected patient was adapted for growth in HepG2C3A human hepatoma cells. The adaptation of the Kernow C-1 P6 HEV to propagate in HepG2C3A cells selected for a rare virus recombinant that contains an insertion of a 171-nucleotide sequence encoding amino acids 21 to 76 of the human ribosomal protein S17 (RPS17) within the hypervariable region (HVR) of the HEV ORF1 protein. When the RPS17 insertion was placed into a strain of genotype 1 HEV which infects only humans, it expanded the host range of the virus, allowing it to infect cell lines from multiple animal species, including cow, dog, cat, chicken, and hamster. In this study, we utilized forward and reverse genetics to attempt to define which aspects of the RPS17 insertion allow for the ability of the Kernow C-1 P6 HEV to adapt in cell culture and allow for expanded host tropism. We demonstrate that the RPS17 sequence insertion in HEV bestows novel nuclear/nucleolar trafficking capabilities to the ORF1 protein of Kernow P6 HEV and that lysine residues within the RPS17 insertion, but not nuclear localization of the ORF1 protein, correlate with the enhanced replication of the HEV Kernow C-1 P6 strain. The results from this study have important implications for understanding the mechanism of cross-species infection and replication of HEV.

IMPORTANCE
HEV is an important pathogen worldwide. The virus causes high mortality (up to 30%) in pregnant women and has been recognized to cause chronic hepatitis in immunocompromised populations. The life cycle of HEV has been understudied due to a lack of sufficient cell culture systems in which to propagate the virus. Recently, insertions and rearrangements of the hypervariable region (HVR) within the HEV genome, allowing for cell culture adaptation and expansion of the host range, have been reported. We utilized these cell culture-adapted HEV strains to assess how the HVR may be involved in virus replication and host range. We provide evidence that insertion of the RPS17 sequence in HEV likely confers nuclear trafficking capabilities to the nonstructural protein of the virus and that lysine residues within the RPS17 insertion are important for enhanced replication of the virus. These data will help to elucidate the mechanism of cross-species infection of HEV in the future.
Effect of study design and setting on tuberculosis clustering estimates using Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR): a systematic review
Authors: Mears Jessica , Abubakar Ibrahim , Cohen Theodore , McHugh Timothy D , Sonnenberg Pam 
Published: January 2015

ObjectivesTo systematically review the evidence for the impact of study design and setting on the interpretation of tuberculosis (TB) transmission using clustering derived from Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR) strain typing.Data sourcesMEDLINE, EMBASE, CINHAL, Web of Science and Scopus were searched for articles published before 21st October 2014.Review methodsStudies in humans that reported the proportion of clustering of TB isolates by MIRU-VNTR were included in the analysis. Univariable meta-regression analyses were conducted to assess the influence of study design and setting on the proportion of clustering.ResultsThe search identified 27 eligible articles reporting clustering between 0% and 63%. The number of MIRU-VNTR loci typed, requiring consent to type patient isolates (as a proxy for sampling fraction), the TB incidence and the maximum cluster size explained 14%, 14%, 27% and 48% of between-study variation, respectively, and had a significant association with the proportion of clustering.ConclusionsAlthough MIRU-VNTR typing is being adopted worldwide there is a paucity of data on how study design and setting may influence estimates of clustering. We have highlighted study design variables for consideration in the design and interpretation of future studies.
KRAS Mutant Allele-Specific Imbalance (MASI) assessment in routine samples of patients with metastatic colorectal cancer
Authors: Malapelle Umberto , Sgariglia Roberta , De Stefano Alfonso , Bellevicine Claudio , Vigliar Elena , de Biase Dario , Sepe Romina , Pallante Pierlorenzo , Carlomagno Chiara , Tallini Giovanni , Troncone Giancarlo 
Published: January 2015

AimsPatients with colorectal cancer harbouring KRAS mutations do not respond to antiepidermal growth factor receptor (anti-EGFR) therapy. Community screening forKRASmutation selects patients for treatment. When aKRASmutation is identified by direct sequencing, mutant and wild type alleles are seen on the sequencing electropherograms.KRASmutant allele-specific imbalance (MASI) occurs when the mutant allele peak is higher than the wild type one. The aims of this study were to verify the rate and tissue distribution ofKRASMASI as well as its clinical relevance.MethodsA total of 437 sequencing electropherograms showingKRASexon 2 mutation was reviewed and in 30 cases next generation sequencing (NGS) was also carried out. Five primary tumours were extensively laser capture microdissected to investigatedKRASMASI tissue spatial distribution.KRASMASI influence on the overall survival was evaluated in 58 patients. In vitro response to anti-EGFR therapy in relation to different G13DKRASMASI status was also evaluated.ResultsOn the overall,KRASMASI occurred in 58/436 cases (12.8%), being more frequently associated with G13D mutation (p=0.05) and having a heterogeneous tissue distribution.KRASMASI detection by Sanger Sequencing and NGS showed 94% (28/30) concordance. The longer overall survival ofKRASMASI negative patients did not reach statistical significance (p=0.08). In cell line model G13D KRAS MASI conferred resistance to cetuximab treatment.ConclusionsKRASMASI is a significant event in colorectal cancer, specifically associated with G13D mutation, and featuring a heterogeneous spatial distribution, that may have a role to predict the response to EGFR inhibitors. The foreseen implementation of NGS in communityKRAStesting may help to defineKRASMASI prognostic and predictive significance.
Association of Antigen-Specific T-cell Responses with Antigen Expression and Immunoparalysis in Multiple Myeloma
Authors: Fichtner Sabrina , Hose Dirk , Engelhardt Melanie , Meißner Tobias , Neuber Brigitte , Krasniqi Fatime , Raab Marc , Schönland Stefan , Ho Anthony D. , Goldschmidt Hartmut , Hundemer Michael 
Published: January 2015

AbstractPurpose: Cancer testis antigens (CTA) are immunotherapeutical targets aberrantly expressed on multiple myeloma cells, especially at later stages, when a concomitant immunoparesis hampers vaccination approaches.Experimental Design: We assessed the expression of the multiple myeloma antigen HM1.24 (reported present in all malignant plasma cells) and the CTAs MAGE-A2/A3 and NY-ESO-1 (aberrantly expressed in a subset of patients with myeloma), in CD138-purified myeloma cells by qRT-PCR (n = 149). In a next step, we analyzed the antigen-specific T-cell responses against these antigens by IFNγ EliSpot assay (n = 145) and granzymeB ELISA (n = 62) in relation to stage (tumor load) and expression of the respective antigen.Results: HM1.24 is expressed in all plasma-cell samples, whereas CTAs are significantly more frequent in later stages. HM1.24-specific T-cell responses, representing the immunologic status, significantly decreased from healthy donors to advanced disease. For the CTAs, the probability of T-cell responses increased in early and advanced stages compared with healthy donors, paralleling increased probability of expression. In advanced stages, T-cell responses decreased because of immunoparesis.Conclusion: In conclusion, specific T-cell responses in myeloma are triggered by antigen expression but suppressed by tumor load. Future CTA-based immunotherapeutical approaches might target early plasma-cell diseases to establish prophylactically a specific T-cell response against late-stage antigens in immunocompetent patients. Clin Cancer Res; 21(7); 1712–21. ©2015 AACR.
Detection, Characterization, and Inhibition of FGFR–TACC Fusions in IDH Wild-type Glioma
Authors: Di Stefano Anna Luisa , Fucci Alessandra , Frattini Veronique , Labussiere Marianne , Mokhtari Karima , Zoppoli Pietro , Marie Yannick , Bruno Aurelie , Boisselier Blandine , Giry Marine , Savatovsky Julien , Touat Mehdi , Belaid Hayat , Kamoun Aurelie , Idbaih Ahmed , Houillier Caroline , Luo Feng R. , Soria Jean-Charles , Tabernero Josep , Eoli Marica , Paterra Rosina , Yip Stephen , Petrecca Kevin , Chan Jennifer A. , Finocchiaro Gaetano , Lasorella Anna , Sanson Marc , Iavarone Antonio 
Published: January 2015

Abstract
Purpose: Oncogenic fusions consisting of fibroblast growth factor receptor (FGFR) and TACC are present in a subgroup of glioblastoma (GBM) and other human cancers and have been proposed as new therapeutic targets. We analyzed frequency and molecular features of FGFR–TACC fusions and explored the therapeutic efficacy of inhibiting FGFR kinase in GBM and grade II and III glioma.
Experimental Design: Overall, 795 gliomas (584 GBM, 85 grades II and III with wild-type and 126 with IDH1/2 mutation) were screened for FGFR–TACC breakpoints and associated molecular profile. We also analyzed expression of the FGFR3 and TACC3 components of the fusions. The effects of the specific FGFR inhibitor JNJ-42756493 for FGFR3–TACC3–positive glioma were determined in preclinical experiments. Two patients with advanced FGFR3–TACC3–positive GBM received JNJ-42756493 and were assessed for therapeutic response.
Results: Three of 85 IDH1/2 wild-type (3.5%) but none of 126 IDH1/2-mutant grade II and III gliomas harbored FGFR3–TACC3 fusions. FGFR–TACC rearrangements were present in 17 of 584 GBM (2.9%). FGFR3–TACC3 fusions were associated with strong and homogeneous FGFR3 immunostaining. They are mutually exclusive with IDH1/2 mutations and EGFR amplification, whereas they co-occur with CDK4 amplification. JNJ-42756493 inhibited growth of glioma cells harboring FGFR3–TACC3 in vitro and in vivo. The two patients with FGFR3–TACC3 rearrangements who received JNJ-42756493 manifested clinical improvement with stable disease and minor response, respectively.
Conclusions: RT-PCR sequencing is a sensitive and specific method to identify FGFR–TACC–positive patients. FGFR3–TACC3 fusions are associated with uniform intratumor expression of the fusion protein. The clinical response observed in the FGFR3–TACC3–positive patients treated with an FGFR inhibitor supports clinical studies of FGFR inhibition in FGFR–TACC–positive patients. Clin Cancer Res; 21(14); 3307–17. ©2015 AACR.
See related commentary by Ahluwalia and Rich, p. 3105
HER Targeting in HER2-Negative Breast Cancers: Looking for the HER3 Positive
Authors: Campbell Marcia R. , Moasser Mark M. 
Published: January 2015

Abstract
Targeting HER2 for the treatment of HER2-positive breast cancers is now a validated treatment paradigm. However, evidence suggests that this family of receptors may have important roles outside of the realm of HER2 amplification. There is considerable interest in the development of biomarkers to identify such breast cancers. Clin Cancer Res; 21(13); 2886–8. ©2015 AACR.
See related article by Leary et al., p. 2932
Assessing and Improving the Local Added Value of WRF for Wind Downscaling
Authors: García-Díez M. , Fernández J. , San-Martín D. , Herrera S. , Gutiérrez J. M. 
Published: January 2015

AbstractLimited area models (LAMs) are widely used tools to downscale the wind speed forecasts issued by general circulation models. However, only a few studies have systematically analyzed the value added by the LAMs to the coarser-resolution-model wind. The goal of the present work is to investigate how added value depends on the resolution of the driving global model. With this aim, the Weather Research and Forecasting (WRF) Model was used to downscale three different global datasets (GFS, ERA-Interim, and NCEP–NCAR) to a 9-km-resolution grid for a 1-yr period. Model results were compared with a large set of surface observations, including land station and offshore buoy data. Substantial biases were found at this resolution over mountainous terrain, and a slight modification to the subgrid orographic drag parameterization was introduced to alleviate the problem. It was found that, at this resolution, WRF is able to produce significant added value with respect to the NCEP–NCAR reanalysis and ERA-Interim but only a small amount of added value with respect to GFS forecasts. Results suggest that, as model resolution increases, traditional skill scores tend to saturate. Thus, adding value to high-resolution global models becomes significantly more difficult.
Recent Intensification of the Western Pacific Subtropical High Associated with the East Asian Summer Monsoon
Authors: Matsumura Shinji , Sugimoto Shiori , Sato Tomonori 
Published: January 2015

Abstract
The summer western Pacific subtropical high (WPSH) has intensified during the past three decades. However, the underlying mechanism is not yet well understood. Here, it is shown that baiu rainband activity in midsummer, which is part of the East Asian summer monsoon, plays an important role in recent intensification in the WPSH along the baiu rainband. In contrast with the WPSH, the summer Okhotsk high, which is located to the north of the baiu rainband, has weakened during the past three decades. The north–south contrasting changes between the two highs reflect a response to northward-moved and enhanced baiu heating, which intensifies the upper-tropospheric ridge, resulting in the baroclinic intensification of the WPSH. Regional climate model experiments also support the observational analysis. Therefore, baiu convective activity in midsummer can act as a major driver for the WPSH intensification. The results here suggest that the mechanism intensifying the summer North Pacific subtropical high clearly differs between the western and eastern Pacific.
The Redesign of a Community Pharmacy Internship Program
Authors: Pattin Anthony J. , Kelling Sarah E. , Szyskowski Jim , Izor Michelle L. , Findley Susan 
Published: January 2015

Background: Pharmacy internships provide students with practical experiences that lead to enhancement of clinical skills and personal growth. Objective: To describe the design and implementation of a structured 10-week summer pharmacy internship program in a supermarket chain pharmacy. Methods: The pharmacy leadership team developed and piloted a new format of the pharmacy internship during the summer of 2013. Pharmacy students in professional year 1 (P1), 2 (P2), and 4 (P4) were invited to apply for a paid internship. Pharmacy students were recruited from all colleges of pharmacy in the state of Michigan. The goal of the new program was to create a focused learning opportunity that encouraged students to develop knowledge, skills, and abilities about patient care, pharmacy management, and working within a team. Results: A total of 19 interns were recruited (P1 = 7, P2 = 7, and P4 = 5). Students practiced 40 hours per week and participated in the medication dispensing process and employee biometrics screening program. Interns provided approximately 500 assessments on pharmacy employees and all P1 and P2 interns completed a patient care project. Conclusions: The restructured internship program provided pharmacy students with a 10-week program that exposed them to many aspects of community pharmacy practice. The program needs future refinement and assessment measures to verify interns improve skills throughout the program.
Analyzing the Validity of the Adult-Adolescent Parenting Inventory for Low-Income Populations
Authors: Lawson Michael A. , Alameda-Lawson Tania , Byrnes Edward 
Published: January 2015

Objectives: The purpose of this study was to examine the construct and predictive validity of the Adult-Adolescent Parenting Inventory (AAPI-2). Methods: The validity of the AAPI-2 was evaluated using multiple statistical methods, including exploratory factor analysis, confirmatory factor analysis, and latent class analysis. These analyses were conducted using data collected from a culturally diverse sample of 2,160 low-income parents. Results: Although the AAPI-2 yielded high reliability coefficients, analyses of the instrument’s validity diverged significantly from the results reported by the instrument’s developers. Specifically, the instruments’ reported five-factor structure was not supported in this study. Moreover, parents’ AAPI-2 scores were not associated with child abuse as originally hypothesized. However, when the AAPI-2 was analyzed as a categorical latent variable, the results were useful in identifying parents who were unlikely to abuse or neglect their children. Conclusion: Further replication and extension research on the AAPI-2 with other low-income populations is warranted.
Developing Dynamic Innovative Capabilities: The Growing Role of Innovation and Learning in the Development of Organisations and Skills in Developed and Emerging Nations of Europe
Authors: Makó Csaba , Mitchell Brian , Illéssy Miklós 
Published: January 2015

The concepts of ‘high performance working system' (HPWS) and lean production represent the theoretical and methodological foundations of this article. We make a distinction between three theoretical strands of the HPWS and the lean production approaches, namely: ( i) the diffusion of the Japanese-style management and organisational practices both in the US and in the Europe (Aoki, 1990; Ramsay, Scholarios and Harley, 2000; Wood, 1999); ( ii) the approach developed by advocates of the sociology of work, which deal with the learning/innovation capabilities of new forms of organisation of work (Makó, 2005; Valeyre et al., 2009); and ( iii) the various types knowledge and learning process and their relations with the innovation capabilities of the firm (Lam, 2005; Makó, Illéssy and Csizmadia, 2012). We develop our arguments in both spatial and temporal contexts. A micro-level analysis accompanying our macro-level enquiry enables us to illustrate the key factors driving or impeding innovation and learning at both country- and firm-specific scenarios. We carry out international comparative analysis using both employer- and employee-focused surveys to demonstrate the diffusion and outcomes of workplace innovation in knowledge-based (information and communication technology [ICT] and business services) firms. We present the results of the various waves of the employers-oriented community innovation surveys (CIS) with special focus on the periods of ‘pre' and ‘after' financial crises and the economic downturn. We also draw on some of the empirical lessons on the innovation/learning capabilities of the work-organisations based on the European working conditions surveys (EWCS) and the views of employees. Finally, we select the fast-growing knowledge intensive business service (KIBS) sector to illustrate the key role of workplace/organisational innovations and their drivers in two selected post-social countries: Hungary and Slovakia. The aggregated country-level data do not help us to understand the drivers and enablers of innovation. We contend that sector-focused analysis may help us to better understand the roles of these factors in the overall innovation performance of each country. For the purpose of illustration, the diffusion of organisational innovations and company knowledge development practices were analysed in the Hungarian and Slovak KIBS sector. Slovak firms had a leading position compared to the Hungarian firms implementing more radical forms of organisational innovations which were accompanied with more robust learning practices. Drivers explaining this variety were the degree of countries' involvement (embedding) in the internationalisation of the service activities and the development of networking (company group membership) process.
Community Health Needs Assessments: Filling Data Gaps for Population Health
Research and Management
Authors: Alberti Philip 
Published: January 2015

Introduction: Community health needs assessments (CHNA) are completed to meet
varied regulatory and statutory requirements for local public health departments,
tax-exempt 501(c)(3) hospitals, and Federally Qualified Health Centers. Although
compliance is a motivating factor, these entities are committed to understanding the
communities they serve and to developing strategies to address health needs and
inequities in health and health care.Filling Data Gaps: CHNAs have the potential to
improve the health of communities and populations by giving crucial qualitative and
quantitative context to hospital and patient data, thereby enhancing opportunities for
health services and clinical outcomes researchers. Filling in these data gaps can help
to improve population health by highlighting communityand social determinant-related
dynamics relevant to the improved health of the community.CHNAs and EHRs for Population
Health: Successful models exist that that have used CHNAs and the resulting data to
improve population health management and reduce inequities, as do health systems that
have used the EHR and community-based performance measurement data to achieve population
health goals.
The crystal structure of 4-bromobenzoic acid — triphenylphosphane oxide — water (1:2:1), C79H69BrO8P4
Authors: Mukiza Janvier , Gerber Thomas I. A. , Hosten Eric C. , Betz Richard 
Published: January 2015

Abstract C79H69BrO8P4, triclinic, P1̅ (no. 2), a = 8.8310(4) Å, b = 9.7790(4) Å, c = 20.4514(8) Å, α = 87.361(2)°, β = 78.463(2)°, γ = 76.439(2)°, V = 1682.2 Å3, Z = 1, Rgt(F) = 0.0331, wRref(F2) = 0.0907, T = 200 K.
A Secondary Ion Mass Spectrometry Study on the Mechanisms of Amorphous Silicon Electrode Lithiation in Li-Ion Batteries
Authors: Hüger Erwin , Jerliu Bujar , Dörrer Lars , Bruns Michael , Borchardt Günter , Schmidt Harald 
Published: January 2015

Abstract
Electrodes made of amorphous silicon are a promising alternative to
graphite as anode material for the next generation of high-capacity
Li-ion batteries. In order to optimize such batteries the
mechanism of lithium incorporation into the electrode during charging
has to be elucidated. In the present study we measured the
modification of lithium distribution taking place during galvanostatic
lithiation of about 600 nm thick amorphous silicon film
electrodes at low current densities of about
30 μA/cm2 (∼ C/14) by Secondary Ion
Mass Spectrometry. The results were confirmed by X-ray Photoelectron
Spectroscopy. The results indicate a two-step lithiation procedure
where the electrode is transformed first into a homogeneously
lithiated Li
x
Si phase with a low Li content of
x ≈ 0.3. During later stages of the lithiation process, the
results are in agreement with the penetration of a highly lithiated
phase via a moving phase boundary, as also observed for crystalline
silicon.
Shared rhytidectomy continued to lateral canthoplasty in a Mastiff with excessive facial folding and macroblepharon
Authors: Steinmetz A. 
Published: January 2015

SummaryA 3.5-year-old male Neapolitan Mastiff was presented with an obstructed visual axis because of excessive facial skin folds, brow droop, macroblepharon, upper eyelid entropion and lower ectropion-entropion. To address these major defects a technique was performed which combines rhytidectomy with shortening of the palpebral fissure and stabilization of the lateral canthus. Postoperatively the dog showed an unobstructed visual axis with comfortable and symmetrical eyes.